PB84-232560
Use of Short-Term Bioassays to Evaluate Environmental Impact of  Land
Treatment of Hazardous Industrial Waste
Texas A&M University
College Station, Texas
Aug 84
                     U.S. DEPARTMENT OF COMMERCE
                  National Technical Information Service
                                   KITS

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                                        EPA-600/2-84-135
                                        August 1984
    USE OF SHORT-TERM BIOASSAYS TO EVALUATE
   ENVIRONMENTAL IMPACT OF LAND TREATMENT OF
           HAZARDOUS INDUSTRIAL WASTE
                       by
  K. W. Brown, K. C. Donnelly and J. C. Thomas
     Texas Agricultural Experiment Station
              Texas A&M University
          College Station, Texas 77843
             Grant No. CR-807701-01
                Project Officer
                 John Matthews
Robert S. Kerr Environmental Research Laboratory
                 P. 0. Box 1198
              Ada, Oklahoma 74820
ROBERT S. KERR ENVIRONMENTAL RESEARCH LABORATORY
      U.S. ENVIRONMENTAL.PROTECTION AGENCY
              ADA, OKLAHOMA 74820

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                                   TECHNICAL REPORT DATA
                            (Please read Instructions on the reverse before completing)
 1. REPORT NO.
   EPA-600/2-84-135
                                                           3. RECIPIENT'S ACCESSION-NO.
                    PB8U-232560
 4. TITLE AND SUBTITLE
 Use of Short-term Bioassays  to Evaluate Environmental
 Impact of Land  Treatment  of  Hazardous Industrial Waste
             5. REPORT DATE
                August 1984
             6. PERFORMING ORGANIZATION CODE
 7. AUTHOR(S)
 K.  W.  Brown, K. C. Donnelly,  and J.  C.  Thomas
                                                           8. PERFORMING ORGANIZATION REPORT NO,
9. PERFORMING ORGANIZATION NAME AND ADDRESS
Texas Agricultural Experiment  Station
Texas A&M University
College Station, TX  77843
             10. PROGRAM ELEMENT NO.

                 CBRD1A
                                Coop.  Agree
                                                                    CR807701
 12. SPONSORING AGENCY NAME AND ADDRESS
 R.  S.  Kerr Environmental Research  Laboratory
 P.  0.  Box 1198
 Ada, OK  74820
              13. TYPE OF REPORT AND PERIOD COVERED
               Final  9/1/80 -  11/30/83
              14. SPONSORING AGENCY CODE
                                                             EPA/600/15
 15. SUPPLEMENTARY NOTES
            A four phase study was conducted to evaluate utility of short-term bioassays
in monitoring environmental impact of  land  treatment of hazardous waste.   During phase
one,  three microbial bioassays were conducted to define chronic toxic potential of
each  waste selected for study.  Acid,  base,  and neutral fractions of each  of  three
wastes  studied induced genetic damage  in  at least two of the three bioassays.
      Phase two was conducted to evaluate  efficiencies of blender and soxhlet  extraction
procedures,  as well as potential interactions between known mutagens and soil compo-
nents.  Results indicate that there was no  appreciable difference in mutagenicity of
the extract  using either procedure.  Using  the blender procedure extraction efficiency
for pure  compounds added to soil averaged greater than 85%, as measured by High Pressur
 iquid  Chromotography.
      Phase three consisted of a greenhouse  study in which each of three wastes  was
applied to two soils.   Results from chemical  analyses indicate that waste  constituents
*ere  degraded in soil  during a 360 or  340 day interval.   Increased mutagenic  activity
*as exhibited in some  soil and water extracts during this same interval.   When  compared
an an equivalent volume basis,  however, mutagenic  potential of waste-amended  soils was
reduced over  time and, in some cases,  was reduced  to a non-mutagenic level.
     Wood-preserving bottom sediment was applied to  barrel-sized lysimeters in  the fina'
>roject phase to compare results of soil-core and  soil-pore liquid monitoring.  Differed
:vpes of compounds  TJPT-O ijofoq^o^ jn EOJl-Corc 3nd  Tm'1  nnrj 1i~i..i.l 	 l"
                              ~~  ™ •••— — — _ _ „ *p^^^^^T^^^^ u \J .i. ,fc, 1^•"^•^^•••W
 7.
                                KEY WORDS AND DOCUMENT ANALYSIS
                  DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS  C. COS AT I Field/Group
 Industrial Wastes
 Bioassays
 Waste'Treatment
 Land
Land Treatment
Operational Monitoring
Mutagenicity
Microbial Tests
     68C
 8. DISTRIBUTION STATEMENT

     Release to public
19. SECURITY CLASS (ThisReport/
     Unclassified
21. NO. OF PAGES
    386
                                              20. SECURITY CLASS (Thispage)
                                              	Unclassified
                                                                        22. PRICE
EPA Form 2220-1 (9-73)

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                               DISCLAIMER
     Although the research described in this article has been funded wholly
or in part by the U.S. Environmental Protection Agency under assistance agree-
ment CR807701 to Texas A&M University, it has not been subjected to the Agency's
peer and administrative review and therefore may not necessarily reflect the
views of the Agency, and no official endorsement should be inferred.
                                    ii

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                                 FOREWORD
     EPA is charged by Congress to protect the Nation's land, air and water
systems.  Under a mandate of national  environmental  laws focused on air and
water quality, solid waste management  and the control  of toxic substances,
pesticides, noise, and radiation, the  Agency strives to formulate and imple-
ment actions which lead to a compatible balance between human activities and
the ability of natural systems to support and nurture  life.

     The Robert S. Kerr Environmental  Research Laboratory is the Agency's
center of expertise for investigation  of the soil  and  subsurface environment.
Personnel at the Laboratory are responsible for management of research pro-
grams to:  (a) determine the fate, transport and transformation rates of
pollutants in the soil, the unsaturated zone and the saturated zones of the
subsurface environment; (b) define the processes to  be used in characterizing
the soil and subsurface environment as a receptor of pollutants; (c) develop
techniques for predicting the effect of pollutants on  ground water, soil and
indigenous organisms; and (d) define and demonstrate the applicability and
limitations of using natural processes, indigenous to  the soil  and subsurface
environment, for the protection of this resource.

     This project was initiated to determine the utility of short-term
bioassays in monitoring the operation  of land treatment systems.  Results
indicate that selected organic hazardous wastes can  be treated in land
treatment units and that bioassays can be used to monitor detoxification
of organic hazardous waste constituents.  This information should prove
useful  to those responsible for regulating, designing, and operating
hazardous waste land treatment systems.
                                       Clinton W.  Hall
                                       Director
                                       Robert S.  Kerr Environmental
                                         Research  Laboratory
                                   m

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                                ABSTRACT
     A  four  phase  study  was  conducted  to  evaluate  the  utility  of
short-term  bioassays  in monitoring the  environmental  impact of the  land
treatment of  hazardous industrial wastes.  In the waste  characterization
phase, the  acute  toxicity of ten wastes was  evaluated  in bioassays using
Bacillus    subtilis,    Salmonella    typhimurium,   and    haploid    and
diploid  forms  of  Aspergillus  nidulans.  Based  on the  results  of   the
acute  toxicity  study  and a chemical  characterization,  three wastes  were
selected  for  an  evaluation  of  chronic  toxicity.  The  acid,  base,   and
neutral fractions  of  each of the three  wastes  induced genetic damage in
at least two of the three bioassays.

     In  the second  phase,   the  additive  effect  of  2-nitrofluorene  or
benzo[a]pyrene  to  the  soil  was  evaluated,  using both  the  prokaryotic
point  mutation assay  and  high  performance  liquid chromatography.   The
results from  this  portion  of the  study have  been used  to evaluate  the
efficiency  of  the blender and soxhlet extraction procedures,  as well  as
the  potential  interactions between  known mutagens  and  soil  components.
The  results indicate  that while greater quantities of hydrocarbons  were
extracted using  the Soxhlet method,  there  was  no appreciable difference
in the mutagenicity of the extract using  either  procedure. In addition,
when  pure  compounds were  added  to  the  soil,  the extraction efficiency
averaged  greater  than 85%,  as  measured  by HPLC; while   there  was  no
statistical difference in  the mutagenicity  of the pure  compound or  the
extract of  the soil plus the compound.

     Phase  three  consisted  of a greenhouse study in which  each of three
wastes was  applied to  two soils.   Soil,  plant,  and runoff samples  were
collected at various  times over  a  360 or  540 day  interval.   The  results
from chemical  analysis  indicate  that waste constituents  were  degraded in
soil;  however,   the  bioassay  results  indicate   that   the  degradative
process may have  increased  the  mutagenic potential  of  soil and water
extracts,   as   well as  converting  indirect  acting  mutagens  to  direct
acting compounds.

     Barrel-sized  lysimeters  were  used in the  final phase  of  the  project
to compare  soil-core  and soil-pore  liquid monitoring.  A wood-preserving
bottom sediment  waste  was applied  to  three  lysimeters.  Three additional
lysimeters  to  which no waste was applied  served  as a  control.  Leachate
and  soil  samples were  collected  prior  to,   30,  and 90 days after waste
application. The  results  from this portion of  the  study  indicate  that if
a   land   treatment  facility   is   not   properly  managed,   mutagenic
                                  iv

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constituents from  land  applied waste may migrate  through the soil.   The
results  from  this research  have demonstrated  that hazardous industrial
wastes may  contain significant  quantities  of mutagenic materials.   Soil
incorporation   of   three  wastes   resulted   in  the  transformation   or
degradation  of mutagenic  materials,  although  these  reactions  did  not
always reduce  the  mutagenic activity of soil extracts.   In  addition,  for
the  waste,  soil,  and  loading  rate  evaluated  in  the  lysimeter  study,
attenuation  of  waste  constituents  was   not  sufficient  to   prevent
mutagenic compounds  from migrating to a depth  of  90  cm.   This  research
has  demonstrated   that  short-term  bioassays can  be  used   to  trace  the
environmental  fate of mutagenic constituents  in  land applied hazardous
industrial wastes.

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                               CONTENTS

Abstract	
Figures	    vi
Tables	    xviii
Acknowledgements 	xxvi
  1.  Introduction  	   1
  2.  Conclusions 	   5
  3.  Recommendations  	   7
  4.  Biological Analysis  	   8
       Introduction  	   8
         Differential  DNA  Repair  	   9
           Test System Description  	    9
           Test System Protocol	9
           Test System Results	11
         Point Mutations:  Prokaryote  	   15
           Test System Description	15
           Test System Protocol	18
           Test System Results	21
         Point Mutations and  Chromosome  Damage:  Eukaryote	   36
           Test System Description	36
           Test System Protocol	37
           Test System Results	44
         Evaluation  of the Battery  of Bioassays	48
  5. Waste Characterization 	  50
       Introduction  	  50
       Materials and Methods	51
         Wastes	51
         Extraction	55
         Chemical analysis	57
         Biological  analysis	57
       Results  and  Discussion 	  61
  6. Soil Characterization	135
       Introduction	135
       Materials and Methods	136
         Soil	136
         Biological  analysis	137
       Results  and  Discussion 	  138
  7. Quantification of Soil Extraction	155
       Introduction 	  155
       Materials and Methods	156
         Selection  of  Mutagenic Compounds and Soils	157
         Soil  Preparation  and Chemical Addition	157
                                   vi

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         Extraction Procedure and Sample Preparation	159
         Bioassay	159
         High Performance Liquid Chromatography	160
       Results and Discussion	160
  8.  Mutagenic Activity of Runoff Water From Hazardous
     Waste Amended Soil	176
       Introduction	176
       Materials and Methods	176
         Waste	176
         Soil	177
         Greenhouse boxes	177
         Extraction procedures	180
         Chemical analysis	180
         Biological analysis	181
       Results and Discussion	182
  9.  Affect of Degradation on the Mutagenic Activity of
     Waste Amended soil	217
       Introduction	217
       Materials and Methods 	  218
         Waste	218
         Soil	218
         Extraction Procedures	218
         Chemical analysis	218
         Soil Sample Collection	218
         Biological analysis	219
       Results and Discussion 	 220
 10.  Soil Mobility and Degradation of Mutagenic Constituents
     from a Wood-Preserving Bottom Sediment	321
       Introduction	321
       Materials and Methods	321
         Soil	321
         Waste	323
         Lysimeters	323
         Leachate Sample Collection	323
         Soil Sample Collection	325
         Biological analysis	 325
       Results and Discussion	325
 11.  Literature Cited	340
Appendices (on file at Ada, Oklahoma).
     A.  Quality Assurance Program
     B.  Standard Operating Procedures
       1.  Biological
       2.  Chemical
       3.  Agricultural  (Greenhouse)
     C.  Raw Data
       1.  Waste characterization
       2.  Greenhouse study
       3.  Lysimeter study
       4.  Extraction study
       5.  Aspergillus
     D.  Computer Programs
                                 vii

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                                    FIGURES
Number                                                               Page

  1   Potential effects of environmental mutagens on human
      cells	3

  2   Lethal effect of increasing doses of benzo(a)pyrene on
      repair proficient (168 wt) and deficient strains of
      B.subtilis with metabolic activation 	      16

  3   Lethal effect of increasing doses of 2-aminoanthracene
      on repair proficient (168 wt) and deficient strains of
      B.subtilis with metabolic activation   	      17

  4   Variability of mutagenic activity of TA100 induced by MMS.  .  .   27

  5   Variability of mutagenic activity of TA100 induced by MNNG.  .  .  28

  6   Variability of mutagenic activity of TA98 induced by 2NF.  ...  30

  7   Variability of mutagenic activity of TA100 induced by B(a)P.  .  .31

  8   Variability of mutagenic activity of TA100 induced by 2AA.  .  .  .32

  9   Variability of mutagenic activity of TA98 induced by B(a)P.  .  .  33

  10  Variability of mutagenic activity of TA98 induced by 2AA.  ...  34

  11  Genotype of Aspergillus nidulans diploid 20	43

  12  Fractionation scheme used for waste and waste-amended soils  .  .  56

  13  Percent survival of JB. subtilis strain 168, j>.
      typhimurium strain TA100, and A. nidulans diploid 109,
       after exposure to (a) wood-preserving bottom sediments  waste,
      (b) acetonitrile purification column waste,  (c) wood
      preserving liquid waste,  (d) slop-oil  emulsion solids waste  .  .  62

  14  Percent survival of IJ. subtilis strain 168, j>.
      typhimurium strain TA100, and A. nidulans diploid 109,
      after exposure to (a) dissolved air floatation float waste,
      (b) methyl ethyl ketone waste,(c) storm-water runoff impound-
      ment waste, (d) combined API separator/waste-water treatment
      sludge waste  	  63
                                viii

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                              FIGURES  (continued)

Number                                                             page

  15  Mutagenicity, as measured with j>. typhimurium
      strain TA98, of fractions of acetonitrile waste   	    65

  16  Mutation frequency induced by neutral  fraction of
      methyl ethyl ketone  (MEK) waste  in A.  nidulans
      methionine system  	    69

  17  Growth inhibition induced by fractions of methyl  ethyl
      ketone waste in DNA  repair proficient  (168 wt) and
      deficient strains of IJ. subtilis	        71

  18  Mutagenic activity,  as measured  in j>.  typhimurium
      strain TA98, of fractions of methyl  ethyl ketone  waste
      (MEK)	72

  19  Mutagenic activity,  with metabolic activation, of crude
      (A), acid (B), base  (C), and neutral (D) fraction of
      PENT S (wood preserving bottom sediment) from  two blender
      extractions and one  soxhlet extraction 	  74

  20  Mutagenic activity of fractions  of the PENT  S  (wood
      preserving  bottom sediment) waste 	  78

  21  Mutagenic activity,  as measured  in S_.  typhimurium
      strain TA100, of fractions of PENTS  (wood preserving
      bottom  sediments) waste  	  79

  22  Mutagenic activity of acid fraction  of PENT  S  waste as
      measured with high,  medium, and  low  levels of  S9  in the
      S9 mix	82

  23  Mutagenic activity of base fraction  of PENT  S  waste as
      measured with high,  medium, and  low  levels of  S9  in the
      S9 mix	83

  24  Mutagenic activity of neutral fraction of PENT S  waste  as
      measured with high,  medium, and  low  levels of  S9  in the
      S9 mix	84

  25  Growth inhibition induced by  fractions of the  wood
      preserving bottom sediment in repair proficient  (168 wt)
      and deficient strains of  B. subtilis	87
                               —  ~~^^^^^^~—         *
  26  Induced mutation frequency and  fractional survival in A.
      nidulans following exposure to  acid  fraction of  PENT S
      waste	89
                                 ix

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                              FIGURES (continued)

Number                                                              Page

  27  Induced mutation frequency and fractional survival  in
      A. nidulans following exposure to base fraction of
      PENT S waste	90

  28  Induced mutation frequency and fractional survival  in
      A. nidulans following exposure to neutral fraction  of
      PENT S waste	91

  29  GC/MS chromatograph of acid fraction of  PENT  S waste	100

  30  GC/MS chromatograph of base fraction of  PENT  S waste	101

  31  GC/MS chromatograph of neutral fraction  of  PENT S waste.  .  .  .  102

  32  Mutagenic activity of fractions of  SWRI  waste	106

  33  Mutagenic activity of subfractions  of neutral fraction
      of SWRI waste	107

  34  Induced mutation frequency and fractional survival  in  A.
      nidulans following exposure to acid fraction  of SWRI
      waste	112

  35  Induced mutation frequency and fractional survival  in  A.
      nidulans following exposure to base fraction  of SWRI
      waste	113

  36  Induced mutation frequency and fractional survival  in  A.
      nidulans following exposure to neutral  fraction of  SWRI
      waste	114

  37  Mutagenic activity of fractions of  COMBO waste  	  117

  38  Mutagenic activity of subfractions  of neutral fraction of
      COMBO waste	119

  39  Mutagenic response of base fraction of  COMBO  waste  using
      metabolic activation  from Aroclor  1254  or phenobarbitol
      induced rat  liver	120

  40  Induced mutation frequency and fractional survival  in  A.
      nidulans following exposure to acid fraction  of COMBO
      waste	124

  41  Induced mutation frequency and fractional survival  in  A.
      nidulans following exposure to base fraction  of COMBO
      waste	125

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                            FIGURES  (continued)

Number                                                           Page

42  Induced mutation frequency and fractional survival
    in A. nidulans following exposure to neutral
    fraction of COMBO waste	    126

43  GC/MS chromatograph of acid  fraction of  COMBO waste	    128

44  GC/MS chromatograph of base  fraction of  COMBO waste	    129

45  GC/MS chromatograph of neutral fraction  of  COMBO waste.  .  .  .   130

46  Mutagenic activity of organic extract  of three  agricul-
    tural soils as measured with J3.  typhimurium,  strain
    TA98, with metabolic activation	140

47  Mutagenic activity of organic extract  of three  agricul-
    tural soils as measured with £5.  typhimurium,  strain
    TA100, with metabolic activation 	  141

48  Mutagenic activity of one  gram of soil as compared  to
    cigarette smoke condensate  	  142

49  Mutagenic activity of organic extract  of three  agricul-
    tural soils as measured with j>.  typhimurium,  strain
    TA98, without metabolic activation  	  144

50  Induced mutation frequency  and fractional survival  in
    A. nidulans following exposure to organic extract of
    Bastrop soil	146

51  Induced mutation frequency  and fractional survival  in
    A. nidulans following exposure to organic extract of
    Norwood soil	147

52  GC/MS chromatograph of organic extract of Norwood soil ....  150

53  GC/MS chromatograph of organic extract of Bastrop soil ....  151

54  Extraction efficiency, as  measured  with  j>.  typhimurium
    strain TA98, of 2-nitroflourene  from  Norwood  soil	162

55  Extraction efficiency, as  measured  with  J5.  typhimurium
    strain TA98, of 2-nitroflourene  from  Bastrop  soil	163

56  Extraction efficiency, as  measured  with  J3.  typhimurium
    strain TA98, of benzo(a)pyrene from Norwood soil  	  166
                               xi

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                              FIGURES (continued)

Number                                                               Pag£

  57  Extraction efficiency, as measured with j>. typhimurium
      strain TA98, of benzo(a)pyrene from Bastrop soil  	   167

  58  HPLC chromatograph from (A) dimethylsulfoxide and  (B)
      Norwood soil	169

  59  HPLC chromatograph from (A) dimethylsulfoxide and  (B)
      Bastrop soil	170

  60  HPLC chromatograph from (A) 5.0 mg/ml 2-nitroflourene,
      and (B) Norwood soil +5.0 mg/ml 2-nitrof lourene	171

  61  HPLC chromatograph from (A) 5.0 gm/ml 2-nitroflourene,
      and (B) Bastrop soil + 5.0 mg/ml 2-nitrofluorene	172

  62  HPLC chromatograph from (A) 5.0 gm/ml benzo(a)pyrene, and
      (B) Norwood soil + 5.0 mg/ml benzo(a)pyrene	173

  63  HPLC chromatograph from (A) 5.0 gm/ml benzo(a)pyrene, and
      (B) Bastrop soil + 5.0 mg/ml benzo(a)pyrene	174

  64  Schematic diagram of greenhouse boxes used  in degradation
      study	179

  65  Mutagenic activity with metabolic  activation of runoff
      water  from  PENT S amended Norwood  soil	183

  66  Mutagenic activity without metabolic activation of runoff
      water  from  PENT S amended Norwood  soil	186

  67  Mutagenic activity with metabolic  activation of runoff
      water  from  PENT S amended Bastrop  soil	187

  68  GC/MS  chromatograph of organic extract  of  runoff  water
      from   unamended Bastrop soil collected  on  day 360	190

  69  GC/MS  chromatograph of organic extract  of  runoff  water
      from PENT S amended Bastrop soil collected  on day 0	191

  70  GC/MS  chromatograph of organic extract  of  runoff  water
      from PENT S amended Bastrop soil collected  on day 360	192

  71  Mutagenic activity with metabolic  activation of runoff
      water  from  SWRI amended Norwood soil	198

  72  Mutagenic activity with metabolic  activation of runoff
      water  from  SWRI amended Bastrop soil	199
                                xii

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                              FIGURES  (continued)

Number                                                                Page

  73  Mutagenic activity with metabolic activation of  runoff
      water from COMBO amended Norwood  soil.
                                                                       200
  74  Mutagenic activity with metabolic activation  of  runoff
      water from COMBO amended Bastrop soil	204

  75  Extractable hydrocarbons (mg/1) and mutagenic activity
      (revertants/10 ml) in  runoff water  from PENT  S amended
      Norwood soil	207

  76  Total mutation frequency per 10  survivors  in A.
      nidulans  induced by  the extractable hydrocarbons in
      runoff water  from waste amended  soils  	   208

  77  Extractable hydrocarbons  (mg/1)  and mutagenic activity
      (revertants/10 ml) in  runoff water  from control  and
      PENT  S amended Bastrop soils	209

  78  Extractable hydrocarbons  (mg/1)  and mutagenic activity
      (revertants/50 ml) in  runoff water  from control  and SWRI
      amended Norwood  soils  	 212

  79  Extractable hydrocarbons  (mg/1)  and mutagenic activity
      (revertants/50 ml) in  runoff water  from control  and SWRI
      amended Bastrop  soils  	 213

  80  Extractable hydrocarbons  (mg/1)  and mutagenic activity
       (revertants/50 ml)  in  runoff water  from control  and COMBO
      amended Norwood  soils	214

  81  Extractable hydrocarbons  (mg/1)  and mutagenic activity
       (revertants/50 ml)  in  runoff water  from control  and COMBO
      amended Bastrop  soils	215

  82  Degradation  rate of  total  extractable hydrocarbons in
      Norwood and  Bastrop  soils  amended  with PENT S (PS), SWRI
       (SI),  and COMBO  (CO) waste	225

  83  Mutagenic activity  of  acid fraction of PENT S amended
      Norwood soil  as  measured  with  jj typhimurium strain
      TA98  with and without  metabolic activation	228

  84  Mutagenic activity  of  base fraction of PENT S amended
      Norwood  soil  as  measured  with  J3 typhimurium strain
      TA98  with and without  metabolic activation	229
                                 xiii

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                              FIGURES  (continued)

M  v                                                                   Page
Number                                                                 —

  85  Mutagenic activity of neutral fraction of  PENT  S  amended
      Norwood soil as measured with j>  typhimurium  strain
      TA98 with and without metabolic  activation 	   230

  86  Mutagenic activity of acid  fraction of PENT  S amended
      Norwood soil as measured with ji  typhimurium  strain
      TA100 with and without metabolic activation  	  231

  87  Mutagenic activity of base  fraction of PENT  S amended
      Norwood soil as measured with J5  typhimurium  strain
      TA100 with and without metabolic activation  	  232

  88  Mutagenic activity of neutral fraction of  PENT  S
      amended Norwood soil as measured with J5  typhimurium
      strain TA100 with and without metabolic  activation  	   233

  89  Mutagenic activity of acid  fraction of PENT  S amended
      Bastrop soil as measured with j>  typhimurium  strain
      TA98 with and without metabolic  activation	240

  90  Mutagenic activity of base  fraction of PENT  S amended
      Bastrop soil as measured with J5  typhimurium  strain
      TA98 with and without metabolic  activation	241

  91  Mutagenic activity of neutral fraction of  PENT  S  amended
      Bastrop soil as measured with j»  typhimurium  strain
      TA98 with and without metabolic  activation 	   242

  92  Mutagenic activity of acid  fraction of PENT  S amended
      Bastrop soil as measured with j>  typhimurium  strain
      TA100 with and without metabolic activation  	  246

  93  Mutagenic activity of base  fraction of PENT  S amended
      Bastrop soil as measured with j>  typhimurium  strain
      TA100 with and without metabolic activation  	  247

  94  Mutagenic activity of neutral fraction of  PENT  S  amended
      Bastrop soil as measured with j>  typhimurium  strain
      TA100 with and without metabolic activation  	  248

  95  Mutagenic activity of acid  fraction of  SWRI  amended
      Norwood soil as measured with j>. typhimurium strain
      TA98 with and without metabolic  activation	252

  96  Mutagenic activity of base  fraction of  SWRI  amended
      Norwood soil as measured with j>. typhimurium strain
      TA98 with and without metabolic  activation	256
                                 xiv

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                              FIGURES  (continued)

Number                                                                page

  97  Mutagenic activity of neutral  fraction  of  SWRI  amended
      Norwood soil as measured with  j^.  typhimurium strain
      TA98 with and without metabolic  activation	257

  98  Mutagenic activity of acid  fraction  of  SWRI  amended
      Bastrop soil as measured with  J3.  typhimurium strain
      TA98 with and without metabolic  activation	262

  99  Mutagenic activity of base  fraction  of  SWRI  amended
      Bastrop soil as measured with  £.  typhimurium strain
      TA98 with and without metabolic  activation	263

 100  Mutagenic activity of neutral  fraction  of  SWRI  amended
      Bastrop soil as measured with  J5.  typhimurium strain
      TA98 with and without metabolic  activation	264

 101  Mutagenic activity of acid  fraction  of  COMBO amended
      Norwood soil as measured with  j>.  typhimurium strain
      TA98 with and without metabolic  activation	268

 102  Mutagenic activity of base  fraction  of  COMBO amended
      Norwood soil as measured with  j>.  typhimurium strain
      TA98 with and without metabolic  activation	269

 103  Mutagenic activity of neutral  fraction  of  COMBO amended
      Norwood soil as measured with  Si.  typhimurium strain
      TA98 with and without metabolic  activation 	  270

 104  Mutagenic activity of acid  fraction  of  COMBO amended
      Bastrop soil as measured with  j>.  typhimurium strain
      TA98 with and without metabolic  activation	273

 105  Mutagenic activity of base  fraction  of  COMBO amended
      Bastrop soil as measured with  J5.  typhimurium strain
      TA98 with and without metabolic  activation	275

 106  Mutagenic activity of neutral  fraction  of  COMBO amended
      Bastrop soil as measured with  £.  typhimurium strain
      TA98 with and without metabolic  activation 	  277

 107  GC/MS  chromatograph  of  base fraction of PENT S amended
      Norwood soil collected  on  day  0	283

 108  GC/MS  chromatograph  of  neutral fraction of PENT S amended
      Norwood soil collected  on  day  0	284
                                 xv

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                              FIGURES  (continued)

Number                                                              Page

109   GC/MS chromatograph of acid fraction of PENT S amended
      Norwood soil collected on day 360	285

110   GC/MS chromatograph of base fraction of PENT S amended
      Norwood soil collected on day 360	286

111   GC/MS chromatograph of neutral fraction of  PENT  S  amended
      Norwood soil collected on day 360	287

112   GC/MS chromatograph of acid fraction of PENT S amended
      Bastrop soil collected on day 0	288

113   GC/MS chromatograph of base fraction of PENT S amended
      Bastrop soil collected on day 0	289

114   GC/MS chromatograph of neutral fraction of  PENT  S  amended
      Bastrop soil collected on day 0	290

115   GC/MS chromatograph of acid fraction of PENT S amended
      Bastrop soil collected on day 360	291

116   GC/MS chromatograph of base fraction of PENT S amended
      Bastrop soil collected on day 360	292

117   GC/MS chromatograph of neutral fraction of  PENT  S  amended
      Bastrop soil collected on day 360	293

118   GC/MS chromatograph of acid fraction of SWRI amended
      Bastrop soil collected on day 360	296

119   GC/MS chromatograph of base fraction of SWRI amended
      Bastrop soil collected on day 360	297

120   GC/MS chromatograph of neutral fraction of  SWRI  amended
      Bastrop soil collected on day 360	   298

121   GC/MS chromatograph of acid fraction of COMBO  amended
      Norwood soil collected on day 0	   301

122   GC/MS chromatograph of base fraction of COMBO  amended
      Norwood soil collected on day 0	302

123   GC/MS chromatograph of neutral fraction of  COMBO amended
      Norwood soil collected on day 0	303

124   GC/MS chromatograph of acid fraction of  COMBO  amended
      Norwood soil collected on day  360	304
                                xvi

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                              FIGURES  (continued)

Number                                                                Page

125   GC/MS chromatograph of base fraction of  COMBO  amended
      Norwood soil collected on day 360	305

126   GC/MS chromatograph of neutral fraction  of COMBO  amended
      Norwood soil collected on day 360	306

127   GC/MS chromatograph of acid fraction of  COMBO  amended
      Bastrop soil collected on day 0	307

128   GC/MS chromatograph of base fraction of  COMBO  amended
      Bastrop soil collected on day 0	308

129   GC/MS chromatograph of neutral fraction  of COMBO  amended
      Bastrop soil collected on day 0	309

130   GC/MS chromatograph of acid fraction of  COMBO  amended
      Bastrop soil collected on day 360	310

131   GC/MS chromatograph of neutral fraction  of COMBO  amended
      Bastrop soil collected on day 360	311

132   Total extractable hydrocarbons and  mutagenic potential
      of equivalent volumes of PENT S  amended  Norwood  (NW)
      and Bastrop  (BA) soils as measured  with  ^. typhimurium
      strain TA98 with and without metabolic activation.
      Dashed line  (	) is equal  to 2.5 times  solvent  control.  .  .  .   314

133   Total extractable hydrocarbons and  mutagenic potential
      of equivalent volumes of SWRI amended  Norwood  (NW)  and
      Bastrop (BA) soils as measured with J3. typhimurium
      strain TA98 with and without metabolic activation.
      Dashed line  (	) is equal  to 2.5 times  solvent  control.  .  .  .   315

134   Total extractable hydrocarbons and  mutagenic potential
      of equivalent volumes of COMBO amended Norwood (NW) and
      Bastrop (BA) soils as measured with J3. typhimurium
      strain TA98 with and without metabolic activation.
      Dashed line  (	) is equal  to 2.5 times  solvent  control.  .  .  .   316

135   Total induced mutation frequency of equivalent volumes
      of PENT S  amended Norwood  (NW) and  Bastrop  (BA)  soils  as
      measured in A.  nidulans methionine  system with and
      without metabolic activation.  Dashed  line  (~7~)  is equal
      to total induced mutation  frequency of 5.0/10  survivors  .  .     317
                                  xvii

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                              FIGURES (continued)

Number

136   Total induced mutation frequency of equivalent volumes
      of SWRI amended Norwood (NW) and Bastrop  (BA) soils  as
      measured in A. nidulans methionine system with and
      without metabolic activation.  Dashed line  (~g~)  is  equal
      to total induced mutation frequency of 5.0/10  survivors  .  .     318

137   Total induced mutation frequency of equivalent volumes
      of COMBO amended Norwood (NW) and Bastrop (BA) soils as
      measured in A. nidulans methionine system with and
      without metabolic activation.  Dashed line  (~T~)  is  equal
      to total induced mutation frequency of 5.0/10  survivors  .  .     319

138   Schematic diagram of leachate collection  system used in
      the lysimeter study	324

139   Extractable hydrocarbons and mutagenic activity from soil
      core samples collected at various depths  on day 90	327

140   GC/MS chromatograph of crude extract of  soil core sample
      collected on day 90 at a depth of 0 to 15 cm from unamended
      Norwood lysimeter 	  331

141   GC/MS chromatograph of acid  fraction of  soil core sample
      collected on day 90 at a depth of 0 to 15 cm from PENT  S
      amended Norwood lysimeter	332

142   GC/MS chromatograph of base  fraction of  soil core sample
      collected on day 90 at a depth of 0 to 15 cm from PENT  S
      amended Norwood lysimeter	333

143   GC/MS chromatograph of neutral fraction  of  soil core
      sample collected on day 90 at a depth of  0  to 15  cm
      from PENT S amended Norwood  lysimeter	334

144   Mutagenic activity of  leachate water  from control and
      PENT S waste amended lysimeters	335

145   GC/MS chromatograph of soil  pore  liquid  sample  collected
      from unamended Norwood lysimeter  on day  90	337

146   GC/MS chromatograph of soil  pore  liquid  sample  collected
      from PENT S amended lysimeter on  day  90	339
                                 xviii

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                                    TABLES
Number                                                                 Page

  1    Strains of Bacillus subtilis used  for mutagen
       testing.
10
  2    Comparison of lethal effect of various  samples  on DNA
       repair deficient and proficient  strains  of  B.
       subtilis	    12

  3    Survival of wild-type and repair-deficient  strains
       of %._ subtilis exposed  to varying  concentrations
       of DNA damaging chemicals	13

  4    Survival of wild-type and repair-deficient  strains
       of B_._ subtilis exposed  to varying  concentrations
       of 2-aminoanthracene and benzo(a)pyrene with and
       without metabolic activation  	 14

  5    Characteristics of  Salmonella strains  used  for
       mutagenesis testing	19

  6    Effect of a 1:10 MeCl_:DMSO solution on the
       spontaneous reversion and induced  mutation  frequency
       in S_._ typhimrium	     23

  7    Response obtained in prokaryotic mutagenesis assays
       using S_._ typhimurium or B_^  subtilis with
       negative and  positive controls  	   24

  8    Variability of  S^_ typhimurium strains  TA98  and
       TA100 with negative and positive controls for each year
         of  the project	25

  9    The  effect of storage at 4  C  on  the mutagenic activity
       of two runoff samples  (samples were received 5/13/82)	 35

  10   Surviving  fraction  and  induced mutants per  survivor
       in haploid A.  nidulans  following treatment  with
       solvent and positive controls	45

  11   Summary of genotoxic effects  induced by controls  in
       segregant  colonies  of diploid A._ nidulans	     46
                                 xix

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                              TABLES (continued)

Number                                                               Pa§e

  12   Summary of genotoxic effects induced by controls  in
       abnormal colonies of diploid A^ nidulans  	     47

  13   Gross characteristics of hazardous wastes collected
       for study	52

  14   Biological systems used to detect genotoxic  compounds
       in environmental samples 	 59

  15   Mutagenic activity of liquid stream  from  acetonitrile
       purification column as measured with S. typhimurium
       strain TA98 and TA100 with and without metabolic
       activation	66

  16   Comparison of  lethal effects of acetonitrile (ACN)
       waste fractions on DNA repair deficient and  proficient
       strains of B^_  subtilis	      67

  17   The effect of  the neutral  fraction of a methyl  ethyl
       ketone waste on the frequency of  induced  mutations  in
       Aspergillus nidulans	      70

  18   Mutagenic activity of methyl ethyl ketone waste	, .  .  73

  19   Distribution of mutagenic  activity in fractions of
       wood-preserving bottom sediment  (PENT S)  waste
       extracted using blender or soxhlet technique 	  75

  20   Mutagenic activity of fractions of wood-preserving
       bottom sediment	76

  21   Mutagenic activity of PENTS waste in four plasmid
       containing strains of S^_ typhimurium 	      80

  22   Mutagenic activity of PENTS waste fractions  as  measured
       with j>. typhimurium, strain TA98,  with high  (0.5 ml
       S9/ml: S9/mix), medium  (0.3 ml  S9/ml S9/mix),  and low
       (0.1 ml S9/ml  S9 mix) concentrations of  aroclor 1254
       induced rat liver in 59 mix	81

  23   Capacity of fractions of wood-preserving  waste  to
       induce increased lethal damage  in DNA repair deficient
       strains of ]$._  subtilis	      86

  24   Fractional survival of repair proficient  and deficient
       strains of B.  subtilis	      88
                                 xx

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                              TABLES (continued)

Number                                                                Page


  25   Surviving fraction and induced mutation  frequency of
       A._ nidulans following exposure to acid fraction
       of PENT S waste	92

  26   Surviving fraction and induced mutation  frequency of
       A.^ nidulans following exposure to base fraction  of
       PENT S waste	93

  27   Surviving fraction and induced mutation  frequency
       of A^ nidulans following exposure to neutral
       fraction of PENT S waste	94

  28   Summary of genotoxic effects observed  in segregant
       colonies of diploid A^ nidulans  following exposure
       to controls and waste fractions	95

  29   Summary of genotoxic effects observed  in abnormal
       colonies of diploid A. nidulans  following exposure
       to controls and waste fractions	97

  30   Selected properties of compounds  identified  in the
       fractions of the wood-preserving  bottom  sediment (PENT S).  .   103

  31   Mutagenic activity of fractions  of  storm-water runoff
       impoundment	105

  32   Fractional survival of repair proficient (168 wt) and
       deficient strains of B^ subtilis  exposed to
       subfractions of combined API-seperator/slop-oil  emulsion
       solid  (COMBO) or storm-water runoff impoundment  (SWRI).
       Survival was measured in the presence  of metabolic
       activation	108

  33   Surviving fraction and induced mutation  frequency of  A._
       nidulans following exposure to acid fraction of  SWRI
       waste	109

  34   Surviving fraction and induced mutation  frequency of  A._
       nidulans following exposure to base fraction of  SWRI
       waste	110

  35   Surviving fraction and induced mutation  frequency of  A._
       nidulans following exposure to neutral fraction  of  SWRI
       waste	Ill
                                 xxi

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                              TABLES (continued)

Number                                                                Page

  36   Mutagenic activity of fractions of combined API separator/
       slop oil emulsion waste	H8

  37   Surviving fraction and induced mutation  frequency of A._
       nidulans following exposure to acid fraction of COMBO
       waste	 •  •   •   121

  38   Surviving fraction and induced mutation  frequency of A.
       nidulans following exposure to base fraction of COMBO
       waste	•	122

  39   Surviving fraction and induced mutation  frequency of A.
       nidulans following exposure to neutral fraction of  COMBO
       waste	123

  40   Selected properties of compounds  identified in the
       fractions of the combined API-seperator/slop-oil
       emulsion solids COMBO waste	131

  41   Summary of results obtained from  testing waste
       fractions in biological  test  systems  	   133

  42   Physical properties of the  three  soils  	   137

  43   Mutagenicity of organic  extracts  of three  soils as
       measured with and without metabolic activation  	   139

  44   Effect of increasing doses  of organic extract of
       Bastrop and Norwood soils on  survival and  induced
       mutation frequency in Aspergillus nidulans with
       and without metabolic activation  	   145

  45   List of compounds identified  in Norwood  and Bastrop
       soils	148

  46   Diagnostic mutagens used to evaluate  the efficiency of
       extraction procedures	158

  47   Mutagenic activity, as measured with  S.  typhimurium
       TA98, of 2-nitrofluorene, and the solvent  extract  of the
       Norwood and Bastrop soils amended with various  levels  of
       2-nitrofluorene  	  161

  48   Mutagenic activity, as measured with  j>.  typhimurium
       TA98, with metabolic  activation,  of benzo(a)pyrene, and
       the solvent extract of the  Norwood and Bastrop  soils
       amended with various  levels of benzo(a)pyrene  	  165
                                xxii

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                              TABLES  (continued)

Number
  49   Extraction efficiency, as measured with HPLC,  of  the
       Bastrop and Norwood soils amended with mutagenic
       compounds.	168

  50   Distribution of mutagenic activity in fractions of
       hazardous waste and the  two  soils used in  the  greenhouse
       study	178

  51   Mutagenic activity, as measured with S^_ typhimurium
       strain TA98 of runoff water  from PENT S amended Norwood
       soil	184

  52   Mutagenic activity, as measured with S^ typhimurium
       strain TA100 of runoff water from PENT S amended  Norwood
       soil	185

  53   Mutagenic activity, as measured with S. typhimurium
       strain TA98 of runoff water  from PENT S amended Bastrop
       soil	188

  54   Mutagenic activity, as measured with S. typhimurium
       strain TA100 of runoff water from PENT S amended  Bastrop
       soil	189

  55   Mutagenic activity, as measured with S^_ typhimurium
       strain TA98 of runoff water  from Norwood soils amended
       with SWRI waste	194

  56   Mutagenic activity, as measured with S. typhimurium
       strain TA100 of runoff water from Norwood  soils amended
       with SWRI waste	195

  57   Mutagenic activity, as measured with J5._ typhimurium
       strain TA98 of runoff water  from Bastrop  soils amended
       with SWRI waste	196

  58   Mutagenic activity, as measured with S.  typhimurium
       strain TA100 of runoff water from Bastrop  soils  amended
       with SWRI waste	197

  59   Mutagenic activity, as measured with j>^_ typhimurium
       strain TA98 of runoff water  from Norwood  soils amended
       with COMBO waste	201
                                 xxiii

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                              TABLES  (continued)

Number

  60   Mutagenic activity, as measured with js._  typhimurium
       strain TA100 of runoff water from Norwood  soils  amended
       with COMBO waste	   202

  61   Mutagenic activity, as measured with S.  typhimurium
       strain TA98 of runoff water from Bastrop soils amended
       with COMBO waste	203

  62   Mutagenic activity, as measured with ^-_  typhimurium
       strain TA100 of runoff water from Bastrop  soils  amended
       with COMBO waste	206

  63   Total hydrocarbons extracted from runoff water using
       combined XAD2 and XAD7 resins	211

  64   Total hydrocarbons extracted from soil amended with
       wood-preserving bottom sediment	221

  65   Total hydrocarbons extracted from soil amended with
       storm-water runoff impoundment 	   222

  66   Total hydrocarbons extracted from soil amended with
       combined API separator/slop-oil emulsion solid	224

  67   Mutagenic activity of acid  fraction of PENT S waste
       amended Norwood soil as measured with  S^. typhimurium
       strain TA98 with and without metabolic activation	234

  68   Mutagenic activity of base  fraction of PENT S waste
       amended Norwood soil as measured with  S.typhimurium
       strain TA98 with and without metabolic activation 	   235

  69   Mutagenic activity of neutral  fraction of  PENT  S waste
       amended Norwood soil as measured with  S_. typhimurium
       strain TA98 with and without metabolic activation	236

  70   Mutagenic activity of acid  fraction of PENT S waste
       amended Norwood soil as measured with j>. typhimurium
       strain TA100 with and without  metabolic  activation	237

  71   Mutagenic activity of base  fraction of PENT S waste
       amended Norwood soil as measured with J5. typhimurium
       strain TA100 with and without  metabolic  activation	238

  72   Mutagenic activity of neutral  fraction of  PENT  S waste
       amended Norwood soil as measured with j>. typhimurium
       strain TA100 with and without  metabolic  activation	239
                                xxiv

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                              TABLES  (continued)

Number                        •                                       ^SS£

  73   Mutagenic activity of acid  fraction  of  PENT  S  waste
       amended Bastrop soil as measured with J5.  typhimurium
       strain TA98 with and without metabolic  activation	243

  74   Mutagenic activity of base  fraction  of  PENT  S  waste
       amended Bastrop soil as measured with j>.  typhimurium
       strain TA98 with and without metabolic  activation	244

  75   Mutagenic activity of neutral  fraction  of PENT S waste
       amended Bastrop soil as measured with js.  typhimurium
       strain TA98 with and without metabolic  activation	245

  76   Mutagenic activity of acid  fraction  of  PENT  S  waste
       amended Bastrop soil as measured with j>.  typhimurium
       strain TA100 with and without  metabolic activation	   249

  77   Mutagenic activity of base  fraction  of  PENT  S  waste
       amended Bastrop soil as measured with j>.  typhimurium
       strain TA100 with and without  metabolic activation	250

  78   Mutagenic activity of neutral  fraction  of PENT S waste
       amended Bastrop soil as measured with J3.  typhimurium
       strain TA100 with and without  metabolic activation	251

  79   Mutagenic activity of acid  fraction  of  SWRI  waste
       amended Norwood soil as measured with j>.  typhimurium
       strain TA98 with and without metabolic  activation	253

  80   Mutagenic activity of base  fraction  of  SWRI  waste
       amended Norwood soil as measured with j>.  typhimurium
       strain TA98 with and without metabolic  activation	255

  81   Mutagenic activity of neutral  fraction  of SWRI waste
       amended Norwood soil as measured with J3.  typhimurium
       strain TA98 with and without metabolic  activation	258

  82   Mutagenic activity of acid  fraction  of  SWRI  waste
       amended Bastrop soil as measured with j^.  typhimurium
       strain TA98 with and without metabolic  activation	259

  83   Mutagenic activity of base  fraction  of  SWRI  waste amended
       Bastrop soil  as measured  with  S^.  typhimurium strain
       TA98  with and  without metabolic activation	260

  84   Mutagenic activity of neutral  fraction  of SWRI waste
       amended Bastrop soil as measured with  £!.  typhimurium
       strain TA98 with and without metabolic  activation	261
                                 xxv

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Number
                              TABLES  (continued)

                                                                     Page
  85   Mutagenic activity of acid fraction of  COMBO  waste
       amended Norwood soil as measured with j^.  typhimurium
       strain TA98 with and without metabolic  activation	265

  86   Mutagenic activity of base fraction of  COMBO  waste
       amended Norwood soil as measured with J5.  typhimurium
       strain TA98 with and without metabolic  activation	266

  87   Mutagenic activity of neutral  fraction  of COMBO waste
       amended Norwood soil as measured with S^  typhimurium
       strain TA98 with and without metabolic  activation	267

  88   Mutagenic activity of acid fraction of  COMBO  waste
       amended Bastrop soil as measured with j>.  typhimurium
       strain TA98 with and without metabolic  activation	272

  89   Mutagenic activity of base fraction of  COMBO  waste
       amended Bastrop soil as measured with J3.  typhimurium
       strain TA98 with and without metabolic  activation	274

  90   Mutagenic activity of neutral  fraction  of COMBO waste
       amended Bastrop soil as measured with J3.  typhimurium
       strain TA98 with and without metabolic  activation	276

  91   List of compounds detected in  PENT S waste amended  soil .  . .  280

  92   List of compounds detected in  COMBO waste amended soil. .  . .  299

  93   Chemical properties of  the Norwood soil series  and
       physical properties of  the Norwood soil series	322

  94   List of compounds detected in  soil core sample  collected
       on day 90 from control  Norwood soil at  0-15 cm  depth ....   328

  95   List of compounds detected in  soil core samples
       collected on day 90 from  PENT  S waste amended Norwood
       soils at various depths	329

  96   List of compounds detected in  soil pore samples
       collected on day 90 from  PENT  S waste ameded  Norwood
       soil	336
                                 XXVI

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                            ACKNOWLEDGEMENTS
     Valuable advice  and  assistance was obtained  from  Carlton Wiles,  EPA
Project  Officer  for  years  1  and  2,  and  from  John  Matthews,  the  EPA
Project Officer  for  the third year.  Dr. D. Kampbell of  the  USEPA's  R. S.
Kerr  Environmental   Research   Laboratory  at  Ada,  Oklahoma   performed
analytical work on waste and soil extracts.

     A great  deal of technical support was provided  in all phases  of  the
project  by Phebe  Davol.  Rosella  Saltarelli  assisted  in maintenance  of
microbial  strains  and Lea  Maggard  conducted  the  study  on extraction
efficiency.    All   biological   analyses   using   A.   nidulans   were
conducted  by  Dr. B.  R. Scott with  Phoenix  Co.,  Smithville,  Texas.   Mr.
D.  Anderson  assisted  in the  location and  collection  of  the  wastes.  A
special acknowledgement is  also  given to  Nora Sai  and  Pamela Antilley
for patient typing and editing of the text, respectively.
                                  xxvn

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                               SECTION 1

                              INTRODUCTION
     Industrial  activities  in  the  United States  have undergone a rapid
expansion over  the  past three decades concurrent with  the development of
numerous  new  chemicals.  These activities have  been responsible in part
for  a  dramatic  improvement  in the  quality of  life  while  affecting a
reduction  in  the  frequency  of  infectious  disease.   An  unavoidable
by-product  of our  industrial  growth has been  the  generation  of large
volumes  of  complex industrial wastes.   Since  1950,  the world production
of  organic  chemicals has  risen from  7  million  tons  to a projected 150
million   tons  by  1985  (U.S.  Tarriff   Commission,   1974).   Presently,
approximately  700  new chemicals are  introduced  into commerce each year,
in  addition  to  the  more than one-half  million  chemicals  already in use
(National Cancer  Institute,  1976).   For  the majority  of these chemicals,
there  is little information  available  pertaining to  their toxicological
and environmental aspects (Fishbein,  1979).

     This lack  of  sufficient information and the  fact that the majority
of  chemical carcinogens are considered  to be  products of our increasing
agricultural  and technological sophistication  (Chemical and Engineering
News,  1975)  dictate  the  need  to develop techniques  for  monitoring the
disposal  of  hazardous   chemicals.    The  EPA  (1983)  estimated  that  150
million  metric  tons  of hazardous  waste  are  generated annually  in the
United  States.  Past disposal practices  have generally included deep sea
dumping,  incineration,  and  landfilling.   All  of  these methods  have
environmental  or economical  drawbacks  which  limit  their  utility.   The
alternative disposal  method  of  land treatment,  i.e., the incorporation
of  waste into the surface layer of  soil resulting in  the degradation or
attenuation   of   hazardous  waste   constituents,   is  being  used  more
frequently  for  the disposal  of selected  industrial wastes.   EPA (1980)
regulations state  that  a  waste cannot  be land  applied unless the waste
is  rendered less or non-hazardous by chemical or biological reactions in
the  soil.    In  order  for  land  treatment  to  be  a  viable method  of
disposal, techniques  are needed  for the  monitoring of  hazardous waste
constituents  and  their  metabolites.  The  use of a combined biological and
chemical  testing  protocol  may  provide  the  most  practical  means  of
efficiently monitoring   hazardous  waste  disposal.   The use  of chemical
analysis  alone  fails to  account  for  the interactions of the components
of  a  complex  mixture,  the  production  of mutagenic metabolites  via
degradative   pathways,   and   chemical   reactions    between   non-toxic
precursors  that  may  result  in the  formation of mutagenic compounds. An

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appropriately  selected bioassay  should  be  capable  of integrating  these
effects.  The  use of  biological  analysis  alone, however,  could fail  to
account   for   artifacts   generated  in  the    collection   or   extraction
process.   A combined  testing  protocol  utilizes microbial bioassays  to
measure primary  DNA damage and a chemical analysis  to  identify causitive
agents  in  genotoxic  samples.  Although  not  all  chemical  mutagens" are
established carcinogens,  most  chemical  carcinogens  have been  determined
to  be mutagenic  in  sub-mammalian systems  (Stolz   et_  al. ,  1974; Miller
and   Miller,   1974;   Committee   17,  1974).   The  utility   of   microbial
mutagenesis assays  is further  enhanced  by  recent  evidence that a  point
mutation  in a  human cell can  give the  cell malignant  properties  (Santos
ejt  al.,   1984).  Thus, microbial   bioassays  may be  utilized to  evaluate
the   mutagenic   activity   of  waste  and  environmental  samples  as  an
indication  of  their  potential  for  inducing   mutagenic  damage  in  the
human  population.   Mutagenic  compounds  in  the  environment   affecting
somatic cells  may  induce  cell death, cancer,  aging,  and  heart disease
(Ames, 1979);  while mutations in  germ cells may result in  birth defects,
sterility,  and abortions  (Brusick,  1981)  (Figure  1).   The human genome
is  our   most   precious   heritage  (de  Serres,  1979),  and   analytical
techniques  must be  developed  to reduce  the  transmission of  mutagenic
defects to  future  generations.  A need  exists to  determine if  mutagenic
constituents of  land  treated industrial waste will  migrate  from the site
of application  to  locations where the human population could  be exposed
to them.

      The  objectives  of this research were  to characterize  the  genotoxic
constituents of  three hazardous  wastes, to  monitor  waste degradation  in
soil,  and  to  determine   the  environmental   fate   of mutagenic   waste
constituents   following   land  application.     In  order  to meet   these
objectives  and to develop  a  set  of test protocols  which  can be used  to
monitor environmental  contamination,  this  project was  divided into four
main  phases.    The   waste  characterization   phase included   an   acute
toxicity  evaluation of  ten wastes,  a  complete characterization of  the
mutagenic  potential  of seven subfractions of  three  selected wastes,  and
a  chemical  characterization  of  major  organic  constituents.   In  the
second phase,  direct  and indirect acting mutagens were added to the soil
in order  to quantify  extraction  procedures  and to  determine  the affect
of soil components on  the activity of mutagenic  compounds.

      Phase  three  consisted of  a  greenhouse  study  in which three wastes
were  applied   at  one  loading rate  to   two  soil types packed   in boxes.
Simulated   rainfall  was   applied  and  runoff  and soil   samples   were
collected at various  time intervals during  a  360  or 540 day period. The
results from this  phase  of the project  were used to evaluate  the affect
of degradation on  the mutagenic activity of  waste  amended soil and  the
potential  for  the  removal of  mutagens  in  runoff   water.   In   the  final
phase  of  the  study,  one  waste was  applied  to   an  undisturbed   soil
enclosed  in lysimeters  in  order to  monitor  the   movement  of mutagens
through soil.   The  information generated by this research  should provide
a  sound   basis  for  determining  the  utility  of short-term bioassays  to

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                                    HUMANS
                        GERM CELLS
                      (REPRODUCTIVE)
                                             DOMINANT
                                             MUTATIONS
ALTERATION
  IN DNA
   OR
CYTOPLASMIC
  MATERIAL
MUTATION
                               RECESSIVE
                               MUTATIONS
                             SOMATIC CELLS
                           (NON-REPRODUCTIVE)
                                                 BIRTH DEFECTS
                                                 GENETIC DISEASE
                                                 ABORTIONS
                                                 STERILITY
EXPRESSED AS GENETIC
DISEASE IN FUTURE
GENERATIONS

CELL DEATH.
CANCER
AGING
HEART DISEASE
OTHER ILLNESS
                  Figure 1'.  Potential effects of environmental mutagens on human cells.

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evaluate  the  environmental  impact  of  the  land treatment  of hazardous
industrial wastes.

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                                  SECTION 2

                                 CONCLUSIONS
1.   The  battery of  biological test  systems  employed  in  this research
     provided detection  capabilities  for a range of genotoxic  damage and
     a variety of genotoxic compounds.

2.   The  acid,  base, and  neutral  fractions of  each  of three hazardous
     wastes  contained compounds  capable  of  inducing  DNA  damage,  point
     mutations, or chromosome damage.

3.   An  agricultural  soil  with no previous history of waste application
     will  have  an inherent  level  of  mutagenic  activity.  The magnitude
     of  this  activity will  be directly  related to  the past history of
     agricultural     practices,     including     biocide    applications,
     fertilization, and cultivation.

4.   Through  use   of   the   soxhlet   technique,  significantly   greater
     quantities  of hydrocarbons were extracted  from  the waste than were
     extracted using  the blender technique.  However,  the composition of
     the  extracted  hydrocarbons  appeared to   be  similar  using  either
     technique,   as   there   was   no  appreciable   difference  in  the
     mutagenicity of the residues.

5.   The  extraction   efficiency for  2-nitrofluorene  and benzo(a)pyrene
     from  soil using  the blender technique and  measured  by HPLC averaged
     greater  than  85%,  while  the  mutagenic  activities   of  the  pure
     compound and  the  pure compound extracted from soil were within one
     standard deviation of each other.

6.   The mutagenic potential  of runoff water from  soil amended with two
     of  the  three wastes  was reduced  360  days  after waste  application.
     For   the  third   waste,   the  mutagenic  potential  was   increased,
     although  the  amount  of  extractable hydrocarbons  in the  runoff had
     decreased.

7.   Degradation  increased the  mutagenic  potential   of  the extractable
     hydrocarbons  present  in  the  acid and base fractions  of  all  three
     waste   amended   soils.    However,   the    mutagenic   potential  of
     equivalent volumes  of waste amended soils  was  reduced  and,  in some
     cases, was reduced to a nonmutagenic level.

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8.   The  wood-preserving  waste   collected  for  this  study  contained  a
     limited number  of highly mobile  and highly  mutagenic constituents
     that   were   identified   by   chemical   and   biological  analysis.
     Different types  of compounds  were  detected  in  soil  core  and soil
     pore liquid samples.

9.   Chemical  assisted   biological  analysis   provided  more  accurate
     information for monitoring  complex  mixtures in the environment than
     either method alone.

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                                  SECTION 3

                               RECOMMENDATIONS
1.   A  battery  of bioassays,  capable of  detecting point mutations,  DNA
     repair  damage,  and chromosome  damage should  be  used to define  the
     genetic toxicity of a hazardous  industrial waste.

2.   The bioassay(s)  used  for environmental monitoring need  only  consist
     of  the  least complex  test system(s)  found  to be  sensitive to  the
     type of genetic  damage and the  types  of  genotoxic compounds in  the
     waste.

3.   Both  chemical and  biological  analysis  should  be  used to  monitor
     hazardous waste  land treatment.

4.   A  field study would  provide a  more  accurate  representation of  the
     potential  of  the  three  wastes  used in  the   present   study  to be
     rendered less hazardous by soil  incorporation.

5.   A  biological testing  protocol used to monitor hazardous waste  land
     treatment should include both chronic and acute toxicity bioassays.

6.   Additional  areas of  research  not  evaluated  in  the present  study
     which merit  future  investigation include the  mutagenic  potential of
     different wastes and   the  affect on  detoxification  of  loading  rate
     and fertilizer additions.

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                               SECTION 4

                          BIOLOGICAL ANALYSIS
INTRODUCTION

     Bioassay  techniques  measure  the  toxic  effects  of  a  substance by
comparing its  effect  on a living organism to that of standard substances
with known  toxicological  effects.   A battery of short-term bioassays was
used  in this  research to  evaluate  the  genotoxic  potential  of various
samples  associated with  land  treatment  of hazardous  industrial waste.
Through  the use of a  battery of bioassays to  detect  a range of genetic
damage,  environmental monitoring can  be made  both more economical and
environmentally sound.

     Genotoxic  compounds  in  a  hazardous waste  should  be  monitored in
order  to  control   accidental  exposure   to  mutagenic,  carcinogenic,  or
teratogenic  agents and  to  prevent  the  transmission of  related genetic
defects  to  future   generations.  Because no  single test  system  has been
identified  which   can  detect  all  types  of  genetic   damage  and  all
genotoxic  compounds,   genetic toxicity  can  best  be determined using  a
battery  of  biological  test  systems.   The battery  of test systems should
be  capable  of detecting  inhibition  of  DNA  repair, gene mutations, and
various  types of chromosome damage.

     The most common  biological  test  systems  employ  microorganisms to
detect  point  mutations in a  haploid genome. Since the  composition of DNA
is  essentially  the   same  in  all  organisms,  an  agent which induces
mutagenesis in a microorganism is also assumed to be capable of mutating
mammalian  DNA.   While  chemical  mutagenesis  is  a   relatively  simple
process  involving   the induction  of  heritable  change  in  the genome,
mutagenic events may  constitute  only the initial  step of a multi-stage
process  in   chemical   carcinogenesis  (Brusick,  1981).   The  eventual
outcome  of  chemical carcinogenesis will  be  greatly  influenced  by enzyme
activation  and detoxification systems (Miller  and Miller, 1974), as well
as  cocarcinogenic   and  promotional  factors  (Brusick,  1980).   Therefore,
not all  microbial  mutagens  will also be  carcinogens; although in several
validation  studies, 80 to  90% of carcinogens  were  detected as mutagens
(McCann  e^ aj^., 1980).

     The most efficient battery  for evaluating  the genotoxic  potential
of  environmental samples  should be capable of  detecting  both a range of
genetic  damage and a  range  of  genotoxic  compounds.  Each  test system

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should  include provisions  for solvent  and positive  controls that  will
demonstrate the sensitivity of the test  systems,  the functioning  of  the
metabolic  activation  system,  and  act as  an  internal  control  for  the
biological  system.    The  following   discussion  concerns  the  standard
protocols  for the  bioassays  utilized in  this  research, as  well as  a
comparison  of the  variability over  time  of  each system,  the  types  of
damage and compounds detected, and  the limitations  of  each system.

A.   Differential DNA  Repair

1. Test System Description—

     Repair assays  are used  to detect  primary DNA  damage and  evaluate
differential  growth inhibition  of  DNA  repair  proficient and  deficient
pairs of  bacteria.  Increased growth  inhibition  in  a DNA repair deficient
strain of  bacteria  implies that the  agent  being tested has  reacted with
cellular  DNA  to  produce  a repairable DNA  lesion.  Agents which produce
DNA  damage  are  likely  to  be  mutagenic,   carcinogenic,   as  well  as
effectors  of  chromosome aberrations  (Kada,  1978).  Numerous  test systems
are   available  which  employ   pairs  of   IS.  coli   (Slater   et^  al. ,
1971),   B.  subtilis   (Kada   et^   al.,   1977;  Tanooka,   1977;   Felkner
et_   al. ,   1979),   J?.  mirabilis    (Adler  et^   al. ,  1976),   and   J5.
typhimurium   (Ames   e_t^  al. ,  1975).    These   test   systems   offer  the
advantage  of  being  rapid,  simple,  and  inexpensive.   In  addition,  since
these tests are  capable of detecting DNA damage at any locus and  by any
mechanism,  they are capable of detecting many compounds  not  detected  by
point  mutation   assays  (Kada,  1980;  Rosenkranz  and  Poirier,  1979).
Limitations  of   DNA   repair  assays   in  bacteria  include  the   minimal
response  from  many  compounds that  are poorly  soluble in  water,  the lack
of  response from large molecules  due to  the  impermeability  of  the cell
wall, and an  inability to interpret borderline responses from  the spot
test  (Leifer   et  al.,  1981).    The  following   modifications   to  the
standard  protocol were used to enhance the sensitivity  of the DNA repair
assay.

2. Test system protocol: DNA repair—

     To   test  for   lethal  DNA-damage,   five   different   strains  of  IJ.
subtilis  deficient  in  different   recombination  (Rec )  and/or  excision
(Exc )   repair   were   employed. _ These   included   the   Rec   _ strains
recAS,   recE4,   and   mc-1;    Exc     strain  her-9;   and    Rec ,   Exc
strain  fh2006-7.   These  strains   are  all isogenic  with  ]}.  subtilis
strain  168 which has  all  repair intact  (Table 1). The DNA-repair assay
was  performed  using the procedure  of Felkner  (1977)  on  strains Dr. I.  C.
Felkner kindly supplied.   Metabolic  activation  was incorporated  into the
spot  test by  combining 0.5 ml  of  the test chemical  with 0.5 ml  of S-9
mix. The  S-9  mix is composed of enzymes  obtained  from the supernatant  of
homogenized rat   liver  which  was centrifuged  at  9,000  x  g,  and a NADPH
generating  system.    This  mix,  when  incorporated  into   the  bioassay,
simulates  the in vivo  biotransformation  of  the  test  material (Muller

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  TABLE 1.  STRAINS OF BACILLUS SUBTILIS  USED  FOR MUTAGEN TESTING
Strain
Genotype
      Source
168 wt
rec E4
rec A8
rec B2
hcr-9
fh2006.;
mc-1
TKJ5211
TKJ6321
Wild-type
trp, thr, Rec_
trp, thr, Rec
trp, thr,. Rec
trp, thr, Exc_
trp, thyz Rec , Exc
trp, Rec
his, meth, Exc                 .
his, meth, polAlSl, spp-1, Exc
Dr. I. C. Felkner
1.  Auxotrophic mutations: trp  (tryptophane),  thr  (threonine),  thy
    (thymine), his (histidine), meth  (methionine).

    Repair Deletions: Rec  (recombination), Exc   (excision),  polAlSl
    (polymerase).

    Additional Mutations:  spp-1 (spore-repair  deficiency marker).
                                  10

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et_  al.,  1980).  Aroclor  1254  induced  rat   liver  was   obtained   from
Litton  Bionetics  (Charleston,  S.C.)  and  prepared   according   to   the
procedure  of Ames  £t  al.  (1975).   The chemical  and  S-9 mixture  were
incubated  with  shaking  for   30  min  at 37 C.   Inocula  from overnight
cultures  were  streaked  radially on  a nutrient  agar  plate  to either  a
centered  sensitivity disk  containing  100  pi  of  the   test  sample  or  a
well  in  the  agar  plate containing  200 pi of  the  chemical S-9 mixture.
The  plates  were  incubated   overnight  at  37 C,  and  the  distance  of
growth  inhibition  was measured  from the periphery  of  the disk or well.
Dimethyl  sulfoxide  (DMSO) was used as  a  negative  control.  Mitomycin  C
(Sigma),   methylmethane   sulphonate   (Aldrich),   and   sensitivity   to
ultraviolet light were used as appropriate positive controls.

     Fractional  survival  (N/N )  was  evaluated  for  the  most sensitive
strains  and  for  strain  168 using  the  procedure  of  Felkner  et   al.
(1979).   Cells  were  inoculated  into  Difco  brain-heart  infusion broth
(BHI)  and  incubated  for  approximately 16 hours  until  an O.D.-,,. of  0.3
was  reached.   The cells  were then diluted with  fresh  BHI to  an  O.D.,.,-
of  0.1 (approximately  1.2 x 10   cells/ml)  and  serially  diluted  witn
Spizizen's  Minimal   Salts  (Spizizen,  1958).  To  determine   fractional
survival, 100  ul of the bacterial  suspension  at  a minimum of  three  cell
concentrations  was  added  to  2.5 ml of nutrient top agar in a  dry  bath at
47°C.•  To  this  mixture,  either  100  pi of  the  test   sample  or  200  pi
of  the sample  S-9  mixture was  added at  37  C  and  plated onto nutrient
agar  in duplicate.   Plates   were   incubated  for 24  hours at 37 C,  and
the  surviving fraction was  determined by  dividing the  colony count  on
the  treated  plate   (N)  by   the  colony  count  for  the  solvent   control
(N ).   The    results   shown   are   the   average   of   two   independent
experiments   with   duplicate   platings   at   each    of   three   cell
concentrations.

3. Test system results—

     The  results  presented   in  Table  2  indicate  that  water   soluble
mutagens such  as mitomycin C  (MitC) are  readily detected using the  spot
test,  while compounds such as benzo(a)pyrene  [B(a)p]  or  2-nitrofluorene
(2-NF)  which require  metabolic  activation or  are  sparingly  soluble  in
water  give  no  response.  An evaluation  of  fractional  survival  in  two
repair-deficient  strains  recE4  and  fh2006-7  (Table   3)  indicates  that
2-NF  does  produce   increased  lethal  damage  in  the  repair-deficient
strains.  The use of  a plate-incorporation  assay  to   evaluate survival
apparently  provided  a greater opportunity for  cellular exposure to 2-NF,
and  thus   the   positive  response  was  obtained.   Both  MitC and   MMS
continued  to  induce  a positive   response  in  the  plate incorporation
assay,  and  results  from  this assay were more  easily  transformed into  a
dose-response curve than for  the spot test (Table 3).

     For  the  indirect-acting mutagens B(a)p  and 2-AA,  no response  was
obtained in the spot test with or without activation,  or  in  the survival
assay  without  activation  (Table   1  and  4).   However,  when metabolic

                                   11

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         TABLE 2.  COMPARISON OF LETHAL EFFECT OF VARIOUS SAMPLES ON DNA REPAIR DEFICIENT
                            AND PROFICIENT STRAINS OF B. SUBTILIS

Inhibition Radius
Sample
Mit C
MMS
2NF
B(a)p

2AA

DMSO

S-9 Dose/Plate
(pg)
20
2
500
+ 50
50
+ 100
100
100 ill
+ 100 pi
168 wt
RP
4.3
6.8
0
0
0
0
0
0
0
recE4

12.4
13.0
0
0
0
0
0
0
0
fh2006.7

7.2
15.9
0
0
0
0
0
0
0
(mm)
recAS
— repair
11.5
15.6
0
0
0
0
0
0
0

mc-1
deficier
10.2
17.8
0
0
0
0
0
0
0

n
her. 9 Response'"
ll_
15.1
12.1
0
0
0
0
0
0
0

+++
•H-+
-
-
-
-
-
-

1- Repair Proficient
2- Response: (zone of inhibition in repair deficient strain-zone of  inhibition  in  repair
   proficient strain) <3 = -; 3,4 = +; 5-7 = +•»•; >7 = +++.

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               TABLE  3. SURVIVAL OF WILD-TYPE AND  REPAIR-DEFICIENT STRAINS OF
                     IJ. SUBTILIS EXPOSED TO VARYING CONCENTRATIONS  OF
                                   DNA DAMAGING  CHEMICALS
u>

Sample

Methylme thane
sulfonate



Mitomycin C



2-nitrof luorene





Dose/Plate
(pg)

20
2
0.2
0.02
2
1
0.1
0.01
1,000
500
250
25
2.5
Fractional
168 wt


0.27
0.83
0.92
1.04
0.72
0.91
0.97
0.91
0.95
0.82
1.04
0.99
1.00
Survival
recE4


0.0007
0.60
0.43
0.69
0.03
0.13
0.62
0.77
0.47
0.60
0.53
0.51
0.90
(N/N )
o
fh2006.7


0.0005
0.26
0.70
0.44
0.20
9.14
0.62
0.57
0.34
0.52
0.42
0.39
0.45

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TABLE 4. SURVIVAL OF WILD-TYPE AND REPAIR-DEFICIENT STRAINS OF B.  SUBTILIS EXPOSED
           TO VARYING CONCENTRATIONS OF 2-AMINOANTHRACENE AND BENZO(A)PYRENE WITH AND
                              WITHOUT METABOLIC ACTIVATION
Fractional Survival N/N
Sample

Benzo(a)pyrene




2-aminoanthracene




Dose/Plate
(ug)
10
5
0.5
0.05
0.005
10
1
0.1
0.01
0.001
168 wt
+ S-9
0.70
0.91
0.86
0.81
0.85
0.52
0.47
0.57
0.86
0.102
- S-9
_
0.71
0.60
0.65
0.82
0.73
0.81
0.85
0.83
0.94
recE4
+ S-9 •
0.24
0.39
0.33
0.29
0.65
0.24
0.35
0.49
0.42
0.76

- S.9
_
0.46
0.73
0.63
0.69
0.54
0.86
0.61
0.76
0.94
fh2006.
+ S-9
0.38
0.43
0.48
0.57
0.47
0.37
0.38
0.49
0.67
0.71
7
- S.9
_
0.75
0.83
0.93
0.76
0.43
0.51
0.47
0.61
0.55

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activation was  incorporated  into the survival assay by pre-incubation of
the chemical  S-9,  both B(a)p and 2-AA induced increased lethal damage in
DNA repair deficient  strains (Table 4, Figures 2 and 3).  After exposure
to the  2M:S-9  mixture at the highest  dose level,  the survival ratio of
recE4:168 was  0.46.   This  would be considered  a positive response, and
atlower  dose  levels  this  effect  was  reduced.  The  survival ratio for
recE4:168  at  5  and   0.5  ug/plate  exposure  to  B(a)p:S-9  mixture was
0.43  and  0.33,  respectively.    These  results  indicated  that while both
2-AA  and  B(a)p  induced  increased  lethal  damage  in DNA-repair deficient
bacteria  after  metabolic activation,  the  DNA-damaging  activity of  B(a)p
appeared  to be greater.

     This protocol increased the utility  of a plate-incorporation  assay
that  employed  several  different DNA repair-deficient strains of bacteria
with  metabolic  activation.   In   the  Salmonella/microsome   assay, the
frequency of  induced  mutations  per nanomole was  found  to be four  times
greater  for  2AA  than  for  B(a)p (McCann  et  al. , 1975).   This  may have
been  due  in  part  to  increased lethal damage  induced by  B(a)p  in the
excision  repair  deficient   strains  used  for  mutagenesis  testing.  The
addition  of  a  DNA-repair  assay   to  a  battery  of  test  systems for
detecting  potential carcinogens should  enhance the  sensitivity  of the
battery  towards  compounds  such  as MitC  which  cause DNA  damage  at low
dose  levels.    By  utilizing a  plate incorporation  assay  with metabolic
activation,  the  sensitivity of  the DNA  repair  assay  can  be enhanced
toward  compounds   which  are  indirect-acting  or  sparingly  soluble   in
water.  This  slight modification to the standard procedure  for measuring
fractional  survival  in  15.  subtilis  produces  an  increased  sensitivity
towards certain genotoxic  compounds and  should  increase its utility  as
part  of a battery  of  biological test  systems.  The DNA repair assay using
13.    subtilis   offers   the    additional   advantages   of  increased
permeability  of  the   gram  positive organisms  and  the  use  of multiple
strains  of  repair deficient  organisms which  can  detect inhibition  of
different types  of  DNA repair  (Tanooka, 1977).

B.    Point Mutations:  Prokaryote

1. Test system  description—

     Microbial   mutagenesis  assays   measure  primary   DNA  damage   by
detecting  small  changes  in  the nucleotide  sequence of  DNA.  The more
common  reverse  mutation  assays   detect  changes  (point  mutations)   by
measuring bacterial growth  in a media  free  of  a  specific  substrate which
the bacteria  require   for growth.   Increased  colony  formation (or  growth)
following  exposure  to  a  specific agent implies  that  the  agent has
induced reverse mutations.   Damage  to  DNA by environmental  mutagens may
contribute  to  human   cancer, genetic  defects,  aging,  and heart  disease
(Ames,  1979).  However,  since reverse  mutations are  highly  specific  in
the type  of  required  DNA interaction,  a  compound that does  not increase
the  frequency  of  reverse   mutations  may still  induce  other  types  of
genetic effects  (Anderson and Longstaff,  1981).  For this reason,  a more
                                15

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    1.0-
   0.9-
   0.7-
   05-
I

I
tr
u.
   0.3-
                                             • 168 wt
                                               rec E4
                                               fh2006-7
    0.1-
                            3      4      5       10

                         DOSE/PLATE (>rg-B(a)p)
        Figure 2.  Lethal effect of increasing doses  of  benzo(a)pyrene
                  on repair proficient  (168 wt) and  deficient strains
                  of B.subtilis with metabolic  activation.
                           16

-------
                                             STRAIN
                                             168 wt
                                             recE4
                                             fh2006-7
e
   OJ-
                   1.0
 2345       10

DOSE/PLATE  (*g-2AA)
          Figure 3,   Lethal effect of increasing doses  of  2-amino-
                     anthracene on repair proficient  (168.wt)  and
                     deficient  strains of B.subtilis  with  metab.olic
                     activation-.
                           17

-------
accurate  risk assessment  is  obtained when  a battery  of bioassays  are
used to detect a range of genetic damage.

     The  most  widely  validated  microbial  mutagenesis   assay   is   the
Salmonella/microsome  assay  developed  by  Ames  et  al.  (1973).   Using
the  Salmonella  assay, test  data has  been published  on more  than 5,000
chemicals  (Environmental  Mutagen  Information  Center  Index,  1982)   and
several  validation studies  have  been conducted  (McCann  et_ al., 1975;
Purchase   et^   al.,   1976;   Sugimura   ej^   al.,   1976;   Bartsch    et
al.,  1980;  De  Flora,  1981).    The  correlation  between  carcinogenicity
and mutagenicity using  this  test is currently  estimated to be about  83%
(McCann  and  Ames,  1981).   Categories of  carcinogens  which  are  poorly
detected  by  the  Salmonella  assay  include  azonapthols,  carbamyls,   and
thiocarbamyls;   phenyls;   benzodioxoles;   polychlorinated    aromatics,
cyclics,  and  aliphatics;  steroids;  antimetabolities;   and   symetrical
hydrazines (Rinkus and Legator,  1979).

     In  the  present  study,  two bacterial  assays have  been utilized  to
evaluate  the  capacity of various samples  to induce  point  mutations.   The
IJ.  subtilis   reverse  mutation  assay,  as  described  by  Tanooka  (1977),
was  used  with  selected waste  fractions  to  supplement  the  Salmonella
assay.   The  IJ.  subtilis assay  has  been  found  to  be  sensitive   to many
compounds  poorly  detected  by the  Salmonella assay (Felkner,  1981)  and
offers  the  advantage of  being  a  gram  positive organism that   is more
permeable  to  certain  compounds  (Tanooka,  1977).  The following  discussion
will  include  the   protocols   used  for  the  two  prokaryotic mutagenesis
assays and the results obtained  using various diagnostic mutagens.

2.   Test system protocol: prokaryote mutagenesis—

     The   Salmonella/microsome  assay  as   described  by  Ames   et   al.
(1975) was used  to measure the  ability  of a sample to  revert  strains of
bacteria   to   histidine   prototrophy.     A  description  of    the   J3.
typhimurium  strains  that  were  provided  by  Dr. B.  N.  Ames  (University
of  California,  Berkeley,  CA)  is given  in Table  5. The  procedures used
were  essentially   the same  as  Ames  et^ al.  (1975).  Overnight  cultures
were  grown  from  individual  colonies  picked  from  nutrient agar master
plates  and  inoculated  into  Oxoid  Nutrient  Broth  No.2  (KC  Biological,
Lenexa,  KS).   Cultures  were  incubated for  16 hr  at 37 C.  All  strains
were   checked   quarterly  or  when  new   master   plates  were  made   for
nutritional  markers  for the  following characteristics:  the  deep rough
character, the  presence  of the  R  factor,  and sensitivity  to  ultraviolet
light.   Top  agar  and petri  plates were  prepared  as  described   by Ames
e_t  al.  (1975).    Samples  were  tested with  strains  TA98 and  TA100  in
two  independent experiments  at  five dose  levels  on  duplicate  plates with
and  without  metabolic activation  (0.3 ml  rat  liver/1.0  ml S9  mixture;
0.5  ml S9 mixture/plate).   Aroclor 1254-induced rat liver was  obtained
from Litton  Bionetics (Charleston,  S.C.).   Positive controls,  as  well as
solvent   and  sterility  controls,   were   run  on  each  test  date.   The
positive  control  used to verify functioning of the metabolic  activation
                                18

-------
TABLE 5.  CHARACTERISTICS OF SALMONELLA STRAINS USED FOR MUTAGENESIS TESTING
Histidine
Strain
TA1535
TA100
TA1538
TA98
TA1537
Mutation
his
his
his
his
his
G46
G46
D3052
D3052
C3076
Additional
Mutations
LPS;
LPS;
LPS;
LPS;
LPS;
Exc
Exc .R
Exc |
Exc R
Exc
2
SMF
39
120
16
26
9
•»
i.
IMF IMF + S9"
2774
2282
2158
2421
160
440
1833
870
1594
371
1- LPS - lipopolysaccharide cell wall.
   Exc - excision repair deficient.
   R - plasmid pKMlOl
2- Historical spontaneous mutation frequency  for  lab with DMSO, without  S9.
3- Induced mutation frequency; TA1535, TA100-MNNG: TA98, TA1538-2NF; TA1537-9AA
4- Induced mutation frequency 2-acetylaminofluorene with activation.

-------
system  for  all strains  was 10  ug 2-aminoanthracene  (Sigma,  St.  Louis,
MO); while  direct acting  positive controls for  TA98  and TA1538 were  25
ug     2-nitrofluorene,      for     TA100     and     TA1535        2     ug
N-methyl-N'-nitro-N-nitrosoguanidine,   for ..  TA97   and  TA1537   10   ug
9-aminoacridine,  and  1  ug mitomycin  C  for  TA102.  Dimethyl  sulfoxide
(DMSO) was used as a negative control.

     A  limited  number of  samples were  also  analyzed  using the  Bacillus
subtilis  reverse  mutation  assay   (Tanooka,   1977;   Felkner   git   al. ,
1979).  The   two   IJ.   subtilis  mutants   were  supplied  by   Dr.  I.   C.
Felkner  (Clements Assoc.,   Washington,  D.C.)  and  are  described  in  Table
1.   These  strains may  be  used  to  detect  either reverse  mutation  £o
His   or  Met   or a  forward  mutation  to  prototrophy  as  His ,   Met .
In the present study, only  the reverse mutation assay  was utilized.

     The  methods  employed  were  basically  the  same  as   described  by
Tanooka  (1977).    Cells  of  TKJ5211  or  TKJ6321  were  grown overnight  at
37°C with shaking in  Oxoid Nutrient  Broth No.  2.   The cells  were then
harvested, resuspended  in  an equal volume of glucose  minimal  medium,  and
starved  for  1  h  at  37 C  with  shaking.   To detect  the His   mutation,
0.2 ml  of culture was  plated  with  2.5 ml soft  agar  on a  suppplemented
minimal  media  (Tanooka,  1977).   Plates  were  incubated  for 72 hrs  at
37°C.

     Statistical   Analysis—Mutagenicity   in   the  Salmonella/microsome
assay  was  determined  using  the modified  two-fold  rule   (Chu e_t  al.,
1981).    To  determine  the  mutagenicity   of  a   sample,  the  mutagenic
activity  ratio  (MAR) is  first  calculated (Commoner,   1976)  at   the four
highest  non-toxic dose levels.   The mutagenic  activity  ratio is defined
as   (E-C)/C.   ,   where  E   is   the   experimental  number  of  revertant
colonies  (average of  four   plates); C  is the number  of revertant colonies
on  the  control  plates (average  of eight plates)  obtained on  the same day
with  the  same   strain  and  microsome  preparation;   and   C.    is  the
historical  average of revertant  colonies  on  control  plates obtained  the
year the  test was run with  the  same strain and microsome preparation.   A
sample  was  considered mutagenic if  the MAR was  greater than 2.0  for  at
least  two consecutive dose levels or in  the  last non-toxic  dose  level.
In  addition, at  least  two of  these  consecutive  doses must  possess  a
dose-response  relationship showing an increase  in  the  number  of  mutant
colonies  at  increasing  dose   levels.  Chu  et^   al.   (1981)  calculated
that when using  the  modified two-fold  rule  to  determine  the  mutagenic
potential of  a  sample,  false positives  and false negatives will occur at
a  rate  of   4.1%   and  1.8%,  respectively.   In  an evaluation   of  seven
different  methods  for  statistical   analysis  of  data  from  microbial
mutagenicity  assays,  Chu  et^ al.  (1981)  determined   that  the  modified
two-fold  rule  was   one   of  three   analytical   methods  that   gave  an
acceptable  rate of false positives and  negatives.   All raw data from the
Salmonella  assay  was  first  entered  into  a  TRS-80  computer  using  a
program   that   calculated   the  means   and   standard   deviations.    This
information  is  provided in Appendix  C.  Selected data  was then entered
                                 20

-------
into a  second  TRS-80 program to calculate the mutagenic activity  ratios.
A  printout  of the  programs utilized to  process  data  is  provided  in
Appendix D.

3.   Test system results: prokaryotic  mutagenesis—

     Prokaryotic  mutagenesis   assays   using  both  J3.  typhimurium  and
B.   subtilis   were   employed   in   this   research.   However,  the   vast
majority  of   the  work  was  conducted  using   the  Salmonella/microsome
assay  of  Ames e_t   al.  (1975).   Recent modifications  to  the standard
protocol  (Maron  and Ames,  1983)  and the  addition  of  two  new  tester
strains  (Levin  ££  al.,  1982a;  Levin  e£  al.,   1982b)   have enhanced
the   sensitivity   of   this   bioassay.   Brusick   (1983)   reviewed   the
sensitivity    (mutagenic   carcinogens/total   carcinogens),   specificity
(nonmutagenic  noncarcinogens/total  noncarcinogens),  and predictive  value
(mutagenic  carcinogens/total   mutagens)   of  the   Salmonella assay  as
reported in  the  literature.   Based on  studies  which  reviewed at  least
100  chemicals, Brusick  (1983)  reports that  the sensitivity  ranges  from
54  to  93%, the  specificity ranges  from 77  to  100%,  and  the  predictive
value ranges  from 87 to 100%.   Overall,  Brusick  (1983) reports that the
true  correlation  coefficient   is  about  80%   when   compared to  tumor
responses  in  mice  and  rats.  Groups  of  chemicals  which  are   poorly
detected  in  bacterial  mutagenesis  assays  include  antimetabolites,  azo
compounds, carbamyls  and thiocarbamyls, halogenated compounds, steroids,
cross-linking  agents,   inorganic   compounds,   and  promoters (Brusick,
1983).   Most   of  these  groups  can be  detected  by using microbial assays
which   employ   DNA   repair  deficient  bacteria  (Shiau  et   al.,  1980;
Kanematsu  et   al.,   1980)  or eukaryotic   organisms  (Scott  et^  al.,
1982;  Kafer  et^ al.,  1982).  Thus,  when employed as  part  of a  battery
of  biological  test  systems,  the Salmonella/microsome  assay  can  provide
a  highly  efficient  tool   for monitoring  genotoxic  chemicals   in  the
environment.

     The   final   interpretation of  the  results  from  the   Salmonella/
microsome  assay may  be influenced by  a variety  of factors  including the
selection  of  solvents,  the size of the inoculum,  the  presence or  absence
of  metabolic  activation,  and the   presence   of  histidine   containing
substances.  Organic  solvents  are used in biological  testing  in order to
dissolve compounds  which  are  sparingly soluble in  water and may affect
the   results   of  the   bioassay  due  to   the   solvents'   toxicity  or
interractions  with  cellular  membranes  and  proteins  (Abbondandolo  et
al.,   1980).    Organic   solvents   which    are  compatible   with   the
Salmonella  test  include  dimethyl  sulfoxide, glycerol  formal, dimethyl
formami'de,   formamide,   acetonitrile,   95%   ethanol,  acetone,  ethylene
glycol     dimethyl     ether,     l-methyl-2-pyrrolidinone,     p-dioxane,
tetrahydrofurfuryl   alcohol,    and    tetrahydrofuran   (Maron   e£   al. ,
1981).   Abbondandolo   et_  al.   (1980) observed  that  ethylene   glycol,
2-methoxyethanol,  and  methanol  were   also   compatible  with  mutagenesis
test  systems.   While   these   15  solvents   provide  a  useful  array  of
characteristics,  certain  fractions  of  a  hazardous  waste  may  contain
                                 21

-------
substances  which  are   insoluble  in  any  of  these  solvents.   The  data
provided  in  Table 6  indicate that a 1:10  mixture of dichloromethane  in
dimethyl   sulfoxide   may   be  used   to   increase   solubility   without
significantly affecting  the  results.   The  use of  such a  combined  solvent
system   can,   however,   affect   the   results   of   the  Bacillus   and
Aspergillus assays  (data not  shown),  and  its use  should be  restricted
to preliminary testing in Salmonella.

     The   standard   procedures   for   the   Salmonella   assay   (Ames   et
al.,  1975) recommend  the  addition of  0.1  ml  of  an overnight   (16  h)
culture,  or  approximately  1  x 10  bacteria to  2.0 ml  of  top agar.  In
the  revised  methods,   Maron  and  Ames   (1983)  suggest  reducing  the
incubation  period to  10 h in  order to  increase  the viability   of  the
cells plated.  Matney  (1981) and Green and Muriel  (1976) state that the
number  of spontaneous  revertants per plate is completely independent  of
the  initial  inoculum  size  within  the  range of  10   to  10  cells  per
plate.  As  for  the effect of inoculum size on mutagen yield,  both Belser
et^  al.   (1981)   and  Salmeen  and  Durison   (1981)  found   no  appreciable
difference  in  the  yield of  revertants  induced  by  2-nitro.f luorene  at
plating   densities   ranging   from   1  x   10   to  1  x  10  ,  although
increasing  the  cell density to  1  x 10   did produce  a   2-fold increase
in  revertant  yield  (Salmeen  and Durison,  1981).   MacPhee  and  Pallister
(1983)  predicted  that  inoculum size would have a  significant  affect  on
the  results  when  testing  a mixture  of  toxic  and  mutagenic  compounds.
They  observed  that  the  sensitivity  of   the  assay fiwas  increased  by
decreasing  the  inoculum  size  to approximately  1  x  10  cells  per plate.
Barber  et^  al.   (1983)  also   observed   a   relationship   between   growth
and  reversion  frequency  in  the  Salmonella assay.   They  found that  the
final   reversion   frequency   will   be   dependent  on   the   L-histidine
concentration in  the top agar, and that  no  reversion takes  place during
the  first  four  hours  after  the  bacteria  are  plated   (Barber   et^  al.,
1983).   The fact  that  no  reversion takes place during  the first  four
hours  after plating  may  explain  the  limited  sensitivity  of the plate
incorporation assay to volatile compounds  (Barber  £_t al.,  1983).

     Additional  factors may  also affect  the reversion  frequency in the
Salmonella   assay.    Peak   £t   al.    (1983)   demonstrated   that   the
liver-microsome  S9 enzyme produces a highly significant  increase in the
spontaneous  reversion  frequency.   This  data  is  consistent with  that  of
the  present  study  (Table  7 and 8) which  indicate that  the  rat-liver  S9
extract  alone  increases  the  number  of  revertant   colonies  on  control
plates.

     Trace  quantities   of  histidine which  may  be present  in  biological
material  can  also affect  the  results  of  the Salmonella/microsome assay
(Aeschbacher  e£  al.,  1983).   This affect  may  be  especially  important
in   the   analysis   of   soil   extracts.     Aeschbacher   et^  al.   (1983)
recommend   using   a   solvent   or   sorbent  extraction  to   eliminate
interference  from  histidine.   In  the   present   study,   XAD  resins  and
dichloromethane   were   used   to   extract   water   and   soil   samples,
                                22

-------
fO
OJ
                      TABLE 6.  EFFECT OF A 1:10 MeCl  -DMSO*  SOLUTION  ON  THE

                              SPONTANEOUS REVERSION AND  INDUCED MUTATION
                                   FREQUENCY IN J5. TYPHIMURIUM
Revertants /Plate
Strain
TA98




TA100
TA1535
TA1538
TA1537
Sample
	
2-nitrof luorene
(25 pg)
2-aminoanthracine
(10 pg)
-
-
-
*~
DMSO
21

3008

2007
96
19
13
10
MeCl2:DMSO
24

2485

1949
91
21
11
9
              * Dichloromethane:dimethyIsulfoxide.

-------
POSITIVE CONTROLS
Total Revertanta Mean » SD
Chemical S-9 Dose/Plate TA1535
None
ONSO

2-NP


MNNC


MMS


B(a)p




2AA



0
t 0
100 |il
» 100 Ml
250
25
2.5
4
2
0.2
20
2
0.2
50
t 500
50
5
.5
10
+ 100
10
1
36 » 9
22 7 4
39 t 10
22 7 6
NT
NT
NT
2,774 * 136
2,547 t 124
36 » 10
494 t 457
268 7 392
222 t 212
31 * 4
49 * 5
54 t 6
50 » 10
32 + 4
54 » 8
440 » 188
346 7 94
44 * 13
TAI538
18
16
35
1,765
2,158
850






22
188
156
124
52
33

870

t 8
NT
* a
* 9
* 572
7 749
+ 253
NT
NT
NT
NT
NT
NT
11
15
30
22
9
t 8
NT
* 343
~ NT
TA98
30
40
26
37
2.421
2.197
632






28
507
524
609
86
37
1,122
1.548
581
+ 8
7 15
* 6
7 10
t 423
+ 445
7 205
NT
NT
NT
NT
NT *
NT
« 7
7 99
7 137
7 152
± *'
* 13
7 469
« 444
+ 319
TA100
127
126
120
122



1,743
2,282
452
1.296
1.826
555
131
778
889
707
197
146
868
1,833
671
* 24
7 36
+ 38
7 27
NT
NT
NT
t 927
7 404
7 455
* 118
7 415
* 294
* 21
+ 247
7 178
7 130
t 31
+ 37
7 133
+ 554
7 446
TKJ5211
25 »
NT
31 *
21 7
417 t
93 7
NT
2,292"
39**
26"
393 «
54 7
29 *_
21 *
329 7
380 *
149 +
26 +
60"
341"
774"
196"
9
8
6
227
49




281
6.4
11
5
96
33
130
0.7




TKJ6321
103 * 14
NT
131 * 40
112 » 45
438 * 205
203 7 78
NT
1.519"
118"
109"
261"
133"
108"
124"
996 t 175
371 7 34
91 7 26
"NT
131 * 3
608 t 81
718 « 274
253 7 46
   Negative controls: none-no additions to top agar; DHSO-100 |il Dimethylsulfoxide; Postive controls: 2-NF-2-Nitrotluoreoe;
   MNNC-N-methyl-N'-nitro-N-nitroaoguanidine; MMS-methyl methane sulfonate; B(a)P- benzo(a)pyrene; 2AA-2-aminoanthracene;
   NT " not tested.

** Represent one experiment with duplicate plates, standard deviation not provided.

-------
                  TABLE 8. VARIABILITY OF S. TYPH1HUR1UH STRAINS TA98 AND TA100 WITH NEGATIVE AND POSITIVE CONTROLS FOR EACH YEAR OF THE
ro
Ol
PROJECT
Strain Sample 3-9 C
TA 98 None
+
DHSO
+
HeCl
2NF
B(a)P
+
2AA
+
TAIOO None
+
DMSO
•f
MeCl
MNNG
MMS
B(a)P
+
2AA
+
Year2 1981
lose/Plate
:
100 pi
10 pi
25 pg
50 pg
10 pg
-
100 pi
10 pi
2 Pg
2 pg
50 pg
10 pg
(N)
(NT)
(NT)
(72)
(105)
(NT)
(NT)
(34)
(NT)
(NT)
07)
(42)
(NT)
(NT)
(56)
(91)
(NT)
(NT)
(28)
(NT)
(NT)
(NT)
(22)
(35)
Hean + SD (N)
(246)
(94)
20 + 4 (529)
28 T 10 (449)
(80)
(60)
1.760+424 (112)
(8)
(10)
24 * 8 (123)
2,142 + 15 (126)
(144)
(88)
87 + 11 (416)
112 + 27 (374)
(83)
(55)
2,374 + 602 (106)
(8)
(6)
(6)
109 + 24 (113)
2,054 + 667 (110)
1982
Hean * SD
29+8
38 + 10
25+6
34 + 10
33 + 12
37 + 12
2.257 + 594
27 + 10
501 + 116
37 + 16
1.878 + 431
119 + 22
123 + 27
113 + 26
114 + 28
116 + 29
114 ^ 27
2.321 + 528
1,854 + 254
124 + 24
603 T 75
142 + 39
1,799 + 580
1983
(N)
(217)
(123)
(440)
(448)
(NT)
(NT)
(93)
(6)
(6)
(96)
(88)
(197)
(135)
(386)
(373)
(NT)
(NT)
(78)
(NT)
(8)
(8)
(91)
(85)
Hean + SD
30 + 8
42 +; 15
29 + 7
42 «; 10
-
1.943 + 315
28 + 9
731 + 88
41 + 12
1.751 + 392
132 + 25
128 + 42
132 + 55
132 + 26
-
2,197 + 549
-
137 + 19
1.104 *. 256
160 + 38
1,787 T 473
                  I. Negative controls: none - 3.0 ml top agar only; DHSO - dimethylsulfoxide; HeCl. - dichloromethane, 1:10 in DHSO;
                     Positive controls: 2NF - 2-nitrofluorene; B(a)P • BerizoU)pyrene; 2AA • 2-aminoanthracene|
                     MHNC » N-methyt-N'-nitro-N-nitrosoguanidine; HMS - methyl methaneaulfonate.

                  2. Year: 1981 - includes data from 6/1/81 through 12/31/81; 1982 Include* data from 1/1/82 through 12/31/82 and 1983
                     includes data from 1/1/83 through 9/31/83; (N) • number of observation*; NT - not tested.

-------
respectively.  It  is anticipated  that these  procedures should  eliminate
any histidine  in water  and soil samples.   Additional factors which may
affect  the  results  of  mutagenicity  tests  include the method  of  media
preparation  and   amount  of  medium  per .  plate  (Friederich  et   al.,
1982),  the  inducer used  for the  liver  enzymes  (Venitt,  1980), and the
presence or  absence of visible light  (MacPhee  and Imray,  1974).   Belser
et  al.   (1981)  reported  that  the  greatest  source  of  variability  is
nonuniformity  of  the   top agar  thickness.   Because   of  these numerous
sources  of  variation,  it  is essential  that  microbial  mutagenesis  assays
be  conducted  under a  Quality  Assurance/Quality Control  Program  with
standardized  protocols  and  that  each  experiment   include   sufficient
positive and negative  controls to accurately  assess the variability.

     The  extent  of inter- and  intralaboratory variation  will  be  an
important factor  in determining the utility  of  short-term bioassays as a
monitoring  tool.   The   results  presented  in  Table  7 demonstrate the
interlaboratory   variation  with   four   Salmonella   strains   and  two
Bacillus  strains  for  negative  controls and  diagnostic mutagens for the
entire  project.   For  the  negative  controls,  the variability ranged  from
14% for  TKJ6321  with no additions  to 50% for TA1538 with  DMSO  (Table 7).
Cheli  et^  al.  (1980)   observed  that  the   plasmid   containing strains
(TA98  and TA100)  were  generally   less  variable  than the  corresponding
non-plasmid  strains   (TA1538  and   TA1535),  although  no  such  trend was
found  in this  laboratory.  While  a  greater degree  of variability was
observed  with  the  diagnostic  mutagens than  with the  negative  controls,
none  of  the  variations  were   sufficient  to  influence   the   final
interpretation  of  the  results.    That  is   to   say,  in  all  cases, the
no-effect dose  level and  the dose  level at which a positive  response was
obtained  were  constant.   The  overall variability of both  prokaryotic
mutagenesis  assays  were comparable; however, for the  compounds  tested, a
greater  mutagenic response  was  obtained in  strains  TA98  and TA100  than
in either of the  TKJ strains.

     The  majority of  the  biological testing performed in this research
was conducted  with strains TA98 and  TA100.   The variability  of  these two
strains  for  each of the three test years is provided in  Table 8.   Both
strain  TA98  and  TA100 exhibited a broad  range  of variability, although
in  general  the mean  for each  year was within  one standard deviation  of
the  mean  for  the  other  two  years.   In   all   three  years,  the  mean
spontaneous  reversion  frequency  falls  within  the  range   considered
acceptable   in  a   survey  of  eight   laboratories   conducted  by the
Environmental Mutagen  Information Center (1978).

     Periodically  during  this  research,  titrations  were  conducted  with
diagnostic  mutagens in  order  to evaluate  the  sensitivity of  the  tester
strains.   The  results from testing  the  direct-acting mutagens MMS and
MNNG  in  strain  TA100  are provided  in  Figures 4   and  5.   For  both
compounds on  all three  test dates,  the  results  are comparable, although
a broad  range  of variation was observed at  all  dose  levels.   The results
from  testing the direct-acting  mutagen  2-nitrofluorene with strain TA98
                                26

-------
  3000
 tn
"c
 a
 >  '500
2
IE
O
O
   600-
   300i
                                    MMS
                                  x 9/24/8!
                                  O 9/2/83
                                    9/5/83
                  5           10
                    DOSE/PLATE (ul)
15
20
Figure 4.  Variability of mutagenic activity of TA100 induced
         by MMS
                         27

-------
   3000-
   2100
   1500
(ft
£
O
O
   600-
   300-
         .25 .5
             MNNG
           X 9/24/81
             7/23/82
             9/13/82
      2           3
DOSE/PLATE (ug)
         Figure 5. Variability of mutagenic activity of TA100 induced
                 by MNNG.
                           28

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is provided  in Figure  6.   While there was  a  broad range of variability
for  the  18 month  monitoring period,  the  variability  was  comparable  to
that observed by Cheli £t al. (1980) over an 11 month period.

     The addition  of  metabolic  activation is  another parameter  which  can
significantly  affect  the  variability  of  the Salmonella  assay.   Cheli
et  al.   (1980)  observed that  the  addition  of S9 and 2-aminoanthracene
resulted  in  a  broad  range  of  mutagenic   responses.    The   responses
obtained  with  benzo(a)pyrene  (B(a)P)  and   2-aminoanthracene  (2AA)   in
strain  TA100  are   given  in  Figures  7 and  8.  The  variability  of  the
response from  activated B(a)P is  smallest  at a  dose  level of 50 ug  per
plate  and  increases  at higher  and  lower  dose   levels.   With  2AA,  the
variability  of  the responses  are greater than  for  B(a)P,  although  the
optimum  dose  level was  consistently 10 ug  per  plate.  Similar  results
were obtained with activated B(a)P and 2AA  in strain TA98  (Figures  9  and
10).  The  response induced  by B(a)P was  less  variable than  that induced
by 2AA;  however,  the overall mutagenic response  induced by  2AA  was also
greater.   For  both strains  TA98 and  TA100,  the  optimum dose  level  for
B(a)P and 2AA with activation remained  constant on all  test  dates.

     An  additional comparison was  conducted  to  evaluate the effects  of
storage  on the variability  of the mutagenic  activity of water  extracts
over  time.  The  results from  two  different  water  extracts  tested  in
three independent  experiments  at intervals  of 2, 5,  and 14  months  after
collection   indicate   that   there  was  no  significant  change  in  the
mutagenic  activity at all  dose  levels  in  either   sample  (Table  9).  There
was  a  large increase in the  total induced mutation  frequency  for both
samples  with activation on  the  last  test  date.  However,  these  results
did  not  deviate  significantly from the mean and  may  have been  influenced
by   the  spontaneous  reversion   frequency  that  was  almost  double  the
spontaneous  reversion  frequency   from the   initial  test   date.   Thus,
microbial  mutagenesis  testing  has  indicated  that  storage  of  extracted
water   samples   at  4 C  will  not  appreciably   alter  their   mutagenic
potential  over  a 14 month interval. While retesting  did  clarify the data
interpretation,  there was no  difference in  the   final interpretation of
the  data when  compared to the results  from  each  individual testing  date.
These  results,   and  those  discussed  previously,   emphasize  the need  for
adequate positive  and negative controls as  well  as duplicate experiments
in  microbial mutagenicity  testing.   In addition,  the  Salmonella  assay
exhibited  a  wide  range  of  variability over time, although  the  optimum,
toxic, and no-effect  dose level remained fairly constant.

     The   Salmonella/microsome   assay   is   a  rapid  and    simple   test
procedure  that  can  be used  to  evaluate  the  mutagenic  and  potential
carcinogenic  activity   of   test  sample.   As  part  of  a  battery   of
biological  test systems,  the  Salmonella/microsome  assay  is  considered
to  be  the most  widely validated  and most  sensitive  test  system (Griem
e_t   al.,   1980).   In  addition,   this  is  one of a   limited  number   of
bioassays  for  which a standard protocol has been developed and  which  has
been  subjected  to numerous  intralaboratory  evaluations  (Dunkel,  1979;
                                    29

-------
   3000
   2 I 00-
 
 
-------
  3000
   2100

-------
300CH
                                      2AA+S9
                                      x 9/24/81
                                      o 6/18/82
                                      * 7/23/82
                                      n 11/12/82
                                      • 9/3/83
                                      A 9/5/83
             10
 20 '     100        300

DOSE /PLATE (ug)
500
       Figure 8. Variability of mutagenic activity of TA100 induced
              by 2AA.
                        32

-------
   30001
   2100^
09
*>»
C
ta
1  1500
00
05
    600-
    300-
         B(a)p+S9
        x 4/2/82
        o 9/13/82
        A 9/24/82
        al1/12/82
        • 5/31/82
        A 9/2/83
        • 9/5/83
                                                   -o
               10
20
100
300
500
                       DOSE/PLATE Cug)
         Figure 9. Variability of mutagenic activity of TA98 induced
                by B(a)P.
                         33

-------
    3000
    2100
 £  1500
 i_
 >
4.
 !E
 oo

 l-

    600-

    300-
                      2AA+S9
                     x  6/18/82
                     o  7/23/82
                     a  9/13/82
                     a  9/24/82
                     •  11/12/82
                     A  9/2/83
                     •  9/5/83
10      20      100
    DOSE/PLATE(ug)
                                                  150
         Figure 10. Variability of mutagenic activity of TA98
                  induced by 2AA.
                        34

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    TABLE  9.   THE EFFECT OF STORAGE AT 4 C ON THE MUTAGENIC ACTIVITY  OF TWO  RUNOFF

                                   SAMPLES (SAMPLES WERE  RECEIVED  5/13/1982)
to
Ul

t

Dose/plate
Sample
0582006





0582007





(rag)
0
.01
.05
.1
.5
1.0
0
.01
.05
.1
.5
1.0
7/9/82
17
33
34
42
91
Toxic
17
34
28
37
48
51

-S9
10/12/82
31
18
23
28
70
Toxic
31
18
18
15
28
26
TA98 his
+ *
Revertants
+ S9
7/18/83
34
17
24
42
60
Toxic
34
22
23
24
29
25
Mean
27
23
27
37
74
Toxic
27
25
23
25
35
34
7/9/82
20
54
32
66
129
120
20
22
65
79
145
115
10/12/82
39
28
48
65
102
107
39
32
55
73
87
70
7/18/83
39
56
58
91
201
275
39
46
56
76
138
164
Mean
33
46
46
74
144
167
33
33
59
76
123
116
     *  Average of two plates.

-------
de  Serres  and Ashby,  1981;  Grafe  et^  al.,   1981).   Because  the  plate
incorporation  assay  does  not provide data as  to the viability  of  exposed
cells,  quantitation  of  this  assay  is  difficult  if  not   impossible
(Matney,  1981).  As  a result, risk assessment from bioassay data  is  also
impossible    (Clive,    1980;   Griem    et^   al.,    1981).     Additional
limitations  of  the  Salmonella/  microsome assay  include  its   inability
to  detect  volatile  compounds,  inorganic  compounds,  and  chlorinated
hydrocarbons   (Brown  et^  al.,  1982).   However,  the  Salmonella  assay
is  generally  accepted  as  the primary  test   in  a battery of  bioassays
because  it has  a high  sensitivity  and  specificity,  and  because it  is
rapid and inexpensive to run  (Brookes and de Serres, 1981).

C.   Point Mutations and Chromosome Damage: Eukaryotic Organism

1.   Test System Description—

     Eukaryotic  assays  for  measuring  genetic  damage  are  capable  of
detecting  point  mutations  and  small  deletions  as well   as  changes  in
mitotic    segregation   resulting    from   induced    nuclear    damage.
Investigations   of   chemical   mutagenesis   in   haploid  Aspergillus
nidulans  using the methionine  assay has  been shown  to detect  base-pair
changes and  small  deletions  (Alderson and Hartley, 1969; Hartley, 1969),
while  investigations using  the  diploid strains  can  detect  changes  in
mitotic   segregation  resulting  from   crossing-over,   non-disjunction,
breakdown   of  mitosis,  or   chromosome  aberrations   (Kafer  e_t   al.,
1982).

     The   Aspergillus  methionine   assay  detects   forward   suppressor
mutations  by measuring colony formation on  a media lacking methionine.
Restoration  of the  ability to synthesize methionine  in Aspergillus  has
been  shown to arise  from a forward  mutation  in any  of six genes (Scott
and  Alderson,   1971;   Lilly,  1965).   For   the  detection  of  mitotic
segregation  or chromosome  aberrations,  diploid  conidia heterozygous  for
recessive   color  markers,    non-utilization   nutritional  markers,   and
resistant  markers  were  utilized.   Agents inducing  mitotic segregation
are initially detected  by visual observation  of phenotypic changes  using
diploid organisms  grown on  a  complete media  that  contains the  chemicals
to  be  tested.  An   increased frequency  of  phenotypic  changes,  e.g.,
changes  in conidial  color  or colony morphology,  implies   that  the  agent
being tested  has induced some  form of genetic  damage.

     Although  Aspergillus  has only  been  tested  with  150  compounds,  the
same response was  obtained  in 26 of the 27 compounds for which data from
both  animal  carcinogenesis  bioassays   and  Aspergillus  were  available.
In  addition,  five  of  the  compounds giving  a positive  response  in  the
Aspergillus   system  and carcinogenesis  bioassays  were  negative  in  the
Salmonella   assay   (Scott    ^t   al.,   1982).    The   following   is   a
discussion  of   the  procedures  utilized  for  the  haploid  and  diploid
bioassay, and  the results obtained with  solvent and positive  controls.
                                 36

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2.   Test System Protocol—

     a.  Methionine  System—The  bioassay  using   the   haploid   form  of
Aspergillus  nidulans has  been  used to  assess  the  mutagenic  potential
of  various  samples by evaluating  the  induction of   mutations  at  the
methionine  suppressor  loci.   The  parent   strain  of   Aspergillus  was
obtained  from  Dr.   T.  Alderson,  MRC  Radiobiology  Laboratory,   Harwell,
England.   The  parent  strain  was stored  in  silica  gel  at 4 C.   Stock
cultures  were  obtained  by  growing  Aspergillus  crystals  on   complete
medium.   Working  cultures   were  grown  from  organisms   picked  from  the
stock  culture.   The requirements for biotin  and methionine were  checked
individually  on  media  lacking  the  appropriate  amino  acid,   and  the
untreated  experimental  controls  indicated  the  presence of an  excessive
number  of  methionine  suppressor  mutants  in  the  conidial  suspension
before  exposure to  the test  chemical.  An acceptable overall  spontaneous
mutation  frequency  should  be within the  range  of  2.5 mutants  per million
conidia  assayed.    Slightly  higher   spontaneous  mutation frequencies  can
be expected when conidia are  exposed to 37  C  or metabolic activation.

     Conidia  from  four to  five  single  colonies  of the  meth  Gl;  biAl
(requiring   methionine  and   biotin)   Glasgow  strain   of   Aspergillus
nidulans  grown  for  5  to   6  days  on a complete medium  (CM)  at  37 C
were  used for  each experiment.  The  conidia were suspended  in  dilution
fluid,  i.e.,  water containing Tween 80,  vortexed for 15 min  to  break up
conidial  chains,  and filtered  through  sterile cotton to remove  mycelial
debris.  The  conidia  were   then  concentrated   on  a  0.45  um  millipore
filter   (Millipore-Flouropore  filters,  Millipore  Corp.,  Detroit,  MI),
washed  with  at  least  20   ml of   dilution  fluid,  and  resuspended  in
phosphate buffer  (pH 7.0) containing Tween  80.

     Removal  of  germination  inhibitory  substances  from the conidia of
Aspergillus   is  essential   to  achieve   consistent  levels  of   survival
after  mutagenic  treatments  (Scott   et   al.,  1972).    Inhibitor-depleted
conidia  were  prepared  by the  addition  of a 1%  (v/v)  solution of diethyl
ether  to  the conidial suspension.   The  flask containing  the  50  ml of
conidial  suspension with  diethyl ether was placed  on a  shaker for 1 hour
at  37  C.  The  conidia were   then  collected   on  a  0.45  um  millipore
filter,  washed  with at least  20  ml  of dilution fluid, and  resuspended at
a  density of 240 million conidia/ml in Tween 80 and  phosphate buffer (pH
7.0).   This  method  for removal of the germination  inhibitor is  described
in Bertoldi e_t  al_.  (1980).

     Test    compounds    were   dissolved   in   DMSO    and   added   to
inhibitor-depleted  conidia  to yield the  appropriate  final  concentrations
of  the  test  chemical.  All  manipulations and exposures  were  completed
under  yellow light.   Throughout  the exposure, the  conidial  suspensions
were  enclosed  in   a teflon sealed  pyrex glass  test tube  and  incubated
with  mild agitation at a  temperature of  37 C  for  the desired  period.
The  treatment was  stopped  by the addition of  9 ml of  ice  cold  dilution
fluid  to  1  ml of  the reaction  mixture.  For  the non-activated  system,
                                  37

-------
1 ml  of approximately  24  million  conidia  in  Tween  80 phosphate  buffer
was added  to the exposure  tube.   At the appropriate  time,  10 pi  of  the
appropriate  concentration  of  the  chemical  in  DMSO  was  added  to  the
conidial suspension.

     For  the  activated  system,   0.1  ml  of  approximately  240 million
conidia  in  Tween  80  phosphate buffer  was  added  to  the  exposure  tube
containing 0.9 ml  of the S9 mix.  Thus,  the exposure  concentration  of  the
conidia  was  24 million  conidia per  ml.  At  the  proper time,  10  ul  of
the appropriate  concentration  of  the chemical in  DMSO was added  to  the
conidial  suspension,  and   the  previously  described   procedure  was  then
followed.

     Immediately   before   and   after   treatment,    the   viability   and
mutability  of  a  conidia   population from the  biAl, methGl  strain  of
Aspergillus  was  assayed  by  platting  on the  appropriate minimal  media.
To  estimate  the viability, minimal medium plates  containing  methionine,
biotin,  and  sodium  deoxycholate  were   used.    Appropriately  diluted
suspensions  were spread over the  surface  of  five  plates  and  incubated
for at   least  two  days at  37 C before  the  viable colonies were manually
counted.   Media of a  similar composition,  although  lacking  methionine
and   sodium   deoxycholate,   were   used   to  detect  all   the   methionine
suppressors.  The methionine-free   minimal  media was  melted  in a water
bath  at  45  C  to   prevent  gelling.  Mutants  were  assayed  by  pipetting
samples  of an appropriately  diluted  conidial  suspension into  100  ml  of
melted  minimal media.  The  resultant  suspension  was  then poured onto  12
petri  dishes.   The volume  added  was   regulated  by  the  potency  of  the
agent.  These  plates  were  incubated  for five  to  six  days  at  37  C.   At
this  time,  the  mutants  were  classified as A  (large  green colonies),  B
(brown  heavily pigmented colonies), and C (small  green colonies  with a
white   hyaline  edge)  in  accordance   with   the   classification  system
described  by Lilly  (1965).

     For meaningful quantitative  data  with  this  system, not only is  it
important  to  ensure  complete  removal  of  any "germination  inhibitory"
substance  but also  to restrict  the average total  number of  methionine
mutants  per  100  mm  diameter petri  dish  to  less  than 20   (Scott  et
aj^.,  1973).

     For the haploid mutation  system, 8-methoxypsoralen  (8-MOP) and near
ultraviolet  light  were used  for  the positive  control.   In  the absence of
near  UV,  8-MOP  can also act as  a negative control.   The advantage  of
using  this chemical is twofold.   First, this  particular  photosensitizing
reaction  randomly   induces   mutation   at  all   loci;   therefore,   it
quantitatively  and  qualitatively  checks the  response of  the  multilocus
system,  in  addition   to   acting   as  a positive  control.  Second,  the
compound  alone   exhibits   no  mutagenic   properties  with   the   biAl;
methGl   strains  in  the  absence   of  light  (Alderson  and  Scott,   1970;
Scott  and Alderson,   1971).  DMSO  exposures  under  non-growth  conditions
yield   a  negative   response   in   this   system.  This  control  and  the
                                   38

-------
activation mixture  control were  included in  the experimental  procedure
to ensure  that no  undetected substances  were inadvertently included  in
the   experiment   which   could   lead  to   a  false  positive   response.
Benzo(a)pyrene requires  activation in this  assay  system  and  was  included
in  the procedure  to  insure  the  proper  functioning of  the  activation
mixture.

     Each  piece  of  raw  data  was  recorded  following  good  laboratory
procedures.   Raw  data was not averaged,  transformed, or  corrected before
recording.  Data  was  recorded  in tabular  form  to   indicate  numbers  of
identified  mutants  and  classification  of  mutants  e.g., morphological
types.   Sufficient  detail was recorded  so  that verification of  survival
and mutation  frequencies  could be  undertaken if necessary.

     The data generated from this study  was  interpreted  in  the following
four ways.   First,  data was  analyzed  by a 3  x N contingency chi square.
Second,  mutation  frequency  vs   concentration   was  compared   to   the
spontaneous  background  mutation frequency.  Third, mutation  frequency vs
exposure time at  a fixed  sample  concentration was compared  to  background
mutation frequency.  If the mutation  frequency of the latter  two analyses
exceeded  twice the spontaneous level,  the  test was  considered positive.
The  fourth   method   of   analysis  employed  an  adapted  version  of  the
mathematical  model  of  Munson and   Goodhead   (1977).   The  points  were
plotted according to  the  equation:
                 M-M  = -m  In  (S/S  )
                    o             o
where:
     S      = population of viable  cells  at  time  0,
     M      = mutation  frequency/viable cell at  time  0,
     S      = number of viable  cells  after  exposure  to a dose D
              of  the waste fraction in question,
     M      = mutation  frequency/viable cell after exposure to a
              dose D of the compound  in question.

     Data  were  plotted such  that  the y-axis represents  induced mutation
frequency  (M-Mo)  and  the  x-axis denotes lethal hits  (ln(S/S ).   Linear
regression  analysis  was used to determine  the best  fit  of an unweighted
straight  line  through   the data points.   If  the  homogenity as measured by
chi  square was  not significant,   the slope of  the  regression  line  was
obtained.  When  the  slope  is  less  than  or equal  to  2.5  per  million
survivors   for  all  suppressor  mutants, the  compound  is  regarded  as
non-mutagenic.   If the slope has   a  value  of greater than 5  per  million
survivors,  it  is  regarded   as  mutagenic.   The  values  for  a  negative
response  of  the  individual  classes  of  mutants  are  less  than  1.25  per
million  surviving conidia  for A  or  B and  0.25 for C.   Values  greater
than 2.5  (Class  A and  B)  or  0.5  (Class  C)  per  million surviving conidia
are regarded as mutagenic.
                                 39

-------
     b.  Diploid Assay—Treatment  of heterozygous  diploid  conidia with
mutagens and various  chemicals  can either increase  one  of the processes
of  spontaneous  segregation  or  it  can  induce  mutations  that  include
chromosome   aberrations   and  may   lead • to   apparent   increases   in
segregation.  Basically,  the four following  types  of  effects   can be
identified by  the  relative frequencies  and types of stable and unstable
segregants: mitotic crossing-over,  mitotic non-disjunction, breakdown of
mitosis, and mutations with deleterious dominant effects.

     The type  of mitotic  crossing over detected in heterozygous diploids
occurs  between chromatids  at  the  four  strand  stage of  mitosis.   These
reciprocal exchanges  between markers  involving two homologous chromatids
can produce  complementary  diploid  recombinants  that are homozygous for
all markers distal  to the  exchange, i.e., segregants homozygous  for all
markers of one chromosome arm.   No change in ploidy and viability  occurs
in  this exchange,  and the  selection  is not  operative.   This  type of
exchange is  usually  detected  in colonies growing on solid CM by  visual
identification  of  segregant  sectors  that  express  recessive  mutants
present  in the  heterozygous diploid  as  markers.   The  most conclusive
evidence for mitotic  crossing over are twin spots or twin  sectors, i.e.,
recovery  of  both  products  of  a  single  reciprocal  exchange  as   paired
sectors.

     Mitotic  non-disjunction  of  typically  single  chromosomes  produces
2n+l  types  in  the  first  instance;  in  Aspergillus,  the  reciprocal 2n-l
product  is inviable.   The  trisomic  2n+l types  show no  segregation of
recessive  markers  but  have a somewhat  reduced  growth   rate  compared to
the original  diploid.  Although  typically not distinguished from other
genetic  damage in  the  original  growing  conidia,  they  can be identified
through  a  secondary  plating   of  the  original  abnormal  head.  This
secondary   plating   probably   increases   the   rates    of   secondary
non-disjunction or  chromosomal  loss,  as  is common for  trisomics  of many
species.  The  2n+l   types,   therefore,   may  produce  diploid  2nd-order
segregants with  relatively high  frequencies.   The random loss  of  one of
the three  homologues  of a  2n+l  can  easily be seen when  trisomic conidia
are plated at  low  density.  Absence of  competition  leads to fairly good
but not normal growth  of  the 2n+l  type in the  center  of colonies.  At
various  points  in   the  colony,  faster  growing  diploid   sectors  are
observed which are  due to  the loss of the extra chromosome.  One third of
these  diploid  improved sectors  are showing segregation  of a chromosomal
type,  i.e., all recessive markers of 1 chromosome show up  simultaneously
in  the non-disjunctional diploid  sectors.  The  detailed growth pattern,
especially  size and  conidiation of  the trisomic center,  are different
and characteristic  for  each of the 8 2n+l,  trisomics  for  any one  of the
8  linkage  groups  or  chromosomes.   Each  can  be identified  on standard
media   if  no   chromosomal   aberrations   are  present.    For  spontaneous
mutation  frequencies,  non-disjunction  is  the  main  process  producing
spontaneous   haploids,   which   are  rarer  than   non-disjunctional  2n
segregants;  these,  in  turn, are  5  to  10 times  less   frequent  than 2n
mitotic  crossing over.  For  induced  mutation  frequencies,  these  ratios
                                 40

-------
are altered.

     Misdistribution  of  chromosomes  leading  to  haploidization  rarely
occurs but  is  a frequent effect of  treatments  with  spindle poisons.  If
the products  of single  treated nuclei  are  analyzed  carefully,  a  large
number  of  somewhat-related  segregants  are  found,  all of  them  showing
chromosomal  type segregation.   These  include  any  aneuploid  types that
are viable, i.e.,  2n+l  up  to 3  and n+1 up to  3.   Specific aneuploid
types   are  recognizable  only if conidia from  the most abnormal-looking
areas   are  replated  at   low  density.   The   stable  types,  however, are
mainly haploids, in addition to some "non-disjunctional" diploids,  i.e.,
diploid   segregants  homozygous   for   all  markers   of  1  or   several
chromosomes.   Haploids  are  the most viable and  best  growing  types if
mitotic inhibitor is  present during growth of  the mycelium.   Such agents
are,  therefore, used  for  haploidization of  diploids  in order to verify
genotypes or detect translocations and recessive lethals.

      Induced mutation with dominant  effects  on viability,  semi-dominant
lethals,  deletions, and other  unbalanced  aberrations, lead to formation
of  abnormal   colonies.    The  original   unbalanced  nuclei  are   at   a
disadvantage,  resulting  in poor growth  and the formation of  few  conidia
even  if  plated  at  low density.  However, as is  the case of  aneuploids,
the   original   unbalanced  nuclei   spontaneously   produce  well-growing
2nd-order  segregants, either  by mitotic crossing over, non-disjunction,
chromosome  loss, or  any combination of  these.   In competition with the
growing mycelia of  normal nuclei,  only  the euploid  final  segregants will
be  recovered    from   the  original   unbalanced  nuclei.  These   induced
mutations   are  of  the  same  type  as  produced  by  the  three preceeding
mechanisms  and   vary  primarily   in relative  frequencies.  Increase of
haploid  and diploid  crossing  over  is usually diagnostic  for  chromosomal
aberrations, since  none of the preceeding three types of  effects  produce
both   types of  segregants  simultaneously.

      Mutations  in  diploids that result  in recessive  lethals  or balanced
translocations   will   predominantly  produce   no  obvious  change  in
phenotype.  In  other  words,  there  will  be  no change  in morphology or
growth,  nor any detectable  segregation  of  markers.  Such mutations can,
however,  influence  the  recovery of  haploid types  when these are  selected
from   heterozygous    diploids.   Any  recessive  lethal  on   a   specific
homologue   prevents   recovery  of the  marker  located  on this  chromosome.
Balanced  translocations  generally  cause complete  linkage  of markers that
are located in  the  two  involved chromosomes.

      Diploid  strains  of  Aspergillus  are not completely  stable;  test
diploids  must  be synthesized  fresh  from heterokaryons between 2  suitable
haploid  components.   This  has the advantage  that  strains  are  easily
tested for  all markers,  except   for certain  cases  of epistatic types,
using standard  procedures.
                                  41

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     c. Diploid  strains for  analysis  of  induced  segregation—There are
two main  considerations in  the  construction  or  choice of  test diploid
that  work  in  the  opposite  directions.   First,  a  minimum  of testing
should  be  needed   for  the  identification  of  small  increases in  the
frequencies of  the three  main types of stable  segregants  so that large
numbers can be  handled for  preliminary  screening.   Secondly,  a diploid
should  contain  enough  markers  for  detailed  analysis of  the  type of
induced genetic  damage. Ideally,  the  diploid  should have the  following
features:

     a. Markers to distinguish all haploids from diploids by simple
        tests;

     b. Markers on both arms of one or more chromosomes to
        distinguish diploid crossing over  from diploid
        "non-disjunctional" types;

     c. Two recessive color markers on the same chromosome arm,
        heterozygous in repulsion, to identify twin sectors; these
        may also permit visual identification of certain haploids
        from diploid segregants;

     d. One marker in each linkage group to check  segregation  of the
        8 different chromosomes in haploids;

     e. Markers on each homologue, or semi-dominant markers in each
        group to follow all chromosomal segregation in  diploid,  as
        well as haploid segregants;

     f. Many markers on both arms of at least one  linkage group  to
        follow segregation patterns after  induction of  chromosome
        aberrations or  semi-dominant lethals.

     New  diploids   are  constantly  being  constructed to  meet  the above
requirements.  The  diploid used in this investigation was Diploid 20,  a
cross  of  haploids  F475  x F513 (Figure 11). Haploid strains were obtained
from Fungal Genetic Stock Center (FGSC, Arcadia, California).

     Data  from  the diploid assay is expressed as  the induced  segregation
index  with  respect to the negative  control  or the solvent control.   The
induced  segregation  index  is  calculated  by  dividing  the  frequency of
mutations  induced  by  a   specific  sample by  the  spontaneous  mutation
frequency  (negative control).  A response is  considered positive if  the
induced segregation index is  statistically  greater   than 1.0.   Following
treatment  of  heterozygous diploid  conidia, the  abnormal or  segregating
colonies  are replated  to obtain  secondary segregation  or  pure primary
segregation,  respectively. These  isolates are  further characterized by
replicate plating onto various nutritional and resistant media.
                                  42

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CO
            fpaB37  galD5 suAadE20  -I-   rlboA    anA   pabaA   yA2  adE20   blA
            	,	                    •	'	
               -t-     +     +      sulA   •*-+•*-      +   adE20    +
                                                                    sD85 fwA2 4-
             AcrA      ActA     pyroA4  facA303 lacA  sB3    choA     -f    -f  chaA
               H        nr      EZ
                  Figure 11.  Genotype of Aspergllus nidulans diploid 20.

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     The  nature  of  the  genetic  damage  can  then  be  determined  by  the
response  on  the various  nutritional  and  resistant media.  The mutation
frequency  for  each class  and overall genetic  damage  is then  determined
by dividing  the  number of colonies  in each  class by the total number of
colonies examined for each exposure.

3. Test System Results  (Eukaryote)—

     Two groups  of  compounds were used  as  solvent  and positive controls
in  the haploid  and  diploid assays  using  A.  nidulans.  In the  haploid
methionine system,  DMSO and  8-MOP served  as negative  controls, where as
8-MOP+NUV  and  benzo(a)pyrene  (B(a)P)  were positive controls.  Following
exposure  to  10  ul of the  solvent DMSO  for  60 min,  the  frequency  of
induced mutations  per  million  surviving conidia for  colony types A,  B,
C, and the  total  were 0.47, 0.21,  0.041,  and 0.72, respectively  (Table
10).  For  the 8-MOP in the absence  of near  ultraviolet (NUV)  light,  the
total  induced  mutation frequency  was  1.4/10  ,  and the induced mutation
frequencies  for  class  A,B,  and   C  were  0.69,   0.48,  and  0.24/10 ,
respectively  (Table  10).   Mutations were  randomly induced  at all  loci
when  the  8-MOP  was  photoactivated with  near UV  light.   The  total  induced
mutation  frequency  was 250  per million surviving  conidia.  In addition,
activated  8-MOP  induced  89,  88,  and  70 mutations/10  surviving  conidia
in classes  A,B, and  C, respectively  (Table 10).  Benzo(a)pyrene  in  the
presence  of  a rat  liver activation system induced  16 type A and  B,  8
type  C,  and 40  total  mutations  per million  survivors (Table 10).   The
standard  deviation   of  the  induced   mutation  frequencies   for  these
controls  observed  over  the  three  years   of  testing  of  DMSO,   8-MOP,
8-MOP+NUV,  and   B(a)P were  94,  69, 18,  and 50%,  respectively.  In  most
cases,  the  greatest  deviation  was  observed in  class  C colonies.   In no
case,  however,  was  the deviation  sufficient to alter  the interpretation
of the results.

     The  negative   control  used  in  the  diploid  assay was  the top  agar
alone,  while  DMSO served  as  a  solvent  control,   and benomyl  was  the
positive  control.   The results  from  the  negative  and positive controls
for  the  segregant  and  abnormal colonies  recovered from  the  diploid A.
nidulans  are summarized  in  Tables  11  and 12.  The induced segregation
index  for  the segregant  colonies  with  respect  to  DMSO was  0.04  for  the
negative  control and  3.7  for benomyl.   While  the induced segregation
index  for  DMSO  and  benomyl with respect to the negative  control  was  1.4
and  5.2,  respectively.   Benomyl  induced  genetic  damage at  all   loci  in
both  segregant   and  abnormal  colonies.   The  overall  mutation frequency
observed in  the  abnormal colonies induced  by  benomyl  was .157, which is
equivalent  to an  induced segregation  index that  is  approximately  four
times  greater  than both  the  solvent and negative controls.  Significant
increases  were  observed  in  all classes of  abnormal colonies  induced by
benomyl, except  the hyperhaploid class.

     The  two  bioassays  using  Aspergillus nidulans   as   an  indicator
organism  to  detect   primary  genetic   damage   provide  information  not
                                 44

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TABLE 10.  SURVIVING FRACTION AND INDUCED MUTANTS PER SURVIVOR IN HAPLOID A. NIDULANS
FOLLOWING TREATMENT WITH SOLVENT AND POSITIVE CONTROLS
Chemical
DMSO



8-MOP



8-MOP+NUV



B(a)p



Dose/pi Exposure Number of Surviving
(ug) Time (min) Observations Fraction
(Mean + SD)
10 pi 60 14 .98 + .02



50 90 14 .99 + .05



50 5 14 .47 + .13



11.6 20 14 .52 +_ .03



Colony
Type
A
B
C
T
A
B
C
T
A
B
C
T
A
B
C
T
Induced Mutations/
Survivor X 10
(Mean _+ SD)
.47 + .33
.21 + .37
.041+ .057
.72 + .68
.69 + .59
.48 + .46
.24 + .24
1.40 + .97
87.0 + 14.0
88.0 + 17.0
70.0 + 16.0
245.0 _+ 45.0
16.0 + 6.9
16.0 + 8.5
8.0 + 4.7
40.0 + 20.0

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          TABLE 11.  SUMMARY OF GENOTOXIC EFFECTS INDUCED BY CONTROLS IN SEGREGANT COLONIES OF DIPLOID A. HIDULANS


Sample
Control
DMSO
Benomy 1

1
Total1
619
140
299


Overall
1.9
4.0
12.7

Yellow
CO ND
0.3 0.5
0.7 0.7
1 3.5
Phenotype '
Fawn CHAT DC CR
M 2n n 2n n 2n n 2n n
0 0.3 0 0.3 0 0.3 0 0.2 0
00 0.7 2.0 0 0 0 0 0
0.3 1.4 0.3 2.3 0.7 1.0 1.3 1.0 0
ISI*
CT DO

.04
1.4
5.2 3.7
1.  Total " number of segregant colonies examined; overall « total number of induced aegreganta.
2.  Units - total frequency of segreganta per colonies examined.
3.  Phenotype: Yellow-includes only colonies that were completely yellow, all other listed in other sections;
    CO ™ crossing-over, ND -non-disjunction, M • nutations, Fawn • tan sectors; CHAT * chatreuae; DG - dark green
    G " green; 2n - diploid; n - haploid.
4.  Induced segregation index - Total induced aegregants divided by frequency of control aegreganta.  CT = evaluated
    with respect to controla; DO " evaluated with respect to solvent control (DHSO).  If ISI is significantly  greater
    than 1.0, response is considered positive.

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TABLE 12. SUMMARY OF GENOTOXIC EFFECTS OBSERVED IN ABNORMAL COLONIES OF DIPLOID
          A. NIDULANS FOLLOWING EXPOSURE TO CONTROLS


                           	Genetic Damage Observed—	
Sample
CONTROL



DMSO



BENOMYL



Total2
COL=619
MF
ISI(S)
ISI(D)
COL=140
MF
ISI(S)
ISI(D)
COL=299
MF
ISI(S)
ISI(D)
0V
22
.036
-
-
6
.043
1.19
-
47
.157
4.36
3.65
HD
14
.023
-
-
3
.021
.91
-
19
.050
2.17
2.38
NH
. 3
.005
-
- '
2
.014
2.8
-
3
.010
2.0
.71
HH BK
2 1
.003 .002
-
-
0 0
-
- -
- ' -
1 19
.003 .064
1.0 32
_ »
OT
2
.003
-
-
1
.007
2.3
-
5
.017
5.67
2.43
1. Genetic dauage observed:  0V =  overall  summary  of  genetic  damage  observed  in
   all categories; HD = hyperdiploid,  results  from non-disjunction of  chromosomes;
   NH = near hyperdiploid, probably breakdown  products  including  a mixture  of haploid
   and diploid colonies; HH = hyperhaploid,  results from major  deletions  or lethals
   in chromosomes; BK = breakdown, results from mitotic  spindle poisons;  OT ° others,
   results from mitotic recombination  which  has occurred prior  to aneuploidy.

2. Total: col - total number of colonies examined,  and  total  number  of  abnormala  in
   each class; MF =  total mutation frequency = 0V   COL; ISI(S) ° induced segregation
   index with respect to control =• MF  (sample)  MF (control); ISI(D) =  induced
   segregation index with respect  to solvent control  -  MF(sample) MF(DMSO).

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available    from    the    bioassays    using    IJ.    subtilis    or   J3.
typhimurium.  The  methionine  system  employs  a  eukaryotic  organism to
detect  forward  mutations,   and   the   diploid  assay  provides  additional
information on  chromosome  damaging agents.. While the variability  of  the
negative  and  solvent  control was  quite high,  the  spontaneous mutation
frequency is  extremely  low and the frequency of mutations  induced  by  the
positive  controls  is  extremely  high.    The   low  background mutation
frequency  observed  in  Aspergillus  bioassays  does  not  overwhelm  the
response  as would  occur  in a  test  system  with  a high background.   A
compound  inducing  a weak  response might go  undetected  in a test  system
with  a  higher  background   frequency.   Aspergillus,  because   it  can be
used  in  a haploid or  diploid form, can detect  a  broad range  of  genetic
damage and, as a result, detects a  range of genotoxic compounds.

     The   primary   limitation  of   the   Aspergillus  bioassays   is   the
complexity  of  the  test  protocols.    The  time and  expenses  incurred in
conducting  a  complete  Aspergillus  testing  protocol  will  restrict  its
utility  as  part of  a routine monitoring  program.  However, Aspergillus
is  a  critically  important  segment  of   the   initial   waste   screening
protocol  because  it  is  one  of   the  least  complex  and  most   widely
validated test systems used  to detect  chromosome damage.

D.  Evaluation of the Battery of Test  Systems

     Four  different  biological test systems  have  been evaluated  in  this
research  to determine their  utility to  monitor the environmental  impact
of  land  treatment of  hazardous   industrial waste.  The  DNA repair  spot
test  is  severely  limited  by problems with compounds  that are insoluble
in  water  or  require  metabolic   activation   to  reach   their ultimate
mutagenic  form.   The  modified  plate  incorporation assay  (Donnelly et
al.,  1983)  enhances  the  sensitivity  of the  DNA repair  assay but  also
increases  the  cost  per  sample.    However,  since DNA  repair  assays  are
capable   of   detecting   mutagenic   compounds   not  detected  by   the
Salmonella  assay  (Shiau  et  al.,  1980),   they  do   provide   a   useful
compliment  as  part  of a battery of  bioassays.  Thus, the  DNA  repair plate
incorporation   assay  would  be   useful  in  a  waste   characterization
protocol,  while the  utility  of   the  spot  test would  be  limited to  a
monitoring  program provided  its  sensitivity  to the anticipated mixtures
has been previously demonstrated.

     The  Salmonella/microsome  assay  is  perhaps  the   least  complex  and
most  widely  validated  of  all the  microbial  mutagenesis test systems.
This  bioassay   is  known  to  have  a  high  degree  of  sensitivity  and
specificity   (Bridges  et^  al.,   1981),  while   it  is  insensitive  to  a
number  of  compounds  that  might   be  anticipated  in  a  hazardous  waste
(Rinkus  and Legator,  1978).  Although  a negative result in a bacterial
mutagenesis  assay  is  not  a  definitive  indicator of non-carcinogenicity
due  to  the existence  of non-mutagenic  carcinogens, this test  can serve
as  an extremely effective  screening  test  for those compounds  which  are
carcinogenic  by  causing  damage   to  DNA   (Bridges  et^ al.,  1981).   The
                                 48

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bacterial  mutagenesis   assay  using  15.   subtilis   did   not   appear   to
enhance  the  sensitivity  of  the  battery  of bioassays,  although it  was
only   used   to   test   a  limited   number   of  samples.   The   Bacillus
mutagenesis  assay  has  been  found  to  be  sensitive  to  compounds  not
detected  in , the  Salmonella  assay   (Shiau e_t  al. ,  1980)  and  may   be
applicable to  certain  types  of waste not evaluated  in  the present study.
This  research  and  an  earlier evaluation  of  a battery  of bioassays  by
Ashby   (1981)    confirmed   that   the   Salmonella/microsome   assay   is
best-suited as the primary test system.

     Ashby  (1981) also recommended  that  the bioassay used to  compliment
the   Salmonella   test   be  based  on   a  eukaryotic  system.    The  two
eukaryotic   bioassays   utilizing  A.   nidulans   appear   to   offer  the
maximum  specificity  and sensitivity of  all the  test systems  evaluated in
the  present  research   (Scott et   al.,  1982).  Brookes  and  de  Serres
(1981)  suggest  that there  are two  critical requirements  for a  test to
compliment  the  Salmonella  assay.   These  include a high specificity in
order  to prevent increasing  the incidence of false  positives  and  the
ability   to  detect   those   carcinogens  missed  by  Salmonella.    As  a
compliment  to   the  Salmonella  assay,  the  Aspergillus  bioassay  meets
both   these   requirements.   The   primary  utility   of   the   Aspergillus
bioassay  lies  in  its  ability to  detect compounds  and  types  of  genetic
damage   not  detected   in   the   prokaryotic  systems.    Because  of  the
complexity  of   the  Aspergillus   test   protocols,   the  utility  of  this
system   is   limited   if  a   mutagenic   sample   is  also   detected  in  a
prokaryotic assay.

      The  battery  of  bioassays   that  is  employed  to  monitor  hazardous
waste  disposal  should  be  selected through  the evaluation  of  several
factors.   The  test  protocol used   to   characterize a  hazardous  waste
should  include  test  systems  capable   of   detecting DNA damage,  point
mutations,  and  chromosome   damage.   The  composition of  the  battery of
biological   test  systems   used   to  characterize   a  waste   should   be
determined  according  to  the number,  structural type,   and  anticipated
environmental  fate of  the hazardous waste constituents.  Brookes  and de
Serres  (1981)  suggest  that  by considering  these factors  when selecting a
battery   of    bioassays,    sensitivity    (mutagenic   carcinogens/total
carcinogens)  can  be as  high as  100%,  while  specificity  (nonmutagenic
noncarcinogens/total  noncarcinogens) would  be  no  less than 95%.   As  the
waste  characteristics   are  defined  and  the fate of  waste metabolites is
better  understood,  the intensity of the testing protocol can be reduced.
Ultimately,  once the lab and field  evaluations have been completed,  the
monitoring  of   a hazardous  waste   land   treatment  facility  should  be
feasible  using only  one of the more  simple  spot  tests.
                                 49

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                               SECTION 5

                         WASTE CHARACTERIZATION
INTRODUCTION

     Industrial wastes, defined  by regulations as hazardous, may contain
chemicals that are  ignitable,  reactive, corrosive, or toxic  (CFR, 1980).
The present  study  has employed  short-term  bioassays  to  detect mutagens,
as  well   as   other  potentially  genotoxic   agents   present  in  waste
fractions. Genotoxic  compounds constitute  the  relatively  small group of
agents   that   are   highly   specific   for   nucleic   acids  and  produce
deleterious  effects  in  genetic  elements  at  subtoxic  concentrations
(Brusick, 1980).

     All   current   waste  disposal   techniques,   e.g.,   incineration,
landfilling, deep  well injection, and  land treatment, could potentially
result  in  the release   of  genotoxic  compounds  into  the   environment.
Estimates as to  the environmental origin of  cancer  range from 60 to  90%
(Epstein, 1974).  While much  of the environmental cancer may result from
individual exposures,  e.g.,  smoking, drugs,  alcohol,  etc.,  the disposal
of hazardous  waste should  be  carefully monitored,  in order to minimize
any additions  to this burden.

     The  first step  in  monitoring  any method  of waste  disposal  is  to
accurately  assess  the  hazardous  characteristics  of  the,  waste.    The
analytical methodology that is  currently  being utilized to  characterize
hazardous wastes  employs  only  a  chemical  analysis.    Chemical analysis
alone  is insufficient  to  evaluate  the  hazardous  characteristics  of  a
waste.   Component   identification   of  a complex  mixture  cannot account
for  potential  interactions  that  may  occur  between  components  of  the
mixture  or  the  waste and  soil  components.   Interactions  between waste
and/or  soil  components  may be  synergistic,  additive,  or antagonistic.
Biological analysis can  be  used  to evaluate  the  toxic  potential of  the
waste  as  a whole  and   the  subfractions  of  a  waste  or  a waste-soil
mixture.   Chemical analysis  can  be used  to supplement  the results  of
biological  testing  in order  to define  the nature of toxic  constituents
and  verify  the  absence  of  artifacts  generated in  the  collection  or
extraction  process.   Bioassay  directed  chemical  analysis   provides  a
management  tool  which   can  be   used   to  make   semi-quantitative  risk
assessments  when  the  results  are compared  to reference compounds, such
as cigarette smoke  condensate  (Barnes and Klekowski, 1978).
                                 50

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     This  research   has  been  conducted   to   evaluate  the  mutagenic
potential  of  three   hazardous   industrial  wastes.   Microbial bioassays
capable  of  detecting   point  mutations,   lethal  damage   to  DNA,   and
chromosome damage  have  been  conducted on  the  subfractions  of the  three
wastes.   Since  the composition  of DNA in  microorganisms  is the same  as
that  in  humans,  these  test   systems  are  anticipated  to  provide  an
indication  of  the potential of  waste  constituents  to  cause genetic
damage in the human population.

MATERIALS AND METHODS

Wastes

     A group of thirteen wastes were  initially collected for use  in the
project.   These   included  two  wood-preserving  wastes,  four   refinery
wastes,  four  petrochemical  wastes,   a   pulp  and  paper waste,  an  alum
sludge,  and  a  paint  sludge.  A  listing of these wastes  is given  in Table
13.  Ten  wastes  were  selected for acute  toxicity  analysis,  and  three of
the  ten  were   selected  for use  in the  waste  characterization  and
greenhouse   studies.    Waste   selection  for   the  characterization  and
greenhouse   studies   was   based   on   the   results   of   a   chemical
characterization  and   the results  from  the acute  toxicity study.  Each
waste  was collected  on site by study personnel.   A permit was  obtained
from   the   Texas  Department  of  Water   Resources  to  allow   for  the
collection,  transport,  and  storage of  hazardous waste.

     Prior  to  departure  for  collection of  the   waste,  materials  were
assembled  for  waste  collection, personnel  protection,  and waste  storage.
Although   most  wastes  were   collected  in-line   at   a  refinery  or
petrochemical   plant,   shovels,  buckets,   and   a   sludge  pump  were
transported  to each   site   in  order to  facilitate  waste  collection.
Protective  devices included  respirators, gloves,  goggles, and disposable
clothing.  The  collected waste  was  placed  in  a 55  gallon  barrel.  Each
drum was washed with soap  and  rinsed  with  water before use.  Two barrels
containing   approximately  50  gal  of each  waste  were  obtained.  Upon
returning  to  the  laboratory,  a 4  1  reserve  sample  of  each waste was
collected and  stored  at 0°C.

     The  wood-preserving  bottom sediment,  PENT  S,  waste  was  collected
from   a   wood-preserving  plant  utilizing   both   pentachlorophenol  and
creosote  as   preservative  agents.    The  effluent  from  the  treatment
process  was  pumped from  a  concrete storage basin  to  a large lagoon where
the  solids  were allowed  to settle-out while the liquids  evaporated.  At
the  time the waste was  collected,  the lagoon had  been in use  for several
years,  and  the bottom  sediment  was approximately  .9  meters  in depth. The
ultimate  planned  disposal  technique  for  this waste  was  to dredge the
lagoon  and remove  the  sediment to  a  landfill.  There  are, however, six
existing  facilities  in  the U.S. utilizing  land treatment for  disposal of
wood-preserving waste  (Brown and Assoc.,  1981).   Hazardous  constituents
anticipated  in  the   PENT S  waste  include  phenols,  polycyclic  aromatic
                                  51

-------
                        TABLE 13. GROSS CHARACTERISTICS OF HAZARDOUS WASTES COLLECTED FOR STUDY
                                  Waste
                      1          2
EPA No.    Extractable   Physical     Use in
           Hydrocarbons    Form       Study
Ln
S3
Wood-Preserving Bottom Sediment K001
(PENT S)
Wood-Preserving Wasteuater -
Slop-Oil Emulsion Solids K049
Combined API Separator ,
Waste Treatment Sludge (COMBO) K051
Storm-Water Runoff Impoundment (SWRI)
Dissolved Air Flotation K048
Acetonitrile K013
Methyl Ethyl Ketone
.
Phenol production -
Agricultural Chemicals -
Biosolids Waste
Primary Clarifier Pulp and Papermill
Alum Sludge
Paint Sludge
27

NT
86

41
21
5
2
97

0.2

0.2
NT
NT
NT
Sludge

Liquid
Liquid

Sludge
Sludge
Sludge
Liquid

Liquid
Liquid

Liquid
Solid
Liquid
Sludge
A.W.G.L

A
A,W

A.W.G
A.W.G
A
A,W
A,W

A

A
N
N
N
                1- Percent by weight, extracted with dichloromethane; NT = not  tested.
                2- Physical form estimated from visual observation.
                3- N=Not used; A=acute toxicity; W=waste characterization; G=greenhouse;  L=lysimeter.

-------
hydrocarbons,  pentachlorophenol,  other  chlorinated  hydrocarbons,   and
dioxins.  Although  the  volume of wood  preserving  sludge produced by  the
entire  industry each  year  is   less  than  2,000  dry  metric  tons,  these
sludges  contain compounds  that  are toxic . even  at   extremely  low  dose
levels.   This  waste   was   utilized   in  the  acute  toxicity,   waste
characterization, greenhouse, and lysimeter studies.

     A  second wood-preserving waste was  collected from a  facility  using
both  creosote and  pentachlorophenol as  preservative  agents. This  waste
was  collected on  site  by  pumping  the effluent  from a  lagoon  used  for
spray  irrigation.  Being  a wastewater  and  not a  sludge,   this waste  was
only used in  the acute  toxicity  study.

     The  slop-oil   emulsion  solids  waste  was  collected  from  an  API
oil-water  separator  at  a  petroleum refinery.   The  waste is  generated
from  skimming the  emulsified oil-water  layer from an API separator;  it
was  collected by  pumping the waste from  the pit into a  tank  truck and
discharging   from  the  tank  truck  into  collection barrels.   More  than
31,000  metric tons  of  hydrocarbons are  generated in the  U.S.  from this
waste   stream  each   year  (Abrams   et^  al.,   1976).    Slop-oil   emulsion
solids  typically  contain 40% water, 43%  oil,  and  12% solids.  This waste
is   listed   as  hazardous  because   significant  quantities  of  lead  and
chromium may be  encountered in  the waste.  The sample  collected  for the
current study was a  liquid  waste with  a low  solids  content  and composed
of  86% extractable  hydrocarbons.   Considering  the  separation  process
from  which  this waste  was  generated,  the slop-oil emulsion solids should
be  composed of predominantly low molecular weight hydrocarbons.  A waste
that   is  composed  of  predominantly  saturated or other  low  molecular
weight   hydrocarbons   should  degrade   quite  rapidly   following   land
application.   The  slop-oil  emulsion solids  waste was  only  used  in the
acute  toxicity  study.

      The second refinery waste  consisted  of the  combined waste streams
from the API-separator  sludge  and slop-oil emulsion  solids.   The sludge
was  being stored in  a  two acre  lagoon.  The waste was collected from the
lagoon with a backhoe  and placed in the barrels  for  transport.  The API
separator sludge  and slop-oil emulsion solids account for 13.9 and 18.6%
of  the  total hydrocarbons in refinery solid  waste,  respectively (Abrams
et   al.,   1976).    Waste  streams  of   this  nature are  currently  being
treated by land application  at  a large  number of  facilities in the U.S.
 (Brown  and  Assoc.,  1981).   Anticipated  mutagenic  constituents  in  this
waste    include   polynuclear  aromatic  hydrocarbons   and  heterocyclic
nitrogen containing  compounds.  The combined  API-separator  and  slop-oil
emulsion solids  (COMBO)  waste  was  used  in  the  acute toxicity,  waste
characterization,  and greenhouse studies.

      The third waste  common to  petroleum refineries that was  collected
and  used in  the study  was a storm-water  runoff impoundment (SWRI) waste.
This  waste  is generated  from plant housekeeping and  rainfall runoff from
the  plant  site.   All  runoff  water  from  the  refinery  from which  the
                                  53

-------
sample  was  collected  was  channeled  into  a  large  basin.   Two  189.3  1
samples were  collected on-site  from the  settling basin  from which  the
sludge  was   periodically   removed   for  land  disposal.   The  sludge  was
collected at  a  location  on  the  side  of  the settling  basin where  the
water  had  evaporated   and was  shoveled  into  the  collection barrels.
Storm-water  runoff silts  account  for  more  than 12,000  metric  tons  of
hydrocarbons  in  refinery  solid wastes  each  year  (Brown  and  Assoc.,
1980).  The collected  sample  contained 21% extractable hydrocarbons.   As
this waste  was  generated  from runoff and  wash water, the  composition of
hydrocarbons  in  the  SWRI waste   was  be  more  varied  than  the   other
refinery  wastes.   In addition, because this  waste was contaminated  with
soil  particles  from   the  refinery,  it  may  have  had  an  indigenous
microbial  population  that could  enhance  waste   degradation.   The  SWRI
waste  was  used   in  the  acute  toxicity,  waste  characterization,  and
greenhouse  studies.

     The  fourth refinery  waste  collected  for  the  present  study was  a
dissolved air flotation  float  (DAF) waste.   The DAF waste  was obtained
from  a truck load  of waste  at a land  treatment  facility.  This  waste
contained the finely  divided  oil,  clay, and  silt particles that were not
settled out  in the  API-separator.  The DAF  waste is listed  as hazardous
because of  its  lead and chromium content.   A typical DAF  waste consists
of  82%  water, 12.5% oil,  and 5.5%  solids.   The collected sample contains
5%  extractable  hydrocarbons.    The  DAF waste  was only used  in the  acute
toxicity  study.   Each  of  the  four  refinery sludges  collected  for  the
present study are  amenable to  land treatment  because of  their relatively
low  concentration  of  toxic constituents.   These wastes are  produced in
large  volumes  and are  currently  being  treated   by  land  application at
existing  facilities.   Thus, two of the refinery  wastes, SWRI  and  COMBO,
have been used  in  the waste characterization  and  greenhouse studies.

     Four wastes  were  collected from petrochemical  plants.   The  bottom
stream  from  the   acetonitrile  purification  column  (ACN)  is a very  low
solids,   low   organic   liquid  waste  from  the   production  of   organic
chemicals.    This  waste   was  collected  in-line  from  the  acetonitrile
purification  column  using equipment  supplied by plant  personnel.   An
on-site  GC  analysis of the collected  sample indicated  a  composition of
3.5%  acetonitrile,  0.1%  phenols,  0.9%  acetamide, 0.5%  heavy ends,  and
approximately 95% water.   The  extractable hydrocarbon  content  of  this
waste  was  found  to   be   2%.   Anticipated  toxic  constituents   include
hydrocyanic   acid  and  polynuclear   aromatic  hydrocarbons  (Lowenback  et
al.,  1978).  Because  the  physical state  of  this waste  would  limit land
treatment,  the ACN  waste  was  used  exclusively   for the  acute toxicity
study and characterized using  the Salmonella/microsome  assay.

     The  second waste  from the production  of organic chemicals was  the
methyl  ethyl  ketone  (MEK) waste.   The  U.S.  production  of methyl  ethyl
ketone  in 1978  was 300 million  kilograms  (Beck,   1979).   This  waste is a
very  viscous  liquid containing  97% extractable hydrocarbons.  Since  the
MEK  waste  may  contain as much as 40% sulfuric  acid,   land  application
                                 54

-------
must  be  precluded by  a  pH adjustment. The  amenability of this waste  to
land  application  will be  dependent on the  composition of organic  waste
constituents' and  the  concentration of sulfuric  acid.  The MEK waste was
used  in  the  acute toxicity study,  and only  a  limited characterization  in
the bioassays was performed.

     The  bio-solids  waste  from  the production  of phenol should  contain
acetophenone,  phenol,  cumyl  phenol,  and  tars  (EPA,   1980).   The  U.S.
production  of  phenol  in  1978 was  greater  than  one  billion  kilograms.
The  phenol  waste was  collected in-line  at  a  petrochemical  plant  using
equipment  provided  by plant  personnel.   This  waste  is  a  liquid  waste
containing only  0.2% extractable hydrocarbons.   Because of the low level
of  organic waste constituents  and the  physical  state,  this  waste was
used  exclusively  in  the acute  toxicity study.

      The  fourth petrochemical waste collected for the  present  study was
the  bio-solids  from  an  agricultural  chemical   plant.   The  bio-solids
waste  was  collected  from  a concrete  wastewater treatment  pit  using
equipment  supplied  by plant personnel.   This  waste contains  the combined
waste  streams from a  large agricultural  chemical plant and may contain a
variety   of   hazardous  constituents.   The  bio-solids  waste   from  the
agricultural  chemical plant  was  only used  in the acute toxicity  study
because   it  was  a  liquid waste   with  a  0.2%  extractable  hydrocarbon
content.

      Three  additional  wastes were collected  but were  not  used  in the
current  study.   These include  the primary  clarifier  from a pulp  and
paper mill,  an  alum  sludge,  and   a  latex paint  sludge.   None of  these
wastes   contained  sufficient  extractable  hydrocarbons   to  merit  any
further  evaluation.

Extraction

      Two  procedures  were used  for1 the  extraction of  hydrocarbons from
wastes  and waste-amended  soils.   The  majority of  samples were extracted
using the blender  technique, and  comparisons were made  with  a  limited
number of samples using  a Soxhlet  extractor.

      Dichloromethane was selected  from a  group of agents to extract the
organic   fractions   of   the   wastes  and   the   soil;   dichloromethane
consistently  provided the greatest  extraction efficiency for the type of
materials  anticipated  (McGill  and  Rowell,   1980).    Six   volumes  of
dichloromethane   were   added   to   approximately  25 g   of  the  waste  or
waste-soil  mixture  and mixed in  a Waring blender  for  thirty  seconds.
This  extraction  was  repeated  twice   or until   the  extracting  solvent
remained  colorless.    Solvent  extractions  were then combined  and taken to
dryness  on a Brinkman Bucci  Rotary Evaporator.   The  residue  from this
extraction  was   partitioned   into   acid,   base,   and   neutral   fractions
following the  scheme outlined  in  Figure  12.   The  neutral fraction  of
each  waste was further  separated  into  four  subtractions using  sequential
                                 55

-------
                                           CRUDE SAMPLE IN MeClg
Ul
                                                EXTRACT WITH
                                                   IN NaOH

ORGANIC
BASE AND NEUTRALS]
2N
EXTRAC
T WITH IN HCI
1
NaOH AQUEOUS
1
BASE|


ORGANIC

EXTRACT WITH MeCI2
1
3RG
ANIC
BASES
AQUI
:ous
WATER SOLUBLE

AQUEOUS 2N HCI
I ACIDl
EXTRACT WITH MeCI2
ORGANIC AQUEOUS
iNEUTRALSl |ACIDS| |WATER SOLUBLE|

SILICA GEL
1 1 1 1
HEXANE
1 PET ETHER: MeCU METHANOL
4 MtClg *
               Figure 12.  Fractionation scheme used  for waste and waste-amended soils.

-------
solvent   extraction   on   a   silica   gel   column.    This   extraction
approximately  separated  the  neutral  fraction into  saturate,  aromatic,
and  condensed  ring  fractions  according to  the procedures  of Warner  et_
a_l.  (1976).

     A  limited   number  of  waste  and  waste-soil   samples   were   also
extracted using  a Soxhlet apparatus to compare the efficiency of  the two
procedures.   Fifteen   to   twenty  grams  of   the  homogenized  waste  or
waste-soil  mixture were weighed into  a cellulose extraction  thimble and
mixed  with  a glass  rod.   The  thimble  and glass  rod  were placed  in  a  20
ml capacity  Soxhlet extractor.  Condensers and boiling  flasks containing
200  ml of  dichloromethane were assembled  with the extractor  and placed
on  the heater  apparatus.   Refrigerated coolant  was circulated  through
the  condensers.   A  30 ml  volume  of solvent was   introduced into  the
extractor  from  the top  to  facilitate  flushing of the extractor chamber.
Heat  was   applied  to  the  boiling  flask  to   initiate  a  6 hour  solvent
extraction  of  the organic components;  the  temperature  was  adjusted  to
give  six  flushings  per hour.   The  solvent extracts were  then combined,
taken  to  dryness,  and  partitioned  according to  the  same  procedures  as
used for  the blender extracts.

Chemical  Analysis

     A chemical  analysis  of  waste and soil-waste extracts  was conducted
by  the USEPA's RS  Kerr Environmental  Research Laboratory.   The compounds
were  identified using  a  Finnigan  OWA  Automated GC/MS.   The GC capillary
column used was  a J&W Scientific DB-5-30W.   One pi aliquots were used
with a helium carrier  gas  flow  near  36 cm/sec.   The  GC oven temperature
program   was   60 C  for   1   minute  and   then  increased  at  6 /min  to
260  C  with  a  hold time  of  12  minutes.   The OWA unit  had  a splitless
mode  injector.   The   software  used  for   analysis  had  a  mass  spectra
library of  31,331 organic compounds.

Biological  Analysis

     Acute  toxicity  was  determined  for  the  crude  extract  of  all ten
wastes  using  at  least one strain  in each  of the microbial bioassays.
Overnight  cultures of the  appropriate  strain   were grown   to  a  cell
density   of  approximately  1   x  10  cells  per  ml and   serially  diluted
from  10     through  10      To   2.0  ml   of   top  agar,  0.1   ml  of  the
microbial culture  and 0.1 ml  of the crude  extract  of  each  waste were
added,  mixed  on  a  vortex mixer, and  plated  on a complete medium.  Cells
were exposed  to  a  minimum of four dose levels of the crude extract.  The
plates  were  incubated  for  24  hours   at  37°C,  and   fractional  survival
(N/N )  was  determined  by comparing  cell  counts  on exposed  plates  to
the  cell  count  on plates exposed to  the  solvent DMSO without the waste
extract.   Three of  the  10  wastes  were then selected  for characterization
of  the chronic toxic  effects  and  for  use  in  the  greenhouse and lysimeter
studies.
                                 57

-------
     The  ability  of  samples  to  induce  genetic damage  was  measured  in
three  microbial  systems  (Table  14).   The  eukaryotic  bioassay  which
employs  Aspergillus  nidulans  (a  fungus)  can  be  used   to  detect  point
mutations and  small  deletions  induced in a haploid  genome  or  can  be used
as   a   diploid  organism  to  detect  chromosome   aberrations,   mitotic
recombination,  gene  mutation,  non-disjunction,  recombinogenic  events,
recessive  lethals,  and  spindle  poisons.   These systems  are  capable  of
detecting  changes  in  the genetic  entity that  are of  relevance  to  the
human  species  and  are  sensitive   to  compounds  not  detected  in  the
Salmonella   assay    (Lilly,   1965;   Scott   e£   aU ,   1978;    Scott   et^
al.,   1982).    In   the  first  phase  of  this   study,   the   Aspergillus
bToassay  will  be  used  to  assess the  mutagenic potential  of  the  acid,
base,  and neutral  fractions  of hazardous industrial wastes by evaluating
the  induction of mutations  at the  methionine suppressor  loci.   Conidia
from 4  to  5  single  colonies  of  the methGl  biAl   (requiring  methionine
and  biotin)   Glasgow  strain of  Aspergillus  nidulans  were grown  for  5
to  6  days  on  a  complete  medium  at  37 C   and  were  used  for  each
experiment.  Samples  were tested  at  a minimum  of  three dose  levels  and
four  exposure  times.   The  procedures used  were  the  same  as Scott  et
al.  (1978).  Mutant  colonies  were assayed  by  spreading  exposed cells  on
a  methionine free  medium.  Mutant  colonies  were scored  after  incubation
for  5  days  at 37 C.   Colonies  were  divided  by colony morphology into
three  classes, i.e.,  A,  B,  C, and  the  total  number of  mutant  colonies.
Each  of  these three  classes  is  believed  to  involve  two  genes.   The
morphology of  Class  A colonies appear green,  Class B brown,  and  Class C
green  with a white hyaline edge.   The frequency of mutations  induced by
a  sample  was  determined by  subtracting  the  frequency of  spontaneous
mutations which occurred in Classes  A, B,  C,  or the total from the total
mutation  frequency  in Classes  A,   B,  C and  the  total.  A  sample  was
considered  mutagenic  if  there  was  a  positive  slope  on  the mutation
induction  curve,  or   the  induced mutation  .frequency  for at   least  two
exposure  times was more  than twice the spontaneous mutation  frequency.
Positive  controls  included  8-methoxypsorlen   (Sigma,   St.  Louis,  MO),
8-methoxypsorlen   plus   near   UV    light   without    activation,    and
benzo(a)pyrene  (Aldrich, Milwaukee,  WI)  with metabolic activation.  The
three  waste  fractions were  also tested  in a diploid bioassay.   Diploid
20   (Kafer  £t  al.,   1982)  was  used to   test  the   ability  of  waste
fractions  to   induce  mitotic  crossing  over,  mitotic  non-disjunction,
breakdown  of mitosis, and  mutations  with  deleterious  dominant effects.
The  procedures used  were  essentially the  same  as were  used with  the
methionine system and  are described  in Section 4.

     A microbial DNA repair assay was  used to measure  the  capacity of a
sample   to   produce  increased   lethal  damage   in  DNA  repair  deficient
strains.     Six   strains   of   B   subtilis   deficient   in    different
recombination  (Rec )  and/or  excision  (Exc )  repair  were  used  to test
for  lethal  DNA  damage.   These   included  the  Rec    strains   rec  A8^
rec    B2,    rec   E4,    mc-1;   Exc   strain    hcr-9;    and    Rec /Exc
fh   2006-7.    All   of  these  strains  are  isogenic   with !$._  subtilis
strain  168  which  has  all  repair  intact.   These strains  were  kindly
                                58

-------
                               TABLE 14.   BIOLOGICAL SYSTEMS USED  TO  DETECT GENOTOXIC COMPOUNDS IN ENVIRONMENTAL SAMPLES
Ui
Organism
PROKARYOTES
Bacillus
subtilis
Salmonella
typhimurium
Genetic Event
Detected
Increased lethal
damage in DNA
Point mutation
Advantages
Sensitive to bacteriocides,
inorganics; can evaluate
several DNA repair mechanisms;
Well-validated; well defined;
Disadvantages
Insensitive to volatiles;
difficult to quantify.
Insensitive to volatiles;
References
Felkner et al., (1979).
Kada et al., (1974).
Tanooka et_ aU ,(1978).
Ames et al.,(1975).
                                                   end-point.
                                  toxic mutagens, certain
                                  chlorinated hydrocarbons.
                            Skopek et^ a^. ,(1978).
                            Haroun and Ames, (1981).
            EUKAHYOTES

            Aspergillus
               nidulans
                               Point mutation;
                               chromosome damage.
Detects range of genetic
damage including terratogens;
good correlation in compounds
Limited data base;
insufficient number of
trained personnel.
Scott et. a\_., (1982).
Scott et al., (1978).
Bignami et. a_l. , (1891).

-------
supplied  by  Dr.   I.  C.  Felkner  of  Clements  Assoc.,  Washington,  D.C.
Overnight  cultures  were  grown   in  brain-heart  infusion  broth  (Difco,
Detroit, MI)  incubated  at  37°C.   Each  strain  was  streaked radially  on
a nutrient  agar  plate to a centrally  placed sensitivity disc  containing
100  ul  of  the  test  chemical.   After incubation  at  37 C  for 18  hours,
the  distance  of  growth  inhibition  from   the  disc  was   measured  in
millimeters  (Kada  et  al. ,  1974).  A response  was  considered  positive
if the  distance  of growth inhibition  was more than  2.5  mm  greater in one
of  the  repair  deficient  strains than  in  the  repair proficient  strain
168.   Mitomycin  C   (Sigma),  methylmethane sulphonate  (Aldrich),  and
sensitivity  to  ultraviolet  light  were  used  as   appropriate  positive
controls.   Quadruplicate  plates  were  run  at  each  dose   level  for all
samples.

     Fractional   survival  (N/N  )   was   determined   for   those   strains
showing the  greatest sensitivity  (inhibition) to the test  chemical using
the  procedures   of  Donnelly  et_   al.   (1983).    Brain heart  infusion
broth  was  inoculated  with  the   appropriate strain and    incubated  at
37°C  for   approximately- 16  h   until   an   ODcAQ   of  °'3  was   reached
(approximately  1.2  x 10   cells  per  ml).   The  cells were  then  diluted
with -brain heart  infusion media to an  OD,-,0 of 0.16  (approximately 1.2
x  10   cells  per  ml),  Aerially  diluted  with   Spizizen's  Minimal  Salts
from  10    through  10   ,  and  plated  onto nutrient  agar  (Felkner  et_
al., 1979).

     The  Salmonella/microsome  assay  of  Ames   et   al.  (1975)  was  used
to  evaluate  the  mutagenic  activity  of   waste  fraction   samples.  The
Salmonella   strains  were  kindly   supplied  by   Dr.   Bruce  N.   Ames -
(University  of  California,  Berkeley,  CA).   The procedural  methods  were
the  same  as Ames   et  al.  (1975)  except  that  overnight  cultures  were
prepared  by  inoculation  into   10  ml  of   Oxoid  Nutrient   Broth  #2  (KC
Biological,  Inc.,  Lenexa, KS) and incubated with shaking  for 16  hours  at
37 C.    Waste  fractions   were   tested   on  duplicate  plates   in   two
independent  experiments  in  the   standard  plate  incorporation  assay  at a
minimum of  5  dose levels  of   the  sample with   and without  enzyme
activation  (0.3 ml  rat   liver/ml  S-9  mix)  using strains TA98  and TA100.
Positive    controls   included    2ug/plate    N-methyl-N'-nitro-N-nitroso-
guanidine  (Sigma) for  TA100,  25  ug/plate   2-nitrofluorene  (Aldrich) for
TA98, and  10 ug/plate 2-aminoanthracene (Sigma) which was  used  with all
strains  to  verify   the  functioning  of  the  metabolic activation  system.
All  reagents  and extracts were tested for  sterility; DMSO  was used as a
negative control.

     The  sensitivity of  in vitro bioassays can be  greatly  enhanced  by
incorporating  mammalian  metabolism  into  the testing protocol  (Ames  et
al. ,   1973).    This  metabolic   activation  system   serves   to   convert
promutagens  into  their  ultimate mutagenic  form.    Metabolic  activation
can  be  incorporated  into the testing protocol  by  the addition of an  S9
mix  which  consists of a  9,000 x  G supernatent from homogenized rat liver
and  an  NADPH generating  system.   Rat  liver  was  utilized as the source  of
                                60

-------
enzymes because  studies  conducted  to evaluate  the  activity of  S9  liver
fractions  from   various   species  concluded  that   rat   liver   provides
activation  for  the  broadest  range  of  chemicals  (Baker et  al.,   1980;
Muller  £t  al.,   1980).   A  50  ml  batch  of  S9 mix  consists  of  85  mg
glucose-^phosphate   (Sigma),  160  mg   NADP   (Sigma),  10  ml  of  0.5  m
phosphate  buffer, 25  ml  cation solution,  and  15  ml of  S9 (Matney  et
al.,  1979).   The majority  of testing  was conducted  using Aroclor  1254
induced rat  liver which  is considered  to  activate the broadest  range of
chemicals  (Maron and  Ames,  1983).  In addition,  a  limited  number  of
fractions  were  also  tested   using  phenobarbitol  induced  S9  which  is
considered  to work  more  efficiently with  the  basic  fraction (Epler  et
al.,  1978).   Both  Aroclor  1254  and   Phenobarbitol   induced  rat  liver
were  obtained from Litton Bionetics  (Charleston,  SC).   The  concentration
of  rat  liver  in the  S9  mix   is  critical  for obtaining  the  optimum
response  and will be variable  from  one compound  to  another  (Maron and
Ames,   1983).    A  limited  number   of  samples  were  tested   at   three
concentrations  of S9/plate  to determine  the  optimum  concentrations for
the  types of  mixtures  being studied.   The  standard  test was run  at 0.3
ml  rat  liver/ml S9 mix with  additional testing conducted  at  0.5 and 0.1
ml  rat  liver/ml  S9 mix.

RESULTS AND  DISCUSSION

      The  acute toxicity  of the  crude extract  of ten  hazardous  wastes was
determined   in  bioassays  using  A.  nidulans,  JJ.   subtilis,   and  J3.
typhimurium.   The results  for eight of the  ten  wastes  are  provided in
Figure  13a-d and Figure  14a-d.  These studies  were conducted  in  order to
establish maximum dose  levels   for  the chronic  toxicity  study and  to
determine  the  potential  short-term  effects  of  waste  application  on
bacteria  and fungi.  The  acute  toxicity of the bio-solids wastes  from the
production  of phenol  and from  the agricultural  chemical plant are not
included  as  these   wastes  had  very  low  organic content and almost no
acute toxic  effects  in  the bioassays  at  the  levels tested. For most of
the  wastes  studied,  the  acute  toxic  effects were greatest in prokaryotic
Salmonella     and    Bacillus,     and    least    in    eukaryotic    diploid
Aspergillus.   Only  the crude  extract  of  the methyl ethyl ketone  waste
(Figure  14b) was more  toxic  in  the eukaryotic system than in the systems
using  prokaryotic   organisms.    For  the  Aspergillus  system,  only  the
wood-preserving  liquid waste  (Figure 13c) exhibited  a definite  increase
in   toxicity  with  increasing  dose  of the   waste,  while  the  slop-oil
emulsion  solids exhibited  a  slight increase  in  toxicity with  increasing
dose.  For   the  Salmonella  and  Bacillus  systems,   all waste  extracts
studied  produced an increase  in  toxicity  with increasing dose.   At  least
one  dose level  was  determined for each waste at which  less  than  10% of
the  exposed  prokaryotic  cells survived.   This  dose  will be used  as the
maximum dose level  for all  subsequent   testing with  the  waste  as well as
with soil or water extract.

      The  mutagenic  potential  of the  fractions  of five  hazardous  wastes
was   evaluated  in  the  battery  of  bioassays.    The  results   of  the
                                 61

-------
                      a irr»~«u-fv» IKMUIO n
                      • •. mnm ina^tta *•«• i
                                                   .«   *   4   4  I
Figure 13a.  Percent survival of  B.
             subtilis strain 168,  S_.
             typhimurium strain TA100,
             and _A. nidulans Diploid
             109.  The cells were
             plated on a complete  medium
             after exposure to various
             concentrations of wood-
             preserving bottom sediments
             waste.  The percent survival
             (N/No x 100Z) was then   •
             determined.
JL      Figure 13b.
Percent survival of JJ.
sub tills strain 168, .S.
typhimurium strain TA100,
and A>. nidulans Oiploid
109. The cells were
plated on a complete medium
acetonitrile purification
column waste.  The percent
survival (N/No x 100%) was
then determined.
                                                         DOSE/PLATE
  Figure  13c.   Percent survival of ]J.
               subtilis strain 168, £.
               typhimurium strain TA100,
               and  A.  nidulans Diploid
               109.  The cells were
               plated  on a complete mediua
               after exposure to various
               concentration  of wood-
               preserving liquid waste.
               The percent  survival (N/No
               x 100%)  was  Chen determined.
        Figure 13d. Percent survival  of £.
                    subtilis  strain 168,  S_.
                    typhimurium strain TA100,
                    and A. nidulans Diploid
                    109.  The  cells were
                    plated on  a complete  medium
                    after exposure to various
                    concentrations of slop-oil
                    emulsion  solids waste. The
                    percent survival  (N/No x
                     100%) was then determined.
                                      62

-------
                          i.rr»-i«u«iuM(Htnaa TUMI
                          t. rj«TT>.n i tango i««»t i
                                                                          inn nm Tim
                .
               OOSE/ PLATE 
-------
Salmonella/microsome  mutagenicity assay  of  the acetonitrile  waste  are
presented  in  Figure  15  and  Table  15.   These  results  indicate  that
mutagenic  activity  could be  detected in  all three  waste  fractions  and
that   primarily   indirect   acting   mutagens   were    detected.     The
dose-response  curves  for all fractions  were non-linear, indicating  that
the  fractions  are composed of  constituents with non-equivalent  kinetics
of  mutation  induction.   The  base  and   neutral   fractions   induced  a
two-fold  increase in  revertant  colonies  in  both  strain TA98  and  TA100,
while  the acid  fraction  only induced  a significant  increase  in  strain
TA98.   The basic fraction  of the waste induced  the greatest number of
revertant  colonies  in both strains.   At  an exposure level equivalent to
almost  11 g of  the original waste  material  (5.0  mg/plate of extract),
the basic fraction  induced 328 and 366 revertant colonies  in strain  TA98
and  TA100,  respectively  (Table  15).   In   the   absence  of  metabolic
activation,  a  doubling of  revertant colonies  was   induced by  all  three
fractions  in TA98 at dose levels  greater than 5 mg/plate.  The  addition
of  metabolic  activation  to  the assay system resulted in an increase of
at  least  twice  the  number  of  revertant  colonies  than was  obtained
without metabolic activation.

     One  of the known  constituents  of  this  waste, acetamide,  induced
less  than 14  revertant  colonies/mg  at  a  dose  level of 5 mg  (McCann et
al. ,   1975).   At  the  same   dose level,   the  acid,  base,  and   neutral
fractions  induced   31,   71,  and  21  net   revertants/mg,  respectively.
Although  the acetonitrile waste  contained  the experimental carcinogens
acetamide  (Sax,  1979), it  also  contained  small concentrations  of other
mutagenic  agents or  agents  that promoted  the  activity  of acetamide in
the various waste fractions.

     An   evaluation  of  the   acid,  base,  and  neutral  fractions of  the
acetonitrile  waste  using the  IJ. subtilis DNA repair  assay   (Table  16)
indicates  that  none  of  the  waste  fractions  induced  increased  lethal
damage  in  the   repair  deficient  strains.   Two  limitations  of  the  DNA
repair  spot  test are  limited sensitivity to  compounds which are  indirect
acting  and  limited  sensitivity   to  compounds  which  are  insoluble  in
water.   The  negative response in the DNA repair assay  may have  been due
to  the  absence  of  metabolic activation in  this  test, since metabolic
activation   was   required   to   obtain   the   maximum  response   in   the
Salmonella assay.

     In  conclusion,  the determination of the mutagenic potential  of the
fractions  of  acetonitrile  waste  indicates  that   the  fractions  contain
primarily indirect  acting mutagens,  and  the  base  fraction was  the  most
active.    The    base  fraction   induced   306   net   revertants   in   the
Salmonella  assay at a dose  level equivalent  to  approximately  11  g of
waste.     By    comparison,    the    basic    N-heterocyclic     compound
10-azobenzo[a]pyrene  induced 130,000  revertants/mg  in  an evaluation by
Ho  et  al.  (1981).  Thus,  the mutaganic  potential  of  the components of
the base  fraction appears to be  much lower than that of the substituted
polycyclic aromatic hydrocarbon.
                                 64

-------
   300-
U

5
a.
N»
(O
   200-
OC

10
X

00
    loo-
    ACN WASTE
 -S-9         +S-9
A—A  AGIO   A—A
O—O  BASE   •---•
D—D NEUTRAL •—•
                  200
       tOO         600         1000

              DOSE/PLATE (mg.eq.)
5000
10000
         Figure 15.  Mutagenicity, as measured with S^. typhimurium strain TA98, of fractions of
                     acetonitrile waste. .

-------
       TABLE  15. MUTAGENIC  ACTIVITY OF LIQUID STREAM FROM ACETONITRILE PURIFICATION COLUMN AS
                 MEASURED WITH S.  TYPHIMURIUM STRAIN TA98 AND TA100 WITH AND WITHOUT
                                      METABOLIC ACTIVATION
ON
Sample

Acid





Base




Neutral




DMSO
Dose Level
(mg/plate)

5.0
2.5
1.0
0.5
0.1
0.01
5.0
1.0
0.5
0.1
0.01
10.0
5.0
1.0
0.1
0.01
100 pi
Strain
TA98
+ S-9
Total His+
162 + 31
122 + 2
45 + 13
30+5
30 + 14
20+4
328 + 5
97 + 32
62 + 1
35 + 15
20 _+ 2
126 + 10
106 + 21
55+5
36 + 19
21+3
22 +_ 5
- S-9
TA100
+ S-9

- S-9
revertants/plate - Mean + S.D.
69 + 3
36 + 5
32+5
36 + 7
15+4
17+4
77 + 12
36+4
28 + 2
20 + 1
17 _+ 0
67 + 1
55 + 2
27+8
13 + 1
15 + 3
19 + 3
197 + 31
NT*
145 + 14
155 + 3
140 + 18
140 + 24
366 + 76
173 + 4
143 + 15
120 + 18
140 +_ 8
326 + 47
289 + 15
87+34
97 + 39
79 + 25
117 + + 21
188 + 58
149 + 1
85 + 11
149 + 6
80+9
80+5
109 + 5
112 + 17
182 + 12
92 + 14
87 + 15
131 + 21
NT
102 + 35
93 + 20
85+4
103 + 164
        * NT = Not  tested.

-------
TABLE 16.  COMPARISON OF LETHAL EFFECTS OF ACN WASTE FRACTIONS ON DNA REPAIR DEFICIENT
                            AND PROFICIENT STRAINS OF B. SUBTILIS

Inhibition Radius (mm)
Sample

Acid
Base
Neutral
MMS2
Mit.C3
DMSO4
Dose/pt

1 mg
1 mg
10 mg
2 pi
10 pg
100 pi
168,wt
RP1
0
0
0
14
6
0
fh2006.7


1
1
0
26
11
0
recEA


0
1
0
25
11
0
mc-1
•
— repair
i
0
1
20
12
0
her. 9
deficient
0
2
0
21
13
0
recAS


0
1
0
21
13
0
recB2


0
1
0
18
13
0
1- Repair Proficient
2- Methyl methane sulfonate
3- Mitomycin C
4- Dimethylsulfoxide

-------
     The methyl  ethyl  ketone waste was found  to be  genotoxic  in only one
of  the  three  bioassays.   In  the  Aspergillus  methionine   system,   a
positive response  was  obtained with the  neutral  fraction (Figure  16 and
Table 17).  These  results indicate that for  colony A,  B,  C and the  total,
there was  a significant  increase in mutant colonies.  The results  from
the   Aspergillus  bioassay   are  in   contrast  with   those    from   the
Bacillus  and  Salmonella  assays  (Figures 17  and  18 and  Table  18).  The
DNA  repair  deficient  strain  mc-1  gave  a  weak  positive response  when
exposed  to 2.5 rag of  the acid  fraction,  while no response was obtained
in  any  of  the  other  strains  with  the base and  neutral  fractions.   The
acid  and neutral  fractions  induced a  doubling of revertant  colonies  in
£.  typhimurium  strain   TA98  with  metabolic activation  only  at   the
highest  tested  dose  level.   Using the  modified 2-fold rule described  by
Chu  et^  al.  (1981),  this would not  be  considered  a positive  response.
Biological  analysis   of  the  methyl  ethyl  ketone  waste disclosed  the
presence   of  marginal  genetic  toxicity.   The   neutral  fraction   was
positive   in   Aspergillus   and  negative    in   both    Salmonella   and
Bacillus;  however,  the   acid  and  base   fractions  were  negative  in  all
three bioassays.

     The  most  intensive  analysis  was  conducted  on the  wood-preserving
bottom  sediment  (PENT  S).   Samples of  the PENT S waste were collected on
two  separate occasions and  returned  to the  laboratory  for  fractionation
and  characterization.    A subsample of  the  second  sample  collected was
also   extracted   using   the  Soxhlet  apparatus   and   evaluated   using
Salmonella strain TA98.  The  first  waste sample collected was used  in
the greenhouse  study,  while the second  sample was used  in  the lysimeter
study.  The results presented  in Table  19 indicate that  although greater
amounts  of  extractable  hydrocarbons  were  recovered  using  the  Soxhlet
apparatus,  there was no  appreciable  difference in  the  specific activity
of  the  fractions.  The  similarity of   the mutagenic activity obtained
from  the three extractions  is most evident  when  the dose response curves
for  the crude,  acid,  base, and  neutral  fractions are  compared (Figures
19a-d).   At  lower dose  levels, the  mutagenic  responses  obtained  from
each  of the three extractions were within 10% of  each other.   At the two
highest  dose levels tested, the mutagenic  activity of  the crude, base,
and neutral fractions  of the  Soxhlet extraction was lower than the other
two  extractions  by  20  to  50%.   These  results  indicate  that  greater
quantities  of  hydrocarbons  can be  extracted from  the soil  using  a
Soxhlet  apparatus  than with the Blender  procedure.   Both procedures  did,
however,   give  approximately  equivalent  responses   when tested  in  the
Salmonella/microsome    assay,    indicating  that   the    composition   of
mutagenic  compounds  in  the extracts was  similar.

     The  results  from  biological analysis of  the  PENT S  fractions using
four  strains  of  J3.   typhimurium are  provided  in  Table  20.   A positive
response  was obtained  from  the  crude,  acid, base, and  neutral fractions
of  the  PENT S waste with strains TA98, TA100, and  TA1538 in the presence
of  metabolic activation.  None  of the  waste fractions  induced a positive
response   in  the  absence of  metabolic   activation,  and  none  induced  a
                                  68

-------
cr
§
a
\
o
z
UJ
tr
u_
o
s«>
O  O
 'O
                               MEK: NEUTRAL- 200>ig

                               NOV. 81=  T •	0 T  DEC. 81
                                        A A	A A
                                        B •	D B
                                        C *	o C
              i
             20
          MINUTES
  I        i
 40       60
EXPOSURE  TIME
                                      80
Eigure 16.
           Mutation frequency induced by neutral fraction of
           methyl ethyl ketone (MEK) waste in A. nidulans
           methionine system.
                            69

-------
TABLE 17. THE EFFECT OF THE NEUTRAL FRACTION OF A METHYL ETHYL KETONE WASTE ON  THE
                  FREQUENCY OF INDUCED MUTATIONS IN ASPERGILLUS NIDULANS

Exposure
Dose
(rag/pi)
0.2

0.2

0.2
0.2

0.2
0.2
Time
(min)
0

15

20
30

45
80
Number of
Cells Plated
2.4 x 10^
7
2.8 x 10'
7
1.4 x 10_
1.7 x 10,
/
1.3 x 10'
0.9 x 10
t.

Surviving Mutation Frequency Per 10 Survivors
Fraction
1.0

0.89

0.83
0.55

0.72
0.52
A


4.27

6.19
14.4

10.6
17.1
B


2.27

9.67
4.80

8.9
11.1
C


.076

.222
.409

.393
2.4
Total


6.61

16.1
19.6

19.6
30.6

-------
                     METHYL ETHYL KEYTONE  WASTE

                     B . SUBTILIS DMA  REPAIR
168 wt
rec E4
rec A 8
her-9
f h 2006-7
MC-I
ACID 125 mg
(POSITIVE
IRESPCNS
y^S^XXXX^

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1
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v\\\\\\\N

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i
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.
BASE 10 mg
!._„. -
i *
i
x£>Q<
•
•
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i
\\NvN

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— 0
Xs

i
NEUTRAL lOmg

$£

\\

X-



\\
i
i

\\v

• i
i
i
l
l
1
1
\\\\
1
N\
\


IGBwf
rec E4
rec A8
her- 9
fh200&7
MC-1
               2468        024024

                        GROWTH  INHIBITION   (mm)

             Figure 17.  Growth inhibition induced by fractions of methyl ethyl ketone
                       waste in DNA repair proficient (168 wt) and deficient strains
                       of B. subtilis.

-------
ro
        
-------
            TABLE 18. MUTAGENIC ACTIVITY OF METHYL ETHYL KETONE WASTE
Sample Dose Level
(mg/plate)
Strain
TA98
+ S-9
Revertant
Acid



Base





Neutral



2
1
0
0
5
2
1
0
0
0
5
1
0
0
.5
.0
.5
.1
.0
.5
.0
.5
.1
.01
.0
.0
.5
.1
43 +
22 +
29
14 +
33 +
18 +
24 +
28 +
29 +
22 +
49 +
25 +
24 +
24 +
3*
2

1
2
1
1
1
1
2
6*
8
1
8
- S-9
Colonies per
30
22
27
40
36

21
18
17
17
20
21
18
25
+ 9
+ 7
+ 9
+ 23
+ 4
NT
+ 6
+ 1
+ 2
± 4
+ 6
+ 7
+ 2
+ 4
TA100
+ S-9
plate + S.D.
NT**
NT
NT
NT
65+3
NT
78 + 1
NT
70+2
NT
100 + 14
79 + 5
NT
NT
- S-9

77
70
80
74
94
84
75
81
80

110
67
73
86

+
+
+
+
+
+
+
+
+

+
+
+
+

9
1
2
0
5
5
5
1
2

16
2
4
2
* - significant increase.
**- NT = Not tested.

-------
                                             I
                                           000.
                          inumucTio*
                          tl< CmUCTIOM

                          •01W.IT CXTMCT
                 PCHT S-ACIO
                   iitonucnm
                   TUCT
     0    OJ   M   OU   Qa   1.0
                        I    I
              omc/ftATi €••»
                                            0   (XI   0.4
                           itt cxnucnon
                M«T t-MUTHM.
                   i iMCxnucnon
                  k IM tmueno"
                  > M tXT««CT10"
         O.t   0.4   0.«   0.1   1.0

               00«I/>
O.I  0.4   0.1  O.I   1.0


     DOU/FLATI <•«)
Figure 19.   Mutagenic  activity, with metabolic activation,  of  crude
              (A),  acid  (B), base  (C), and neutral '(D)  fraction  of
              PENT  S (wood preserving bottom sediment)  from two
              blender extractions  and one  soxhlet extraction.
                                   74

-------
TABLE 19.  DISTRIBUTION OF MUTAGENIC ACTIVITY1 IN FRACTIONS OF PENT S WASTE
                     EXTRACTED USING BLENDER OR SOXHLET TECHNIQUE
Sample
Blender (1)
Crude
Acid
Base
Neutral
Blender (2)
Crude
Acid
Base
Neutral
Soxhlet
Crude
Acid
Base
Neutral
1. Mutagenic
2. Revertants
Extractable
Hydrocarbon
(mg/g)

270
23
24
223

271
9
3
259

590
21
8
561
Specific
Activity
(rev/mg)

1,282
771
1,204
860

1,154
828
1,657
1,186

1,162
904
1,209
1,036
Weighted,
Activity
(rev/g)

346
18
29
192

313
7
5
307

686
19
10
581
activity as measured with strain TA98 with microsomal activatii
/mg = slope of mutation induction curve calculated using three
   highest non-toxic dose levels.
   Revertants/gram eq = revertants/gram material extracted; calculated by
   multiplying revertants/mg x % extractable hydrocarbons.

-------
    TABLE  20.   HUTAGENIC ACTIVITY  OF FRACTIONS OF WOOD-PRESERVING  BOTTOM  SEDIMENT
Total hit revertanti
Sample
Crude





Acid






Base
,




Neutral





Dose/Plate
(lag)
0
1
.5
.1
.05
.01
.005
0
1
.5
.1
.05
.01
.005
0
1
.5
.1
.05
.01
0
1
.5
.1
.05
.01
TA98
25
17
31
30
27
21
23
27
Tox
26
24
25
26
24
26
26
25
24
27
27
21
28
23
23
28
21
42
172
183
132
108
61
44
41
Tox
111
77
66
48
37
41
167
222
131
93
48
33
123
140
86
72
34
TA100
+
144
48
111
145
149
147
124
133
Tox
Tox
108
112
122
109
116
72
88
121
103
104
121
101
91
103
%
98
133
243
521
466
377
187
155
139
Tox
403
331
247
159
149
139
415
563
543
408
175
133
328
391
527
209
176
TA153S
NT





25
Tox
Tox
11
24
18
15
25
19
18
15
15
14
25
18
IS
14
16
20
NT





17
Tox
13
IS
IS
16
17
17
15
IS
16
17
17
17
15
16
10
15
IS
TA1538
NT





13
Tax
Tox
10
8
13
NT
11
16
15
10
15
8
13
19
19
20
19
15
NT





17
Tox
Tox
58
36
19
15
16
60
38
37
32
32
17
47
17
33
24
23
NT - not tested.

-------
positive response  in  strain TA1535 with or without metabolic  activation.
The maximum  response was  obtained with  the  base  fraction using  strain
TA98 with  metabolic activation  (Figure 20).   At  the optimum dose  level
of  500  ug/plate,  the  base fraction  induced  222  revertant colonies,  or
greater  than  five  times  the  background  for  strain  TA98  (Table 20).  At
the same dose  level,  the base fraction induced 563 revertant  colonies  in
strain  TA100,  or  slightly  greater than  four  times the  background  level
(Figure  21).  The  mutagenic  response  in  the  two   plasmid   containing
strains  (TA98  and TA100)  were  comparable;  however,  the absence  of  a
positive  response  in  strain  TA1535  indicates  that  constituents in  the
PENT S  waste may  be  selective for frameshift  mutants such as  TA1538.  A
review   of   the   literature  by  Wassom   e_t  al.   (1977)  observed   that
tetrachlorodibenzodioxin selectively  induces frameshift mutations.

     The   sensitivity  of  the   Salmonella/microsome   assay    has   been
further  enhanced by  the  addition of two new  plasmid carrying strains,
TA97   and   TA102   (Levin  et^  al.,   1982a;   Levin   et  al_. ,   1982b).
Strain  TA97  detects frameshift mutants and is  intended  to replace  TA1537
(Levin   jjt   al.,   1982a),  while    strain   TA102   detects    base-pair
mutations  and  has  been   found  to  be  sensitive   to  oxidative  mutagens
(Levin   et   al.,   1982b).   The   results   obtained   from a   biological
analysis  of  the   fractions of the  PENT  S  waste using  strain  TA97  and
TA102  were  comparable  to  those  obtained using  strains TA98  and  TA100
(Table  21).

     Additional  testing  of the PENT  S waste fractions was conducted with
strain  TA98  with  high  (0.5 ml  S9/ml S9  mix),  medium  (0.3  ml  S9/ml  S9
mix), and  low  (0.1 ml S9/ml  S9  mix)   concentrations  of  liver  microsomes.
Maron  and  Ames  (1983)  recommend  that these titrations  be conducted  as
the  concentration  of  S9  per  plate  is critical  for   optimum  mutagenesis
and  can  be  variable  from compound to  compound.   Rao  e±  al.  (1978)
also   observed   that   the   concentration  of   microsomal  enzymes  can
significantly  affect  the  results of the biological  testing  of complex
mixtures.  The  results  presented in  Table 22  and Figures  22,  23,  and 24
indicate   that    maximum   mutagenicity.  was  detected   with    the   high
concentration  of   S9.   There was,   however,  no  appreciable  difference
between  the  level  of  mutagenic activity  in  the  acid and  base  fractions
with the high and medium concentrations  of S9 (Figures 22 and 23).   In
the neutral  fraction,  the mutagenicity with the high concentration of S9
was significantly greater than the medium and  low concentrations (Figure
24).   However,  for  all  three waste  fractions, the  optimum,   toxic,  and
no-effect  dose  levels were the same  with all  concentrations  of S9 mix.
These  results  indicate that while  the medium  level  of S9 in  the  S9 mix
provides  an  adequate  source  of  metabolic  activation  of  most  waste
fractions, slightly greater levels of mutagenic activity may  be observed
in  the  presence  of higher  levels of S9.

     A   bioassay  using  15.   subtilis  was   utilized  to  evaluate  the
capacity   of  wood-preserving   bottom  sediment  fractions   to  produce
increased  lethal  damage  in  DNA  repair  deficient  bacteria.    The  acid
                                   77

-------
   600
•  400-
e
o>
   200-
                        PENTS-WASTE
                    X—X   CRUDE  B	B


                    &—&   ACID   A	A


                    O—O   BASE  •—•

                    0—O NEUTRAL •	*
                      -S9
 +S9
               I 00
300
                            DOSE /PLATE(uj)
500     I 000
   Figure 20.  Mutagenic activity of fractions of the PENT S (wood

              preserving bottom sediment) waste.
                              78

-------
600
                                          CRUDES—H
                                           ACID
                                    0-0  BASE
                                    D-Q NEUTRAL
             too
300
500
I 000
                          DOSE/PLATE Cug)

 Figure 21.  Mutagenic activity, as  measured in _§..  typhimurium
            strain TA100, of fractions of PENT S (wood preserving
            bottom sediments) waste.
                           79

-------
oo
o
    TABLE  21.  MUTAGENIC  ACTIVITY OF PENT S WASTE IN FOUR PLASMID CONTAINING STRAINS OF

                                                 S TYPHIMURIUM

Strain (+ Metabolic Activation)
Fraction TA98 TA100 TA97 TA102
- + - +- + - +

Acid LB1 333 LB 1556
Base LB 463 16 1721
Neutral 25 278 LB 1550
70 1419 LB 2300
15 229 LB 7
122 1975 LB 1186
     1  -  LB = Less  than background.

-------
         TABLE 22.     MUTAGENIC ACTIVITY OF  PENT  S WASTE  FRACTIONS AS MEASURED WITH S.
                       TYPHIMURIUM STRAIN TA98 WITH HIGH (0.5  ML S9/ML S9 MIX), MEDIUM
00

(0.3 ML
S9/ML S9 MIX) AND LOW
(0.1 ML S9/ML S9 MIX)
CONCENTRATIONS
OF AROCLOR 1254 INDUCED RAT LIVER IN S9 MIX
Fraction


Acid




Base





Neutral





Dose/plate
(rag)

0
1
.5
.1
.05
.01
0
1
.5
.1
.05
.01
0
1
.5
.1
.05
.01

High


37 + 7
NT*
126 + 10
85 + 14
53 + 10
53 + 5
37 + 7
222 + 51
226 + 24
113 + 17
95 + 11
61 + 23
37 + 7
201 + 17
210 + 32
102 + 12
88 + 7
52 + 8
Metabolic Activation
Medium
A -»- rt .-• 1 1-1 •»- lO^/i
• Arocior i/ jQ —
41+3
Tox
111 + 17
77+2
66 + 13
48 + 11
41+3
167 + 11
222 + 18
131 + 16
93 + 17
48 + 14
33 + 7
123 + 36
140 + 29
86 + 24
72 + 15
34 + 16

Low


37 + 6
NT
79 + 29
83 + 3
53 + 10
50 j+ 10
37+6
143 + 62
162 + 53
115 + 19
79 + 20
47 + 9
37 + 6
108 + 46
135 + 74
108 + 12
104 + 9
50+6
    * NT = Not tested.

-------
500n
400'
I   300
«0
200-
100-
                                ACID FRACTION
                                    HIGH   S9

                                    MED   S9

                                    LOW   S9
                                                     1.0
                     DOSE /PLATE Cmg)

  Figure  22.  Mutagenic activity of acid  fraction of PENT S waste
             as measured with high, medium, and low levels of S9
             in the S9 mix.
                         82

-------
    500i
    400
    300
0
**
e
    200-
co
O)
    100-
                                      BASE  FRACTION
•   HIGH   S9


A   MED   S9

•   LOW   S9
                          DOSE /PLATE Cmg)


    Figure 23,  Mutagenic activity of base fraction of PENT S waste
               as measured with high, medium, and low levels of  S9
               in the S9 mix.
                               83

-------
    500
    400
2   300
c
ta
05   200
0>
    IOOH
                                     NEUTRAL FRACTION
                  HIGH   S9


                  MED   S9


                  LOW   S9
                0.2
0.4       0.6       0.8



 DOSE /PLATE (mg)
1.0
  Figure 24.  Mutagenic activity of neutral fraction of PENT S

             waste as measured with high, medium and low levels

             of S9 in the S9 mix.
                             84

-------
fraction was  the  only fraction to induce a  significant  inhibition  in  the
repair  deficient  strain when  evaluated in  the spot  test (Table  23  and
Figure  25).  When tested  in the modified  plate incorporation assay,  the
base  fraction  also  produced  increased  lethal  damage  in  the  repair
deficient strains,  while  the response  obtained  from  the neutral  fraction
was  less  conclusive (Table  24).   The  different responses obtained using
the  two procedures  may  have been  a result of  the  lack of diffusion of
waste  fractions  in  the  spot  test.   The  modified  plate  incorporation
assay  did,   however,   conclusively  demonstrate  that  the acid  and base
fractions of  the  PENT S waste contained constituents  that are capable of
producing increased lethal damage  in repair  deficient  bacteria.

     The  capacity  of  PENT  S  fractions  to  induce  genetic  damage in  a
eukaryotic  system  was  measured  using  both the  Aspergillus  methionine
system  and  a diploid  bioassay.   All  three  fractions induced a  doubling
of   revertant   colonies   both   with  and  without  metabolic   activation
(Figures  26,  27,  and  28).  The   frequency  of  induced mutations  per
survivor  for  the acid  and base fractions at  the highest exposure level
with  metabolic:  activation  was  100 and  three  times,  respectively,  the
response obtained in  the absence  of metabolic  activation (Tables  25  and
26).  For the  neutral fraction  at  the highest dose  level,  the  induced
mutation  frequencies  were  almost  the same with  or without metabolic
activation  (Table  27).  The results in  Figures 27  and 28 show  that in
the  absence  of  metabolic activation,  the  surviving fraction  and  induced
mutation  frequencies  for  the base and  neutral  fractions  are  almost
identical  at all  exposure  levels.   The maximum mutagenic  response  was
obtained  with  the   acid  fraction  at  the  greatest   exposure time with
metabolic  activation  (Figure  26).   Thus,   the  acid,  base,  and  neutral
fractions of the PENT  S waste  induced a  significant  increase  in point
mutations  at  the  methionine  suppressor   loci  both  with  and   without
metabolic activation.   While  the  addition  of  metabolic  activitation to
the  assay  system  -did  increase  the  frequency  of  induced  mutations,
significant  increases were  also  obtained  in  the  absence  of metabolic
activation.

     Additional   tests   were   conducted   on   the    fractions   of   the
wood-preserving  bottom  sediment   using  A.  nidulans   diploid  20.   The
diploid  assay,  while  more costly  and  time consuming  than the prokaryotic
assays,  offers  the  advantage of detecting  a range of genetic damage  and
genotoxic   compounds   comparable   to   that   detected   using   in  vitro
mammalian  cell  culture  bioassays  (Kafer  e£  al.,   1982).    The  summary
of  the  genotoxic effects  observed  in  segregant colonies and induced by
the  fractions of the  PENT S waste  (Table  28)  indicates  that each waste
fraction  preferentially  acted  on  a   different group  of  genes   in  the
diploid  Aspergillus.   The  genotoxic   constituents  present   in the  acid
fraction  induced predominantly  fawn and dark  green  segregants,  whereas
the  base  and  neutral  fraction   induced  yellow,  fawn,  and  chartreuse
                                   85

-------
oo
             TABLE 23.   CAPACITY OF FRACTIONS OF WOOD-PRESERVING WASTE TO INDUCE INCREASED LETHAL
                                DAMAGE IN DNA REPAIR DEFICIENT STRAINS OF B. SUBTILIS

Waste Metabolic
Fraction Activation
Acid +
10 mg/pt
Base +
10 mg/pt
Neutral +
10 mg/pt

Strain: 168
13.9
12.0
0
0.38
0.43
2.3
Growth
wt recE4
17.6*
14.6*
0
0.35
0.37
2.2
Inhibition
recA8
14.6
11.7
1.2
0.68
0.20
3.0
(mm)
hcr-9
15.3
12.9
0
0
0
1.3

fh 2006-7
15.0
13.4
1.1
0.2
1.0
2.3

mc-1
14.2
12.9
1.5
0
0
2.1
             * Significantly Inhibited.

-------
                            PENTA- S  WASTE
                            _B.  SUBTILIS  DMA  REPAIR (+METABOLIC ACTIVATION)
oo
      168 wt
      rec E4
      rec A8
      her- 9
      fh 2006-7
      me- I
                    ACID lOmg
BASE 10 mg
NEUTRAL 10 mg


      I68wt


      rec E4


      rec A8


      her-9


      fh 2006-7


      me-1
                           8     12     16
                                GROWTH INHIBITION   (mm)
                Figure .25.  Growth inhibition induced by  fractions of the wood-preserving
                           bottom sediment in repair proficient (168 wt) and deficient
                           strains of B.  subtilis.

-------
                 TABLE 24.  FRACTIONAL SURVIVAL OF  REPAIR PROFICIENT AND  DEFICIENT STRAINS OF
                                 B. SUBTILIS EXPOSED TO  SUBFRACTIONS OF WOOD-PRESERVING
                                  BOTTOM SEDIMENT.  SURVIVAL WAS MEASURED  IN  THE PRESENCE
                                                OF METABOLIC ACTIVATION
00
oo
Fractional Survival (N/N ) %
o
Sample
Acid


Base


Neutral


Dose/Plate 168 wt
(pg) RP
100
50
10
1000
100
10
1000
100
10
35 + 28
88 + 28
92 j+ 12
20+3
43 + 28
MOO
5+5
17+6
.66 + 44
fh2006.7

19 + 13
34+22
50 + 17
3+2
13 + 11
63 +_ 15
6+5
15+6
43 + 12
recE4
repair deficien
6+4
26 + 28
41**
2 + 0.5
4 + 0.5
9 + 1.5
2**
2**
36**
mc-1
—
NT*
NT
NT
4+1.
33 + 12.
16 + 2.
76**
64**
58**





5
0
0



                 * - NT = not  tested
                 **- Standard  deviation not provided  because  only  one  test  conducted.

-------
    i65j
i
LJ
UJ
.6^
                                  PENT- S- ACID
                             -S-9  !25*Q/pt.  +S-9
                            A	-A          A	A
    !0TJ
O
LJ
O

O
                                                               100 _
                                                                  15
                                                               10
                                                                  o
                                                                  fc
                                                                  (9
                                                                  CO
           10
                    30
                         50
70
90
                       MINUTES EXPOSURE TIME


 Figure 26.  Induced mutation frequency and fractional survival
             in A. nidulans^ following exposure to acid fraction
             of PENT S waste.  Data based on results from two
             independent experiments.
                            89

-------
                    o
i*
                                  PENT- S- BASE
 -S-9
o	o
                                             *S-9
I   tf
e
                                  rioo^
                                                              •10
                                                                  o
                                                                  i
                                                                  CO
           10        30       50       70       90

                      MINUTES EXPOSURE TIME


   Figure 27.  Induced mutation frequency and fractional survival
               in _A. nidulans following exposure to base fraction
               of PENT S waste.  Data based on results from two
               independent experiments.
                               90

-------
.64
                D-—O--..
               '           — -.
                            PENT -S- NEUTRAL
                          -S-9  I25itg/pt.  +S-9
                         a	a        •	1
o
|
a
1
                                         --a
                                                          100 --.
                                                          10   £
                                                              o


                                                              a:
                                                              (O
       10      30       50        70      90

                  MINUTES EXPOSURE TIME
   Figure 28.   Induced mutation frequency and fractional
               survival in A. nidulans following exposure
               to neutral fraction of PENT S waste. Data
               based on results from two independent
               experiments.
                        91

-------
        TABLE  25.  SURVIVING FRACTION AND INDUCED MUTATION FREQUENCY OF A. NIDULANS
to
FOLLOWING EXPOSURE TO ACID
Dose/Plate
(ug)
Exposure
Time (min)
Surviving
Fraction
FRACTION OF
Mutation
A
PENT S WASTE
Frequency Per
B

io6
c

Survivors
Total
Without Metabolic Activation
41.7
62.5
125.0
250.0
With Metabolic
41.7
62.5
125.0
250.0
40
40
40
40
Activation
20
20
20
20
.75
.75
.54
.31
.75
.82
.56
.26
.84
1.4
2.4
5.4
1.9
2.2
3.8
7.1
1.4
1.8
3.6
6.8
3.2
4.2
8.7
17.6
.51
.40
.90
2.5
.51
.93
1.3
1.4
2.7
3.6
6.9
14.9
5.5
7.3
13.9
26.3

-------
        TABLE  26.  SURVIVING FRACTION AND INDUCED MUTATION FREQUENCY OF A. NIDULANS
VO
CO

Dose/Plate
(pg)
FOLLOWING
Exposure
Time (min)
EXPOSURE TO BASIC
Surviving
Fraction
FRACTION OF
Mutation
A
PENT S WASTE
Frequency Per
B

106
c

Survivors
Total
Without Metabolic Activation
41.7
62.5
125.0
250.0
With Metabolic
41.7
62.5
125.0
250.0
40
40
40
40
Activation
20
20
20
20
.76
.94
.64
.40

.82
.91
.64
.40
.98
1.6
3.1
2.4

1.6
2.8
6.7
10.4
1.7
6.1
4.2
6.9

2.7
9.5
10.6
17.6
.50
.88
.98
1.4

.46
1.3
3.2
3.9
3.2
8.6
8.3
10.7

4.9
13.6
20.6
31.9

-------
TABLE 27. SURVIVING FRACTION AND INDUCED MUTATION FREQUENCY  OF  A.  NIDULANS
                  FOLLOWING EXPOSURE TO NEUTRAL FRACTION OF  PENT S WASTE
Dose/Plate
Exposure
Time (min)
Surviving
Fraction
Mutation Frequency Per 10 Survivors
A
B
C
Total
Without Metabolic Activation
41.7
62.5
125.0
250.0
With Metabolic
41.7
62.5
125.0
250.0
40
40
40
40
Activation
20
20
20
20
.77
.83
.57
.44

.70
.78
.40
.34
.63
1.3
.96
4.1

3.3
.74
3.5
5.4
1.8
5.3
3.4
12.8

6.0
3.1
9.3
12.4
.16
.17
.22
.50

.21
.37
.91
1.1
2.6
6.8
4.6
17.4

9.5
4.2
13.7
18.9

-------
                           TABLE 28.
SUMMARY OF CENOTOXIC EFFECTS OBSERVED IN SEGBEGANT COLONIES OF DIPLOID A. NIDULAHS FOLLOWING
                       EXPOSURE TO WASTE CONTROLS AND FRACTIONS
VO
Ln
„ 2,3
Phenotype
Sample
Control
DMSO
Benomyl
Pent S - Acid
Base
Neutral
SWRI - Acid
Base
Neutral
COMBO - Acid
Base
Neutral
Total'
619
140
299
248
306
318
369
348
332
285
285
261
Yellow
Overall
1.9
4.0
12.7
4.4
10.0
6.9
11.1
10.9
9.6
14.7
11.2
11. S
CO
0.3
0.7
1
0
2
0.6
1.6
1.4
2.1
3.9
1.8
1.1
NO M
0.5 0
0.7 0
3.5 0.
0 0
1.0 0
1.9 0
2.7 0
1.0 0
2.7 0
3.2 0
3.5 0
2.7 0
2n
0.3
0
3 1.4
0.8
1.6
1.3
1.4
2
1.5
2.1
2.5
3.1
fawn
n
0
0.7
0.3
0.8
1.3
0.3
0
0.6
0.3
0.4
0
1.5
1. Total « number of segregant colonies examined; overall • total number of
2. Unit - Total frequency of segregants per colony examined.
3. Phenotype: Yellow-includes only colonies that were completely yellow, all
CHAT
2n
0.3
2.0
2.3
0.4
2.6
1.9
2.4
2.0
2.4
1.4
1.1
1.1
induced
other
DG
n 2n
0 0.3
0 0
0.7 1.0
0 0.8
0.3 0
0 0
0 0.3
0 0.9
0 0
0 0
0 0
0.4 0
GR
n 2n
0 0.2
0 0
1.3 1.0
0.8 0.4
0.3 1.0
0 0.9
1.4 1.4
1.4 0.6
0 0.6
2.5 1.4
1.8 0.7
0.4 0.8
n
0
0
0
0.4
0
0
0
0.3
0.0
0
0
0.4
ISI*
CT DO
.04
1.4
5.2 3.7
4.2 2.9
1.6 .1
2.6 .8
2.7 .9
2.1 .5
2.6 .8
1.6 .1
1.9 .3
2.3 .6
segregants.
listed in other sections;
                    CO ° crossing-over, ND "non-disjunction, H • mutations. Fawn » tan sectors; Chat - chatreuae; DG - dark green
                    G " green; 2n ™ diploid; n " haploid.
                    Induced segregation index - Total induced aegregants divided by frequency of control segregants.  CT " evaluated
                    with respect to controls; DO • evaluated with respect to solvent control (DMSO).  If ISI is significantly greater
                    than 1.0, response is considered positive.

-------
segregants  (Table  28).    Both  crossing  over  and  non-disjunction were
observed  in  the yellow  segregants  induced  by the  base  fraction, while
predominantly non-disjunction was  observed in yellow segregants  from  the
neutral   fraction.   No   yellow   segregants  were  induced  by   the  acid
fraction.   When  the  induced  segregation  indexes  are  compared  with
respect   to  the  spontaneous  control,  all  three  waste  fractions   are
positive  with the  genotoxic potential of  the  acid fraction slightly less
than  benomyl,   the  positive  control.   When  the  responses  are  compared
with respect to the solvent control,  the  acid and neutral fractions  are
positive;  while  the induced  segregation  index  of the  base  fraction,
which  is  slightly  greater  than  one,  would be  considered  a  borderline
positive  response.

     In  abnormal  colonies, the  acid,  base,  and neutral fractions induced
31, 15  and 25  abnormal colonies, respectively (Table 29). For  all  three
fractions,   the  maximum  mutation   frequency  was   observed   in   the
hyperdiploid class.  The  acid  fraction induced significant increases  in
hyperdiploid colonies,  breakdown of  the  mitotic  spindle apparatus,  and
mitotic   recombination;   the  neutral   fraction   induced   significant
increases  in the  hyperdiploid  class and  mitotic recombination.   Thus,
the acid fraction induced the maximum amount  of genetic damage  observed
in  abnormal   colonies,   while   the   neutral   fraction   also   induced  a
significant  positive  response,   and  the   base   fraction   induced   a
borderline positive  response.

     The  results from  biological  analysis  of the  wood-preserving  waste
indicate  that   the  base  fraction   induced the maximum  response  in both
prokaryotic  point  mutation assays,  the  DNA  repair plate  incorporation
assay,   and  the   eukaryotic   point  mutation   assay  with   metabolic
activation.  In the  prokaryotic DNA  repair spot test and the  eukaryotic
point  assay,  the  acid  fraction induced  the maximum genotoxic  response.
Although   the  genotoxicity  of   the  acid   fraction  was  greatest in  the
presence  of metabolic  activation, a positive response  was  obtained  in
the   absence   of  metabolic  activation   in  both   bioassays.   The  acid
fraction,  however,  was   toxic  at   higher  dose levels  in the  Salmonella
and   Bacillus   assays,   possibly   a  result   of  the   presence   of
pentachlorophenol.  The  acid fraction induced  the  maximum  response  in
j>.   typhimurium  strain   102.    The   wood-preserving   bottom   sediment
contained a  diverse range of constituents including compounds  capable of
causing  induction,  promotion,  and  inhibition,  as  well as mutagenic  and
carcinogenic  effects  (Figure  29,  30,  31,  and  Table  30).    Biological
analysis  of the  fractions  of  this  waste  detect  compounds  capable  of
causing  point   mutations, lethal  damage  to DNA,  and  various   types  of
chromosome damage.   While the results  of  biological testing do  not  rule
out  the  PENT S waste as candidate  for  land  treatment,  the presence  of
pentachlorophenol  and other  compounds that are resistant to  degradation
or  mobile in the  soil  indicate  that  land  treatment should probably  be
conducted at a lower  loading  rate  or be precluded  by a  pretreatment
method  such as  composting or  anaerobic digestion.
                                  96

-------
TABLE 29. SUMMARY OF GENOTOXIC EFFECTS OBSERVED IN ABNORMAL COLONIES OF DIPLOID
          A. NIDULANS FOLLOWING EXPOSURE TO CONTROLS AND WASTE FRACTIONS

Sample
CONTROL



DMSO



BENOMYL



PENT S
(Acid)


PENT S
(Base)


Total2
COL=61 9
MF
ISI(S)
ISI(D)
COL=140
MF
ISI(S)
ISI(D)
COL=299
MF
ISI(S)
ISI(D)
COL=248
MF
ISI(S)
ISI(D)
COL=306
MF
ISI(S)
ISI(D)

0V
22
.036
-
—
6
.043
1.19
-
47
.157
4.36
3.65
31
.125
3.47
2.91
15
.049
1.36
1.14
Genetic
HD
14
.023
-
-
3
.021
.91
-
19
.050
2.17
2.38
21
.085
3.70
4.05
10
.033
1.43
1.57
Damage Observed
NH
3
.005
-
—
2
.014
2.8
-
3
.010
2.0
.71
3
.012
2.4
0.86
1
.003
.06
.21
HH BK
2 1
.003 .002
-
- -
0 0
- -
-
-
1 19
.003 .064
1.0 32
-
0 2
.008
4.0
-
1 1
.003 .003
1 1.5
- -
OT
2
.003
-
-
1
.007
2.3
-
5
.017
5.67
2.43
5
.020
6.67
2.87
2
.006
2.0
0.0

-------
                                 TABLE 29  CONTINUED
VO
oo
Sample
PENT S
(Neutral)


SWRI
(Acid)


SWRI
(Base)


SWRI
(Neutral)


COMBO
(Acid)


Total2
COL=318
MF
ISI(S)
ISI(D)
COL=369
MF
ISI(S)
ISI(D)
COL=348
MF
ISI(S)
ISI(D)
COL=332
MF
ISI(S)
ISI(D)
COL=285
MF
ISI(S)
ISI(D)

QV
25
.079
2.19
1.84
28
.076
2.11
1.77
27
.078
2.17
1.81
21
.063
1.75
1.47
14
.049
1.36
1.14
Genetic
HD
15
.047
2.04
2.24
16
.043
1.87
2.05
19
.055
2.39
2.05
10
.030
1.30
1.43
7
.056
1.09
1.19
Damage Observed
NH
5
.016
3.2
1.14
4
.011
2.2
.78
2
.006
1.2
.36
7
.021
4.2
1.5
2
.007
1.4
.5
HH BK
0 1
.003
1.5
- -
1 2
.003 .006
1 3
- -
0 0
-
-
- -
1 2
.003 .006
1 3
-
0 4
.014
7
- -
OT
5
.013
4.3
1.86
5
.014
4.67
2.00
6
.017
5.67
2.43
5
.003
1
.42
1
.004
1.3
1.3

-------
                                TABLE 29  CONTINUED
VO

Sample
COMBO
(Base)


COMBO
(Neutral)



Total2
COL=285
MF
ISI(S)
1SI(D)
COL=261
MF
ISI(S)
ISI(D)

0V
20
.70
1.%
1.63
15
.057
1.58
1.33
Genetic Damage Observed
HD NH HH
16 1 0
.056 .004
2.43 .8
2.67 .29
300
Oil
.48
.52

BK OT
0 3
""" •
3.
1.
1 11
.004
2 14
6



Oil
66
57

042


     1. Genetic damage observed:  0V = overall summary of genetic damage observed in
        all categories; HD = hyperdiploid, results from non-disjunction of chromosomes;
        NH = near hyperdiploid, probably breakdown products including a mixture of haploid
        and diploid colonies; HH = hyperhaploid, results from major deletions or lethals
        in chromosomes; BK = breakdown, results from mitotic spindle poisons; OT = others,
        results from mitotic recombination which has occurred prior to aneuploidy. Units =
        Total frequency of abnormal segregants per colony examined.

     2. Total: col = total number of colonies examined, and total number of abnormals in
        each class; MF = total mutation frequency = 0V   COL; ISI(S) = induced segregation
        index with respect to control = MF (sample)  MF (control); ISI(D) = induced
        segregation index with respect to solvent control = MF(sample)  MF(DMSO).

-------
                                                                              PENT-3-ACID
o
o
RIC
                     vO  CO
                            o
                            CM
                 CM
                 CM
                 CM
                         200
                            300
400
500
600
                                                      RT
                    Figure 29.  GC/MS  chromatograph  of acid fraction of PENT S waste.

-------
                                     co
                                     ro
                                     
-------
                                                                 a\
                                                                 n
o
to
RIG
                in
                to
                                     CM
                                     CM
                                     CO
                           r--
                           m
                                     o\
                                     CM
                                    CO
                                    oo
                                    CM
                                            VO
                                            CO
                                                    CM
                                                    f-
                                                    CO
                                                                         PENT 8-NEUTRAL
                   200
                                300
400
500
                                                 RT
                     Figure 31.  OC/MS chromatograph of neutral,  fraction of PENT  S waste.

-------
          TABLE  30.   SELECTED  PROPERTIES  OF COMPOUNDS IDENTIFIED IN THE FRACTIONS OF THE
                                       WOOD-PRESERVING WASTE
o
LO
Sample
Acid Fraction









Basic Fraction



Neutral Fraction








Peak
Number
287
322
331
335
342
363
434
483
537
553
239
322
336
363
185
237
288
322
335
342
363
536
553
Compound
Dimethyl napthalene
1-2 Dihydro-acenapthylene
Methylethyl napthalene
Dibenzofuran
Trimethyl napthalene
Phenalene
Pentachlorophenol
Methyl phenanthrene
Fluoranthene
Pyrene
Methyl napthalene
1-2 Dihydro-acenapthylene
Dibenzofuran
Phenalene
Napthalene
Methyl napthalene
Dimethyl napthalene
1-2 Dihydro-acenapthylene
Dibenzofuran
Trimethyl napthalene
Phenalene
Fluoranthene
Pyrene
CAS f
573-98-8
83-32-9

132-64-9
879-129
203-80-5
87-86-5
832-69-9
206-44-0
121-00-0
90-12-0
83-32-9
132-64-9
203-80-5
91-20-3
90-12-0
573-98-8
83-32-9
132-64-9
879-129
203-80-5
206-44-0
121-00-0
Formula
C12H12
P H
12 10
P H
13 14
C12V
C13H14
P H
cjictjo
C15H12
P H
16 10
P H
C16H10
C11H10
C12H10
C.-H-O
C13H10
C10H8
P H
11 10
P H
12 12
P H
12 10
C. HQ0
C13H14
C H
r13H10
16 10
P H
C16H10
Genetic
Activity
MO
Ml
X
X
MO
MO; Cl
Ml
Ml ; CO ; CC
Ml ; CO ; CC
Ml; CO
Ml; CO
Ml
X
X
MO; CO
Ml
MO
Ml
X
MO
X
M1,CO;CC
Ml ; CO ; CC
     1.  Potential  genetic  activity:  P = promoter;  I = inhibitor; CC = cocarcinogenic;
        Ml  = mutagenic;  MO =  nonmutagenic;  Cl  = carcinogenic; CO = noncarcinogenic;
        X = unknown;  references  included in text.

-------
     The  storm-water  runoff  impoundment  (SWRI)  waste  was  one  of  two
refinery  sludges  evaluated  in the  complete battery  of  bioassays.   The
distribution of  mutagenic activity  in the  fractions of  the  SWRI  waste
are  provided  in  Table  31  and  Figure 32. ; These  results  indicate  that
although  the  maximum  response  was obtained  from the acid fraction,  the
specific  activity of  all  three   fractions  was  approximately  equal.  In
addition, when  the  neutral  fraction was  separated  on a silica  gel  column
into  subfractions,  the  specific  activity  of  neutral fraction three  was
approximately  three times  the  specific  activity  of the  unfractionated
neutral   fraction  (Figure  33).    The   dose-response  curves  for  the
extractable  hydrocarbons of  the  SWRI  waste fractions  (Figure 32)  also
indicate  that  the overall  maximum response  was obtained  from the  acid
fraction, although  the maximum mutagenic response  at a single  dose level
was  obtained with the  neutral  fraction at  a dose  of  1.0 mg/plate.  With
the  exception  of  the neutral  fraction  at the highest dose,  there  was no
mutagenic  activity  detected in the  absence of metabolic activation.   In
the  three  subfractions  of  the   neutral  fraction  (Figure  33),  higher
levels  of  mutagenic  activity were detected at  the lower doses  than were
present  in  the  composite  neutral  fraction.   The  maximum  amount  of
mutagenic  activity  was  detected  in fraction  three which  represents  the
condensed  ring fraction.  The  results from biological  analysis  of  the
SWRI  waste  indicate  that  predominantly  indirect acting  mutagens  were
detected  in  the waste  fractions,  and  there was  no  appreciable  difference
in  the mutagenic potential  of each of  the three  primary  fractions.  The
analysis  of  fractions  of the  storm-water runoff impoundment  waste  in the
spot  test or  plate  incorporation assay  using DNA repair  proficient  and
deficient  strains   of  ]3.   subtilis   did   not   provide   any  conclusive
results   (Table  32).   Thus,  the storm-water   runoff impoundment  waste
contained  constituent(s) that  were  capable  of  inducing point  mutations
but  not  lethal  damage  to DNA.

      The   fractions  of   the   SWRI  waste  were   also  evaluated  in  the
Aspergillus  methionine  and diploid  bioassays.   When the results  from
testing  the  three  waste fractions  in  the  haploid methionine assay  are
compared,  the  maximum  mutagenic response was  obtained  from the  acid
fraction  in  the presence of metabolic  activation  (Tables  33,  34  and 35;
and   Figures  34,  35,   and   36).   While  a positive  response  was  also
obtained  from  the  base and   neutral  fractions,  the  induced  mutation
frequencies  were  consistently lower  than  were obtained  with the acid
fraction.   In  contrast  to  the   results  of  the  prokaryotic  bioassay,
mutagenic   responses   were   observed    for   all  waste  fractions   in
Aspergillus in  the absence  of  metabolic activation.

      Each   of   the    three   subfractions   of   the   storm-water   runoff
impoundment  waste induced  a positive  response  in the diploid bioassay.
The  results  presented  in Table  28  indicate  that  in segregant  colonies
the  maximum  genotoxic  response  was  obtained  with  the  acid  fraction,
although   the   genotoxic potential  of  the  neutral  fraction  was  not
significantly   lower   than   the  acid  fraction.    Yellow  and  chartreuse
segregants  were predominantly  induced  by the acid and neutral  fraction,
                                 104

-------
                                            TABU 31.   MUTAGENIC ACTIVITY Of RUCTIONS OF STOHM-UATER RUNOFF  IMPOUNDMENT
O
Ul
Fraction

TA
98
TA 100
TA1535
TA1538
TAJ 537
Doaa/plata 89- + - » - * - » - *
<•«>
Total taia ravertaota
Acid





Baa a





Neutral





0
1
.5
.1
.05
.01
0
1
.5
.1
.OS
.01
0
1
.5
.1
.05
.01
26 * 2
S3 7 18
32 7 S
28 7 7
24 7 7
23 7 6
26 » 2
47 7 18
34 7 3
31 7 6
28 7 6
26 7 3
25 2
79 44
49 21
28 13
25 9
36 10
29 » 6
222 7 23
158 740
88 7 23
68 7 8
34 7 10
45 » 1
1S1 7 30
144 7 23
82 7 12
68 7 9
44 7 9
44 » 6
235 7 111
134 7 25
74 7 10
66 7 24
50 7 7
US * 13
114 7 19
116 + 11
114 7 25
102 7 11
105 7 24
130 * 5
126 7 9
137 7 7
109 + 11
112 7 17
113 * 10
125 «• 9
147 7 11
123 7 16
115 7 9
120 7 6
130 7 IS
109 »
249 7
25S 7
245 7
198 7
133 7
124 +
349 7
337 7
230 7
185 7
132 7
109 *
290 7
283 7
227 7
166 7
119 7
7
27
36
31
10
12
6
49
120
43
12
21
7
26
14
21
54
19
(Maaa » SO)
28 * 8
36 7 10
47 7 16
53 7 15
49 7 27
36 7 17
28 * 8
52 7 17
52 7 16
41 7 12
38 7 12
37 7 6
28 * 8
21 7 6
23 7 7
26 7 1
20 7 6
21 7 7

21 »
28 7
38 7
25 7
25 7
24 7
20 »
28 7
28 7
20 7
22 7
21 »
19 »
25 7
22 7
24 7
19 7
23 »

4
S
3
S
4
S
4





2
7
4
3
4
6

12 +
67 7
52 *
18 7
19 7
14 7
12 +
34 7
23 »
17 7
16 7
18 7
12 *
26 7
20 7
16 7
14 7
14 7

2
8
14
5
7
2
2
6
6
5
3
5
2
5
3
1
2
2

21 » 4
75 7 11
78 7 8
61 7 9
42 7 17
17 7 3
25 » 2
111 7 51
90 7 30
46 7 14
25 7 18
19 7 5
25 * 4
66 7 11
52 7 2
20 7 5
32 7 7
17 7 3

9 *
42 7
38 7
10 7
15 7
13 *_
10 *
25 7
16 7
13 7
H 7
16 7
10 *
20 7
14 7
12 7
10 7
8 7

2
4
5
2
4
3
2
6
5
2
S
2
2
12
3
4
3
3

14 * 2
42 7 14
44 7 8
33 7 11
26 7 14
25 7 3
24 » 5
27 7 8
22 7 8
20 7 5
21 7 6
13 7 1
21 * 6
42 7 10
43 * 17
39 » 16
28 '7 10
25 * 7

-------
 300'
 •x
 •a
*«
.c

CO
               SWRI WASTE
      ACID   £r-4

0—0  BASE   O—o

D—O NEUTRALO—a
 100-
              0.2
                               0.8
1.0
                 0.4       0.6


                 DOSE/PLATE  Cmg)


Figure 32.  Mutagenic activity of fractions of SWRI waste.
                           106

-------
   600
   400
CD
0)
  200-
               I 00
SWRI NEUTRAL
NETJTRAL. — '•
FRACTION 1-8
ALL+S9
£-•
3— A
300
500     1000
                             DOSE/PLATECug)

   Figure 33.  Mutagenic activity of subfractions  of neutral fraction
             . of SWRI waste.
                              107

-------
TABLE 32.  FRACTIONAL SURVIVAL OF  REPAIR PROFICIENT  (168 WT) AND
           DEFICIENT STRAINS OF IJ. SUBTILIS EXPOSED TO  SUB-
           FRACTIONS OF COMBINED API-SEPARATOR/SLOP-OIL EMULSION
           SOLID (COMBO) OR STORM-WATER RUNOFF  IMPOUNDMENT  (SWRI).
           SURVIVAL WAS MEASURED IN THE PRESENCE OF METABOLIC
                               ACTIVATION

Sample

COMBO
Acid



Base




Dose/Plate
(ug)

500
100
50
10
1000
500
100
50
Fractional
168 wt
RP

72 + 0.6
97+8
MOO + 24
96+4
31**
43 + 27
87 + 14
MOO
Survival (N/N ) %
hcr-9 ° recAS
— repair deficient -

27+9 NT*
54+5
55 + 17
MOO**
27+13 NT*
64 + 10
60+8
50 + 21
SWRI
Acid




2500
1000
500
100
50
8**
52 + 33
64 + 14
100 + 0
96+8
21**
53
NT
MOO +
MOO +



0
0
32**
66
MOO
MOO

* - NT = not tested
**- Standard deviation not provided because only one test conducted.
                                 108

-------
              TABLE  33.  SURVIVING FRACTION AND INDUCED MUTATION FREQUENCY OF A. NIDULANS
o
vo
FOLLOWING EXPOSURE TO ACID
Dose/Plate
(ug)
Exposure
Time (min)
Surviving
Fraction
FRACTION OF
Mutation
A
SWRI WASTE
Frequency Per
B

io6
c

Survivors
Total
Without Metabolic Activation
99
199
248
497
With Metabolic
124
248
331
497
40
40
40
40
Activation
20
20
20
20
.54
.24
.23
.03
.44
.17
.29
.09
7.7
30.0
30.7
124.0
119.0
44.4
36.2
87.1
7.2
19.0
20.3
88.6
67.4
37.2
31.1
61.0
1.0
2.3
3.9
8.9
35.4
10.5
1.4
8.7
16.0
51.0
54.9
221.5
221.9
92.1
68.6
156.9

-------
TABLE 34. SURVIVING FRACTION AND INDUCED MUTATION FREQUENCY  OF  A.  NIDULANS
FOLLOWING EXPOSURE TO BASE FRACTION OF SWRI WASTE
Dose
(ug)
Exposure
Time (min)
Surviving
Fraction
Mutation Frequency
A

B
Per

10 Survivors
C
Total
Without Metabolic Activation
42
84
168
226
336
With Metabolic
42
84
128
168
226
40
40
40
40
40
Activation
20
20
20
20
20
.78
.46
.21
.12
.04

.76
.61
.39
.23
.21
0
1
7
9
91

0
7
8
24
8

.9
.8
.9
.0


.0
.4

.6
1
0
19
26
242

3
1
2
14
25
.7
.7




.4
.3
.7


0
0
0
0
15

0
0.8
1.6
5.8
0
1
2
26
35
348

3
9
12
44
33
.7
.6
.8
.8


.4
.1
.7
.0
.6

-------
TABLE 35. SURVIVING FRACTION AND INDUCED MUTATION FREQUENCY OF A. NIDULANS
FOLLOWING EXPOSURE TO NEUTRAL
Dose

Without
93
185
463
719
925
Exposure
Time (rain)
Metabolic Activation
40
40
40
40
40
Surviving
Fraction

.94
.82
.51
.35
.41
FRACTION OF
SWRI WASTE
Mutation Frequency Per
A

1.2
3.6
6.2
9.8
13.0
B

1.1
1.0
1.3
2.1
2.7


10 Survivors
C

0
0
0
0
0.5
Total

2.3
4.6
7.5
11.9
16.2
With Metabolic Activation
185
370
555
719
925
20
20
20
20
20
.74
.67
.49
.45
.40
9.5
4.9
13
14
11
2.4
0
1.9
2.9
1.4
0
0.6
1.3
0
1.2
11.9
5.5
16.2
16.9
13.6

-------
tr
o
(E
O
   -4
UJ

o
UJ
cc  -
u- 10
o
UJ
o

0
    -6
   10
SWRI ACID
                                   -S 9  248ug/pt  + S 9
                               •-&
                                                             100
                                                             10
                          o
                          <
                          cr
                          u.
                          o
                                                                  (C


                                                                  CO
         10       30      50      70       90



                     EXPOSURE TIME  Cmin.)



 Figure 34.   Induced mutation  frequency  and fractional survival

             in A. nidulans  following exposure to acid fraction

             of SWRI waste.  Data based  on results from two

             independent  experiments.
                              112

-------

-------
en
o
>

(E
D
CO
X
>-
o
z
UJ
3
O
UJ
(T
U.
 -4
10
 -5
10
      -6
     10
                                          SWRI NEUTRAL
                                   -S9  925ug/plate -»-S9


                                   O—O              •—•
O
UJ
O
13
a
                                                        rioo *

                                                             o
                                                              10
                                                             o
                                                             <
                                                             cr
                                                             LL.

                                                             CD
           I  0
               30
50
70
90
                   MINUTES EXPOSURE TIME



    Figure 36.   Induced mutation frequency and fractional  survival in

                A.  nidulans  following exposure to neutral  fraction of

                SWRI  waste.  Data based on results from two

                independent  experiments.
                                 114

-------
while the  base  fraction induced a  range  of segregant colonies  including
all  possible  phenotypes.   The  majority  of  yellow segregants induced  by
the  acid  and  neutral  fractions  were  a  result  of  non-disjunctional
events,  while yellow  segregants induced by the  base  fraction  resulted
predominantly  from  crossing  over.    In  addition,  a   relatively   high
frequency  of  diploid colonies were recovered from chartreuse segregants
induced  by each  of the  three fractions  (Table 28).   The  results from the
diploid  assay demonstrate  that constituent(s)  of the  fractions of  the
SWRI waste are  capable of  inducing a broad range of genotoxic  damage in
segregant  colonies.

     In  abnormal  colonies,  the  observed  induced  segregation index  with
respect  to DMSO  for  the acid,  base,  and  neutral fractions of  the  SWRI
waste  was  1.77,  1.81  and  1.47,  respectively (Table  29).  The  acid and
base  fractions   induced  primarily  hyperdiploid   colonies  and  mitotic
recombination,  while the neutral  fraction induced hyperdiploid  and  near
hyperdiploid  colonies.   All three  fractions  of  the SWRI  waste  induced a
positive response  in  the  abnormal colonies.   In addition, the  maximum
genotoxic   response  was  induced   by  the  base   fraction,  although  the
induced  segregation  index  of  the  acid fraction was  not  significantly
lower.

     The results  from  the  chemical  analysis   of the   fractions  of  the
storm-water   runoff  impoundment waste  were  far less   conclusive.  The
components of  the acid,  base,  and  neutral fraction of the SWRI  waste
were  present  at  levels that  were  below the  detection  limits  of  the
procedures used.  Thus,  the  results  from the  chemical  analysis of the
waste  fractions  are,  to  a limited  extent,  in contrast to the  results
from biological  testing.

     Biological  analysis detected  genotoxic constituent(s) in  all  three
fractions  of  the storm-water runoff  impoundment waste,   and three  of the
four bioassays  detected  the  maximum  genotoxic   response in  the  acid
fraction  with  metabolic  activation.   Genotoxic   constituent(s)  in  the
SWRI  waste  were  capable  of  inducing  point   mutations and  chromosome
damage;  however,  the  concentrations  of the genotoxic  compounds in the
waste  were below the  detection  limits of  the  analytical  instruments.
The  potential of the SWRI  waste to be treated by  land  application should
be  enhanced by the fact  that genotoxic compounds  are present  in such low
concentrations.    Since   adsorption   and   degradation   are   frequently
concentration dependent, the SWRI  waste  can possibly be  treated  by land
application,   in  spite  of  the   presence  of  genotoxic  constituents.
However,   because  of  the  inability  of  chemical analysis  to  identify
compounds  present at genotoxic  levels  in the waste,  short-term bioassays
appear   to  provide  the  only  analytical  method  capable of  efficiently
monitoring land application of  this waste.

     The second  refinery waste  evaluated in this  research was  a combined
API  separator slop-oil emulsion solids  (COMBO)  waste.   The dose-response
                                 115

-------
curves  for  the  acid,  base,  and neutral  fractions,  as  measured  in  the
Salmonella/microsome  assay  are  provided   in  Figure  37  and  Table  36.
Theseresults  indicate  that the maximum mutagenic response was obtained
from  the  neutral fraction  in the  presence of metabolic activation  and
that  significant  quantities of mutagenic  activity were also detected  in
the  neutral  fraction  in  the  absence   of  metabolic   activation.    In
addition, none of  the  subfractions  of  the  neutral  fraction  induced  a
greater mutagenic  response  than  the  whole  fraction  (Figure 38).   Tests
were  also  conducted with  the base fraction  using phenobarbitol  induced
rat  liver.   Epler  et_ al.   (1978)  found   that Aroclor-induced  rat  liver
reacted best  with the neutral  fraction,  while phenobarbitol-induced  rat
liver reacted  best with  the base  fraction of synthetic fuel  extracts.
However,  the  results in  Figure 39 indicate  that  for  both strains  TA98
and  TA100,  the maximum  frequency of  induced mutations  was observed  in
the  presence  of  Aroclor   1254  induced   S9.    Thus,   all   three  waste
fractions induced a mutagenic response  in  the  Salmonella assay.

     The  analysis of  fractions  of the  combined API-separator/slop  oil
emulsion  waste   in   the    spot   test   using   DNA  repair  deficient  and
proficient  bacteria did  not  provide  any conclusive  results   (data  not
shown).   The   use  of the   modified  plate  incorporation assay  (Donnelly
e_t  al.,  1983)  did,  however,  provide  more  conclusive  results.   The
acid  fraction  induced the  maximum response  in  the  modified DNA repair
assay  (Table  32).   The  survival ratio of the  repair  proficient strain
(168)  compared to  the  repair deficient strain  (hcr-9) was 0.37  for  the
acid  fraction,  while the  base  fraction induced a survival  ratio of 0.69.
There  was  no  appreciable  difference  in the   survival  of  the  repair
proficient  and  deficient   strains  following  exposure  to  the  neutral
fraction.

     Mutagenic  activity was also detected in  the fractions of  the COMBO
using   the  Aspergillus  methionine   assay  (Tables  37,  38  and  39  and
Figures  40, 41  and  42).    The  maximum mutagenic response was  obtained
from  the   neutral   fraction  with  metabolic  activation,  and   mutagenic
activity  was  also  detected   in  the  absence  of metabolic  activation
(Figure   42).     The   neutral   fraction   induced  2575   mutations/10
survivors.   This  was  the  maximum mutagenic  response induced   in  the
Aspergillus methionine  system  by any  of  the waste  fractions   tested  in
the  present study.   Mutagenic  activity  was  also detected  in the  acid
fraction  both  with  and  without metabolic activation;  whereas,  the base
fraction  induced a  positive response  only in the presence of  metabolic
activation  (Figures 40  and  41).  In  the  diploid  system,  the  neutral
fraction  of  the  COMBO  waste  induced  the maximum  genotoxic  response.
Significant  increases   in  the  induced   segregation   index  were  also
observed  in the base fraction;  whereas,  the  induced  segregation index in
the   acid   fraction,   with  respect  to   DMSO,   would   be   considered  a
borderline  positive  response.   The   acid  and  base  fractions  induced
predominantly  yellow  segregants,  while  constituent(s) of  the  neutral
fraction  appeared to preferentially  induce  fawn segregants (Table 28).
The  overall mutation  frequencies  in  abnormal   colonies  induced  by  the
                                 116

-------
  400
 300-
€>

>
£200-
oo
o>
  100-
                            DOSE/PLATE (mg)
      Figure 37.  Mutagenlc activity of fractions of COMBO waste.
                              117

-------
                                  TABLE 36.  HUTAGENIC ACTIVITY OF FRACTIONS OF COMBINED API SEPARATOR/SLOP OIL EMULSION WASTE
                Fraction
Dose/plate
   (mg)
                                      S9 -
                                             TA 98
                                                                     TA 100
                                                                                                  TA1535
                                                                                                                             TA1538
00
                                                                   Total hi*  revertaats (Mean + SD)
Acid





Base





Neutral





0
1
.5
.1
.0$
.01
0
1
.5
.1
.05
.01
0
1
.5
.1
.05
.01
24+2
45 + 26
26 + 12
22+9
24+4
22+3
17 + 1
24+6
21+4
20 + 10
22+6
17 + 1
27+4
179 + 81
100 + 39
50 + 13
43 + 13
33+9
27+6
217 + 37
118 + 13
65 + 10
51 + 15
31 * 13
25+7
224 + 13
139 + 70
53 + 10
52+3
33 + 12
32+7
269 + 97
161 + 28
90 + 26
54+8
34+17
99 + 6
98 + 15
102 + 9
86 + 16
86 + 19
78 + 10
85 + 11
100 + 41
108 + 19
85 + 16
95+9
80 + 15
117 + 6
147 + 12
123 + 16
114 + 3
120 + 6
130 + 15
99 + 16
118 + 7
128 + 24
: 144 + 29
121 + 31
103 + 23
114 + 13
NT*
207 + 35
138 + 29
112 + 19
106 +_ 35
112 + 10
248 + 40
206 + 18
172 + 18
144 + 29
113 + 12
22+3
28+6
27 + 10
34 + 13
30+9
27 + 12
23+4
22 + 13
34+9
39 + 11
39+9
24+6
21+2
26+5
33+7
37 + 12
39+3
33 + 13
18 +
24 +
29 +
29 +
20 +
20 j+
23 +
28 7
35 +
27 +
18 +
22 ±
26 +
27 +
23 +
22 +
24 +
23 +
1
4
7
6
4
3
4
3
8
6
5
7
4
13
7
4
5
5
13 +
17 +
19 +
13 +
16 +
26 +_
13 +
14 +
17 +
13 +
12 +
14 +
17 +
16 +
16 +
13 +
17 +
19 +
3
2
3
3
4
17
3
2
7
4
3
2
2
5
4
5
5
13
24+4
20 + 1
49 + 12
25 + 17
32+5
26 jf. 3
25+4
290 + 86
185 + 56
58+8
34+4
28 +_ 4
21+5
65 + 11
60+4
40+6
32+8
21 + 1
                * - NT - not tested.

-------
  400^
0
o
  200-
             COMBO  NEUTRAL CALL+S9)
               NEUTRALCwholc)  0	O
               IOO
300
500
I 000
                            DOSE/PLATECug)



     Figure 38.  Mutagenic activity of sub fractions of neutral fraction
               of  COMBO waste.
                            119

-------
   600-
• 400-
ui
  20QJ
               I 00
                                COMBO-BASE
                          TA98-Aroclor  S9       O—O

                          TA98-Phenobarbitol  S9

                          TAI 00-Aroclop S9

                          TA I 00-Phenobarbitol S9
                    300
                             DOSE/PLATE(ug)
500
I 000
     Figure  39.
Mutagenic response of base fraction of COMBO waste
using metabolic activation from Aroclor 1254 or
phenobarbitol induced rat liver.
                             120

-------
TABLE 37. SURVIVING FRACTION AND INDUCED MUTATION  FREQUENCY OF A.  NIDULANS

Dose/Plate
(pg)
FOLLOWING
Exposure
Time (min)
EXPOSURE TO ACID
Surviving
Fraction
FRACTION OF
Mutation
A
COMBO WASTE
Frequency Per
B

106
C

Survivors
Total
Without Metabolic Activation
131.5
436.5
657.5
873
1315
With Metabolic
164
436.5
655
873
1315
40
40
40
40
40
Activation
20
20
20
20
20
.62
.28
.11
.09
.08

.59
.34
.15
.04
.30
2.2
25.4
8.6
69.6
10.0

4.0
36.8
12.9
176.4
9.4
.39
0
2.0
0
0

3.7
68.2
24.9
367.6
20.0
0
0
0
0
0

1.0
15.8
5.9
73.5
3.6
2.6
25.4
10.6
69.6
10.0

8.7
120.8
43.7
617.4
33.1

-------
              TABLE 38. SURVIVING FRACTION  AND  INDUCED MUTATION FREQUENCY OF A. NIDULANS
ro
Ni
FOLLOWING EXPOSURE TO BASIC
Dose/Plate Exposure
(pg)
Without
130
221
275
441
550
Time (min)
Metabolic Activation
40
40
40
40
40
Surviving
Fraction

.75
.69
.49
.37
.34
FRACTION OF
COMBO WASTE
Mutation Frequency Per 10 Survivors
A

3.2
6.0
6.0
12.6
9.0
B

.29
.89
1.8
1.6
3.1
C

0
0
0
0
0
Total

3.5
6.9
7.8
14.2
12.0
With Metabolic Activation
110
221
330
441
550
20
20
20
20
20
.83
.66
.48
.43
.39
4.7
7.0
8.3
22.7
7.9
1.7
6.7
5.8
19.1
8.8
.66
3.7
1.4
8.6
1.8
7.1
17.4
15.5
50.4
18.5

-------
              TABLE 39. SURVIVING FRACTION AND  INDUCED MUTATION FREQUENCY OF A. NIDULANS
KJ
CO

Dose/Plate
(ug)
FOLLOWING
Exposure
Time (min)
EXPOSURE TO NEUTRAL
Surviving
Fraction
FRACTION
Mutation
A
OF COMBO
Frequency
B
WASTE
Per 106
C

Survivors
Total
Without Metabolic Activation
85
171
214
320
428
550
With Metabolic
106.9
213.8
221.0
427.5
441
40
40
40
40
10
40
Activation
20
20
20
20
20
.87
.69
.46
.43
.82
.30

.75
.38
.34
.19
.04
3.9
7.7
8.6
15.0
1.6
17.1

2.0
5.4
36.7
34.7
176.3
3.4
6.9
8.2
13.7
2.4
15.7

.76
2.8
68.2
39.0
367.6
0
0
0
0
0
0

.68
1.4
15.8
13.0
73.5
7.3
15.4
16.8
28.7
4.0
32.8

3.4
9.6
120.7
86.7
617.4

-------

-------
cr
o
>

o:
=>
(a
o

LJ

O

tr.
u.

z
o

•-
<
o
Ul
o
 -4

10
      -5
     10
      -€
     10
                                         COMBO BASE
                                -S3  550ug/pt
                                                              •100 *


                                                                   O
                                                              10
                                                             o
                                                             <
                                                             (E
                                                             u.

                                                             o
            I 0
               30
                             SO
70
90
                   MINUTES EXPOSURE  TIME



        Figure   41.  Induced mutation frequency and fractional

                    survival in A^. nidulans following  exposure

                    to base fraction of COMBO waste.   Data

                    based on results from two independent

                    experiments.
                               125

-------
                      2575
tr
o


>
ce
3
CO
o
z
LU

o
Ul
ec
<
*-
O
Ul
o
      -4

     10
      -5
     10
      -€
     10
                                     COMBO  NEUTRAL
                                  -S9   488ug/pt   + S9

                                  o—a
                                                            •100 *


                                                                 o
                                                            -I 0
                                                                 O
           I 0
                    30
50
70
90
                   MINUTES EXPOSURE TIME
   Figure 42.   Induced mutation frequency and fractional

               survival in ^. nidulans  following exposure to

               neutral fraction of COMBO waste.  Data based

               on results from two independent experiments.
                           126

-------
acid, base and  neutral fractions of  the  COMBO waste were  .049,  .70,  and
.057,  respectively  (Table  29).  The  induced  segregation   index  with
respect  to DMSO was 1.14 for  the  acid, 1.63  for  the  base, and 1.33  for
the  neutral  fraction  (Table  29).   The acid and  base  fractions  induced
the  maximum  mutation   frequency in  the  hyperdiploid  class,  while  the
neutral  fraction induced  the  maximum mutation  frequency  in the  class
representing  mitotic  recombination.   In  addition,  the  acid  fraction
induced  a  significant  increase  in the breakdown  of the mitotic  spindle
apparatus.  These results  indicate that in  abnormal colonies  the  maximum
genotoxic response  was  induced  by the base fraction,  with the  neutral
and  acid  fractions  inducing slightly  lower  responses.  Thus, in both  the
haploid  and   diploid  Aspergillus  assays,  the  maximum overall  genotoxic
response  was  obtained with the neutral  fraction,  with an intermediate
response  in   the  acid fraction,  and  a borderline response  in the base
fraction.

     Chemical  analysis  identified  a  total  of eleven,  seven, and  eight
compounds in  the acid, base,  and neutral fractions, respectively, of  the
COMBO waste  (Figures 43, 44,  45, and  Table  40).   In all  three fractions,
at  least half of the  compounds  identified  were substituted napthalenes.
Only  one compound,  dimethyl  phenanthrene,identified  in the  COMBO  waste
fractions would be  considered a potential  source of mutagenic  activity,
and  it was  identified in  the neutral fraction.   A study by 'LaVoie  et
al.   (1983)   determined   that  several  substituted   phenanthrenes  were
mutagetiic in  Salmonella with metabolic activation.

     Bioassay  directed   chemical   analysis   of   the   fractions  of  the
combined  API  separator/slop-oil  emulsion   waste  detected  compound(s)
capable  of  inducing point  mutations,  lethal damage to DNA,  and  various
types  of chromosome   damage.   Toxic  effects were  not  observed  in  the
prokaryotic  point  mutation  assay  even at  the highest dose levels.   The
maximum  genotoxic  response   in   the   Salmonella,   Aspergillus  haploid,
and  Aspergillus diploid bioassays  was induced by the  neutral  fraction;
while  the acid fraction  induced  the maximum  rsponse  in the  Bacillus
DNA  repair  assay.  The neutral  fraction  induced a  significant  mutagenic
response  both with  and without metabolic activation.   This fraction also
contained  dimethyl  phenanthrene,  the only  potential  mutagen  identified
in  the  COMBO waste.   Substituted  phenanthrenes, however,  are known  to
require  metabolic  activation  in order to  reach their  ultimate  mutagenic
form  (LaVoie  £t  al.,  1983).   Thus,   these  results   indicate   that
additional  compound(s),  not identified by  chemical analysis  and  present
in  the COMBO waste,  are likely to  be responsible for  the direct-acting
mutagenic  activity detected  in  the  neutral   fraction  and  for  the
indirect-acting mutagenic  activity  of the  other  waste  fractions.   Both
the  chemical and the  biological  analysis  of  the  COMBO waste  indicated
that  the  neutral   fraction  contained  the   maximum  mutagenic  potential.
The  constituent most   likely to  be responsible for the mutagenic activity
of   the  neutral  fraction,  dimethyl   phenanthrene,  was  detected  by  a
chemical  analysis.   However,  land application of the  COMBO waste should
be   monitored  using   a  combined  testing   protocol  because   biological
                                127

-------
            RIG
to
              ZOO
                                                   COMBO ACID
                                                                           12
ZOO
                                                                       400
                                                                                                   5OO
                                                         RT
                Figure 43.  GC/MS chroraatograph of acid fraction of COMBO waste.

-------
VO
          RIG
                                                                            COMBO BASE
             100
 i
200
300
400
                                                                                500
                                                  RT
              Figure 44.   GC/MS  chromatograph of base  fraction of COMBO waste.

-------
                                                0>
                                                n
RIG
                                                          COMBO NEUTRAL
 20O
                     300
400
                                                           500
                                 RT
   Figure  45.   GC/MS  chromatograph of neutral fraction  of  COMBO waste.

-------
     TABLE 40.   SELECTED PROPERTIES OF COMPOUNDS IDENTIFIED IN THE FRACTIONS OF THE
                   COMBINED API-SEPARATOR/SLOP-OIL EMULSION SOLIDS WASTE
Sample
Acid Fraction


287,





Basic Fraction





Neutral Fraction
287,





Peak
Number
229
237
277
294
315
331
342
392
414
230
237
288
315
331
342
277
294
315
331
342
392
528
Compound
Trimethyl octane
Methyl napthalene
Ethyl-methyl octane
Dimethyl napthalene
Trimethyl decane
Methyl ethyl napthalene
Trimethyl napthalene
Dimethyl undecane
Hexyl tridecane
Trimethyl octane
Methyl napthalene
Dimethyl napthalene
Trimethyl decane
Methyl ethyl napthalene
Trimethyl napthalene
Ethyl-methyl octane
Dimethyl napthalene
Trimethyl octane
Methyl ethyl napthalene
Trimethyl napthalene
Dimethyl undecane
Dimethyl phenanthrene
CAS #
-
90-12-0
—
573-98-8
-
—
879-129
-
—
-
90-12-0
573-98-8
-
—
879-129
-
573-98-8
-
—
879-129
—

Formula
C11H24
C11H10
C11H24
r H
12 12
r H
13 28
C13H14
C3H4
X J A*T

C11H24
r H
11 10
C12H12
r it
13 28
C13H14
C13H149
C11H24
r it
12 12
r H
11 24
C13H14
r it
13 14
C13H28
r H
C16H14
Genetic
Activity
X
Ml; CO
X
MO
X
X
MO
X
X
X
Ml; CO
MO
X
X
X
X
Ml; CO
X
X
MO
X
M1;C1
1. Potential genetic activity: P = promoter; I = inhibitor; CC = cocarcinogenic;
   Ml = mutagenic; MO = nonmutagenic; Cl = carcinogenic; CO = noncarcinogenic;
   X = unknown; references included in text.

-------
analysis detected trace  quantities  of additional genotoxic compounds not
identified by a chemical analysis.

     Biological and  chemical  analysis have been  employed in the present
study to evaluate the  mutagenic potential of the acid, base, and neutral
fractions  of  three  hazardous  industrial  wastes.   A  summary of  the
results obtained in  the  different biological test  systems is provided  in
Table 41.   The base  fraction of  the wood-preserving  waste  induced the
maximum  mutagenic   response   in  the   1J.   subtilis  DNA  repair  plate
incorporation  assay,   the   Salmonella/microsome   assay   (strains  TA98,
TA100  and  TA1538)  and  the  Aspergillus  methionine  assay.   In  the DNA
repair  spot  test  and Aspergillus  diploid  assay,   the  acid  fraction  of
the  wood-preserving  waste induced  the maximum  response.  One  component
of  the  acid fraction  which  may be responsible  for its  genetic  toxicity
is   pentachlorophenol   (Fishbein,   1979).   Pentachlorophenol   does  not
induce  a  mutagenic  response   in  the   Salmonella  assay   (Anderson   et
al.,   1972).  However,   in   the  recently   developed  S>.   typhimurium
strain  TA102,  the maximum response was  induced by  the  acid  fraction. The
results of biological  analysis  indicate  that  all three  fractions  of the
wood-preserving  waste   contain   genotoxic   compounds,  while   chemical
analysis  identified  compounds   that may  be  mobile  and  resistant   to
degradation.   Thus,  land treatment of  a wood-preserving waste  should  be
carefully monitored  and preferrably  conducted at  low  application  rates.
Although chemical analysis  failed to  identify any  of the constituents  of
the   storm-water  runoff   impoundment,   biological  analysis   detected
mutagenic  activity  in  all  three waste  fractions.   The maximum  mutagenic
response  observed  in  three  of four  bioassays  was  induced  by  the  acid
fraction  of   the  SWRI  waste.  Biological  analysis  detected  genotoxic
compounds  in  the SWRI  waste;  however,  these compounds  were present  in
quantities   that  were   below   the   detection   limits   of   the   chemical
analysis.    Thus,  the   storm-water   runoff  impoundment  may  be  a  good
candidate for  land  treatment because  of  its  relatively low  concentration
of mutagenic compounds.

     Chemical  and  biological  analysis agreed that the  neutral  fraction
of   the  combined API  separator/slop-oil  emulsion   solids  possessed  the
maximum mutagenic  potential.  In the  COMBO waste, biological  and chemcial
analysis  identified  the fraction  with the greatest  mutagenic  potential,
although  chemical  analysis was unable  to  identify all  of  the  mutagenic
constituents.  These  results  indicate  that  for  both   refinery wastes,
biological analysis  may provide  the  most efficient tool  for  monitoring a
land treatment facility.

     This  research   has  demonstrated  the utility  of a  combined  testing
protocol using biological  analysis to measure the  genotoxic  potential  of
waste  fractions  and  a chemical  analysis  to  define  the  type  and quantity
of   genotoxic  compounds.   These   results   have  also   demonstrated   the
inability  of  chemical analysis  to  provide a comprehensive evaluation  of
the  genotoxic  potential of  a  hazardous  industrial  waste.   While it  is
possible  that  a more  intensive  chemical analysis   could have  identified
                                132

-------
     TABLE 41.  SUMMARY  OF RESULTS OBTAINED FROM TESTING WASTE FRACTIONS IN BIOLOGICAL
                                    TEST SYSTEMS
u>
u>
     Sample
                                                     Bioassay '
DNA
SALM
BAG PM
              S9"
ASPMT
ASPDP
PENT S


SWRI


COMBO


Acid + +
Base - ++
Neutral
Acid - -
Base
Neutral
Acid - +
Base
Neutral
+
- ++ -
+
++ 0
+ 0
++ o
- ++ 0
++ 0
+ ++ 0
+ +
+ +
+
0 +
0 +
0 +
0 +
0 +
0 +
H+ + 0
>+ + Q
H + 0
t-+ + 0
M- + 0
H + 0
^ + 0
i- + 0
n- + 0
     1.   DNA  = _B.  subtilis  DNA repair assay;  SALM = £>.  typhimurium reverse
         mutation  assay;  BAG PM = E.  subtilis reverse mutation assay; ASPMT = A.
         nidulans  methionine assay;  ASPDP = A.  nidulans diploid assay.
     2.   Response:  0  = not  tested; - = <2 times background; _+ = >2 <2.5 times background;
         +  =  >2.5  <5  times  background; + + = >5 times background.
     3.   S9 = 9000 x  g supernatant from Aroclor 1254 induced rats.

-------
genotoxic  compounds  present  in  trace  concentrations,  information would
still  be  lacking as  to  the  interactions  of  the  waste  constituents.
However, the  results  also  indicate that chemical analysis is a necessary
component  of  a hazardous  waste  analytical  protocol.  Chemical  analysis
is  the  only  procedure  that  can be  used  to  identify waste constituents
and  to  verify the absence of artifacts  generated  in  the  collection  or
extraction process.
                              134

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                               SECTION 6

                         SOIL CHARACTERIZATION
INTRODUCTION

     As  the  products of our industrialized  society become more  complex,
the  need correspondingly  increases to  develop the  technology that  can
provide  for  the  safe disposal of  the  waste.   The use of  soil  to  receive
and  degrade  waste  materials has  gained general  acceptance  while  other
methods  of waste  disposal have become more  restricted for economical  or
environmental  reasons.   In  order  to prevent  further loss of  an  already
diminishing  natural resource,  land disposal  of  waste should  be  managed
in order to  provide the most  efficient  use  of the  land and  monitored  in
order  to evaluate the progress of  waste degradation.  Land treatment is  a
method   of  waste   disposal  that   is  designed  to  utilize  the  diverse
microbial  population of  a  fertile soil  for  the  degradation of  waste
constituents,  while  the  adsorptive  capacity   of  the   soil  prevents
environmental  deterioration.  EPA  (1982)  regulations  require  that  land
treatment   be  restricted   to   wastes   that  are   rendered   less   or
non-hazardous  through  chemical and biological  reactions in the soil.   In
order  to provide  information  that can  demonstrate  the  effect  of  soil
incorporation  on  the  hazardous  characteristics  of a waste,  techniques
need   to  be  developed  for   monitoring   the  mutagenic  potential   of
environmental  samples before and after waste application.

     Short-term  bioassays  have  been  proposed as a tool   for  monitoring
land  treatment because biological  analysis can  often be   used  to detect
the   synergistic,   antagonistic,   or   additive   interactions   of   the
components  of a  complex  mixture.  The first  step in establishing  a land
treatment  program  is  to  demonstrate that the waste is rendered  less  or
non-hazardous  by  soil  incorporation.    This   treatment demonstration
should  be preceded  by  an evaluation  of  the  mutagenic potential  of both
the  waste  and the  receiving soil.  This  study  reports on the  results of a
mutagenic  potential  evaluation of  the  organic  extract of  three  native
soils  used  solely  for  agricultural purposes.   These procedures may also
prove  useful  for  evaluating the  point  of sufficient  reclamation  for  a
soil contaminated by a  chemical spill.
                              135

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MATERIALS AND METHODS

Soil

     Three soils  were  selected to represent  a range in soil  texture  and
management practices.   Physical  characteristics of  these  soils  are  given
in Table 42.   A Norwood sandy clay  (Typic Udifluvent) was  obtained from
the  Texas  A&M  University  Research Farm.   This  soil had been fallow  for
four to  five  years prior to being cropped  to  a  sorghum-sudan  hybrid.  The
Norwood  soil  has  a  Class  I  land use  capability  which  indicates  this
series  has   very  few  limitations   and   can  be  used  for   intensive
cultivation  practices.  Potential  sources  of mutagenic  contaminants  in
the  Norwood   soil   include   exhaust   from   the   tractors   and   direct
application or  drift  of biocides from  sprayed  crops.  The Bastrop clay
(Udic  Paleustalf)  was collected from  a  range area  being  used  for cattle
grazing  at the  Texas  A&M University  Research Annex.  The soil  series at
this  site  consisted  of a  well-drained   fine  sandy  loam  surface  soil
approximately 45  cm thick and underlain by a massive  clay  loam subsoil.
Because  of the  limited permeability  of the  subsoil,  the Bastrop series
is primarily  used as  rangeland and  is rarely cultivated. The  range area
had  been  sprayed  with a herbicide mixture of 2,4-D and  2,4,5-T  in July
and  August preceeding  the  October collection of  soil.  Dr. W.  D.  Surge
supplied  a sample of  Sassafrass  sandy loam (Mesic  Typic  Hapludult) from
the  Beltsville Agricultural Research  Center.   This soil  had  been fallow
for  about five   years  until  being   cropped  to   corn   (Zea  mays)  and
fertilized during the  three  years prior   to  soil  collection.   Herbicide
treatments that had  been  applied at  acceptable  rates to  the  Sassafras
soil   included   atrazine,  lasso,  simazine,   paraquat,  carbofuran,  and
toxaphene.    Hydrocarbons    were   extracted    from   the   soil   using
dichloromethane  following  the  methods  of  Brown  and Donnelly  (1983).
Solvent  extractions  were  taken  to  dryness  on  a  Brinkman Bucci Rotary
Evaporator,  and  the  residue  was  dissolved in  dimethyl-sulfoxide  (Grade
1,  Sigma  Chemical Co.,  St.   Louis,   MO)  for  testing in the  biological
systems.

Biological Analysis

     The   ability  of  the  organic extract  of   soil   samples  to  induce
genetic  damage  was  measured  in a   prokaryotic   and  eukaryotic system
capable   of   detecting  compounds  that  induce  point  mutations.   The
Salmone1la/microsome    assay   of   Ames   e£   al.    (1975)   utilizes   a
prokaryotic organism to evaluate  the  capacity of a sample for inducement
of   reverse   mutations  to  histidine  prototrophy.   The  two  Salmonella
strains  TA98   (a  frameshift  mutant)  and TA100  (a  base-pair substitution
mutant)  were   supplied  by  Dr.   B.  N.  Ames   (University  of  California,
Berkeley,  CA).   The  methods used  were the  same as  Ames e£ al.  (1975)
except  that   overnight  cultures  were  prepared by inoculation into  10 ml
of  Oxoid  Nutrient  Broth  No.   2 (K  C Biological,  Lenexa,  KS).   Soil
extracts  were  tested  on duplicate plates  in  two  independent  experiments
in  the  standard  plate  incorporation  assay   at  a  minimum  of  four dose
                                 136

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TABLE 42. PHYSICAL PROPERTIES OF THE THREE SOILS
Soil

Bastrop
Norwood
Sassafrass
Sand

60.3
48.2
57.27
Silt

10.0
15.2
34.86
Clay

29.7
36.6
7.87
Texture

SCL
SC
SL
PH

6.9
7.7
5.6
Extractable
Hydrocarbon

.229
.057
.025

-------
levels with and  without enzyme activation  (0.3 ml rat  liver/ml  S.9 mix).
Aroclor  1254  induced  rat  liver  was  obtained  from  Litton  Bionetics
(Charleston,    SC).    Positive    controls    included     2     ug/plate
N-methyl-N -nitro-N-nitrosoguanidine   (Sigma)   for  TA100,  25   ug/plate
2-nitrofluorene,  (Aldrich  Chemical  Co., Milwaukee, WI)  for  TA98, and  10
ug/plate   2-aminoanthracene   (Sigma)  which   was   used  to   verify   the
functioning  of  the  metabolic  activation  system.    All   reagents   and
extracts  were  tested  for sterility;  dimethylsulfoxide  was  used  as  a
negative control.

     The  eukaryotic  test  employed  Aspergillus  nidulans  (a  fungus)  to
assess  the  mutagenic  potential  of  soil  extracts  by  evaluating  the
induction  of  foreward  mutations  at  the  methionine  suppressor  loci.
Conidia   from  four   to   five  single   colonies   of  the  methGl   biAl
(requiring   methionine  and   biotin)   Glasgow   strain  of Q  Aspergillus
nidulans  grown  for  5-6  days  on  a  complete  medium  at  37 C  were  used
for  each  experiment.   Samples  were  tested  at  a minimum  of  five  dose
levels  and  four exposure times  with and  without metabolic  activation.
The  procedures  used  were  the  same  as  Scott  et al.  (1978).  Mutant
colonies  were  assayed  by spreading  exposed  cells  on a  methionine-free
medium.   Mutant  colonies  were  scored after  incubation  for 5 days  at
37 C.   Colonies  were divided by  colony morphology  into three Classes,
A,  B,  C,  and  the total  number of mutant;, colonies.  Each  of  the  three
classes  is  believed  to  involve two  genes (Scott  and Alderson,  1970).
The  morphology  of Class  A colonies  appear  green,   Class  B brown,  and
Class  C  green with  a white hyaline  edge.   The  frequency of  mutations
induced  by the soil  extract was  determined by subtracting  the  frequency
of  spontaneous mutations  which  occurred  in  Class A,  B, C or  the  total
from  the  total  mutation  frequency  in Classes A,  B,  C and  the  total.   A
sample  was  considered  positive  if  a positive  slope  occurred on  the
mutation  induction curve,  or the induced  mutation frequency for at  least
two   exposure  times  was  more  than  twice   the  spontaneous   mutation
frequency.    Positive   controls  included   8-methoxypsoralen   (Sigma),
8-methoxypsoralen    plus    near   UV-light    without    activation,    and
benzo(a)pyrene  (Aldrich)  with metabolic activation.  Only the  Bastrop and
Norwood  soil  extracts were tested in the  Aspergillus  assay.

RESULTS AND DISCUSSION

      The   results  from   testing   each   of   the  three  soils  in  the
Salmonella/microsome  assay  (Table  43, Figures  46 and 47)  indicate that
all  soil  extracts contained mutagenic activity,  with the greatest amount
of  activity  being detected  in  the  Bastrop  soil.  In strain  TA98  with
metabolic   activation,  1,000   ug   of   the   extract   of   the   Norwood,
Sassafrass,   and  Bastrop   soils induced  67,  119,   and  469  revertant
colonies,  respectively.  The mutagenic  activity  of  the organic extract
from  one  gram  of  the Bastrop  soil  was greater  than  the  Norwood  or
Sassafrass soils  by almost  two orders  of magnitude  and   less  than  the
condensate from  the  smoke  of one  cigarette  by  one  order of  magnitude
(Figure 48).
                                138

-------
     TABLE 43.   MUTAGENICITY OF ORGANIC EXTRACTS OF THREE SOILS AS MEASURED WITH
               S.  TYPHIMURIUM STRAINS TA98 AND TA100 WITH AND WITHOUT METABOLIC
VO
ACTIVATION
Total his Revertants (Mean + SD)
TA98
Soil

Norwood






Sassafrass






Bastrop






Dose/plate
(pg)
0
10
50
100
500
1000
5000
0
10
50
100
500
1000
2500
0
10
50
100
500
• 1000
5000
-S9

26 + 6.9
23 + 3.3
NT*
27 + 6.9
NT
32 + 8.3
51 + 23
19 + 3.1
25 + 5.0
37 + 6.2
31 + 21
59 + 10
69 -i- 14
112 _+ 20
23 + 5.8
28 + 0.8
47 + 8.0
183 + 81
256 + 22
423 + 34
515 +256
+S9
.-
32 + 7.7
38 + 9.2
NT
33 + 11
NT
67 + 16
122 + 45
21 + 5.3
30 + 7.6
42 + 4.9
36 + 6.7
61 + 5.6
199 + 35
179 + 16
35+6.7
48 + 6.6
62 + 3.2
95 + 29
264 + 90
469 + 96
716 + 108
TA100
-S9

88 + 14
76+9.7
NT
87 + 15
NT
116 + 19
88 + 14
106 + 16
115 + 11
172 + 43
185 + 80
251 + 78
265 + 115
276 +_ 18
124 + 22
121 + 23
143 + 56
142 + 50
306 + 33
416 + 13
605 + 72
+S9

130 + 27
122 + 49
NT
107 + 35
NT
140 +8.1
188 +_ 52
117 + 17
146 + 20
147 + 25
117 + 18
186 + 28
288 + 65
NT
94+12
101 + 15
111 + 27
142 + 52
381 + 119
429 + 74
NT
     *NT  -  Not  tested.

-------
  500
6300
  100
                                        UNAMMENDED  SOILS
                                           TA98 +S-9
                                         O BASTROP
                                           SASSAFRASS
                                         o NORWOOD
                                                      2X-BKG
                      0.5                1.0

                         DOSE/PLATE (mg)
                                                        5jO
Figure 46.
               Mutagenic  activity of organic extract of three agricultural
               soils as measured with £.  typhimurium, strain TA98,  with
               metabolic  activation.
                                 140

-------
   500-
   300
o
o
5
                              UNAMMENDED   SOILS
                                 TA-IOO +S-9
                               Q BASTROP
  SASSAFRASS
o NORWOOD
                       0.5               1.0

                           DOSE/PLATE  (mg)
       Figure 47.  Mutagenic activity of organic extract of three
                  agricultural soils as measured with S_. typhimurium,
                  strain TA100, with metabolic activation.
                                141

-------
             MUTAGENIC ACTIVITY OF  I g. eq. SOIL EXTRACTS AS
             COMPARED TO CIGARETTE SMOKE CONDENSATE
               S9
-S9
S3
                                         -ONE CIGARETTE
                                          (from Kler et. al., 1974)
                                  -BASTROP SOIL
                    -SASSAFRASS SOIL
                  -NORWOOD SOIL
               10      100   1,000   10,000

                  TA98 hl8*revertant8

          Figure 48.  Mutagenic activity of one gram of soil as compared to cigarette
                   smoke condensate.

-------
     The dose-response  curves  for  all three  soils in  strain TA98  with
and without metabolic  activation (Figures 46 and 49)  indicate that  while
direct  acting  mutagens  were  detected   in  the  Sassafrass  and  Bastrop
soils,  the   addition   of  metabolic  activation   to   the   assay   system
increased  the number of  revertant colonies.   The  addition of metabolic
activation  produced  almost  twice  the  number  of   revertant  colonies
obtained in  the absence  of metabolic activation  in both  the  Sassafrass
and Norwood  soils  in  strain TA98  at  the  highest  dose levels.   For the
Bastrop soil,  there was  only  a  slight   increase in the total number  of
revertant  colonies  when  metabolic activation  was  added   to  the  assay
system (Table 43).

     The organic  extracts  of  the Bastrop  and  Norwood soil  were  also
tested  in  an  eukaryotic  bioassay  using  A.  nidulans.  This bioassay
has been found  to detect  95% of  carcinogens as mutagens and is  sensitive
to  some  compounds  not  detected  in  the  Salmonella  assay  (Scott  et
al. ,  1982).   The  results  presented in  Table 44  and  Figures  50  and  51
indicate  that  the  organic  extract  of  the  Bastrop  and  Norwood  soils
induced increased  mutation frequencies with increasing exposure times  in
the  absence  of  metabolic  activation.   The  frequencies  of  mutations
induced by  the  two soils were  comparable,  although the Norwood soil was
tested  at  a  dose level  ten  times greater  than the  Bastrop soil.   For
both   soils,   survival   of  Aspergillus  in   the   absence   of  metabolic
activation  was  decreased  as   the  exposure   time  or  dose   level  was
increased.   The  effect of  increasing dose  level  on  the frequency  of
induced  mutations   was  less  conclusive.    In  the   Norwood  soil,  an
increased  mutation   frequency  was  observed  as   the  dose   level  was
increased, while this effect  in the Bastrop  soil was  not observed.

     When  metabolic activation  was  added   to  the  system, the response
obtained  in  the  Aspergillus  assay was  much  less  conclusive  (Table  44
and  Figures  50  and 51).  Survival  of  Aspergillus was not  appreciably
altered at increased dose levels  or  exposure times.   In  addition,  the
frequency  of mutations  induced  by the  extract  of either soil  was  not
significantly affected  by increasing the dose  level or exposure  time  in
the  presence of  metabolic  activation.   Thus,  while  mutagenic activity
was detected in the organic  extract of  the  two  soils  in  the  absence  of
metabolic  activation,   the addition  of  metabolic  activation reduced  or
eliminated this effect.

     An  analysis  of   the  extracts  of   the  two   soils  using  gas
chromatographic  and mass  spectrometric  techniques detected  the presence
of  several  low molecular weight  chemicals.  A  total of thirteen compounds
were  identified in  the Norwood  soil  and eight compounds  in  the  Bastrop
soil  (Table 45).   The  chromatographs of the  Norwood and  Bastrop  soils
are provided  in Figures  52 and 53, respectively.   All thirteen compounds
identified  in the  Norwood soil  are  saturated alkanes ranging from C,,
(tetradecane)  to  C    (docosane).   Eight  compounds  were   identified  in
the Bastrop  soil  including eight  alkanes,  four of which  were  saturated
n-alkanes.    The  three  additional  compounds  identified in  the  Bastrop
                                 143

-------
   500
o
r  300
o
3
    100
                    UNAMMENDED SOILS
                       TA98  -S-9
                     a BASTROP
                     A SASSAFRASS
                     o NORWOOD
                       as                to
                            DOSE/PLATE  (mg)
                              2.0
         Figure 49.
Mutagenic  activity of organic  extract of three
agricultural soils as measured with S_. typhimurium.
strain TA98, without metabolic activation.
                            144

-------
Ln
    TABLE 44. EFFECT OF  INCREASING  DOSES  OF  ORGANIC EXTRACT OF BASTROP AND NORWOOD SOILS
              ON  SURVIVAL AND  INDUCED  MUTATION FREQUENCY IN ASPERGILLUS NIDULANS
                         WITH  AND   WITHOUT METABOLIC ACTIVATION
Dose/Plate
(pg)
-S9 (Exposure Time - 40 min
Surviving Induced Mutation
Fraction Frequency (x 10 )
+S9 (Exposure Time - 20 min)
Surviving Induced Mutation^
Fraction Frequency (x 10
Bastrop Soil

   10
   18.75
   25
   37.5

Norwood Soil
                     0.90
                     0.80
                     0.71
                     0.61
144
288
566
755
1133
0.94
0.75
0.69
0.52
0.41
0.55
1.2
0.29
1.3
                                         <0
                                          0.53
                                          0.74
                                          2.2
                                          2.8
1.6
1.1
0.99
0.95
                                                        0.97
                                                        0.92
                                                        0.99
                                                        1.00
                                                        0.97
<0
<0
<0
 0.33
                                        <0
                                         0.37
                                         0.40
                                        <0
                                        <0

-------
   i64
   lO"5
g io€
a
UJ
S io7
o
UJ

8
                                 p.- —
                                       BASTROP SOIL
                                         50 *g/pt


                                    +S-9          -S-9

                                  •	•        o	o

                                  81	B        X	K
                                          X
                                                              100^
                                                              10
                                                                 (O
          10  20   30       SO            80


                       MINUTES EHX5SURE TIME
 Figure  50.  Induced mutation frequency and fractional survival in A.

            nidulans  following exposure to organic extract of Bastrop

            soil.  Data based on results from two independent

            experiments.
                             146

-------
     I04
     10
    i67J
 O
 UJ
            o— .,
NORWOOD SOIL



566 icg/pt
+S-9 -5-9


B    H   H
 ~""~~X--«. x-
         ^^  "X1" ••-••»
,00-
                                                        o
                                                        I
                                                    K)   £
            10   20   30  40       60       80

                         MINUTES  EXPOSURE  TIME


Figure 51.  Induced mutation frequency and fractional survival in
            A. nidulans following exposure to organic extract of
            Norwood soil.  Data based on results from two independent
            experiments.
                            147

-------
             TABLE 45.  LIST OF COMPOUNDS IDENTIFIED IN NORWOOD AND BASTROP  SOILS
00
Soi 1 Compound
Norwood Tetadecane
Pentadecane
Methyl hexadecane
Hexadecane
Dimethyl hexadecane
Heptadecane
Trimethyl hexadecane
No octadecane
Tetramethyl hexadecane
Nonadecane
Eicosane
Heneicosane
Docosane
Formula
CH3(CH2)12CH3
CH3(CH2)13CH3
C17H36
CH3(CH2)14CH3
C18H38
CH3(CH2)15CH3

CH3(CH2)16CH3
C20H42
CH3(CH2)lgCH3
CH3(CH2)19CH3
CH,(CH0)onCH,
Genetic ,
Activity
P;CC
X
X
I
X
X

CC
X
X
P;CC
X
X

-------
                                TABLE 45 CONTINUED.
Soil
Bastrop






Compound
Dodecanol
Ethyl methyl pentanol
Dimethyl undecane
Trimethyl decane
Octadecane
Trimethyl dodecane
Nonadecane
Benzenedicarboxylic acid
Eicosane
Heneicosane
Docosane
Fo'rmula
C12H26°
C8H18°
C13H28

C18H38
C19H40
C8H16°4
C20H42
C22H46
Genetic
Activity
P;CC

X
X
CC
X
MO; CO
P;CC
C
1. Probable genetic activity: P = promotor; I = inhibitor; CC = cocarcinogenic
   X = unknown; References listed in test.

-------
Ol
o
           pic
                                                             NORWOOD SOIL
             400       5OO        600       700        800       900       1000


                                              RT
                Figure 52.  GC/MS chromatograph of organic extract  of Norwood soil.

-------
Ln
      RIG
                                                            BASTROP  SOIL
        200        300         4OO        500        600        700         800




                                             RT




            Figure 53.  GC/MS chromatograph of organic extract of Bastrop soil.

-------
soil  include  two  alcohols,  dodecanol  and ethyl  methyl  pentanol,   and
benzene dicarboxylic  acid.   The  conclusive determination  of the  source
of the compounds identified  in the soil  extracts  is difficult given  the
limited amount of  available  information.  A chemical characterization of
the resin-  and asphalt-free  components  from a  mineral soil by Morrison
and Bick  (1967) identified  a  number  of n-alkanes,  n-alkan-2-ones,  and
primary n-alkanols.  The  n-alkanes  comprised  approximately  6.4%  of  the
wax fraction  of the  soil and  consisted of a mixture  of n-alkanes with
carbon  numbers  ranging  from  16  to  33  (Morrison  and Bick,  1967).   In
addition,    Ogner   and   Schnitzer   (1970a)   identified   normal  plus
branched-cyclic  alkanes  in  the  water-soluble  soil   fulvic  acid.   An
alternative  source  of   the  compounds   identified  in  the  Norwood  and
Bastrop soil  is  the  particulate matter from  diesel   tractors  used  to
cultivate the  soil.   One of the major  organic constituents  identified in
diesel  particulate  matter  is  n-tetradecane   (Yergey  e£  al.,   1982).
Although  this  and  other alkanes  have  been  identified  in  particulate
matter, the  absence  of the more complex polycyclic  aromatic hydrocarbons
indicates  that  the  source  of  the  alkanes  in  the  soil  extracts   is
probably not diesel particulate.

     The Bastrop soil  also contained several  alkanes  in addition  to  two
alcohols and  benzene dicarboxylic acid.  The most  probable source of  the
alkanes  is   the  waxy  fraction of  the  soil (Morrison and  Bick,  1967),
whereas  the  alcohols  may be  hydroxylated  metabolites  of  soil  alkanes.
The   initial  oxidative   reaction  in   alkane  decomposition   generally
involves  one  terminal  methyl  group and  results in the formation  of  the
corresponding  alcohol, aldehyde,  and  fatty acid (Rowell,  1977).   Esters
of  benzene  dicarboxylic acid have been identified  in  soil organic matter
(Cifrulak,  1969)  and   in  the  fulvic  acid  fraction of soil  (Ogner  and
Schnitzer,  1970).   Ogner  and  Schnitzer  (1970)  state   that  the origin of
these  compounds   is   uncertain   although  they  may  have  been  produced
biosynthetically.  One  potential  source  of  the  benzenedicarboxylic  acid
in  the Bastrop soil is  the degradation of  2,4-dichlorophenoxyacetic acid
(2,4-D).   The primary  pathway   for   2,4-D biodegradation  is   through
dichlorocatechol with  complete dehalogenation usually  following  cleavage
of  the  benzene ring  (Bourquin   and   Gibson,   1978).   It  is  possible,
however,  that dehalogenation  of  the 2,4-D in  the Bastrop  soil  preceded
ring  cleavage, resulting  in  the  formation of  benzenedicarboxylic acid.
Benzenedicarboxylic  acid  may  also  have reached  the  Bastrop  soil as  a
result of  its use  as  a plasticizer,  pesticide  carrier  (Fishbein,  1979),
or as  a trace  contaminant of  the  pesticides  (EPA,  1980).

     The results  from the biological analysis  of  the  organic  extract of
three  soils  indicate that mutagenic activity  may  be associated with  the
waxy  fraction (alkanes).   Mutagenic activity was  detected  in all three
soils,  with  the  greatest  amount of  activity  detected  in the  Bastrop
soil.   The  extract  of the Bastrop  and  Norwood soils   induced  increased
mutation  frequencies  in  both  the  Salmonella  and  Aspergillus  assays,
although   the  mutagenic   activity   in  Aspergillus   was   significantly
reduced  in  the presence  of   metabolic activation.   The  discrepancies
                                 152

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between  the  results  of  the  bioassays  may have  resulted  from several
factors. While  the sensitivity  of the  Aspergillus  bioassay is  reported
to  be  96%  (Scott £t  al.,  1982),  there  are  some  carcinogens  which
give   a   positive   response    in   Salmonella   and   no   response    in
Aspergillus   (Bignami  e£  al.,   1980).   It   is   also  possible   that
Aspergillus,   which   is  more  metabolically  competent   than   Salmonella
(Dunkel, 1981), was  able  to detoxify mutagenic compounds with  the  aid  of
microsomal activation.

     Using chemical  analysis,  only saturated  n-alkanes were detected  in
the   extract  of   the   Norwood   soil.   Of   the   identified   compounds
n-tetradecane  has  been  found   to  have  promoting  activity  (Lankas   et.
al.,    1978)   and    cocarcinogenic    activity    with   benzo(a)pyrene
(Goldschmidt, 1981);  whereas,  octadecane and eicosane  were  also found  to
have  cocarcinogenic  activity,  and hexadecane  acted as  an  inhibitor  of
benzo(a)pyrene  (Goldschmidt,   1981).   The  mutagenic   activity in   the
Bastrop  soil  may  have  been   produced  by  degradation products  from
previously  applied  herbicides.  Benzene  dicarboxylic  acid, one of   the
constituents  of  the  Bastrop  soil,  is  non-mutagenic  in the  Salmonella
assay  (Omori,  1976).  In addition, while  2,4-D,  2,4,5-T, and mixtures  of
these   compounds    gave   negative   results  in   the  Salmonella  assay
(Anderson  e_t al.,  1972),  a  review  of  the  literature  by  Grant  (1979)
indicates  that  component(s)  of  2,4,5-T  can  cause  various  types  of
chromosome  damage.  Interactions  of   the metabolites  of biodegradation
represent  another  possible  source  of  the mutagenic   activity in  soil
extracts.  Catechol,  a frequent metabolite  from the  oxidation  of aromatic
hydrocarbons  in  soil  (Gibson,   1971),   has  been  found to  enhance  the
mutagenicity  of polycyclic aromatic  hydrocarbons (Yoshida  and Fukuhara,
1983).  Other  soil  metabolites  including  dodecanol,   octadecanol,   and
eicosaine  have  been  found  to  have cocarcinogenic activity  (Goldschmidt,
1981).

     The biological  analysis  of the organic  extract of  three  soils  used
solely  for  agricultural   purposes  has  demonstrated   the   presence  of
mutagens and potential  carcinogens.   These results  are in agreement  with
those  of  previous reseachers  who have demonstrated  that   agricultural
soil  (Goggelman and  Spitzauer,  1982;  Withrow,  1982) and municipal water
obtained   from   an  agricultural  area   (Heartlein   zt_  al. ,   1981)   may
contain  significant  quantities  of  mutagenic  activity.   In  addition,
epidemiologic  studies  have  identified  a  higher   incidence  of certain
types  of  cancer   in  the  residents  of  rural  communities (Lilienfeld  e_t^
al.,   1972;  Higginson,   1980)  which  may  be   a  result  of  the  use  of
agricultural  chemicals.   A chemical  analysis  of  two of the  three soils
used  in this research was  unable  to  conclusively identify  the mutagenic
contaminants.   However,   the past  history  of  these  soils indicates  that
the  most  probable  source  of mutagenic  activity is  trace  quantities  of
the  partially oxidized residues from  previous  biocide  applications.  It
also  appears that the mutagenic activity of  these  trace contaminants may
have been  enhanced by the presence of  promotors and  cocarcinogens.
                                 153

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     This  research  has  defined the  level  of background contamination  in
three  soils.   While  chemical  analysis  was  unable   to   identify  any
mutagenic  compounds,  biological  analysis  indicated that  the soil  that
had  received  the  most  recent  applications  of  herbicide  yielded the
greatest  amount  of mutagenic  activity. Natural  sources cannot be ruled
out  as  being  responsible  for the  elevated mutagenic activity  of the
Bastrop  soil;  however,  the  presence  of  direct-acting mutagens  in the
soil  indicates  an exogenous  source,  since  natural  mutagens  such  as
mycotoxins  and   plant   toxins  are  indirect  acting   (Garner  e_t_  al.,
1982; Brown  and  Dietrich,  1979). The presence of organic mutagens  in the
soil does  not present  a human health  risk  provided these materials are
retained  in  the  soil.  Indeed, organic mutagens  in soil may  enhance the
capacity  of  soil microorganisms to  degrade  complex molecules  (Poglazova
et  al.,   1967).   These  results  have  also  demonstrated the  utility  of
a  combined testing protocol.   Biological analysis  defined the level  of
mutagenic  activity  in each soil, while chemical  analysis  indicated  that
the activity was  not  produced by an  artifact, e.g., histidine or  solvent
residues,  from the  collection  or extraction  process.
                                 154

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                               SECTION 7

                 QUANTIFYING SOIL EXTRACTION PROCEDURES
INTRODUCTION
     Industrial  activities  generate  large  quantities  of hazardous waste
that must be  disposed  of  in  an  economical  and  environmentally sound
manner.   These  wastes have  been shown  to  contain constituents that may
be mutagenic,  carcinogenic, or  teratogenic.  Chronic  exposure of large
populations  to  genotoxic  compounds   in hazardous  wastes  represents   a
serous threat to public health.

     Genotoxic  compounds  constitute  a relatively small  group of agents
which  are  highly  specific  for  nucleic acids  and  produce  deleterious
effects  in  genetic elements at  subtoxic concentrations (Brusick, 1980).
An  environmental   mutagen   is  an   agent   that   is  released  into  the
environment  and  can  alter  the  genome  or  the  proper  functioning  of  a
genome  (Plewa,  1981).   Environmental  mutagens   have  the  potential  of
changing  human   genetic   material  by  inducing  mutations.   Mutations
affecting  somatic  cells may  induce  cancer,  heart  disease,  aging,  or
other  illnesses  (Ames, 1979),  whereas mutations affecting germ cells may
induce birth defects, sterility, or  other  teratogenic effects (Brusick,
1980).  A carcinogen  is  an agent  that significantly  increases the yield
of malignant neoplasms  in  a population (Clayson, 1962).  A teratogen  is
an agent  that acts  during pregnancy  to produce  physical  or  functional
defects  in  the  embryo,  fetus, or  offspring (Meyers and  Beyler, 1981).
Evidence  that most carcinogens are mutagens lends validity  to  the theory
that cancer  can  be caused by somatic  muations or  damage to  DNA (Brusick,
1980).

     Hazardous  waste  must be  disposed  of  properly in  order   to  prevent
environmental contamination  and  the transmission  of genotoxic  effects  to
future   generations.     The   usual   methods  for  disposal  have   been
incineration,  landfilling,  and  deep  well  injection.   Because  these
techniques  of waste  disposal  are  not economical and/or do not  provide
for  the  desired destruction of  genotoxic  constituents, their  utility  is
limited.   Using  non-destructive  methods of waste disposal on the  land
results  in  sites  that  must  be  permanently removed  from  productivity.
However,  land  treatment  of   a  waste  can  result in  land  that  may  be
reclaimed  and may  provide  for  the destruction  of the genotoxic  organic
waste  constituents (Donnelly  and  Brown, 1981).   When  properly designed
and  managed, a  land  treatment  facility  provides for  the  recycling  of
                                  155

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nutrients  and  water, while  toxic organic  constituents are retained  and
degraded  in the  upper  layer  of  soil or  soil treatment  zone (Brown  e_t
al.,  1982a).   In  order   to   prevent  contamination  of  the  environment
with  mutagenic   compounds,   land  application  of  hazardous  waste   is
restricted  by  Environmental  Protection  Agency  (1982)  regulations   to
include  only those  wastes  in which  the  hazardous  constituents can  be
completely  degraded,  transformed, or  immobilized in  the soil treatment
zone.

     The  present  research  is an  integral part  of  a  larger  project  to
evaluate  land  treatment  as  an  environmentally  sound  alternative   in
hazardous  waste  disposal.  This  research  was  designed  to  evaluate  the
efficiency  of   extraction  procedures  for  recovering  mutagenic  activity
from  soil  using  the   Salmonella/microsome  assay  (Ames  e±  al.,   1975)
and  high performance  liquid chromatography  (HPLC)  analysis.   Microbial
test  systems  such   as  the  Salmonella/microsome  assay  can be  used  to
evaluate  the  potential  of  hazardous  waste  constituents   for  causing
genetic  damage  and,  also,  to  accurately predict the fate  and  mobility of
mutagenic  constituents  when hazardous wastes  are  land applied (Donnelly
and Brown, 1981).

     Hazardous  industrial  wastes contain  a  complex  mixture of chemicals
which may have additive,  synergistic,  or  antagonistic interactions with
regard  to  their  toxic or  genotoxic effects.   These  interactions  are
further  complicated  when  wastes  are  mixed  with  the  soil.   Chemical
analysis  alone  may   fail  to  account for the  transformations in  the soil
or  various  interactions   which  occur  between  chemicals  in  a  complex
mixture   (Donnelly  and  Brown,  1981).   The   Salmonella/microsome   assay
provides  a  rapid  and  inexpensive  means  of  measuring the mutagenic
potential of chemicals  in a soil extract.

     This  segment of  the  research  evaluated  two  extraction procedures
and  determined which  method  most   efficiently  extracted  the mutagenic
activity  from  the soil.  An efficient extraction procedure  is a  critical
element  for  monitoring a  land treatment  facility.   Levels  of mutagenic
activity  at a  chosen  site must  be  monitored  in  order  to  evaluate  the
degradation rate of toxic organic chemicals.

MATERIALS AND METHODS

     The  procedures  for this  study  involved  the selection and treatment
of  the  soils  and  the organic  compounds.  A comparison  of  soil extraction
procedures  and their  reproducibility  on  treated  soils was evaluated
using  the  Salmonella/microsome   assay  and  HPLC  analysis.    Statistical
analysis  was  by  the  ANOVA procedure and  the  Duncan  Multiple Range test
(Steel and Torrie, 1976; Freund, 1982).
                                  156

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Selection of Mutagenic Compounds and Soils

     Most of  the experiments involved  the  use of either  2-nitrofluorene
(Aldrich, Milwaukee,  Wis)  or benzo[a]pyrene  (Sigma,  St. Louis,  Mo.).   In
addition, a  complex  waste  mixture of  known mutagenic activity was  also
used  for comparison.  The  Salmonella/microsome  assay is  sensitive  to
2-nitrofluorene  (2NF),  benzo[a]pyrene  (B[a]P)  (McCann  and Ames,  1977),
and  the  complex waste  mixture, i.e.,  a wood-preserving  bottom  sediment
(Donnelly  et_  al.,   1982).    B[a]P and  2NF  were selected  because  they
are nonpolar  and polar  compounds, respectively;  therefore,  they  may  have
different  binding   affinities   to  the  soil.    This  may  effect   the
efficiency of the extraction  procedures  to  recover the  cmpounds.

     Two  soils  including a  Norwood sandy  clay  (Typic Udifluvent) and  a
Bastrop   sandy   clay  loam   (Udic  Paleustalf)   were  used.   The   soil
characteristics are given in  Table 42.

     Analysis  of  specific   organic  compounds   in  the  soils   that   may
influence  the  mutagenicity  of   chemical  additions  to  the  soil  were
carried out  by  the  U.S.  Environmental  Protection Agency  Robert S.  Kerr
Environmental  Research  Laboratory.   Research on  the mutagenic  activity
of untreated  soil  is necessary because  information  in the  literature  on
this  topic  is  almost nonexistent.   Chemical constituents  found in  the
soil  may  enhance  or  reduce  mutagenic   activity   or  may effect   the
efficiency of extraction.  A comparison was  made between  the mutagenic
response of the  known mutagens, the soil extract, and  the known  mutagens
or  waste after  soil incorporation  to  determine  the  effect  of  soil
incorporation on the mutagenicity  of these  mixtures.

Soil Preparation and  Chemical Addition

     Each soil  was sieved  through a  4  mm  sieve  and  oven  dried at 100  C
for  24  hours.   To prevent  biological  degradation  from influencing  the
test results,  the soils  were  autoclaved before chemical  addition.   The
soil was  measured  into  glass  jars  and heat  sterilized  for  90 min  at
121 C  and 15  psi for  three consecutive days.   The  soils  were brought
to  field  capacity  of  18  and  22% for  the  Norwood and  Bastrop  soils,
respectively, with  sterile  deionized water.   All soils were checked  for
sterility by plating on nutrient agar plates before chemical addition.

     The chemicals  that  were used were  of  the highest purity  available.
A  description of the chemicals used  in this  segment of the research  is
provided in Table  46. Treatment levels  were  selected to  fall  within  the
detection limits  of  the  Salmonella/microsome test.   Soils were treated
with three  different dose  levels of the chemical;  the dose levels were
selected  from  the  optimum  response  in the  Salmonella/microsome  assay.
The dose  at which the maximum  mutational response occured was  the  medium
dose  level.   The high  and  low dose  levels  were an  order of magnitude
higher  and  lower  than the  optimum dose level   for  B[a]p  (5  ug/plate).
For 2NF,  the  high dose level was  half  an  order  of magnitude higher  than
                                157

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                   TABLE 46.  DIAGNOSTIC MUTAGENS USED TO EVALUATE THE EFFICIENCY OF  EXTRACTION
                                                    PROCEDURES .
             Compound
Structure
Mutagenicity
Polarity    Source
Ul
oo
             2-Nitrofluorene
                      Direct Acting      Polar
                             Aldrich,
                             Milwaukee,  WI
             Benzo(a)pyrene
                      Indirect Acting    Nonpolar  Sigma,
                                                   St.  Louis, MO

-------
the optimum  dose,  and the low dose  level was an order  of magnitude  lower
than  the  optimum  dose   (25  pg/plate).   Soils  were  spiked  with  the
chemicals or wood-preserving waste and incubated  in  a  closed  environment
at room  temperature  for different time intervals  to be studied  prior to
extraction.

Extraction Procedure and Sample Preparation

     Hydrocarbons were  extracted  from the soil using a Waring laboratory
blender  following procedures  of  Brown and  Donnelly  (1983). A  Soxhlet
blender  technique was  used  on   the  wood-preserving bottom  sediment  to
compare  the  efficiency  of  both  extraction  techniques  (Brown  e_t  al.,
1982b).   The  extracting   solvent,   dichloromethane,  was    removed   by
evaporating  the  sample   to  near  dryness  on  a  Brinkman-Bucci  Rotary
Evaporator.  Dichloromethane  was  used to transfer  the  organic residue to
a glass  culture  tube.   The sample was taken to dryness under  a stream of
nitrogen.   The  dried extract  was dissolved  in 5  ml dimethyl  sulfoxide
(Sigma,  St.  Louis, Mo.)  and brought  to  its  original  concentration  with
reference  to the  low,  medium,  or  high  dose  level.  The  samples  were
filtered  through  a 0.45  pm millipore  filter  (Millipore Corp.,  Bedford,
Mass.)  to remove  soil  particles.   The  sample was  serially  diluted  in
dimethyl  sulfoxide  to  a  10    dose  level so  that  four concentrations  of
each soil dose level were  tested  in  the mutagenicity  assay.

Bioassay

     The  Salmonella/microsome  mutagenicity  test  was   used  to  measure
the mutagenic  potential  of  the  extracted  samples.   Dilutions of  each
extract  were tested  with  Salmonella  typhimurium strain  TA98  supplied
by  Dr.   B.  N.   Ames,   University   of   California  at  Berkeley,   CA.
Salmonella  TA98  is  a  frameshift  mutant  which  contains  a  histidine
D3052 mutation  and a deletion which  invokes  a requirement  for  biotin.
Frameshift mutations  occur by shifted pairing  in  repetitive sequences  of
DNA.   The  mutation   is in  a  reverse  direction  to  independence  from
histidine  auxotrophy.    This   bacterial   strain   is  capable  of  being
reverted  from  a  histidine  requirement  back  to  prototrophy   by  a  wide
variety of mutagens.

     Overnight bacterial  cultures were grown in Oxoid  Nutrient Broth No.
2  (KG Biological,  Lenexa,  Kansas)  with  shaking  at 37 C  for 16  hours.
Liver homogenates  (S9 from rats  induced  with  a polychlorinated  biphenyl
mixture   [Aroclor  1254])   (Litton  Bionetics,  Charleston,  S.C.)   were
incorporated into  the  test  system  to allow  indirect acting  mutagens  to
reach  their ultimate  mutagenic  form.   This  incorporates  an  important
aspect  of mammalian  metabolism  into  the  test,   thereby  allowing  those
carcinogens  requiring  metabolic  activation  to be  as easily  detected  as
mutagens.   The  procedures used  for the  preparation of  the  S9 mix  are
described  by Ames  e_t  al.   (1975).   Positive,  solvent,   and  sterility
controls  were  included  in each   test  to  act as  an  internal  control  for
the bioassay, to  demonstrate the sensitivity of  the test system,  and  to
                                  159

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demonstrate the functioning of the metabolic activation  system.

High Performance Liquid Chromatography

     Samples  were  assayed  using  HPLC  to  quantify the  recovery of  the
chemicals  from  soil.    Techniques  used for  HPLC  are  as  described  by
Schram  (1980)  and  Yost  et_  al.  (1980).   The  analysis  of  polynuclear
aromatic hydrocarbons  utilizes  octadecylsilane  bonded stationary  phases
and acetonitrile/water  as  the mobile phase  (Belinki,  1980).   To  optimize
the mobile  phase composition, an  isocratic composition of  acetonitrile/
water  was  used.    This  compound  is   favored   as   it   permits  faster
separations   than   other   solvent  systems   (Donahue  e_t  al. ,   1978).
Acetonitrile has a much lower viscosity than  does  methanol;  therefore,  a
faster flow rate  can be used without exceeding the pressure  limit  of the
column.   Also,  acetonitrile   has  a greater  ability  to  dissolve  many
polycyclic hydrocarbons  than  other  solvents,  thus  greater amounts  can be
loaded into the system per injection (Donahue  et_ a_l.,  1978).

RESULTS AND DISCUSSION

     In  order  to  determine  the  affect  of  storage  on the extraction of
mutagenic activity from soil, the polar compound  2-nitrofluorene or  the
nonpolar  benzo(a)pyrene  was  added to the  two   soils   and extracted
following  24   hours  or  7  days   of  storage  at 0 C.   The  results  from
biological  analysis   of the   extract  of  the Norwood or  Bastrop  soils
amended  with  the  two  compounds  indicated  that  there was no  statistical
difference  (p<.01)   between   samples  stored  for  24 hours   or  7  days.
These  results  demonstrate  that  binding of chemicals  to  soil particles
will  not affect  the mutagenic  activity of  sterile  soil  stored at  0  C
for at least one week.

     The results from  the  biological analysis of  the extract of the two
soils amended  with 2-nitrofluorene  are  provided in Table 47  and Figures
54  and  55.   At  the  optimum dose  level  (25 ug),  2-nitrof luorene induced
85  revertants/ug,  while the  extract  from 500  mg  of  the  Norwood  and
Bastrop  soils  induced  .13 and .11  revertants/mg, respectively.   At  the
highest  treatment  level (25  mg  2NF/50  g soil),  the  2-nitrofluorene  and
2-NF  amended  Norwood  and  Bastrop soils  induced  5.4,  6.1,   and  5.2
revertants/mg,  respectively.   All  of  these  values  fall  within  their
respective  standard   deviations.  Both  the  10    and  10    dilutions  at
the  high  treatment  level  for  the  two soils fell  slightly  below  the
anticipated level  for  2-nitrofluorene.  At  the medium and low treatment
levels,  the  mutagenic  activity  of the  extract  of  the  2-NF   amended
Bastrop  and Norwood  soil was  within the standard  deviation for  the pure
chemical  at all  dose  levels.   These   results indicate  that  a   blender
extraction  of   soil  amended  with  the   direct-acting   polar   compound
2-nitrofluorene will provide  complete  recovery of  the mutagenic  activity
in  the soil.
                                   160

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TABLE 47. MUTAGENIC ACTIVITY, AS MEASURED WITH S. TYPHIMURIUM TA98, OF
2-NITROFLUORENE , AND THE SOLVENT EXTRACT OF THE NORWOOD AND
BASTROP SOILS AMENDED WITH VARIOUS LEVELS OF 2-NITROFLUORENE
Sample
None

2-nitrof luorene
(high)


(med)



(low)
-


Dose/Plate
(mg)
0
-1
-2
-3
0(0.5)
-1(0.05)
-2(0.005)
-3(0.0005)
0(0.25
-1(0.025)
-2(0.0025)
-3(0.00025)
0(0.025)
-1(0.0025)
-2(0.00025)
-3(0.000025)
2-Nitrof luorene Bastrop
Soil
-
-
2711 + 478
- '
-
-
2560 + 409
2122 + 465
682 -i- 173
123 _+ 30
2122 + 465
682 + 173
123 + 30
30 + 7
55 + 18
39 + 17
34+10
32 +_ 11
3074 +509
2632 + 373
1145 + 251
239 + 55
2490 + 271
1870 + 177
490 + 80
93 + 24
2056 + 183
549 + 47
117 + 16
31 + 4
Norwood
Soil
64+31
31 + 12
26 + 10
25 + 10
2600 + 202
2484 + 226
966 + 113
152 + 20
2574 + 518
2231 + 289
593 + 66
103 _+ 12
1930 + 535
825 + 331
153 + 46
36 + 13

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NJ
                              .009

                           cost (•(/tutu
             Figure 54.  Extraction  efficiency, as measured with J3.  typhimurium strain  TA98,
                         of 2-nitroflourene from Norwood soil.

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Figure 55.  Extraction efficiency, as measured with j^. Cyphimurium strain TA98,
             of 2-nitrofluorene trom Bastrop soil.

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     Additional  tests  were conducted  using the nonpolar  indirect-acting
benzo(a)pyrene.  The results  from biological analysis of  the  extracts  of
the  two  soils amended  with benzo(a)pyrene.are  provided in Table 48  and
Figures 56  and  57.   For both soils at all  treatment  levels,  these was  no
appreciable  difference  in  the  mutagenic activity  of the  B(a)p and  the
soil amended with B(a)p.   At the high  and medium treatment  levels,  the
extract of  the  Norwood  soil  plus B(a)p was  consistently  less  mutagenic
than the  pure compound.   However,  the  soil  extract  did fall within  the
standard deviation of  the pure compound  at the same dose  levels.   Thus,
there  was   no  apparent  interraction  between the  benzo(a)pyrene and  the
soil components  which  significantly  affected  the  mutagenic acitivity  of
the soil extract.

     The soil  extracts  were also analyzed  using high performance liquid
chromatography  to determine  the  efficiency of the  blender extraction
procedure.   The  HPLC chromatograms  from  the  solvent   control,  the  two
soils,   and  the   soil  plus  the  chemicals  are provided   in  Figures  58
through 63.  For  the  Norwood soil, the  average  extraction  efficiency  for
both compounds  at all  three  treatment  levels  was  91%  (Table 49),  while
the  average efficiency  for the  Bastrop soil  was 89%  (Table 49).    The
average extraction  efficiency  for benzo(a)pyrene  and 2-nitrofluorene  in
the  Norwood soil was  91  and  99%,  respectively.   For   the Bastrop  soil,
the  average  recovery   was    84%   for   benzo(a)pyrene   and  93%   for
2-nitrofluorene.  These  results  indicate  that   there was  no  appreciable
difference  in  the   extraction  efficiency  from the  Norwood  or Bastrop
soils.   Treatment  level   did  not  appear  to influence  the  recovery  of
benzo(a)pyrene,  whereas  the  recovery  of  2-nitrofluorene  at   the  low
treatment level was 15% less than the high  and medium levels.

     When the  extraction  efficiencies are  compared  for  each of the  pure
compounds,   the  recovery  of  the  polar  compound appears  to  be slightly
greater.    The  extraction  efficiency   from  both  soils   at  all   three
treatment levels was  90%  for  the nonpolar  benzo(a)pyrene  and  96% for  the
polar   2-nitrofluorene.    The   lower   efficiency   observed   in    the
benzo(a)pyrene  amended  soils  was influenced by  the very low recovery
efficiency  in  the  Norwood soil at the medium treatment  level.   The  cause
of the  low  recovery  efficiency for benz(a)pyrene  in the  Norwood soil  is
at this point unknown.

     Biological  and  chemical  analysis  of  two  soils  amended with either
2-nitrofluorene  or  benzo(a)pyrene   have  indicated  that  the blender
extraction   procedure   does  provide   adequate  recovery  of   mutagenic
compounds.    The  results   from  the  Salmonella/microsome  assay  indicate
that there  was  no appreciable  difference  in the  mutagenic  activity  of
the  pure  compound  or   the  extract  of  the soil  amended   with  the  pure
compound  at   equivalent   dose   levels.    In  addition,  the  extraction
efficiency  as  measured  using  high   performance   liquid   chromatography
averaged greater  than  85% for both chemicals  at all treatment  levels  on
both  soils.  This  analytical  approach,   using  combined chemical   and
biological  analysis,  has  demonstrated  that  for  the compounds, levels,
                                  164

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             TABLE 48. MUTAGENIC ACTIVITY, AS MEASURED WITH  j>.  TYPHIMURIUM TA98,  WITH
Ln
METABOLIC ACTIVATION, OF BENZO(a)PYRENE , AND THE SOLVENT EXTRACT OF
THE NORWOOD AND BASTROP SOILS AMENDED WITH VARIOUS LEVELS OF
BENZO(a)PYRENE
Sample
None
B[a]P
(high)
(raed)
(low)
Dose/Plate
(rag)
0
-1
-2
-3
0(0.5)
-1(0.05)
-2(0.005)
-3(0.0005)
0(0.05
-1(0.005)
-2(0.0005)
-3(0.00005)
0(0.005)
-1(0.0005)
-2(0.00005)
-3(0.000005)
B[a]P
-
500 + 139
514 + 123
505 + 163
74 _+ 33
514 + 123
505 + 163
74 + 33
35 + 10
505 + 163
74 + 33
35 + 10
Bastrop
Soil
64 + 5
47 + 8
44 + 9
45 + 14
543 + 79
612 + 122
553 + 124
90 + 17
355 + 61
293 + 195
54 + 16
49 + 9
618 + 82
119 + 18
60 + 11
48 + 7
Norwood
Soil
56 + 23
42 + 22
39 + 19
40 + 21
361 + 50
400 + 68
390 + 185
52 + 11
437 + 944
459 + 118
89 + 41
58 + 36
475 + 163
118 + 71
46 + 15
43 + 16

-------
300
IOO
                                                    900
                                                  '5
                                                  I
                                                   •300
                                                    too
 •OOOOS       .0009        .COS        .05
                     008E
                                                           t BA8TROP B(«>f»0«H>»89
                                                                             i"
                                                     .00003       .0005
                                                                            .005
                                                                          DOSE <»|/pl«U>
                                                                                        .03
                                                                                                    .3
      Figure 56.  Extraction efficiency,  as measured with j>.  typhimurium strain  TA98,
                    of benzo(a)pyrene  from  Norwood soil.

-------
  900
 2
 CD
  IOO
	-f	f
                                          -—-I
                                                        900
                                                       •300
                                                        100
   .OOO03        .OOO3
                           .009         .OS

                        DOSE (•|/»UU>
  SOO
CO
  300
  100
              .0009        .009
                                      .09
                                                               • B(.)f*89

                                                               k BASTROP BU>r
                                                        900
                                                        300
                                                                B<«)»«89

                                                                BA8TROP BU>»»B9
                                .9      .OOOO9       .OOO9
                                                                                 -OO3

                                                                               008E (
      Figure 57.   Extraction efficiency,  as  measured with S^  typhimurium  strain TA98,
                     of benzo(a)pyrene  from Bastrop soil.

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        TABLE 49. EXTRACTION EFFICIENCY,  AS MEASURED WITH HPLC,  OF THE BASTROP AND NORWOOD
                                    SOILS  AMENDED  WITH MUTAGENIC  COMPOUNDS
oo
Compound
2-Nitrof luorene



Benzo(a)pyrene



Application Rate Bastrop
25 mg 2NF/50g soil
12.5 mg/50g
1.25 mg/50g
Average
25 mg B(a)p/50g soil
2.5 mg/50g
.25 mg/50g
Average
Soil
104
91
84
93
89
89
73
84
Norwood Soil
104
108
85
99
97
52
99
83
Average
104
100
85
96
93
71
86
84
        Average  both  compounds                           89           91               90

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                               Dimethyl Sulfoxide

                                    5.0mg/ml
                       Norwood  Soil + Dimethyl Sulfoxide

                                    5.0mg/ml

Figure 58.   HPLC chromatograph from (A) dimethylsulfoxide and
            (B)  Norwood  soil.
                        169

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                              Dimethyl Sulfoxide

                                  5.0mg/ml
                      Bastrop Soil •>• Dimethyl Sulfoxide

                                 5.0mg/ml
Figure 59.  HPLC chromatograph from (A) dimethylsulfoxide and
           (B) Bastrop soil.
                          170

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                                    2-Nitrofluorene
                                       5.0mg/ml
                                Norwood  Soil + 2-Nitrofluorene
                                          5.0mg/ml
Figure 60.  HPLC chromatograph from (A) 5.0 mg/ml 2-nitroflourene,
           and (B) Norwood soil +5.0 mg/ml 2-nitroflourene.
                       171

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                                     2-Nitrofluor«M
                                        5.0mg/ml
                            Bastrop Soil +• 2-Nltrofluorene

                              1        S.Omg/ml
Figure 61.   HPLC chromatograph from  (A) 5.0 mg /ml 2-nitroflourene,
            and (B)  Bastrop  soil +5.0 mg/ml 2-nitrofluorene.
                            172

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                     Benzo(a)pyrene
                        5.0mg/ml
            Norwood Soil +• Benzo(a)pyrene
                     5.0mg/ml
Figure 62.   HPLC chromatograph from (A) 5.0mg./ml benzo(a)pyrene,
            and (B) Norwood soil +5.0 mg/ml benzo(a)pyrene.
                           173

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                  Benzo(a)pyrene

                     5.0mg/ml
             Bastrop Soil + Benzo(a)pyrene
                     5.0mg/ml
Figure 63.   HPLC  chromatograph from (A)  5.0 mg/ml  benzo(a)pyrene,
            and  (B) Bastrop soil +5.0 mg/ml  benzo(a)pyrene.
                        174

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and soils evaluated,  there  are no interractions with soil compounds, and
the  blender  procedure  does  provide efficient  extraction  of  mutagenic
compounds from soil.
                                   175

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                               SECTION 8

  MUTAGENIC ACTIVITY OF RUNOFF WATER FROM HAZARDOUS WASTE AMENDED SOIL



INTRODUCTION

     Land  treatment   of   hazardous   waste  consists  of  a  program  of
controlled  applications   of  waste   to  the   surface   layer  of  soil
accompanied by a  carefully  planned  management and  monitoring program.
This  technique is  designed  to  protect  the environment  by  using  the
surface  layer  of  soil to  transform,  degrade, or  immobilize hazardous
waste constituents. Many  of the more complex organic waste constituents,
particularly those  which  are toxic or genotoxic, may persist in the soil
for  an  extended period of time  (Alexander,  1981).  Scant information is
available  concerning  the  ultimate fate  of resistant organic chemicals in
the  environment.    These   chemicals  may volatilize  from  the  soil,  be
translocated by  plants, be  removed  by  runoff  water,  or be leached into
the  groundwater.   A  variety  of analytical  techniques  could  be used for
characterizing  samples   of  the  various   streams   leaving   the  soil.
Detailed  chemical  analysis would provide  information  on the presence or
probable  presence  of  specific compounds.  A chemical analysis  would not,
however,   be   capable  of   predicting   the   synergistic,  additive,  or
antagonistic interactions  of a mixture  of chemicals or  their effect on  a
biological  system.   Biological  analysis  provides  the  only   analytical
technique  that  can be used to define the  toxic  or genotoxic potential of
an environmental sample.

     This  segment   of the  present  study  was  conducted  to  evaluate the
potential  for  the  removal  of mutagenic waste  constituents by rainfall.
The  EPA  (1980) regulations require that the  runoff  from hazardous waste
land  treatment  facility be retained. However, monitoring  techniques must
be  developed   to  determine  when runoff water   can  be  safely  discharged
following  closure  of  the  facility.  In  addition,  these  results will
provide  information on the  presence of water   soluble  mutagens  in soil
and  the effect of  degradation on  their mutagenic activity.

MATERIALS  AND  METHODS

Waste

     Three petroleum based  sludges  were  utilized  in  the   greenhouse
study.   A  general description of  their characteristics  is  provided in
                                  176

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Table 50,  while a  more detailed  description is  included  in Section  5.
The  calculated amount  of  waste applied  to  the  soi-io ifl  each  box was
based on  the  bulkdensity of  each  soil  (1.44  g cm    for  the  Norwood
soil and 1.49 g, cm"  for  the  Bastrop soil),  the  volume  of soil  in  each
box  (36,225  cm ),   and the  percent  extractable  hydrocarbons  in  each
waste (27%  for PENT S,  21% for  SWRI,  and 41% for COMBO).  The weight  of
waste applied  to  each box was be determined  by multiplying the weight  of
soil times  the desired  level of extractable  hydrocarbons in  each  box and
dividing  this  figure by  the  amount  of  extractable  hydrocarbons  in  each
waste.

     Based  on  these  calculations,  the  wood-preserving  bottom  sediment
(PENT S)  was  applied to the greenhouse  boxes at a rate  of 5.5 kg/box  to
the  Norwood soil and 6.5  kg/box  to the  Bastrop  soil, or a hydrocarbon
loading  rate  of 3.1%.   The application  rate for the  storm-water runoff
impoundment waste   (SWRI)  was  11.2 kg/box to the  Norwood  soil and  11.6
kg/box  to  the Bastrop  soil, or  a  hydrocarbon loading  rate of 4.5%.  The
combined  API-separator/slop oil  emulsion  sludge  (COMBO)  was  also  applied
at  a hyrocarbon  loading  rate of  4.5%.  This  was  equivalent to a sludge
application rate  of 5.7 kg/box  to  the Norwood soil and 5.9 kg/box to the
Bastrop  soil.

Soil

     The  physical  and  chemical  properties  of  the  soils  used  in  the
greenhouse  study  are provided  in  Table  42.  A more detailed  discussion
of  the  Bastrop and Norwood soils  is  provided in  Section 6. Approximately
two  fifty-five  gallon  barrels   of  each   soil  were  collected  from  an
uncontaminated  site for use in the  greenhouse study.

Greenhouse  Boxes

     At  the time  of collection, the  soils used in the  greenhouse  study
were  slightly  moist to  wet.   The  two  soils were  spread  separately  on
sheets  of brown paper  on  greenhouse  benches to  air dry.  Large  clods  were
passed  through an  ore  crusher to  reduce their size.   Air  dried  soil was
passed  through  a 4  mm sieve and  stored until needed.

     Sifted soil  was packed in  wooden boxes (45  cm x 57 cm x 20  cm)  in 5
cm  lifts to a  depth  of 17 cm.   The  surface of  the soil was smoothed  to
level    with    the   runoff   collection    trough    (Figure   64).    Waste
incorporation  into  the soil  was  accomplished by removing  approximately
one-half  of   the   soil from  the  box  and  applying   the  waste  to  the
remaining soil in  the  box.  The  removed  soil  was  added to the  box and
mixed with a  small  trowel  until the  mixture was  homogenous.  Twelve boxes
of  each  soil  were prepared for  the greenhouse  study.  These  included
three  boxes of  each soil  to  serve  as  controls  and  three boxes  of  each
soil  to  receive  the  PENT S,   SWRI,  or COMBO waste.  Soil  samples  were
collected from greenhouse  boxes before,  immediately after, and  45, 90,
180, 360,  and  540 days  following waste application.
                                  177

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00
            TABLE 50. DISTRIBUTION  OF  MUTAGENIC ACTIVITY   IN  FRACTIONS  OF
                      HAZARDOUS  WASTE  AND  THE  TWO  SOILS USED  IN  THE  GREENHOUSE
                                               STUDY
Fraction
PENT S

SWRI


COMBO


Norwood
Bastrop

Crude
Acid
Base
Neutral
Acid
Base
Neutral
Acid
Base
Neutral
Crude
Crude
Extractable
Hydrocarbon
(mg/g)
270
23
24
223
8
5
346
6
3
137
0.057
0.229
Specific
Activity -
(rev./mg)
1,282
771
1,204
860
475
418
420
368
344
497
21
297
Weighted
Activity _
(rev./mg)
346
18
29
192
4
20
145
2
1
68
0.0012
0.068
             1-   Mutagenic  activity as  measured  with  strain TA98  with microsomal
                 activation.
             2.   Revertants/mg = slope  of mutation  induction curve calculated using
                 three  highest non-toxic  dose levels.
             3.   Revertants/mg eq.  = Revertants/milligram material extracted;
                 calculated by multiplying revertants/mg x % extractable
                 hydrocarbons.

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                            SHEET METAL RUNOFF
                            COLLECTION TROUGH
3/4" PLYWOOD
LABEL-BOX
      OUTLET
      PIPE
 TYGON TUBIN
 (to amber glass bottle)
                                                                           20cm
                                               — 57.5cm
     Figure.  64.   Schematic diagram of greenhouse boxes used in degradation study.

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     Runoff  samples  were also  collected before,  immediately after,  and
45, 90,  180,  360,  and 540 days  following waste application.  A rainfall
simulator  that  held  four  boxes  per  simulation  was  used  to   generate
runoff  samples.   The  boxes  were placed  in the  chamber  on a 10   slope,
and  a  3.5  in/hour   intensity  rain  was  applied  with a  rotating  disk
rainfall  simulator  as  described  by  Morin  et  al.  (1967).   The  water
used in  the  simulated rainfall was rain  water  collected  from a  trough on
the sides  of  a  fiberglass  greenhouse.   Collected rain water was  pumped
to  a  600  gallon  capacity  storage  system  where  it  was  stored  until
needed.

Extraction Procedures

     Runoff  samples   were  extracted  using  the procedures  of  Brown  and
Donnelly  (1982).   The  samples  were  passed through  a jmixed bed  of  4.0 g
of  XAD-2  and  6.3 g  XAD-7,  or approximately  20  cm  of  each   resin as
suggested  by  Rappaport  e_t  al.  (1979).   The  resins  were  washed  prior
to  use by swirling  and decanting  three times  with ten volumes  each of
acetone,  methanol,  and  distilled water.  Washed  resins  were  stored at
4 C   ttrior to use.   Glass  econo-columns (Bio-Rad,  Richmond,  CA)  1.5 x
50  cm   were  packed  with  20  cm   of  XAD-2   resin  followed by 20  cm
of  XAD-7  resin.   Dressier (1979) found  that  the  combined XAD-2  and XAD-7
column  provided  the  most efficient recovery  for  a broad  range of organic
compounds,   while   Grabow   et^   al.    (1981)   observed   that   the  XAD
technique  may  be more efficient than  a   liquid-liquid  extraction for  the
recovery of  low  concentrations of mutagens. A  glass  wool plug was placed
above  the  resin  in  order  to  trap  soil  particles.  The  columns  were
flushed  with  1,200   ml  of  distilled  water   before   loading  the  water
sample.  Leachate  or runoff water was  placed  in a  reservoir and allowed
to  pass through  the column by  gravity  flow at  about 50 ml  per minute.
After  loading the water  sample,  dry  nitrogen was  introduced   into  the
column  to  remove  the residual aqueous  phase,  and the column was  washed
with  120  ml  of  distilled  water  to  remove  residual  histidine.   The
adsorbed  organic  compounds  were  eluted with  160  ml of  acetone.   The
acetone  extract  was  filtered  through  about   30  g  of anhydrous  Na_SO,
and Whatman  No.  42  filter paper  into  a  flat bottom flask.   Extract were
reduced  to   less  than   ten  milliliters  on   a  Brinkman-Bucci  Model  R
roto-evaporator.   The  sample  was  added  to  a glass  funnel  filled with
sodium sulfate to remove residual water and  washed  with acetone.   The
sample  was  then  pipetted  off  into  a  small  screw-capped glass culture
tube   and  taken   to  dryness   under   a   stream  of  nitrogen.   Dimethyl
sulfoxide  (Sigma) was  added  to the  dried  extract,  and  the  resultant
solution  was  passed  through   a 0.2  urn average  pore  diameter  Teflon
filter   (Millipore-Fluoropore  Bedford,  Mass.).  Samples  were  stored at
4 C prior  to use.

Chemical Analysis

     The  compounds were identified using a Finnigan OWA  Automated GC/MS.
The  GC  capillary column used  in the   procedure  was a J&W  Scientific
                                   180

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DB-5-30W  (Orangeville,   CA).   One  ul aliquots  were used  with a  helium
carrier  gas  flow near  36 cm/sec.   The  GC  oven Qtemperature  program  was
60°C  for  1  minute  and  then  increased  ..at   6 /min  to  260 C  with  a
hold  time  of 12  minutes.  The  OWA unit  has  a splitless  mode  injector.
The   software   used   has  a  mass   spectra  library of   31,331   organic
compounds.

Biological Analysis

      The  potential  of   the  organic  extracts  of runoff  water to  induce
genetic  damage  was  measured   with two  microbial  systems  capable  of
detecting compounds which  produce  point  mutations.

      The  Salmonella/microsome  assay  of  Ames   et_   al.   (1975)  was  used
to  monitor  the  mutagenic  activity  of  concentrated  water  samples.  The
Salmonella   strains  were  'kindly   supplied   by   Dr.   Bruce  N.   Ames
(University  of  California, Berkeley, CA).   The methods were  the  same as
Ames  e_t  al.  (1975) except  that  overnight  cultures  were   prepared  by
inoculation  into  10 ml  of  Oxoid Nutrient Broth #2  (KG Biological, Inc.,
Lenexa,  KS)  and  incubated  with  shaking for  16 hours  at  37 C.   Water
extracts  were tested on duplicate plates in two independent experiments
in  the  standard plate incorporation assay at  a minimum  of 4 dose levels
of  the  sample  with  and  without enzyme  activation  (0.3  ml  rat  liver/ml
S-9 mix) using  strains  TA98 and  TA100.  Aroclor 1254 induced  rat liver
was  obtained from Litton Bionetics (Charleston, SC).   Positive  controls
included   2   ug/plate  N-methyl-N'-nitro-N-nitrosoguanidine   (Sigma)  for
TA100,  25 jig/plate  2-nitrofluorene  (Aldrich)  for   TA98,  and 10  ug/plate
2-aminoanthracene  (Sigma) which was used with  all  strains  to verify the
functioning   of   the metabolic   activation   system.   All  reagents  and
extracts were  tested for sterility; DMSO was used as a negative control.

      The   bioassay  using  Aspergillus   nidulans   was   used  to   detect
point mutations and  small deletions  induced   in a  haploid  genome using
the methionine system.    Conidia  from four to  five  single colonies of the
methGl   biAl   (requiring  methionine  and  biotin)  Glasgow  strain  of
Aspergillus  nidulans  grown  for 5  to   6  days  on   a  complete  medium at
37  C were  used  for  each experiment.   Samples were  tested  at  one dose
level,  usually  the  extract  equivalent  to  250 ml  of  water,   and  one
exposure  time  selected  to yield  approximately 50% of  survival  on five
plates   in  two  independent  experiments  with  and  without  metabolic
activation.    The  procedures   used were  the  same  as  Scott  e_£  al.
 (1978)  except that  the  cells were  exposed  in  a 13  x 100 mm  screw capped
culture  tube.   The exposed  cells  were plated on  a complete  medium to
determine   survival  and  a methionine-free  medium  to  determine  induced
mutation frequency.  Mutant  colonies  were scored after  incubation for  5
days at  37 C.    Colonies were  divided  by  colony   morphology into three
classes,  A, B, C, as well as the total  mutation frequency represented by
the sum of  induced  mutants  from Class  A, B,  and C.  Each of these three
classes  is  believed to involve  two  genes.   The morphology of  Class   A
colonies  is green,  Class  B  brown, and  Class C green with a white hyaline
                                   181

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edge.  The  frequency  of  mutations induced by  a sample was determined  by
subtracting  the  frequency  of  spontaneous  mutations   from   the   total
mutation   frequency.   A  sample   was   considered   mutagenic   if  the
induced-mutation  frequency  was  greater  than  5.0.    Positive  controls
included  8-methoxypsoralen  (Sigma,  St.  Louis,  Mo),  8-methoxypsoralen
plus  near  UV   light  without  activation,  and  benzo(a)pyrene  (Aldrich,
Milwaukee, WI) with metabolic activation.

RESULTS AND DISCUSSION

     Runoff water was collected from  the  Norwood  or  Bastrop soil amended
with PENT  S waste over  a  540  day period.  The  mutagenic activity of the
residual  hydrocarbons   in  the  runoff   water  from  the Norwood  soil
increased with  each  subsequent sampling  date  (Figure 65). When compared
to  the  runoff  sample from day 0,  the  mutagenic potential of  the  sample
collected on day  540  was  approximately  eight  and  three  times  greater  in
strain  TA98 and  TA100,  respectively  (Tables  51  and  52).  In  addition,
strain TA98  detected  mutagenic activity  without the  S9 mix in the runoff
sample  from day  540, whereas no mutagenic  activity  was   detected  in the
absence  of metabolic activation  in  runoff  samples  collected  prior  to
this date (Figure 66).

     While  similar  results were obtained  with  the runoff water  from the
Bastrop  soil,  the increase in mutagenic activity  over time was much less
dramatic  than  the increase observed  in  the  runoff water  from  the Norwood
soil.   The  mutagenic  potential  of  the residual   hydrocarbons   in  the
runoff water from  the  PENT S amended  Bastrop  soil   increased  from day 0
through  day 360 but  remained  constant  or decreased slightly  from day 360
to  day  540  (Figure  67,  Tables  53  and  54).   As  with the Norwood soil,
direct-acting mutagens  were detected on day  540  (Table  53).  The results
from  a  chemical  analysis of runoff water from control  and PENT S waste
amended  Bastrop soil from day 0 and  360  are  provided in Figures  68,  69
and  70.    There were no compounds  present  in  detectable levels  in the
runoff water  from the unamended  Bastrop soil  (Figure 68). Ten compounds
were  detected  in the  runoff water collected  on day 0 from  the waste
amended     Bastrop     soil,    including    dimethylnapthalene    (DMN),
dihydro-acenaphthylene    (DHN),   dibenzofuran   (DBF),   fluorene   (FL),
methylfluoranthene  (MF), pentachlorophenol  (PCP), methyldibenzothiophene
(MDT),  methyl- phenanthrene  (MP),  fluoranthene  (FA),  and pyrene (PY).
(Figure    69).     Of   these   compounds,   napthalene,  dibenzofuran,
methydibenzothiophene,  pentachlorophenol, and fluorene are not mutagenic
in   Salmonella   (Anderson   et_   al.,    1971;   McCann   et   al.,   1975;
Pelroy  et  al.,  1983),   while  fluoranthene  and  methylphenanthrene are
strongly   mutagenic  (Kaden   e£  al.,   1979;   LaVoie   et^  al.,   1983).
Only  three  compounds  remained in  detectable  levels   in the runoff sample
collected  on day  360.    These  included  pentachlorophenol,  fluoranthene,
and  pyrene  (Figure  70).   In  the  runoff  water,  the impact of  reducing the
concentration  of organic compounds  on  the  mutagenic  potential  of the
mixture  is  difficult to  predict  because mixtures  of polycyclic aromatic
hydrocarbons  have   been  shown   to   cause   synergistic,  additive, and
                                   182

-------
    500
•>
i
   300
00
o>
    100-
           NORWOOD SOIL
       PENT-S RUNOFF  -t-S-9
             o CONTROL
             x DAY 0
               DAY 180
             a DAY 360
             • DAY 540
                 0.2
0.4         0.6
DOSE/PLATE (mg)
0.6
LO
             Figure 65.   Mutagenic  activity with metabolic activation
                         of runoff  water from PENT S amended Norwood
                         soil.
                                  183

-------
        TABLE 51. MUTAGENIC ACTIVITY, AS MEASURED WITH S. TYPHIMURIUM STRAIN TA98 OF RUNOFF WATER
FROM PENT S AMENDED NORWOOD SOIL
Day
BKG
0
180
360
540
S9
20 +
+ 29 +
21 +
+ 30 +
26 +
+ 36 +
25 +
+ 42 +
31 +
+ 39 +
0
1.9
8.0
8.3
4.3
4.6
7.9
3.3
5.4
4.3
3.7
Dose/Plate (rag)
1 .5
NT*
NT
Toxic
65 + 17.1
Toxic
20 +_ 35.2
47 + 11.5
153 + 47.3
166 + 92.6
514 +404.2
17 +
33 +
1.7
3.9
Toxic
87 +_ 10.1
22 +
98 +
68 +
175 +
193 +
373 +
20.0
12.1
13.3
65.5
116.1
232.0
21 +
24 +
18 +
76 +
31 +
60 +
34 +
99 +
82 +
108 +
,1
2.6
8.1
1.3
10.6
2.0
15.0
6.1
38.4
49.0
35.6

11 +
31 +
17 +
58 +
32 +
65 +
36 +
77 +
55 +
72 +
05
11.8
5.2
2.1
7.6
3.5
16.7
7.6
22.6
22.8
15.3
i

16
45
26
46
27
50
27
50
,01
NT
NT
+ 3.6
+ 17.0
+ 5.3
+ 13.9
+ 1.5
+ 2.9
+ 6.4
+ 2.3
* NT = not tested.

-------
             TABLE 52. MUTAGENIC ACTIVITY, AS MEASURED WITH j>.  TYPHIMURIUM STRAIN TA100 OF RUNOFF
oo

Day
BKG
0
180
360
540

S9
104
+ 81
87
+ 101
119
+ 111
167
+ 147
121
+ 120

0
+ 16.7
+_ 35.4
+ 34.4
+ 10.2
+ 8.8
+ 16.4
+ 17.0
+ 7.6
+ 9.5
+ 7.0



127
27
55
25
283
92
306
WATER
1
NT*
NT
Toxic
_+ 27.5
+ 47.9
+ 95.8
+ 42.7
+ 106.5
+ 25.5
+ 82.1
FROM PENT S AMENDED NORWOOD SOIL
Dose/Plate (mg)
.5 .1
51
82
261
63
310
126
501
124
486
+ 60.0
+ 24.7
Toxic
+ 48.0
+ 54.9
+_ 47.7
+ 35.2
+ 202.6
+ 49.2
+ 115.0
56 + 65.3
76 + 17.4
82 + 8.7
288 + 29.5
106 + 18.3
198 + 60.7
158 + 6.0
378 +238.2
112 + 2.1
273 + 79.2
52 +
73 +
81 +
208 +
108 +
239 _+
155 +
313 _+
106 +
198 +
05
58.8
25.7
10.0
27.5
16.6
49.7
10.8
177.1
13.7
28.6
f

79
97
115
143
149
179
100
130
.01
NT
NT
+ 7.2
+ 28.1
+ 10.4
+ 21.1
+ 14.1
+ 20 . 6
+ 9.5
+ 5.7
     * NT = not tested.

-------
   500-,
   300-
fc
5
                             NORWOOD  SOIL
                         PENT-S RUNOFF  -S-9
     o CONTROL
     XDAY  0
     A DAY 180
     O DAY 360
     • DAY 540
oo
O)
    100-
                0.2
                                                            2X-BKG
0.4        0.6        0.8

 DOSE/PLATE  (mg)
        Figure 66.  Mutagenic activity without metabolic activation of
                    runoff water from PENT S amended Norwood soil.
                          186

-------
   500
   300
CD
    100-
                                 BASTROP SOIL
                             PENT-5 RUNOFF   +S-9
       o CONTROL
       x DAY 0
       A DAY 180
       ODAY 360
       • DAY 540
                                                          x 2X-BKG
                02
 0.4        0.6

DOSE/PLATE (mg)
0.8
1.0
        Figure  67.  Mutagenic activity with metabolic activation of
                   runoff water from PENT S amended Bastrop soil.
                                  187

-------
             TABLE  53. MUTAGENIC ACTIVITY,  AS MEASURED WITH S. TYPHIMURIUM STRAIN TA98 OF RUNOFF
co
oo
WATER FROM PENT S AMENDED BASTROP SOIL
Day
BKG
0
180
360
540
S9
20
+ 29
23
+ 28
24
+ 32
34
+ 47
27
+ 39

+
+
+
+
+
+
+
+
+
+
0
1.9
8.0
2.3
4.7
4.1
6.1
7.8
6.2
4.1
3.7

24
31
68
30
103
50
122
71
151
1
+ 2.6
j± 9-3
Toxic
+ 27.1
+ 16.7
+ 21.7
+ 7.1
+ 5.9
+ 33.9
+ 18.4
Dose/Plate (tng)
.5
23
27
15
92
46
112
42
114
52
102
+ 4.7
+ 28.7
+ 2.2
+ 8.4
+ 30.3
+ 4.2
+ 7.5
+ 4.9
+ 18.4
+ 2.8
20
27
18
69
27
72
35
70
31
68
.1
+ 4.8
+ 3.5
+ 5.4
+ 19.4
+ 8.0
± 2-1
+ 3.0
+ 6.1
+ 5.7
+ 7.8
•
22 +
30 +
20 +
57 +
22 +
49 +
31 +
62 +
26 +
59 _+
05
5.0
8.2
1.0
15.6
5.9
8.3
3.2
5.0
6.4
5.7


22
34
22
42
31
55
26
53
.01
NT*
NT
+ 6.2
+_ 5.8
+ 2.6
+ 3.5
+ 3.5
± 3-5
+ 1.4
± 3-5
     * NT  =  not  tested.

-------
                                     TABLE 54.   MUTAGENIC ACTIVITY, AS MEASURED WITH  S. TYPH1HURIUH STRAIN  TA100  OF RUNOFF MATER FROM PENT S
00
v£>
AMENDED BASTROP SOIL
Day
BKG
0
180
360
540
* NT -
S9
104
* 88
88
+ 104
107
+ 99
126
+ 130
136
t 142
not tested.
0
«• 17.1
+ 19.5
* 10.6
+ 9.0
* 18.5
* 16.7
+ 10.7
+ 13.1
+ 12.6
+ 15.4

1
NT*
83 i 17.3
Toxic
253 + 20.6
Toxic
86 + 81.0
75 + 6.8
323 + 13.2
99 + 31.8
384 + 74.2

Dose/Plate (tag)
.5
56 *
79 +
63.0
41.5
Toxic
206 i 27.1
120 +
304 *
121 «•
394 *,
141 +
318 +

16.5
60.12
8.3
51.0
24.0
62.9

50
86
84
239
96
268
122
209
141
209

.1
+ 56.9
+ 34.9
+ 9.5
i 32.5
+ 13.6
+ 11.8
+ 8.4
+ 6.1
+ 11.3
+ 22.6


51 +
86 +
73 +
202 +
105 +
183 j*
112 4
166 +
132 +
163 +

.05
57.9
19.9
12.6
27.0
21.6
25.5
9.5
14.6
16.3
2.8



77
112
101
103
113
139
127
144

.01
NT
NT
* 3.9
+ 20.7
+ 11.3
*_ 8.6
+ 9.2
± 7-5
+ 4.9
+ 30.4


-------
                                           BASTROP CONTROL DAY 360
vQ
O
     RIC
        200
                                                                                   800
               Figure 68. GC/MS chromatograph  of organic extract of runoff water  from
                         unamended Bastrop soil collected on day 360.

-------
RIG
                                                      BASTROP PS  DAY 0
            100
200
300
600
700
800
                             400     500

                                  RT
Figure 69. GC/MS chromatograph of organic extract of runoff water from PENT S
          amended Bastrop soil collected on day 0.

-------
                           PCP
                                                     BASTROP  PS  DAY 360
     RIG '
VD
       300
   40O
500
                                         RT
600
700
         Figure 70.
GC/MS chromatograph of organic  extract of runoff water  from PENT S
amended Bastrop soil collected  on day 360.

-------
antagonistic  responses   (Hass  et^  al^. ,  1981;  Haugen and  Peak,  1983).  A
comparison  of  the runoff  samples  collected  on day  540  indicates  that
greater amounts  of  mutagenic activity were  detected in the runoff  water
from  the  Norwood  soil  than in  the runoff  water from  the  Bastrop  soil
(Tables 51  and  53).  The results  from chemical and biological  analysis of
runoff water  from the  PENT S amended  soils indicate that  the  mutagenic
activity of  the  compounds  residual on day 540 was greater than  the  level
of mutagenicity  present in  the  more complex samples collected prior to
day 540.

     The  results from  the  biological analysis  of  the runoff water from
SWRI waste  amended  soils  are  provided in Figures  71 and 72, and  Tables
55 through  58.   For strain  TA98,  the  mutagenic activity  of the residual
hydrocarbons  in  the runoff  water  from  the  Norwood  soil increased from
day  0  through  day  360   (Table  55);  whereas,  for  strain  TA100  the
mutagenicity  increased  from day 0 to  180 and decreased  slightly  on day
360 (Table 56).

     The mutagenic  potential of  the runoff  water from the  Bastrop  soils
amended with  the  SWRI  waste showed a  similar trend.  The  net  TA98 his
revertants  with  metabolic  activation at  a dose level of  500  ug/plate on
day  0,  180  and  360  was  86^,   88,   and   206,  respectively.    Without
activation,  the  net TA98  his   revertants  at the  same  dose level were
21,  25,  and  196 on days  0+ 180,  and  360,  respectively  (Table  57).  In
strain  TA100,  the  net  his  revertants  at   500  ug/plate with  metabolic
activation  increased from day 0  to 180 and  decreased from day 180 to 360
(Table 58).   The runoff water  collected  on  day  0,  180,  and  360  from both
soils  yielded consistently  similar dose-response  curves  when  the  total
mutation  frequencies   in   strain  TA98   with  metabolic   activation  are
compared  (Figures  71 and 72).  In both  soils, the mutagenic potential of
the  residual hydrocarbons   in  the runoff water  increased  slightly from
day  0 to  180  and  almost  doubled  from day  180 to 360.  In  addition,
direct-acting  mutagens  were detected  in the samples  collected on day
360, whereas  only promutagens were detected  on days  0 and  180.

     The  mutagenic  potential  of  the  runoff water from the combined API
separator/slop-oil  emulsion  solids  (COMBO) waste  amended  soil  did not
follow  a consistent trend  in  either  soil.   In  the  Norwood  soil, the
mutagenic activity  of the residual hydrocarbons  decreased  from day 0 to
180,  and  then increased from day 180 to 360  (Figure 73). The values for
the  net  TA98 his   revertants with metabolic activation  at a dose   level
of  500  ug/plate  were  95, 40,  and   144   on  day  0,   180,  and  360,
repectively  (Table  59). In  strain TA100,  none of the runoff samples from
the  COMBO waste amended Norwood  soil  induced a  positive  response  (Table
60).  The runoff water  collected  from the  COMBO  waste  amended  Bastrop
soil  on  day 0 induced  a positive response only at  the highest dose  level
in  strain TA98  with metabolic  activation (Table 61  and Figure 74).  Using
the  modified  two-fold   rule  (Chu  et  al. ,  1981),   this   sample would be
considered  non-mutagenic.  However, the mutagenic activity induced by the
residual  hydrocarbons  in  the  runoff water  from the  COMBO  waste  amended
                                  193

-------
TABLE 55. MUTAGENIC ACTIVITY, AS MEASURED WITH J3. TYPHIMURIUM STRAIN  TA98  OF RUNOFF WATER
FROM NORWOOD SOILS AMENDED WITH SWRI WASTE
Day S9
0
180
360
0
23
28
30
50
24
39
+
+
+
+
+
2.8
7.4
4.1
4.6
1.6
4.2
37
87
65
64
197
507
Dose/Plate (mg)
1 .5
+ 8.5
+ 9.2
+ 1.0
4- 12.3
+ 106.0
+ 235.1
35 +
102 +_
52 +
148 _+_
123 +
271 +
4.0
39.4
1.0
15.0
48.0
152.8
30 +
82 +_
38 +
71 +
53 +
90 +
,1
8.3
10.2
3.2
14.5
12.0
48.5

28
67
32
57
37
57
.05
-i- 5
± 6
+ 0
± 4
+ 7
+ 14
.01
.3
.8
.6
.0
.0
.3
29 +
38 +
30 +
53 +
26 +
43 ^
2.2
15.0
1.7
8.0
2.1
h 3.0

-------
            TABLE 56. MUTAGENIC ACTIVITY, AS MEASURED  WITH J5.  TYPHIMURIUM STRAIN TA100 OF RUNOFF
VO
WATER FROM NORWOOD
Day
0
180
360
S9
114 +
+ 97 +
128. +
+ 158 +
126 +
+ 123 +
0
9.2
11.9
15.0
11.0
14.3
8.1
1
Toxic
Toxic
167 + 12.2
342 + 21.8
256 + 120.0
328 + 119.4
SOILS
AMENDED WITH SWRI WASTE
Dose/Plate (mg)
.5 .1
122
203
159
301
201
220
+ 32.8
+ 31.4
+ 17.6
+ 10.5
+ 62.9
+ 66.4
101 +
189 +
145 +
207 +
158 +
144 +

8.5
26.8
19.1
36.7
17.9
10.6

91
156
157
172
145
128
.05
+ 17.4
+ 10.0
+ 3.5
+ 9.2
+ 12.7
+ 16.4
.01
112
109
149
162
134
125
+
+
+
+
+
+
26.0
4.2
2.5
6.0
5.1
17.2

-------
            TABLE 57. MUTAGENIC  ACTIVITY,  AS MEASURED WITH S.  TYPHIMURIUM STRAIN TA98 OF RUNOFF
vo

Day
0
180
360

S9
23 +
+ 25 +
31 +
+ 45 +
32 +
+ 43 +
WATER FROM BASTROP
SOILS AMENDED WITH SWRI WASTE
Dose/Plate (mg)
0 1 .5 .
5 . 2 NT*
10.2 NT
5.6 65 + 1.7
3.5 64 +_ 12.3
4.6 306 + 184.5
3.5 475 + 218.6
44 +
111 +
56 +
133 +
228 +
249 _+
4.4
28.7
9.8
25.1
118.1
131.1
22
60
40
62
75
76
+
+
+
+
+
+
1
6.3
12.9
1.2
1.2
37.2
15.0
.05
22 +
46 +
37 +
57 +
56 +
51 +
4.6
3.5
5.6
1.5
23.2
5.7
.01
24 +
37 +
30 +
47 +
33 +
46 _+
6.2
14.2
2.6
8.5
8.9
0.6
    * NT = not  tested.

-------
        TABLE 58.  MUTAGENIC ACTIVITY, AS MEASURED WITH S. TYPHIMURIUM STRAIN TA100 OF RUNOFF
WATER FROM BASTROP SOILS AMENDED WITH SWRI WASTE
Day
0
180
360
S9
114
+ 97
128
+ 158
126
+ 140
0 1
+_ 9.3 Toxic
_+ 12.0 Toxic
+ 15.0 169 + 12.3
_+ 11.0 304 + 7.6
+ 14.0 180*
+_ 16.0 254
Dose/Plate (mg)
.5
104 + 10.7
90 + 103.3
163 + 4.6
276 + 17.6
172
216
.1
102 + 10.5
55 + 62.0
141 + 11.4
196 + 41.6
143
166
.05
118 + 15.5
41 + 46.1
147 + 9.0
163 +14.2
137
174

116
46
147
168
126
157
.01
+ 12.4
+ 52.1
+ 3.2
+ 6.1

*   Mean represents average of only two values; standard deviation not provided.

-------
   600
   400'

CD
CD
  200
                  NORWOOD SWRI RUNOFF
                       O — CONTROL
                      X— DAY 0
                        — DAY  180
                                                              2X-BKG
               0.2
1.0
                    0.4       0.6       0.8
                        DOSE/PLATE  Cmg)
Figure  71. Mutagenic  activity with metabolic activation of
          runoff water  from SWRI amended soil.
                              198

-------
   600
   400
 «
 t-

4
00

0)
   200'
                 BASTROP SWRI RUNOFF
CONTROL


DAY 0



DAY 180



DAY  360
                                      _	-.	2X-6KG
                                                       I .0
                            DOSE/PLATE  Cmg)
        Figure 72.  Mutagenic activity with metabolic activation of

                   runoff water from SWRI amended Bastrop soil.
                               199

-------
   600i
   400-
cd
+*
«.


>
to
O>
   200-
                 NORWOOD COMBO RUNOFF
                                                              - 2X-BKG
                0.2
0.4
0.6
0.8
                                                           1.0
                              DOSE/PLATE Cmg)




         Figure 73.  Mutagenic activity with  metabolic activation of

                     runoff water from COMBO  amended Norwood soil.
                                200

-------
to
o
              TABLE 59. MUTAGENIC ACTIVITY, AS MEASURED  WITH JJ.  TYPHIMURIUM STRAIN TA98 OF RUNOFF
WATER FROM NORWOOD
SOILS AMENDED WITH COMBO WASTE
Dose/Plate (mg)
Day
0
180

360

S9
22
+ 41
35
+ 44
25
+ 42
0
+ 5.4
+ 5.8
+ 2.8
i 2.3
+ 5.4
± l-9

79
54
124
440
430
1
NT*
+ 95.
+ 11.
+ 30.
•«• 50.
+ 4 .

7
1
3
9
9

61
136
43
84
272
186
<
+
+
+
+
+
,5
22.9
16.6
7.5
22.2
43.1
44.5
•
30 +
65 +
33 +
62 +
80 +
63 +
1
11.1
45.5
4.6
11.4
16.3
1.4
•
33 +
61 +
30 +
50 _+
64 +
62 _+
05
16.9
11.9
2.5
1.7
11.3
9.2

34
43
30
47
33
61
.01
+ 13.2
+ 2.9
+ 1.5
+ 2.9
+ 4.9
+ 8.5
      * NT = not tested.

-------
        TABLE 60.  MUTAGENIC ACTIVITY, AS MEASURED WITH S. TYPHIMURIUM STRAIN TA 100 OF RUNOFF
WATER FROM NORWOOD SOILS AMENDED WITH COMBO WASTE
Dose/Plate (rag)
Day
0

180

360
to
o
KJ
S9
96
+ 114
114
+ 112
145
+ 136
0
+ 6.0
+ 12.7
+ 18.0
_+ 11.6
+ 12.8
_+ 11.1
1
NT*
144 + 35.4
96 + 35.6
212 + 15.4
151 + 62.9
176 + 68.6

119
122
92
155
112
148
.5
+ 19.1
+ 24.7
+ 30.6
+ 36.8
+ 53.7
+ 56.6

114 +
136 +
94 +
123 +
108 +
109 _+
.1
17.5
25.0
35.9
12.6
50.2
63.6
•
102 +
111 +
87 +
117 +
100 +
108 +
05
16.6
22.2
31.8
4.9
38.2
50.2

109
83
88
108
100
96
.01
+ 9.3
+ 21.5
+ 34.9
+ 6.1
+ 38.2
+ 48.1
*NT = not tested.

-------
            TABLE 61. MUTAGENIC ACTIVITY, AS MEASURED  WITH S.  TYPHIMURIUM STRAIN TA98 OF RUNOFF
NJ
o

Day
0
180
360

S9
27
+ 45
28
+ 46
25
+ 42
WATER
0
+ 7.2
+ 9.0
+ 4.9
± 4-2
+ 4.9
+ 1.7
FROM BASTROP SOILS AMENDED

39
86
112
175
85
160
1
+ 8.2
+ 19.3
+ 52.0
± 9-7
+ 14.6
+ 37.2
Dose/Plate
.5
39
60
81
123
56
101
+ 1.
+_ 10.
+ 28.
± 14-
+ 8.
+ 16.
WITH COMBO WASTE
(mg)
•
7
9
7
6
5
1
23 +
50 +
43 +
58 +
39 +
60 +
1
9.0
1.9
8.7
4.6
2.1
5.0

35
37
38
54
29
58
.05
+ 16.9
+ 6.7
+ 2.3
+ 3.6
+ 1.2
+ 4.6

30
38
31
40
22
51
.01
+ 10.8
+ 5.9
+ 2.0
+ 2.5
+ 2.5
+ 1.7

-------
   600-
  400'
>
•>
co
0)
  200-
                      BASTROP COMBO RUNOFF
                                CONTROL
                                DAY  0
                                DAY I 80
                                DAY 360
               0.2       0.4        0.6        0.8


                             DOSE/PLATE Gng)
                                                           -  2X-BKG
1.0
        Figure 74.  Mutagenic activity with metabolic activation of

                   runoff water from COMBO amended Bastrop soil.
                                 204

-------
Bastrop soil  in  strain TA98 with metabolic  activation increased  from  15
to  77  to 59  net  revertants  on day 0,  180,  and 360, respectively  (Table
61).   As  with  the  Norwood  soil,  in  strain  TA100, none  of the  runoff
samples  from the  COMBO  waste amended  Bastrop soil  induced a  positive
response  (Table  62).   Thus,   the  mutagenic  potential  of  the  residual
hydrocarbons  in  the  runoff water from  both  soils  was greater  on day 360
than on day  0.   In addition,  direct-acting mutagens were  detected on day
360 but not on day 0.

     Degradation,  infiltration, and  removal will  influence the  quality
and quantity  of  hazardous organic compounds  in runoff water from a land
treatment facility.   In order to evaluate the  influence of these factors
on  the mutagenic  potential  of runoff  water,  the  results   from  the  waste
amended  and  control  soils  were  compared  on  the basis  of  equivalent
volumes. Because  of  the  limited amount  of sample  available,  the extracts
of  runoff  water  samples  were  tested in   the   Aspergillus   assay  at
volumes  approximately  one-fourth  that  tested  in  the Salmonella  assay.
While  it  is  unfortunate  that  equal  volumes were  not tested in  the two
bioassays, some  general conclusions can be  drawn  from the results in the
different  bioassays.   A   comparison  of the   results  from  testing  the
equivalent of 10 ml  of runoff water  from the  PENT S amended Norwood soil
in   the   Salmonella   assay    indicates   that   the  mutagenic   potential
increases consistently from day 0 to  180 to 360  and  from day  360 to 540
(Figure  75).    Contrasting  results  were  observed  in  the Aspergillus
assay  (Figure 76).   In the PENT  S amended  Norwood soil,  the  mutagenic
activity  of   the  runoff water collected  on  day 360 decreased to  a  level
approximately 16% of that detected on  day  0 (Figure  76).   The  surviving
fraction  in   Aspergillus  increased  significantly  from day 0 to  360.  If
this  effect   also  occurred in  the  Salmonella assay,'the  induced mutants
per  survivor in  Salmonella  would be greater  on day 0 and approximately
the  same  on  day 360;  thus,  the results from the two bioassays  would then
be  comparable.   The   observed difference in   the  results  from  the  two
bioassays  is probably  a  reflection  of the  increased  metabolic  and DNA
repair capabilities of the eukaryotic system (Dunkel,  1981).

     In  the  Bastrop  soil,   the  mutagenic  response  in   both  bioassays
decreased from day 0  to  180 and  from day 180  to 360 (Figures 76 and 77).
In  both  bioassays,  the response induced by the sample collected  on day
360  was  at  a level  that  was only slightly greater than twice background.
However,  on  day 540 there was an appreciable  increase in  both  the amount
of  extractable  hydrocarbon  and  the mutagenic potential  of the  runoff
water  from  the  PENT  S  amended  Bastrop  soil  in the Salmonella assay.
The  results  obtained  from the runoff water  from either  soil amended with
the  PENT  S  waste  as  measured  with   the  Salmonella  and  Aspergillus
assays indicate   that significant   levels   of mutagenic  activity  are
detectable   360   days   after   waste  application.   However,  the  overall
results  indicate  that  the   mutagenic  potential  of  the  runoff  water
collected on  day  360 is less  than on  day 0.

     The  runoff water  from soils amended with the SWRI  and COMBO  waste


                                  205

-------
        TABLE 62. MUTAGENIC ACTIVITY, AS MEASURED WITH S. TYPHIMURIUM STRAIN TA100 OF  RUNOFF
WATER FROM BASTROP SOILS
Day
0
180
360
S9
96
+ 114
109
+ 105
150
+ 139
0
+ 6.
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+ 13.
+ 16.
+ 10.

0
7
9
5
3
9.0
1
100 + 19.4
173 +_ 10.8
NT*
NT
150 + 17.7
209 +11.1
Dose/Plate
.5
102
172

143
172
+ 16.
± 3-
NT
NT
+ 9.
± 5.
(mg)
5
6

5
5
AMENDED WITH
.1
95 + 13.6
140 _+ 20.7
NT
NT
145 + 4.5
145 + 9.1
COMBO WASTE
.05
105 + 12.9
131 + 14.9
NT
NT
138 + 7.5
148 + 4.2

.01
95 + 18.
99 + 10.
NT
NT
135 + 4.
130 + 8.


7
8

0
0
*NT = not tested.

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-------
contained lower  levels  of hydrocarbons than  did  the water  from  the  PENT
S waste  (Table  63).   Therefore, the quality  of  runoff water  from  soils
amended with  the SWRI or COMBO  waste  were compared on  the  basis of  a 50
ml volume.   The  amount  of extractable  hydrocarbons  in runoff  water  from
SWRI  waste   amended  Norwood  and Bastrop  soils  was   less  than  that  in
runoff water from unamended  soils on  day 0.  On  day 180, the  level of
extractable  hydrocarbons  in  the  runoff  water  increased  approximately
ten-fold  and  then  decreased by  approximately  50%  on  day  360.    The
mutagenic  potential   of  50 ml  of  runoff  water  from  SWRI waste  amended
Norwood and  Bastrop  soils was non-mutagenic  on day 0,  increased to  3 to
4 times  background  on  day 180,  and increased  still further  on  day 360
(Figures  78  and 79).  In addition,  while greater  amounts of mutagenic
activity were detected  with metabolic  activation,  the mutagenic activity
in the absence of metabolic  activation also  increased significantly  from
day  0 to 180  and  from  day 180  to  360.  The results from  the  Aspergillus
assay  followed  the  same general  trend.   With metabolic  activation, the
mutagenic potential  of  the sample  collected  on day  180 was approximately
three  times  that of   the  sample  from  day 0 (Figure  76).   In addition, the
mutagenic potential  of  the sample  from day 180  was  essentially the same
as  that  of  the  same from day  360.  Thus, the mutagenic  activity of the
runoff water  from both  the  Norwood  and  Bastrop soils amended  with the
SWRI  waste  followed   the  same  general  trend increasing  from day 0 to 180
and   from  day   180  to   360.   In addition,   slightly  greater  levels  of
mutagenic  activity were  detected  in  the  runoff water from  the Norwood
soil  than from the Bastrop  soil.

      The  level of extractable hydrocarbons  in the  runoff  water  from the
Norwood  soil amended with the COMBO  waste decreased by approximately 25%
from  day 0  to  180  and  by approximately  33% from day  180  to  360 (Table
63).  The  level  of mutagenic  activity  in  50 ml of  runoff water decreased
by  approximately 50% from day  0  to  180  but  increased appreciably  from
day  180  to  360  (Figure  80).   The runoff  sample collected on day 180 from
the  COMBO  waste amended  Norwood  soil induced  10  net revertants/50 ml
without  and  50  net  revertants/50  ml  with  metabolic  activation;  while,
the  sample  collected on  day  360 induced  220  net  revertant colonies/50 ml
without   and  130   net   revertants/50  ml   with metabolic  activation.
Similarly,   the  response   obtained   in   the   Aspergillus   assay  with
activation  decreased by  approximately 40% from  day 0  to  180, while the
sample  from  day 360 was  not   tested  (Figure  76).  In the  COMBO  waste
amended  Bastrop  soil,  none  of  the runoff samples  induced a significant
increase  in  revertant  colonies   in the absence  of  metabolic activation.
In  the  presence  of metabolic   activation,   the mutagenic activity  in
Salmonella  of the  sample collected on day  0 was less  than the control,
while the  mutagenic activity  of  the sample  collected  on day  180 was
slightly  greater than two times background;  the sample collected on day
360   induced   a  response  that  was  greater   than   2.5  times  background
(Figure  81).  However,  in  the   Aspergillus  assay  with  activation,  the
mutagenic  potential  of  the  runoff  water  from the   Bastrop  soil  was
approximately equal  on days  0 and  180 and significantly lower on day 360
(Figure  76).  Thus,  the results  from the Salmonella  assay indicate  that


                                 210

-------
              TABLE 63. TOTAL  HYDROCARBONS  EXTRACTED FROM RUNOFF WATER USING COMBINED XAD2 RESINS
ISJ
Extractable Hydrocarbons (mg/1)
Sample
Wood-Preserving Waste
Norwood soil
Bastrop soil
Storm-Water Runoff Impoundment
Norwood soil
Bastrop soil
Combined API-Separator/
Slop-Oil Emulsion Solid
Norwood soil
Bastrop soil
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60
78

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NS
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-------
for  COMBO  waste  amended  soils,  significantly  greater  quantities  of
mutagenic  activity  were detected  in the  runoff water  from the  Norwood
soil than  in  the runoff water  from  the Bastrop soil; and  in both soils,
the  maximum amount  of mutagenic  activity  was observed  in  the  sample
collected 360 days after waste application.

     The  results from  this  segment of  the research  indicate that  the
mutagenic  potential  of runoff  water from  hazardous waste  amended  soils
should  eventually  return  to  background   levels.   The  amount  of  time
required  for  the mutagenic  potential of  runoff  water  to  return  to
background  levels will  be regulated by the  quantity and  degradation rate
of mutagenic  compounds in  the  waste as well  as the waste  loading  rate.
These  results  have  also  demonstrated  that   there  will  be  dramatic
differences  in  the  degradation  rates  between  wastes  and  between soils.
As a general  rule,  the mutagenic  potential  of the runoff  water  from day
0 was  greatest  from  the  PENT  S amended soils  and  least  from the  COMBO
waste  amended  soils;  while  the mutagenic  potential of  the sample  from
the  SWRI  waste  amended  soil   was   greatest   on  day  180  and  360.  In
addition,  the  mutagenic  potential  of  runoff  water  from waste  amended
Norwood  soil was greater  than  that  of  the runoff water  from the  Bastrop
soil.  Thus,  since  different  soils will  have  substantially  different
capacities  to  retain  and  degrade  organic  compounds,  bioassays  provide
the most  effective  analytical tool  for evaluating when runoff water may
be safely  released  following  closure of a hazardous waste  land treatment
facility.
                                  216

-------
                               SECTION 9

            AFFECT OF DEGRADATION ON THE MUTAGENIC ACTIVITY
                    OF HAZARDOUS WASTE AMENDED SOIL
INTRODUCTION

     The  application  of  hazardous  waste  to  soil  is  restricted  by
regulations to  include  only those wastes which  will be rendered  less or
non-hazardous  by  chemical  or  biological  reactions  in  the  soil  (EPA,
1982).   These  regulations  assume  that  degradation,  immobilization, and
transformation  will  serve  to  reduce  the  hazardous  characteristics  of
soil  applied  waste  constituents.  Degradation  in   soil   is  generally
assumed  to  be  biological,  and  biological  degradation normally  accounts
for  approximately  80% of  soil  degradation  (Hamaker, 1971).   However, in
a  soil  contaminated by  the  toxic  and resistant  compounds  frequently
encountered in  a hazardous waste, chemical and  photochemical degradation
will  also  play  an  important role.   Soil degradation may  not result in
the  complete  mineralization  of a hazardous  waste,  but soil degradation
can   certainly   render   waste  constituents   less   or  non-hazardous  by
removing  substituted  groups,  by  breaking   an  aromatic   ring,   or  by
substitutions  that  produce  a  less  reactive  product.   Soil degradation
may  not, however,  always  result in detoxification  of a hazardous  waste.
Thus,  techniques  are needed to evaluate the affect  of degradation on the
mutagenic activity of hazardous waste amended  soil.

     The  technique  which  is  currently being  used  to   monitor  land
treatment  employs  a chemical  analysis  to  define  the  products  of the
various  reactions  that  may  occur in  the soil.   Chemical analysis  alone
may   fail  to  account   for   the  interactions   between  soil   and  waste
components  and  the  affect  of  degradation  on  these  interactions.   In
addition,  the  results  from a  chemical  analysis must be extrapolated  to
estimate  the  toxicological  endpoint  in  a  biological system. The  use  of
bioassay   directed  chemical   analysis   as  an  alternative   monitoring
technique  provides  more accurate information  from which to  obtain a risk
assessment.  This  technique employs a battery of short-term bioassays  to
define  the  acute and chronic toxic potential  of a sample with  a  chemical
analysis to enhance  the  result  from the  biological systems.
                                  217

-------
MATERIALS AND METHODS

Waste

     Three petroleum  based  sludges were used  in  the  greenhouse  study.   A
general  description  of  sludge  characteristics is  provided in  Table  50,
while  a  more  detailed  description   is  included  in  Section  5.    The
wood-preserving bottom  sediment  (PENT  S), storm-water  runoff  impoundment
(SWRI),  and  combined  API-separator/slop-oil emulsion   solids  (COMBO)
wastes  were  applied  to  the  soil at  hydrocarbon loading  rates of  3.1,
4.5,  and 4.5%,  respectively.   Application  rates were calculated  using
the formula discussed in  Section 8.

Soil

     The  physical  and  chemical  properties  of  the  soils used  in  the
greenhouse  study  are   provided   in   Table  42,  while  a  more  detailed
discussion of the Bastrop and Norwood  soils  is included in Section 6.

Extraction Procedures

     Soil  and  waste  samples in  the  greenhouse study were  extracted with
dichloromethane.   Dichloromethane was  selected from a group  of solvents
to  extract  the organic  fractions  of  the  soil  as  it  consistently provided
the greatest  extraction efficiency for the  types of compounds present in
the   waste  (McGill  and   Rowell,   1980;   Donnelly  and   Brown,   1981).
Twenty-five  grams of  the waste  or  waste-soil mixture were blended with
six  volumes  of dichloromethane  in  a Waring  Laboratory  blender for  30
sec.   This  extraction was  repeated  twice  or until  the  extracting solvent
remained colorless.   Solvent extractions  were then  combined and taken to
dryness  on  a   Brinkman-Bucci  rotary  evaporator. The  residue  from this
extraction  was  partitioned   into  acid,  base,   and  neutral  fractions
following  the  scheme  outlined  in Figure 12.

Chemical Analysis

     A  chemical   analysis   was   conducted  on selected   samples  by  the
USEPA's  RS Kerr  Environmental  Research Laboratory.  The  procedures used
were  the same  as  those  discussed in  Section  8.

Soil  Sample  Collection

     A  composite  sample representing approximately  500  g  of  soil  was
collected  from each box  24  to  48 hours following rainfall events,  i.e.,
before,  immediately  after,  and 0, 45,  90,  180,  360,  and  540  days  after
waste  application.   Soil  samples were composited from 6  to  10 randomly
selected plugs, each representing the surface to 17 cm soil.  Each sample
was  stored  at 0  C  in  a  labeled  ziplock bag prior  to  extraction.   In
addition,  reserve samples  from  each  box and each collection date will be
stored for  five years following completion of the project.


                                  218

-------
Biological Analysis

     Two  different   microbial   mutagenicity  assays  were   employed   to
evaluate  the  capacity  of  soil  extracts  to induce  genetic damage.  The
Salmonella/mi crosome   assay  of   Ames  et   al.    (1975)  was   used   to
monitor  the  mutagenic  activity  of  concentrated  water  samples.    The
Salmonella  strains were  supplied  by Dr.  Bruce N.  Ames (University  of
California, Berkeley,  CA).   The  procedural  methods were  the same  as Ames
et   al.   (1975),   except   that  overnight   cultures   were   prepared   by
inoculation  into  10   ml  of  Nutrient  Broth  #2  (KG  Biological,  Inc.,
Lenexa,  KS)  and  incubated  with   shaking   for  16  h  at  37  C.    Water
extracts were  tested  on duplicate  plates  in two independent experiments
in the  standard  plate incorporation  assay  at a minimum  of  4 dose levels
of the  sample  with and without enzyme activation  (0.3 ml rat liver/ml S9
mix)  using  strains TA98  and TA100.  Aroclor 1254  induced  rat  liver  was
obtained  from  Litton  Bionetics  (Charleston,  SC).    Positive  controls
included  2  ug/plate  N-methyl-N'nitro-N-nitrosoguanidine   (Sigma)   for
TA100,  25  ug/plate 2-nitrofluorene   (Aldrich)  for  TA98, and 10 ug/plate
2-aminoanthracene  (Sigma) which  was  used with  all  strains  to  verify  the
functioning  of  the  metabolic  activation   system.   All   reagents   and
extracts were tested  for sterility;  DMSO was used as  a negative control.

      Soil  samples  were also  tested  in  the eukaryotic bioassay using A.
nidulans.   The  Aspergillus  system  was  used   to  assess   the  mutagenic
potential  of  soil extracts by evaluating  the induction of mutations at
the  methionine  suppressor  loci.    Conidia  from  four  to  five  single
colonies   of   the  methGl   biAl    (requiring   methionine   and  biotin)
Glasgow  strain  of Aspergillus  nidulans  grown  for 5   to  6  days  on  a
complete  medium at   37 C were  used for each  experiment.   Samples  were
tested  at  one  dose level,  usually  the extract equivalent to one gram of
soil  and  one  exposure time selected to  yield approximately 50% survival
on five  plates  in two independent  experiments  with and  without metabolic
activation.   The  procedures  were   the  same   as  Scott  e±  al.   (1978)
except  that  the cells were exposed  in a  13  x 100 mm  screw-capped  culture
tube.   The  exposed cells  were plated on  a complete medium to determine
survival  and  on  a  methionine-free medium to  determine  the  induced
mutation  frequency.    Mutant  colonies  were  scored  after incubation  for
five  days  at   37  C.   Colonies  were divided  by colony  morphology  into
three   classes,  A,   B,  C,   as  well as  the  total  mutation  frequency
represented by  the sum of  induced  mutants   from Class A,  B, and C.   Each
of these  three classes is  believed  to involve  two  genes.  The  morphology
of  Class  A  colonies  is green,  Class B brown,  and Class C green with a
white  hyaline  edge.  For the  acid,  base  and  neutral fractions of the soil
extract,  only  the total  induced mutation   frequency was  calculated.  The
frequency   of   mutations    induced   by   each  sample  was  determined  by
subtracting  the   frequency  of  spontaneous  mutations   from  the  total
mutation   frequency.    A   sample    was   considered  positive   if   the
induced-mutation  frequency  was more than twice the  spontaneous mutation
frequency.      Positive      controls     included      8-methoxypsoralen,
8-methoxypsoralen   plus    near   UV  light   without   activation,    and
                                  219

-------
benzo(a)pyrene with metabolic activation.

RESULTS AND DISCUSSION

     The  soils  collected  in  the  greenhouse  study  were  analyzed  using
both  chemical and  biological  techniques.  Residual  hydrocarbon  analysis
was used  as  a gross measurement of degradation, while  GC/MS  analysis  was
used  in  an  attempt  to  identify  the  resistant  and/or  mutagenic  waste
constituents.  Biological  analysis was utilized  to  define the affect  of
degradation  on  the  mutagenic  activity  of residual  hydrocarbons in  the
soil and  to  determine if the wastes  were rendered less or non-hazardous
by soil incorporation.

     The  amount  of  residual  hydrocarbons in  the soil  at  various  time
intervals  following waste application  provides a preliminary  indication
of  the  progress  of  waste  degradation.  The   total  and    extractable
hydrocarbons  in  the  acid,  base,  and neutral  fractions  were  determined
for each  waste/soil  mixture  on days  0,   90,  180,  and 360,  and  for  the
PENT S  waste/soil  mixtures  on day 540.   The results  in Table 64  indicate
that the  overall  degradation rate of  the PENT S waste after 540 days in
the Norwood  and  Bastrop  soils were  83  and 66%,  respectively.   The  most
rapid rate of degradation occurred in  the base fraction.  In the Norwood
soil,  only  5% of  the base  fraction  was  residual  after  540 days,  while
10% of  the  base  fraction was  residual  in the Bastrop  soil.   The neutral
fraction,  which   represented   approximately   90%  of  the   extractable
hydrocarbons  in  the waste,  degraded  rapidly from day 0 to 180  but slowed
appreciably  from day  180  to 540.  The  degradation  rate  for  the neutral
fraction  over the  first 180 days  was 66% in the  Norwood  soil  and 51% in
the Bastrop  soil;  whereas,  the  rate  from 180  to 540  was  only  50% in the
Norwood  soil and  25% in the Bastrop  soil.  These results indicate  that
significant   quantities  of  the   wood-preserving  bottom  sediment   were
degraded  in  both  soils.  In addition,  while less  than 50% of the applied
hydrocarbons  were  residual   180  days  after  waste  application,  those
compounds  residual after day  180 had  a  much  slower rate of degradation
than the  components of  the initial waste/soil mixture.

     For  soils amended with the storm-water runoff  impoundment,  the most
rapid rate  of degradation  was observed  in the Bastrop clay  (Table  65).
The overall  degradation  rate  of  the  SWRI waste  was 53% in  the Norwood
soil  and  61% in the  Bastrop soil.   In  the Norwood  soil, the  most  rapid
rate  of  degradation after  360  days  was 60%  in  the  acid  and  base
fractions.   In  the  Bastrop  soil, the  most  rapid   rate  of  degradation
after  360 days was  62%, which  occurred  in the neutral fraction.   While
the  degradation  rates  for  the first  180 days  were  quite  low  in  both
soils,  less  than  50%  of  the applied  hydrocarbon remained  in  the  soil
after day 360.

     The  combined  API  separator/slop-oil  emulsion  solids exhibited  the
most  rapid  rate  of degradation  of the  three wastes  studied.   The overall
degradation  rate  in  the Norwood soil was 74% after  360  days,  and 83% in
                                 220

-------
                       TABLE 64. TOTAL HYDROCARBONS EXTRACTED  FROM  SOIL AMENDED WITH WOOD-PRESERVING BOTTOM SEDIMENT
to
Extractable Hydrocarbons (mg/g)
Sample
Norwood Soil
Acid
Base
Neutral
Total
Bastrop Soil
Acid
Base
Neutral
Total
0

7.0
3.8
122.2
135.0

11.0
4.0
124.0
139.0
Days After Appplication
90 180

4.8 + 2.1
2.7 + 1.0
42.1 + 3.8
49.7 + 6.4

6.6 + 2.6 5.3 + 2.5
5.7 + 0.2 3.1 * 2.3
82.9 + 43.4 60.6 + 8.7
95.3 + 45.8 69.0 + 4.4
Z Degraded
360

1.5 + 0.5
0.8 + 0.15
34.3 + 8.4
36.7 + 8.9

4.7 + 1.1
1.1 + 0.3
55.2 * 5.7
61.0 + 6.6
540

1.6 + 0.6
0.3 + 0.2
20.9 + 3.0
23.4 + 4.5

3.1 + 0.8
0.4 + 0.1
44.3 * 9.0
47.8 + 9.0
Day 360

79
86
72
73

57
72
55
56
Day 540

77
95
83
83

72
90
64
66

-------
                 TABLE 65. TOTAL HYDROCARBONS  EXTRACTED FROM SOIL AMENDED WITH STORM-WATER RUNOFF

                                                   IMPOUNDMENT
NS '
t-0
to
Extractable Hydrocarbons (mg/g)
Sample
Norwood Soil
Acid
Base
Neutral
Total
Bastrop Soil
Acid
Base
Neutral
Total
0
1
0.5
39.5
41.0
0.5
0.4
52.1
53.0
Days After Appplication
90 180
1.5 +
1.0 +
32.1 +
34.7 +
0.7 +
0.3 +
33.3 +
34.3 +
0.9
1.0
15.5
13.7
0.3
0.05
7.9
8.1
0.5 +
0.4 +
31. 4 +
32.3^
0.7 +
0.4 +
37.6 +
38.7 +
0.3
0.15
6.9
6.8
0.1
0.2
11.0
10.7

%
360
0.4
0.2
18.6
19.2
0.4
0.2
19.9
20.5
+ 0.2
+ 0.1
+ 3.5
± 3-7
+ 0.2
+ 0.03
+ 7.3
+ 7.0
Degraded
Day 360
60
60
53
53
20
50
62
61

-------
the Bastrop soil  (Table  66).  The degradation  rates  of the  fractions  of
the COMBO  waste were  78,  75, and  74%  for  the acid,  base,  and neutral
fractions  in  the  Norwood  soil.   In  the  Bastrop  soil,  the degradation
rate  for  the  acid, base,  and  neutral fractions  were 94,  0,  and  82%,
respectively.    Thus,  for  the  COMBO  waste,  the  most  rapid  rate  of
degradation occurred  in the  acid fraction  and the  least  rapid rate  in
the base  fraction.   In addition, the  average  total degradation rate  for
the COMBO  waste in both soils was 49%  from  day 0  to  180 and  60%  from day
180 to 360.

     A  comparison of  the  average degradation  rates  of the  three  wastes
indicates  that  at  day 360,  the COMBO  waste was  79% degraded, while  the
PENT  S  and  SWRI  wastes  were  degraded  65 and   57%,  respectively.  The
average  total rates of degradation  for day 0  to  180 and  day 180  to  360
were  57  and 18% for the PENT  S  waste,  24 and 44%  for the  SWRI  waste,  and
49  and  60%  for the COMBO waste, respectively.  For  the  COMBO and  SWRI
wastes,  the most rapid rate of  degradation  occurred  in the Bastrop soil;
whereas,  the   PENT S  waste degraded  most  rapidly  in the  Norwood  soil
(Figure  82).   Previous studies  with  two API-separator sludges  found the
rate  of degradation in  the Norwood  soil to  be   from 30  to 60%  greater
than  the  rate  of degradation  in  the  Bastrop  soil  (Brown  and  Donnelly,
1983).   The  half-life  of  all  three wastes,  as measured  by  residual
hydrocarbon  content,  was  less  than  360 days.   Thus, these preliminary
results  indicate that  all  three  wastes were transformed and degraded by
soil  incorporation.

      The  evaluation   of  residual  hydrocarbon  data  does  not,  however,
provide  an  indication of  the  affect  of  degradation  on  the  mutagenic
activi-ty of waste  constituents.  Only  through the  use of  bioassays can
these parameters  be  measured.  One  of the major  limitations  of  using
these  bioassays  is  the   absence   of  a   standard  procedure  for  the
statistical   evaluation  of  environmental  data.   While  there  have  been
several   procedures   suggested   for   the   analysis   of   bioassay  data
(Commoner, 1976;  Munson  and  Goodhead,  1979; Horn  et  al. ,  1983;  Chu
e± al.,  1981;  Katz,  1979;   Bernstein  et  al.,  1982;  and  Moore  and
Felton,   1983),   none  of  these  procedures  include  adjustments  for
background levels  of  mutagenic activity  in  environmental  samples.  The
bioassay  data  from  the   greenhouse  study  were  evaluated  using  two
procedures.   Comparisons  that were made  on a weight  basis  reviewed the
total mutation  frequency  at  five  equally   spaced  dose levels.   Data was
accumulated on each sampling  date  for all  three  fractions  of  each waste
from  three boxes of each  soil.   Thus, each value in Tables 67 to 90 and
Figures  83 through 106 represents  the mean  of   12  plates  from at least
two independent experiments.  This data is  an  expression of  the mutagenic
potential of  the residual  hydrocarbons in   the soil  and  does not account
for losses due  to  degradation.   However,  an indication of  the effect of
degradation on  the mutagenic potential  of the residual  hydrocarbons in
the  soil  is   provided by  the  data.   Comparisons  that  were  made  on a
volume basis  reviewed the  mutagenic  activity  ratio  of a  constant volume
of soil  and   can be  used  to  determine the  reduction of  the  hazardous
                                   223

-------
             TABLE  66.  TOTAL HYDROCARBONS EXTRACTED FROM SOIL AMENDED WITH COMBINED API  SEPARATOR
                                             SLOP-OIL EMULSION SOLID
Ni
N>
Extractable Hydrocarbons (rag/g)
Sample
Norwood Soil
Acid
Base
Neutral
Total
Bastrop Soil
Acid
Base
Neutral
Total
0
1.5
0.4
21.1
23.0
3.6
0.7
29.7
34.0
Days After Appplication
90 180
1.3 +
0.4 +
17.7 +
19.3 +
0.8 +
0.2 +
8.7 +
9.7 +
0.1
0.1
2.3
2.3
0.2
0.1
0.9
0.6
360
0.33
0.1 +
5.5 + 0
6.0 _+ 0
0.2 +
1.0 +
5.3 + 1
5.7 + 1


.09
.4
.45
.05
.02
.2
.3
% Degraded
Day 360
78
75
74
74
94
0
82
83

-------
to
N>
Ln
              I OO-i
           a
           O
           UJ
           O
               60-
20-
                     PS
                                 Cl
                      1
                           SI
1
      I
                    I
                           180
                                         PS
             i
             1
                                          i
                                               SI
                                 I
                    1
                                                     CO


I
                  360
                                     WASTEt
                                       PS-PENTS
                                       SI-SWRI
                                 S     CO-COMBO
                                     SOIL:
                                       NORWOOD   f~]
                                       BASTROP
      i
                                 i
                                              540—-I
                                          TIME (Dtyi)
                   Figure 82.  Degradation rate of total extractable hydrocarbons in Norwood
                              and Bastrop soils amended with PENT S (PS), SVRI  (SI), and
                              Combo  (CO) waste.

-------
waste characteristics  by land application.   Comparisons made  on a volume
basis account  for changes  in the  hydrocarbon content  of the  soil  over
time, as well as variations in the biological  test  system.

     To determine  mutagenicity  on a volume basis,  the mutagenic activity
ratio   (Commoner,   1976)  is   first   calculated   for  the  four  highest
non-toxic dose  levels.   The mutagenic activity ratio  is calculated using
the equation:

                              C   -  C
                         MAR=  n    °
                                  CA
where  C   is  the  total  number  of  revertant  colonies  on  experimental
plate  at  dose   n   (average   of  four   plates);  C   is   the  number  of
revertant  colonies  on  solvent control  plates  the same day  the  test was
run  using  the  same  strain   and  tissue  preparation  (average of  eight
plates);  and  C.  is  the  historical  average  of  solvent  control  plates
for  the  year the test  was  run.   Once the MAR's were calculated for each
set  of  data, the mutagenic activity  ratio for  a  specific  volume of soil
was  calculated using  the  equation:

                        R  =[  V  3[MAR]
                          v     W
                                T

where  V is  the  volume of  soil  (gram  equivalents);  WT is  the volume of
soil  equivalent  to  dose  of  residue   =  DOSE  (mg/plate)  -  extractable
hydrocarbons   (mg/g);  and  MAR  is   the  mutagenic activity  ratio.   The
mutagenic   activity  ratios   which   are  used  calculate   the  Ry  were
calculated  from  the  two  non-toxic  dose levels  closest  to  the  selected
volume  of  soil   which  fell on. the  linear  portion of the  dose-response
curve.   The selected  volume  of soil was  that volume of soil  which fell
between  two  dose  levels  which  were   used   in the  bioassays and   was
comparable  to the  optimum dose for  the volume of soil extracted  on Day
0.   The  extracts  of  the  thre'e  fractions  from each  soil-waste  mixture
were  tested at  five equally  spaced  dose  levels ranging from  .01  to 1.0
mg/plate.    For   the  acid  and base  fractions,  these  dose   levels  are
equivalent  to  the extract  from approximately .05  to  5.0  g of soil.  The
neutral  fraction, which  accounted  for  approximately  90% of  the residual
hydrocarbons  in  the  soil-waste  mixtures,  was tested at  the  same dose
levels  on the basis  of residual  hydrocarbons that were equivalent to the
extract  from approximately 0.2 to  20 milligrams of soil.   Thus, in order
to   calculate  R^  using  MAR's derived  from  the   linear  portion  of  the
dose-response  curve,  the volume  of  soil  used  for comparing the neutral
fraction  will  be  one  tenth   the  volume  used  for  the  acid and  base
fractions.   By employing these  calculations, the  mutagenic  potential of
equal  volumes  or  masses of   soil  can   be  compared.   In addition, these
calculations  will  account  for the  variability of  the bioassay  and the
reduction  in  the  amount of  extractable  hydrocarbon in  the  soil  over
time.   The   data  from  the  Sa Imone 1 la  assay  was evaluated  on   both  a
                                 226

-------
weight and  volume basis,  while the data  from the Aspergillus  assay  was
only evaluated on a volume basis.

     The dose-response  curves  with strains  TA98  and TA100 for  the  acid,
base, and neutral fractions of  the PENT S waste  amended  Norwood soil  are
provided in  Figures  83 through  88 and  Tables  67  through  72.   In the acid
fraction, the  maximum response  in strain  TA98 was induced by  the sample
collected on day 180  (Figure  83  and   Table  67); while,  in  strain  TA100
the  maximum response  was  induced by  the  sample  collected on  day  360
(Figure  86  and Table 70).   In  both  strains,  the  response induced by the
sample  collected  on  day  540   was  appreciably  lower  than  the  maximum
response induced  by  samples collected  prior to  day  540.   A similar  trend
was  observed  in  the  base  fraction  from  PENT  S waste  amended  Norwood
soil.   For  strain  TA98,  the   maximum response observed   in  the  base
fraction was induced  by  the sample collected on day 360  (Figure 84  and
Table 68),  while  in  strain  TA100  the sample collected on day 540 induced
the  maximum response (Figure 87 and Table 71).  In  addition, significant
levels of  direct-acting  mutagens  were detected  on  day  540, whereas  no
direct-acting  mutagens   were   detected in   the  waste  or   soil  samples
collected  prior  to   this  date.  The  maximum  response  induced by  the
neutral  fraction was  observed  in the sample  collected  on day 180  in
strain TA98  (Figure  85 and  Table  69)  and  in  the sample collected on day
360  in TA100 (Figure 88  and Table 72).  These  results  indicate that for
the  PENT   S waste  amended Norwood   soil,   the  factors  affecting  the
mutagenic potential  of the  residual hydrocarbons initially increased but
eventually  decreased the  mutagenicity  of  the acid and neutral fractions.
While  in the  basic  fraction,   the  mutagenicity  was increased  over  the
entire   540  day  period   with   an apparent  increase  in  direct-acting
mutagenicity also occurring.

     In  the  PENT S waste  amended Bastrop  soil,  the  overall  rate  of
hydrocarbon  degradation  and the  rate  of detoxification appeared  to  be
lower than  the rate in the  Norwood soil.   The maximum mutagenic response
induced  by  the   acid,  base, and  neutral  fractions  was  observed in  the
sample collected  on  day  540 in strain TA98  (Figures  89,  90, and 91, and
Tables  73,   74, and  75) and on  day 360 in strain TA100  (Figures  92,  93,
and  94  and  Tables  76, 77,  and 78).   As  occurred  in the  Norwood  soil,
direct-acting  mutagens were detected   in  the base  fraction  collected on
day  540  in  both  strains  (Figures  90 and  93  and Tables 74 and 77).  Thus,
the  mutagenic  activity  of  all  three  fractions from  the  PENT  S  waste
amended  Bastrop  soil appeared  to  reach a  maximum on day 360 as measured
with strain TA100,  while  the maximum  response in strain TA98 was induced
by  the sample  collected on day  540.

     The  dose-response  curves   for  the hydrocarbons extracted  from the
SWRI waste  amended  Norwood  soil  are   given in  Figures  95,  96,  and  97.
The  mutagenic  activity of  the  acid  fraction  increased  from  day 0  to 180
and  from day  180 to 360   (Figure  95 and  Table 79).   While the mutagenic
potential of the acid  fraction of the  soil-waste mixture from days 0 and
180  were less  than  the  mutagenic potential of  the  acid  fraction of the
                                  227

-------
   600-
  400-
co
o>
             NORWOOD-RENTS-ACID
                   WASTE
•	•  DAY 0


B	B   180


•	•   360


T	V   540
             + S9
                -S9
  200-
                I 00
                         300
                             DOSE/PLATECufl)
500
I 000
         Figure 83.  Mutagenic activity of acid fraction of PENT  S

                    amended Norwood soil as measured with £.  typhimurium

                    strain TA98 with and without metabolic activation.
                              228

-------
600
400
200
            NORWOOD•RENTS • BASE
              00
300
500
000
                           DOSE /PLATE
-------
   600
   400
CO
o>
  200
                   NORWOOD • PENTS• NEUTRAL
                I 00
300
500    I 000
                             DOSE/PLATE Cuj)
        Figure 85.  Mutagenic activity of neutral fraction of PENT S
                   amended Norwood soil as measured with S_ typhimurium
                   strain TA98 with and without metabolic activation.
                              230

-------
   600-
NORWOOD- PENTS'ACID

• '•• • DAYO O

H H 180 X
• .• 36O n 	
v n i iir R 
-------
                                                       833
                                    69 I
  600
  400
o
O
  ZOO-
                           NORWOOD -RENTS- BASE
       WASTE
       DAY 0
B	B   180
        360
        540
               100
        300
500    1000
                             DOSE/PLATE Cug)
         Figure 87.  Mutagenic activity of base  fraction of PENT S amended
                   Norwood soil as measured with ^ typhimurium strain TA100
                   with and without metabolic  activation.
                               232

-------
  600i
                                   NORWOOD-RENTS-NEUTRAL
           WASTE £—&
           DAY 0 O—O
    B	S   | 80  X—X
            360  D	O
            540
• 400-
O
O
  200-
                100
300
500    I 000
                             DOSE/PLATECug)
           Figure 88.  Mutagenic activity of neutral fraction of PENT S
                      amended Norwood soil as measured with £. typhimurium
                      strain TA100 with and without metabolic activation.
                                 233

-------
TABLE 67. MUTAGENIC ACTIVITY OF ACID FRACTION OF PENT S WASTE AMENDED NORWOOD SOIL AS MEASURED WITH
                S TYPHIHURIUM STRAIN TA98 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA98 his * Revertants (Mean + S.D.)
Day S9 0
j Day 0 - 21 +
+ 22 *
Jj Day 180 - 27 *
*- + 36 i
Day 360 - 28 +
* 37 ±
Day 540 - 28 4
+ 38 +
2.5
4.4
2.6
2.9
0.2
0.2
0.8
3.3
1
Toxic
Toxic
Toxic
Toxic
Toxic
85 + 35.0
21 * 8.4
44 + 19.8
Dose/Plate (rag)
.5
20
126
34
144
37
157
37
110
+
+
+
+
7
+
+
8.4
11.3
18.8
60.6
5.3
18.9
6.4
12.9
21
49
40
120
42
133
32
111
.1
+ 5.0
± 5-9
+ 5.7
+ 25.3
+ 21.8
* 6.9
+ 7.3
+ 27.9

21
42
37
100
41
112
35
72
.05
+ 5.6
* 17.7
+ 6.2
+ 37.2
+ 25.5
+ 10.5
+ 10.7
+ 23.9
•
17 +
17 +
33 +
59 +
42 +
68 +
23 +
43 +
01
2.6
6.2
4.4
11.3
27.3
18.9
1.1
5.3

-------
N>
CO
U1
                          TABLE 68. MUTAGENIC ACTIVITY OF BASE FRACTION OF  PENT 8 WASTE AMENDED  NORWOOD  SOIL AS  MEASURED WITH

                                                S. TYPHIHURIUM STRAIN TA98  WITH AND WITHOUT METABOLIC ACTIVATION

Total TA98 his Revertants
Day S9
Day 0
+
Day 180 -
Day 360 -
+
Day 540 -
+

21 +
22 +
27 +
36 +_
29 +
39 +
27 +
40 t
0
2.5
4.4
2.6
2.9
0.9
5.0
0.8
3.3
1
24 + 6.3
112 +_ 12.4
60 + 32.9
284 ±137.8
111 + 15.4
540 + 23.7
59 + 11.0
334 ±158.0
(Mean +
Dose/Plate (nig)
.5
21 +
98 +
51 *
293 +
106 «•
417 +
74 +
381 +
4.2
31.3
34.8
115.0
16.7
22.4
40.0
133.0
24 +
62 +
38 +
215 ±
62 +
170 T
52 +
274 +
S.D. )
1
3.6
20.4
9.7
53.0
22.8
14.4
28.0
147.0


20 +
37 +
35 +
157 +
55 +
151 ±
34 +
163 T

.05
7.8
7.8
16.5
26.8
34.6
2.8
29.0

•
19 +
22 +
31 +
72 ±
44 +
75 *_
28 +
68 +

01
3.3
7.0
6.7
25.8
28.5
11.5
.71
13.0

-------
NJ
Co
                     TABLE 69. MUTAGENIC ACTIVITY OF NEUTRAL FRACTION OF PENT S WASTE AMENDED NORWOOD SOIL AS MEASURED WITH
                                           S. TYPHIMURIUM STRAIN TA98 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA98 hia *
Day S9
Day 0
Day 180 -
Day 360 -
Day 540 -

21 +
21 i
26 +
36 +
28 +
36 +
27 +
39 +
0
3.6
1.8
2.4
2.9
1.0
1.0
0.8
2.9
1
22 +
86 +
204 +
281 7
50 +
184 7
50 +
144 +
Revertanta
(Mean + S.D.)
Dose/Plate (mg)
.5
6.7
7.6
154.5
78.3
5.5
24.1
11.5
44.7
19 *
96 7
126 +
220 +
36 +
160 +
41 *
136 +
5.1
28.2
68.3
40.7
1.4
16.9
5.9
22.6
24
62
38
215
62
144
31
128
.1
+ 3.6
+ 20.4
* 9.7
+ 53.0
+ 22.8
+ 20.5
+ 4.1
+ 7.7

20 +
37 *
35 +
157 *
55 +
119 +
27 +
105 +
.05
7.8
7.5
7.8
16.5
26.8
10.7
1.8
10.3
•
19 +
22 +
31 +
72 *
44 *
64 T
24 +
57 +
01
3.3
7.0
6.7
25.8
28.5
9.2
1.1
9.8

-------
ro
u>
                        TABLE 70. MUTAGENIC ACTIVITY OF ACID FRACTION OF PENT  S WASTE AMENDED  NORWOOD  SOIL AS MEASURED WITH

                                              S. TYPHIHURIUM STRAIN TA100 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA100 his * Revertants (Mean + S.D.)
Day S9
Day 0
Day 180 -
•f
Day 360 -
Day 540 -

93 +
40 J_
105 +
107 +
156 +
135 j*
115 +
126 +
0
18.9
11.9
5.1
17.8
6.0
2.2
7.5
0.7
1
Toxic
Toxic
Toxic
Toxic
Toxic
Toxic
Toxic
113 + 25.8
Dose/Plate (rag)
.5
Toxic
226 + 17.3
Toxic
307*
Toxic
287 + 157.4
72 + 11.0
235 + 31.4

84
202
94
362
147
557
113
376
.1
* 7.4
+ 16.7
+ 22.4
+116.9
+ 12.3
+ 88.9
+ 5.6
* 28.1

87
162
105
275
147
419
110
288

+
+
+
+
+
+
.05
25.4
35.4
13.7
61.6
8.8
65.8
4.7
36.6

85 +
118 +
101 +
165 i
139 +
193 +
116 +
166 +
01
11.0
29.2
14.9
5.7
8.3
9.6
14.0
17.7
                 * Mean  represents  average  of  only  tvo  samples;  standard  deviation not  provided.

-------
Co
oo
                           TABLE 71. MUTAGENIC ACTIVITY OF  BASE FRACTION OF  PENT  S WASTE AHENDED  NORWOOD  SOIL AS  MEASURED WITH

                                                  S.  TYPHIMURIUH STRAIN TA100 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA100 his
Day S9
Day 0
+
Day 180 -
+
Day 360 -
+
Day 540 -
+

120
134
US
118
138
120
115
122
0
+ 21.9
± 10.6
+ 13.1
1 5-3
+ 7.7
± 1-1
+ 9.6
+ 3.4

298
56
129
154
486
691
528
1
Toxic
+ 22.0
+ 31.0
i 52.7
+ 10.5
* 98.6
* 90.9
* 53.04
Revertants (Mean -f S.D.)
Dose/Plate (mg)
.5
92 +
395 +
83 4
277 ^
148 +
621 *
433 +
884 +
11.3
86.8
15.0
74.1
22.5
108.8
153.4
63.9
.1
80 + 18.6
317 + 37.1
113 + 18.9
456 ±106.0
118 + 29.1
618 + 76.0
248 + 68.8
652 t 105.5

86 +
181 *
131 +
398 +
114 +
545 +
187 *
536 *
.05
8.8
78.8
25.6
80.8
29.4
65.4
53.6
23.0
•
95 +
119 +
132 +
193 +
111 +
259 +
121 +
259 *
01
15.6
27.03
55.2
51.3
30.7
82.5
6.8
65.4

-------
NJ
LO
VO
                    TABLE 72. MUTAGEHIC ACTIVITY OF  NEUTRAL  FRACTION  OF  PENT S WASTE AMENDED NORWOOD SOIL AS MEASURED WITH

                                       S.  TYPHIMURIUM STRAIN TA100  WITH  AND WITHOUT METABOLIC ACTIVATION

Total TA100 bia
Day S9
Day 0
Day 180 -
Day 360 -
Day 540 -
0
120 + 21.9
122 ±40.1
111 + 12.7
118 ± 5.3
130 * 14.0
120 ± 1.7
120 + 4.4
117 + 8.1
1
94 +
139 *_
136 +
346 +
132 +
375 *
139 +
280 +
L
13.0
44.7
39.1
152.0
28.9
22.9
9.0
51.2
Bevertanta (Mean
Dose/Plate (mg)
.5
105 +
352 *
125 +
364 +
126 +
455 +
122 +
328 +
22.2
45.6
22.1
124.0
22.0
23.2
11.4
40.8
84 +
244 +
136 +
372 +
125 +
571 +
108 +
434 +
+ S.D.)
1
17.0
136.0
29.5
99.0
23.5
30.7
9.4
31.0


77
296
148
315
112
474
111
355

.05
+ 14.1
+ 41.1
+ 41.2
* 59.2
+ 21.6
+ 13.3
+ 15.7
±14.6


43 +
133 +
139 +
156 +
118 +
211 +
115 +
201 +

.01
47.9
5.7
38.6
9.5
14.8
22.8
3.6
39.1

-------
   600i
•  400-
co
0)
   200-
          BASTROP  RENTS ACID
                 WASTE
                 DAYO
          S	3  I 80
                  360
                  540
                                                         500     I 000
                              DOSE/PLATE Cug)
        Figure  89.  Mutagenic activity of acid fraction  of PENT S amended
                   Bastrop soil as measured with £ typhimurium strain TA98
                   with and without metabolic activation.
                                240

-------
   60 O
   400
CD
0>
   200-
                   1006
»-

BASTROP. PENTS'BASE
A 	 A WASTE & 	 &
B 	 B 1 80 * 	 *
+S9 -S9

                100
300
500 " '  I 000
                              DOSE/PLATE
        Figure 90.  Mutagenic activity of base  fraction of PENT S amended
                    Bastrop soil as measured with £ typhimurium strain
                    TA98 with and without metabolic activation.
                               241

-------
   600
  400
0
o>
  200-
                       BASTROP-RENTS•NEUTRAL
                            ,4 WASTE
                            -• DAY 0  O
8 - B   180   X

• - •   360   D

T - T   540   V
                                              K
                          +S9
                -S9
                I 00
             300
                             DOSE/PLATECug)
500
I 000
       Figure 91.  Mutagenic activity of neutral fraction of PENT S
                  amended Bastrop soil as measured with £. typhimurium
                  strain TA98 with and without metabolic activation.
                                242

-------
TABLE 73. HUTAGENIC ACTIVITY OF ACID FRACTION OF PENT S WASTE AMENDED BASTROP SOIL AS MEASURED WITH
                      S. TYPHIHURIUM STRAIN TA98 WITH AMD WITHOUT METABOLIC ACTIVATION







Total TA98 hi* * Revertanta
ro
•P-
U)



Day S9
Day 0
+
Day 180 -
•f
Day 360 -
+
Day 540 -
+

21 +
25 +
28 +
35 +
26 +
43 +
31 *
39 +
0
4.9
4.3
2.0
3.7
2.3
3.3
2.7
5.7
1
Toxic
87 + 37.7
Toxic
Toxic
Toxic
Toxic
Toxic
513 + 390.8

(Mean + S.D.)


Doae/Plate (mg)
.5 .1
77
117
128
110
364
184
647
Toxic
+. 10.5
* 45.8
+ 41.2
+ 140.5
» 432.0
+ 123.8
+ 421.5
17 + 5.1
53 + 5.0
S3 + 3.8
138 ± 26.6
53 + 42.0
139 + 57.5
123 + 8.0
304 + 219.3
16 +
43 T
39 +
86 +
37 +
100 +
60 +
107 +


.05
2.4
4.6
2.6
9.0
6.4
23.4
29.3
29.9


•
16 +
27 _»
27 +
58 +_
32 +
56 +
34 +
59 +


01
1.8
7.1
3.0
2.2
5.1
10.6
8.3
13.4

-------
TABLE 74. MUTAGENIC ACTIVITY OF BASE FRACTION OF PENT S WASTE AMENDED BASTROP SOIL AS MEASURED WITH
                      S. TYPHIMURIUM STRAIN TA98 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA98 his * Revertanta (Mean + S.D.)
Day S9
Day 0
Day 180 -
Day 360 -
Day 540 -

20 *
25 +
28 +
35 *
24 +
43 +
31 *
39 7
0
1.9
4.3
2.0
3.7
3.2
2.9
2.7
5.7
1
17 +
102 *
42 +
213 *
167 +
699 7
1394 +
1718 7
Dose/Plate (ing)
.5
6.3
24.4
6.13
48.0
93.0
372.7
1242.0
151.5
24 *
109 +.
33 +
208 7
137 *
452 +
1195 «•
1600 7
4.7
14.7
3.5
17.9
70.0
169.0
1140.0
410.4
15
69
31
164
60
184
624
1006
.1
+ 7.3
7 25.25
+ 2.4
+ 14.0
+ 17.0
1 *'5
+ 827.6
7 906.0
.05
18 + 2.5
60 7 8.7
26 * 4.9
116 ± 26.0
47 + 11.0
132 > 13.0
409 * 536.0
621 + 671.0
•
19 t
26 7
23 +
5' 1
30 +
69 +
99 +
119 +
01
4.4
2.4
4.7
10.3
6.1
11.0
101.4
59.3

-------
Ul
               TABLE 75. MUTAGENIC ACTIVITY OF NEUTRAL FRACTION OF PENT 8 WASTE AMENDED  BASTROP  SOIL AS MEASURED WITH
                                     S. TYPHIHURIUM STRAIN TA98 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA98 hia Hevertants
Day S9
Day 0
+
Day 180 -
Day 360 -
Day 540 -

20 +
25 +
27 +
35 i
23 +
44 +
31 +
49 +
0
1.9
4.3
0.7
3.7
1.5
3.6
2.7
5.7
1
23 +
122 +
56 +
189 +
43 +
137 +
52 +
226 +

7.7
16.8
21.7
8.2
6.4
45.0
12.0
113.0
Doae/Plate (mg)
.5
NT*
96 + 14.4
50 + 18.5
183 + 7.0
34+5.3
146 + 17.0
38 + 11.0
161 +47.0
(Mean +
•
18 +
56 +
34 +
149 +
34 +
132 +
35 +
121 +
S.D.)
1
4.3
13.6
5.0
15.0
4.9
28.0
.71
13.0


17 +
56 +
33 +
118 +
27 +
113 +
30 +
97 +

.05
2.0
20.6
5.9
30.5
4.9
41.0
2.8
10.6

•
IS +
27.3+
31 +
57 +
25 +
69 +
29 +
66 +

01
3.2
5.6
4.0
5.1
2.5
13.0
1.4
10.3
        ** Not  tested  due  to  limited  amount  of  sample  available.

-------
   600
  400
O
o
  200
                                  BASTROP- PENIS-ACID
                                                      500    1000
                            DOSE/PLATE (ug)
         Figure 92.  Mutagenic activity of acid fraction of PENT S  amended

                    Bastrop soil measured with S_ typhimurium strain TA100

                    with and without metabolic activation.
                                246

-------
  600i
  400-
o
o
  200-
                             BASTROP-PENTS•BASE

                                  A  WASTE

                                     DAY 0

                             ra	B   I 80  x	X
                 00
3DO
500     I 000
                             DOSE/PLATECuj)
        Figure 93.  Mutagenic activity of base fraction of PENT S amended

                   Bastrop  soil as measured with S_ typhimurium strain

                   TA100 with and without metabolic activation.
                              247

-------
   600
  400
o
o
  200-
                            BASTROP•RENTS'NEUTRAL
   WASTE
   DAY  0
     180
     360
     540
               I 00
300
500    I 000
                            DOSE/PLATE Cug)
        Figure 94.  Mutagenic activity of neutral fractionof PENT S amended
                   Bastrop soil as measured with £. typhimurium strain
                   TA100 with and without metabolic activation.
                              248

-------
TABLE 76. MUTAGENIC ACTIVITY OF ACID FRACTION OF PENT S WASTE AMENDED BASTROP SOIL AS MEASURED WITH
                      S. TYPHIMURIUM STRAIN TA100 WITH AND WITHOUT METABOLIC ACTIVATION












Total TA100 his * Revertants (Mean + S.D.)

ro
.p-
VO


Day S9
Day 0
Day 180 -
Day 360 -
t
Day 540 -

120
134
115
118
127
121
121
122
0
t 22.0
* 11.0
+ 13.0
+ 5.0
+ 9.0
± *•>
+ 5.1
+ 0.7
1
Toxic
Toxic
Toxic
Toxic
Toxic
Toxic
Toxic
121 + 18.0
Doae/Plate (mg)
.5

107
61
382
90
258
Toxic
Toxic
Toxic
+ 9.2
+ 21.0
i 121.9
+ 8.0
+ 74.6
.1
82 + 11.0
278 + 64.0
98 + 2.2
358 + 19.0
93 + 21.0
448 + 56.0
119 * 5.8
369 * 14.6

97
154
127
225
97
367
121
305
.05
+ 24.0
+ 35.7
+ 21.0
T 34.0
+ 16.0
+ 46.0
+ 5.2
+ 57.0

88 +
100 +
137 +
137 +
103 +
169 +
125 +
158 +
,01
11.0
21.0
31.0
24.0
29.0
18.0
4.3
17.0

-------
N)
Ul
O
                             TABLE 77. MUTAGEHIC ACTIVITY OF BASE FRACTION OF PENT S WASTE AMENDED BASTROP SOIL AS MEASURED WITH
                                                   S. TYPHIMURIUM STRAIN TA100 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA100 hi*
Day S9
Day 0
+
Day 180 -
4-
Day 360 -
+
Day 540 -
+
0
85 + 12.0
135 + 12.2
106 + 5.1
107 + 17.8
139 + 18.0
123 + 17.0
115 + 7.5
127 i 7.7
1
256 +
73 +
246 +
149 +
419 +
345*
433*
Revertants (Mean
Dose/Plate (mg)
.5
NT**
37.8
7.6
39.3
40.0
146.0

77 +
321 +
73 +
436 +
149 +
588 +
263*
643*
11.6
78.5
7.6
45.6
2.1
252.0

789 +
322 *
103 +
428 +
142 +
635 ±
150*
539*
+ S.D.)
1
19.0
30.7
10.0
138.0
18.0
245.0



66 +
226 +
107 +
450 +
143 +
591 +_
130*
427*

.05
7.1
19.3
7.7
121.0
15.0
260.0


•
84 *
140 i
115 +
184 +
139 +
272 +
121*
212*

01
4.6
28.6
15.2
10.2
16.0
118.0

                     * Mean represents average of only two samples; standard deviation not  provided.
                    ** Not tested due to  limited amount of sample available.

-------
ro
                            TABLE 78.  MUTAGENIC ACTIVITY OF NEUTRAL FRACTION OF PENT S WASTE AMENDED BASTROP SOIL AS MEASURED WITH
                                                  S.  TYPU1MURIUH STRAIN TA100 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA100 his * Revertanta (Mean
Day S9
Day 0
+
Day 180 -
+
Day 360 -
•»•
Day 540 -
+
0
93 + 11.4
140 + 12.9
105 + 5.3
107 j+ 17.8
137 + 14.0
124 + 17.0
115 + 0.0
126 + 0.8

92
310
230
140
368
178
488
1
+ 16.3
+ 30.0
Toxic
+ 95.3
+ 19.0
+ 121.0
+ 75.0
+ 325.0
Dose/Plate (rag)
.5
333
384
141
485
155
426
NT*
+ 39.1
Toxic
* 19.6
+ 15.0
+ 139.0
+ 49.6
+ 128.7
67 +
299 *
100 +
456 +
137 +
620 +
128 +
408 ±
+ S.D.)
1
7.8
24.7
12.6
102.0
16.0
191.0
27.6
73.9


168
93
352
132
572
119
380

.05
NT
* 46.4
+ 18.5
* 79.5
+ 15.0
+152.0
+ 16.9
+ 62.0


99 +
142 +
100 +
158 +
137 +
278 +
114 +
222 t

.01
13.1 .
21.2
8.4
22.1
18.0
93.0
4.8
23.2
                    * Not tested due to limited amount of sample available.

-------
   600-
  400-
                     NORWOOD-SWR!-ACID
CO
en
  200-
       WASTE
       DAY 0  0—0
a—a   I e o   x—x
        360   o—a
               too
              300
500    I 000
                             DOSE /PLATE
-------
S3
Ul
CO
                            TABLE 79. MUTAGENIC ACTIVITY OF ACID FRACTION OF  SWRI WASTE  AMENDED  NORWOOD  SOIL AS MEASURED WITH
                                                  S. TYPHIMURIUM STRAIN TA98  WITH AND WITHOUT METABOLIC  ACTIVATION

Total TA98 hia Revertante
Day S9
Day 0
•f
Day 180 -
Day 360 -

24
30
25
44
27
34
0
* 4.5
*. 5.0
+ 3.0
+ 8.6
+ 2.9
+ 6.5

39
138
55
139
127
650
1
+ 19.4
+ 36.9
+ 2.6
+ 8.4
+ 123.0
+ 678.8
Dose/Plate (mg)
.5
40 + 7.5
102 + 9.0
37 + 1.6
137 * 4.4
92 + 71.2
369 + 336.2
(Mean * S.D.)

32
77
27
86
43
113
.1
+ 7.2
+ 13.8
+ 3.1
± '•*
* 30.6
+ 29.3

26 +
44 +
21 +
69 +
34 +
76 +
.05
7.5
22.4
0.8
13.3
17.5
26.5

22
34
24
46
27
58

+
+
•f
+
i
,01
7.3
10.6
0.8
7.4
9.6
0.2

-------
waste,  the  hydrocarbons  in  the  acid  fraction  collected  on  day  360
induced a  mutagenic  response at higher dose  levels  that  was  two  to three
times greater  than  the response induced by the waste  fraction.   Similar
results were  observed  in  the base  fraction with  the maximum  response
induced by the sample collected on day  360.   The base  fraction  from day
360  also   induced  a mutagenic  response   in  the  absence-  of metabolic
activation,  whereas  neither  the  waste   nor  the  base  fraction of  the
samples collected prior  to day 360 induced a mutagenic  response without
metabolic  activation (Table  80  and  Figure 96).  In the  neutral  fraction
of the  SWRI waste amended Norwood soil, the  maximum response observed in
the  study  samples  was  induced  by  the  hydrocarbons  extracted  from the
waste  (Figure  97).    In  addition,  the mutagenic  activity of  the neutral
fraction  from  day 360 was appreciably  lower  than both  the  waste and the
day  0  sample   (Table  81  and Figure 97).   Since  the  neutral  fraction
accounts  for greater  than 90% of  the total  extractable hydrocarbon in
the  SWRI   waste,  the  reduction in  mutagenic  activity  observed  in  the
neutral fraction  after 360 days should compensate for increases  observed
in  the  acid and  base fractions.   Thus,   the  mutagenic  potential  of the
total  extractable  hydrocarbons  should  be  reduced  360 days  following
application  of the  SWRI waste  to the  Norwood  soil.

     For  the Bastrop soil amended with  the SWRI  waste,  the  same general
trend over time  was observed  (Tables 80,  81, and 82  and Figures 98, 99,
and  100).   The  maximum  response  observed  in both  the  acid  and  base
fractions  was  induced by  the  sample  collected on day  360  (Tables 82 and
83  and  Figures  98  and  99).  In  the  neutral  fraction,  the  mutagenic
activity  of the  residual  hydrocarbons was virtually unchanged from day 0
through  360.  At the  highest dose level, the mutagenic activity  of the
residual  hydrocarbons  in  the  neutral fraction of the  SWRI  waste amended
Bastrop  soil  from  day  0, 180, and  360  was  approximately  one-half the
level  of  activity  induced  by the  hydrocarbons  present in  the neutral
fraction  of the  waste (Table  84 and  Figure 100).   These results  indicate
that  the  mutagenic  activity of total  residual hydrocarbons  in  both the
Norwood and the  Bastrop soils collected  360  days after waste application
were  significantly  less than  the mutagenic activity  of  the  hydrocarbons
present in the waste.

     The  results  from the biological analysis of the COMBO waste amended
Norwood  soil  are  presented  in  Tables 85,  86,  and  87 and  Figures  101,
102,  and  103.   The sample  collected on day  360  induced   the  maximum
response  observed in the  acid  fraction  from COMBO  waste amended Norwood
soil  (Figure  101  and  Table  85).    In  addition, direct-acting  mutagens
were  detected  in the  acid fraction  from  day 360, whereas  there were no
direct-acting   mutagens    detected  in  the  acid   fraction   of   samples
collected   prior  to   day   360.   In   the   base   fraction,  there  was  no
appreciable  difference  in the mutagenic  potential  of the  extract  from
the  waste or  the soil samples collected  on  day  0 and  180;  however, the
mutagenic  potential of the base fraction  from day  360  was  approximately
two  times greater  than  the   response induced by samples  from  previous
dates.   Without  metabolic activation,  the  base fraction  from  day 360
                                  254

-------
TABLE 80. MUTAGENIC ACTIVITY OF BASE FRACTION OF SURI WASTE AMENDED NORWOOD SOIL AS MEASURED WITH
                      S. TYPHIHURIUH STRAIN TA98 WITH AND WITHOUT METABOLIC ACTIVATION












Total TA98 bis * Revertanta (Mean + S.D.)



(S3
Ln
Ui




Day S9
Day 0
+

Day 180 -
*
Day 360 -
+


24
30

25
45
28
33

0
+ 4.5
+ 5.0

+ 3.3
1 7-l
+ 2.6
+ 7.7

1
50 +
100 +

59 +
206 +
171 +
901 +


12.8
33.6

19.4
23.9
69.7
409.4
Dose/Plate (mg)
.5
52 + 5.9
103 + 15.5
"™
46 + 16.5
149 + 6.6
138 + 49.9
400 + 159.9


31 +
65 +

43 +
78 +.
54 +
138 +

,1
5.7
6.3

22.4
9.4
17.6
30.8


24 +
61 T
"™
43 +
66 *
39 +
80 +

.05
7.8
8.8

35.5
4.9
14.9
4.1

.01
19 + 2.4
44 + 10.2
~~"
36 + 21.2
46 + 4.5
25 + 5.4
46 + 8.6

-------
                                                               90
   600
•  400
a
O)
   ZOO-
                  NORWOOD-SWRI • BASE
                I 00
300
500
000
                              DOSE/PLATE Cug)
        Figure 96.  Mutagenic activity of base fraction of  SWRI amended
                   Norwood soil as measured with £.  typhimurium strain
                   TA98 with and without metabolic activation.
                                256

-------
   600i
  400-
                      NORWOOD-SWRI -NEUTRAL
                        +S9
  -S9
CD
ff>
   200-
                I 00
300
500    I 000
                             DOSE /PLATE Cuj)
         Figure 97.  Mutagenic activity of neutral fraction of  SWRI amended
                    Norwood soil  as measured with S_. typhimurium strain
                    TA98 with and without metabolic activation.
                               257

-------
                             TABLE 81.  MUTAGENIC ACTIVITY OF NEUTRAL FRACTION OF SWRI WASTE AMENDED NORWOOD SOIL AS MEASURED WITH

                                                   S.  TYPHIHURIUM STRAIN TA98 WITH AND WITHOUT METABOLIC ACTIVATION
Ln
oo

Total TA98 his Revertanta
Day S9
Day 0
Day 180 -
Day 360 -

23
31
25
44
26
29
0
± 2-*
+ 5.5
+ 2.9
+ 1.2
+ 1.3
+ 2.0

58
125
44
127
39
92
1
+ 12.8
+ 19.0
+ 5.7
+ 24.9
+ 8.4
+ 19.4
Dose/Plate (mg)
.5
42 + 8.5
138 + 7.8
30 + 0.8
122 + 16.6
31 + 5.7
81 + 4.9
(Mean + S.D.)
•
25 +
90 +
27 +
95 +
24 +
66 +
1
6.5
9.8
3.2
11.2
3.1
12.5

30 +
79 +
23 +
71 +
24 +
52 +
.05
9.3
13.3
1.8
11.9
0.8
11.4

27
50
27
53
21
38
.01
+ 2.2
+ 18.7
+ 2.3
+ 2.6
+ 1.9
+ 7.8

-------
TABLE 82. MUTAGENIC ACTIVITY OF ACID FRACTION OF SHRI WASTE AMENDED BASTROP SOIL AS MEASURED WITH
                      S. TYPHIMURIUM STRAIN TA98 WITH AND WITHOUT METABOLIC ACTIVATION
1
Total TA98 hii * Revert ant*
Day S9
Day 0
l-o +
Ui
Day ISO -
t
Day 160 -
t

22
32
29
43
31
40
0
+ 3.4
+ 5.8
+ 8.3
* 4.7
+ 1.8
1
156 +
263 *
52 +
137 »
86 *
341 *

33.4
23.7
4.3
30.1
8.5
151.0
Doae/PUte (ing)
.5
129 + 26.7
188 ± 10.8
45 + 9.2
139 7 19.6
69 «• 8.3
198 + 65.0
(Mean + S.D.)

39
88
32
90
40
94
.1
+ 7.0
^ 20.3
4 6.8
+ 14.2
4 12.0
+ 9.0

31
63
32
76
37
42
.05
+ 7.3
± 10.2
+ 2.3
± 6.9
* 4.2
+ 7.1

26
56
29
61
30
52
.01
4 4.8
+ 11.9
+ 2.7
t 8.0
+ 4.9
+ 5.7

-------
                              TABLE 83. HUTAGENIC ACTIVITY OF BASE FRACTION OF  SWRI WASTE AMENDED  BASTROP  SOIL AS  MEASURED WITH

                                                    S. TYPHIMURIUM STRAIN TA98  WITH AND WITHOUT METABOLIC  ACTIVATION
NJ
C^
O

Total TA98 hia * Revertants (Mean ± S.D.)
Doae/Plate (mg)
Day S9
Day 0
+
Day 180 -
*
Day 360 -
•f
0
22 + 3.4
32 + 5.8
29 + 8.3
43 * 3.0
31 +4.7
40 + 1.8


134
60
243
150
494
1
NT*
+ 30.3
+ 32.9
+ 131.9
+ 101.3
+ 291.0

70 +
120 +
50 +
192 +
84 +
319 +
,5
13.5
40.9
25.8
68.7
11.8
158.8

28 +
71 +
27 +
93 j»
38 +
89 +
1
6.4
15.5
4.1
14.1
10.3
16.0

26 +
44 +;
21 +
69 _+
28 +
73 +
.05
7.5
22.4
0.8
13.3
1.75
6.4
•
22 +
39 *
27 +
55 +
26 +
45 +
01
5.3
4.2
3.9
5.0
4.2
6.5
                      * Not tested due  to  limited  amount  of  sample  available.

-------
                           TABLE 84. MUTACENIC ACTIVITY OF  NEUTRAL FRACTION  OF SWRI WASTE AMENDED BASTROP SOIL AS MEASURED WITH
                                                  S.  TYPHIHURIUH  STRAIN  TA98  WITH AND WITHOUT METABOLIC ACTIVATION


                                                       Total  TA98  his    Revertants (Mean + S.D.)
to
Day S9
Day 0
+
Day 180 -
+
Day 360 -
+
0
23 + 2.8
28+9.2
29 + 8.3
43 + 3.1
31 +4.4
41 + 1.8
1
35 +
117 jf
56 +
142 +_
34 +
117 +

5.6
26.4
35.7
7.8
10.2
8.7
Doae/Plate (mg)
.5
36 +
107 +.
45 +
130 +
27 +
115 +
4.0
7.0
19.0
15.6
2.6
8.7
23 +
63 +
32 +
87 +
24 +
86 +
1
4.9
9.9
4.9
7.5
2.1
10.3

28 +
41 +
28 +
69 +
23 +
73 +
.05
3.3
9.5
4.1
8.0
4.2
0.9
.01
22 +
30 +
24 +
55 +
27 +
52 +
4.9
8.1
7.1
1.6
5.1
4.0

-------
   600
»  400
a
O
   200-
                              BASTROP-SWRI-ACID
                 00
300
500
I 000
                              DOSE/PLATECug)
        Figure 98. Mutagenic activity of acid fraction of SWRI amended
                   Bastrop soil  as measured with _S_.  typhimurium strain
                   TA98 with and without metabolic activation.
                                262

-------
   600-
                   BASTROP«SWRI'BASE
  400-
0
0)
  200;
                 00
300
500
I 000
                             DOSE /PLATE Cug)
        Figure 99.   Mutagenic activity of base fraction of  SWRI amended
                    Bastrop soil as measured with £. typhimurium strain
                    TA98 with and without metabolic activation.
                             263

-------
600-
400-
200-
                   BASTROP'SWRI-NEUTRAL
             I 00
300
500
I 000
                           DOSE/PLATECuj)
       Figure  100.  Mutagenic  activity of neutral fraction of SWRI amended
                   Bastrop soil measured with S^. typhimurium strain TA98
                   with and without metabolic activation.
                            264

-------
                        TABLE 85. HUTAGENIC  ACTIVITY  OF  ACID FRACTION OF COMBO WASTE AMENDED NORWOOD SOIL AS MEASURED WITH

                                          S.  TYPHIMURIUM  STRAIN  TA98  WITH AND WITHOUT METABOLIC ACTIVATION




                                                    Total  TA98  hie  * Revertants (Mean + S.D.)
S3
ON
Ui
Day S9
Day 0
+
Day 180 -
•f
Day 360 -
+
0
33 + 4.2
39 + 6.8
35 +0.7
45 I 2.1
24 +0.7
40 + 5.8

64
151
49
133
105
272
1
+ 5.6
+ 52.7
+ 11.2
+ 20.4
+ 39.3
+144.5
Dose/Plate (rag)
.5
57 +
114 +
42 +
114 +
78 +
148 +
11.0
15.0
5.4
15.4
34.7
49.4
32 +
83 +
30 +
66 +
42 +
66 +
1
6.9
5.9
4.7
4.2
18.0
17.4

30 +
39 _+
25 +
59 +
35 +
51 +
.05
3.6
13.7
15.2
3.5
11.3
3.6
•
25 +
23 +
27 +
56 +
25 +
44 +
01
2.0
8.5
1.5
7.2
2.2
5.6

-------
        TABLE 86. HUTAGENIC ACTIVITY OF BASE FRACTION OF COMBO WASTE AMENDED NORWOOD SOIL AS MEASURED WITH
                         S. TYFHIHURIUM STRAIN TA98 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA98 his * Revertanta (Mean *_ S.D.)
Dose/Plate (mg)
Day S9
Day 0
*
Day 180 -
•f
Day 360 -
•f
0
33 + 4.2
39 + 6.8
35 + 0.7
45 * 2.1
24 + 0.7
37 + 2.3

37
206
69
205

747
1
+ 14.2
+ 8.5
+ 17.9
+ 48.4
NT*
+ 180.0

34 +
140 +
55 +
158 ^
227 +
341 _*
,5
5.3
33.2
17.0
38.0
49.0
13.0

31 +
87 +
34 +
76 +
91 +
69 +
1
10.3
13.9
2.2
. 2.0
4.2
18.0

26 +
58 *
30 +
67 _*
63 +
59 +
.05
7.2
13.1
1.7
5.3
4.2
1.4

30
352
25
55
31
44
.01
+ 5.1
+ 12.9
+ 1.2
+ 7.0
+ 7.8
+ 4.9
* Not tested due to United amount of sample available.

-------
N>
                    TABLE 87. HUTAGENIC ACTIVITY OF NEUTRAL FRACTION OF COMBO WASTE AMENDED NORWOOD SOIL AS MEASURED WITH
                                     S. TYPHIHURIUM STRAIN TA98 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA98 hi» * Revertanti
Day S9
Day 0
Day 180 -
Day 360 -

33
39
35
45
24
36
0
4 4.2
_4 6.8
4 0.7
4 0.9
4 0.7
4 2.3
I
29 4
97 4
37 4
118 4
50 *
148 4

6.2
8.7
0.9
13.5
28.5
56.8
Dose/Plate (nig)
.5
26 4 4.7
85 4 10.8
34 4 2.1
108 4 1.6
40 4 15.8
101 4 27.0
(Mean 4 S.D.)
•
25 4
56 4
26 4
69 4
23 4
58 4
1
3.2
23.5
2.1
4.1
7.5
9.4

22
45
28
61
26
48
.05
4 6.1
4 9.2
4 3.5
4 3.9
4 4.8
4 6.4

23
39
26
49
23
40
.01
4 4.1
4 8.5
4 0.3
4 2.8
4 1.0
4 4.1

-------
   600-
  400-
CD
o>
   200-
                  NORWOOD • COMBO •ACID
       WASTE

•	•  DAY  0 O—o

H	B    I 80   X	X

         360
                                  -S9
                too
                 300
                             DOSE /PLATECug)
500
I OOO
          Figure 101.   Mutagenic activity of acid fraction of COMBO amended
                      Norwood soil as measured with  S_. typhimurium strain
                      TA98 with and without metabolic activation.
                               268

-------
                                                                   I 133
   600'
•  400






NORWOOD • COMBO 'BASE
* 	 A WASTE
• • DAY 0
O 	 D ISO
• 	 • 360
+ S9
A 	 *
0 	 0
X 	 X
0 	 D
-S9
CO
o>
   200-
                I 00
300
500    I 000
                              DOSE/PLATECug)
        Figure  102.  Mutagenic activity  of base fraction of COMBO amended
                    Norwood soil as measured -with £[. typhimuri'im  strain
                    TA98 with and without metabolic activation.
                                  269

-------
   600
   400
0
at
   ZOO-
                NORWOOD -COMBO-NEUTRAL
                100
300
500    1000
                             DOSE/PLATECug)
        Figure 103.  Mutagenic activity of neutral fraction of COMBO amended

                    Norwood soil as measured with J3.  typhimurium strain

                    TA98 with and without metabolic activation.
                                 270

-------
induced a  response that was approximately  nine  times  background,  whereas
none  of  the  samples  from  earlier  dates  induced  a  response  that  was
greater  than twice background  without activation.  The neutral  fraction
of  the  COMBO  waste  amended Norwood  soil  induced  a  consistently  higher
response  at  the  1.0  mg/plate  dose   level  from  day   0  to  180  to  360.
However,  this   increase  was   relatively  small,   and  on  day   360  the
mutagenic  potential   of  the   extractable  hydrocarbons  in  the  neutral
fractions  of  the  COMBO waste amended  Norwood  soil was  approximately
one-half  that of  the  neutral  fraction of  the waste.   After 360  days of
incubation  in the Norwood soil,  the  acid and neutral  fraction  displayed
a  small but  significant  increase  in mutagenic activity,  while  the base
fraction  displayed a  dramatic increase  both with  and without  metabolic
activation.

      The  overall  rate  of  hydrocarbon  degradation in  the COMBO  waste
amended  Bastrop  soil  was much  greater  on day  180 and  slightly greater
than  the  rate of  degradation  in the  Norwood  soil  on day 360 (Figure 82).
The different rates of degradation observed  in the two  soils  appears to
have  been  reflected   in  the  results  from mutagenicity  testing of  the
extracts  of  the  waste amended  Bastrop soil.  In the  acid fraction,  the
mutagenic  potential of  the samples  collected  on  day  0 and  day  180 were
.less  than or  equal to  the  mutagenic  potential of the  acid fraction of
the  waste,  while the  mutagenic  potential  of the acid fraction  from the
sample  collected  on   day 360  was dramatically  increased both  with  and
without metabolic  activation  (Table  88  and Figure  104).  In  the base
fraction,  the mutagenic  potential of the samples  collected on  days  180
and  360 induced  at least twice the  mutagenic  response that was obtained
from  the base  fraction  of  the waste  or the day 0 sample both  with and
without metabolic  activation   (Table  89  and   Figure 105).   The  mutagenic
potential  of the  base fraction from day 180  without activation was equal
to  that of  the  waste  sample with  activation.   The  increase in mutagenic
activity  that was observed in the  base fraction  from day 180  may have
resulted  from  the increased   rate of degradation  that occurred  in  the
Bastrop  soil.    However,   in   the   neutral   fraction,   there   was   no
appreciable  difference in  the mutagenic potential  of the  waste fraction
and   the  soil extract  from  day  360  (Table  90  and Figure 106).   Before
soil  application,  the neutral  fraction of   the  COMBO  waste  induced   a
positive  response in  the absence of metabolic  activation.  In  the waste
amended Bastrop  soil, this effect appears to  have been   inhibited until
day   360  when direct  acting  mutagens were  again  detected (Table  90).
Penalva  e£  al.   (1983)   also  observed  that  a  mixture  of  aromatic
hydrocarbons  could  inhibit  direct  acting mutagens.   Therefore,  as  the
neutral fraction  accounts  for 90% of  the  total extractable hydrocarbons
in  the soil,  the mutagenic  activity of the  total  residual hydrocarbons
in  the COMBO waste amended  soils  appears  to  be slightly  increased after
360 days  of  soil incubation.

      The   alterations   that  were   observed  over  time  in  the  mutagenic
potential  of the three  fractions  of  the  soil-waste extracts  follows
strikingly   similar trends.   In  most cases,   the  hydrocarbons  present in


                                271

-------
                           TABLE 88.  HUTAGENIC  ACTIVITY OF  ACID  FRACTION OF  COMBO WASTE AMENDED BASTROP SOIL AS MEASURED WITH
                                             S.  TYPH1HURIUH  STRAIN  TA98 WITH  AND WITHOUT METABOLIC ACTIVATION
to

Total TA98 his * Revertanta (Mean «
Day S9
Day 0
•*•
Day 180 -
•f
Day 360 -

33
39
32
44
30
41
0
+ 4.2
+ 6.8
+ 3.6
+ 1.4
+ 3.5
+ 7.5
1
55 _*
94 +
39 +
133 +
375 +
1293 +
Dose/Plate (ng)
.5
21.1
19.3
9.0
28.3
30.0
179.0
41 +
102 +
35 +
112 +
283 +
455 +
8.5
37.8
4.2
14.0
16.0
33.0
24 +
69 *
28 +
64 +
110 +
133 +
_ S.D.)
1
9.0
8.9
4.2
5.1
7.8
141.0


26
45
25
52
73
65

.05
+ 9.0
+ 6.5
+ 3.6
+ 4.9
» 49.5
+ 9.4


20 +
30 ^
26 +
53 +
43 +
48 +

01
6.3
17.1
1.2
5.0
7.1
9.2

-------
  400'
o
at
   200
       0
                 BASTROP- COMBO -ACID
                        WASTE
                     -• DAY 0
                 B	E)  180


                         360   O
100
300
                             DOSE/PLATE(ug)
                                                             I 195 *
500
                                                                I 000
       Figure  104.  Mutagenic activity of acid fraction of  COMBO amended

                   Bastrop  soil as measured with JL typhimurium strain

                   TA98 with and without metabolic activation.
                              273

-------
NJ
                     TABLE 89. HUTAGENIC ACTIVITY OF BASE FRACTION OF COMBO HASTE AMENDED BASTROP SOIL AS MEASURED WITH
                                      S. TYPHIHURIUM STRAIN TA98 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA98 his Revertants (Mean ± S.D.)

Day S9
Day 0
+
Day 180 -
*
Day 360 -
+


33
39
29
48
30
41

0
+ 4
± 6
+ 6
* 7
+ 3
* 7


.2
.8
.3
.4
.5
.4

1
28 + 21.3
147 + 13.6
221*
614*
530*
734 _* 144.9
Dose/Plate (mg)
.5
39 + 37.1
149 + 16.2
146*
291*
334 + 188.0
376 + 187.0

.1
27 + 4.7
76 + 4.9
57*
102*
97 + 27.0
75 ^47.0


28 +
50 +
45*
70*
69 +
58 +

.05
8.7
12.0


12.4
21.4


27 +
46 +
26*
54*
61 +
41 +

01
5
7


33
7


.8
.0


.7
.9
             * Mean represents average of only two samples; standard deviation not provided.

-------
                                                             733^
   600i
  400-
0
O>
  200-
                   BASTROP-COMBO-BASE
      WASTE £—a

      DAY 0  0—0

H—B I 8O   X—x

      360   D—O
                                                              1=8
               I 00
               300
                             DOSE/PLATECug)
500
I 000
        Figure  105.  Mutagenic activity of base fraction of COMBO amended
                    Bastrop soil as measured with S^. typhimurium strain
                    TA98 with and without metabolic activation.
                               275

-------
to
                    TABLE 90. HUTAGENIC ACTIVITY OF NEUTRAL FRACTION OF COMBO WASTE AMENDED  BASTROP  SOIL AS  MEASURED WITH
                                     S. TYPHIHURIUM STRAIN TA98 WITH AND WITHOUT METABOLIC ACTIVATION

Total TA98 hit + Revertants (Mean + S.D.)
Dose/Plate (og)
Day S9
Day 0
+
Day 180 -
•f
Day 360 -
+
0
33 + 4.2
39 + 6.8
32 + 3.6
44 + 1.7
30 + 3.5
41 + 7.5
1
29 +
101 +
35 «•
148 +
105 +
302 +
1
13.5
11.7
7.9
15.0
105.7
279.0

27 +
105 +
31 +
102 +
64 +
145 +
.5
10.2
18.7
2.9
7.5
40.0
76.0

23 +
60 i
24 +
67 +
37 +
71 +
1
2.6
7.9
1.7
9.5
13.0
19.0

24 +
57 +
27 +
64 +
29 +
53 +
.05
3.9
7.3
3.0
7.4
1.6
5.9

29 +
31 +
28 +
55 +
27 +
45 +
01
5.4
10.9
1.5
1.5
3.6
11.4

-------
   600-
- 400-
            BASTROP- COMBO-NEUTRAL
H	Q
                               -59
0
09
  200-
               too
                       300
500    1000
                             DOSE/PLATE (ug)
        Figure 106.  Mutagenic  activity of neutral fraction of COMBO amended
                   . Bastrop soil as measured with j^.  typhimurium strain
                    TA98 with  and without metabolic activation.
                              277

-------
the  soil   served   to  inhibit  the  mutagenic  activity  of   the   waste
constituents to  the  extent that the activity  of the soil-waste  extracts
from day 0  were  less than the activity of the waste extracts  alone.   The
nature  of   the   mutagenic  materials  also  appreared  to  be  affected  by
degradation.  The  base fraction  of all  six waste-soil mixtures  induced
direct-acting  mutagenicity   at   some   point  in   time  following   waste
application; whereas,  none of the base fractions  from  the waste  or  day 0
extracts induced direct-acting  mutagenicity.   For the majority of  the
acid  and  base  fractions,  the maximum  level of  mutagenic  activity  was
observed  in   the  final   sample   collected.    However,  the  mutagenic
potential of  the  neutral  fraction did  not exhibit  a similar  increase
over time and in some cases was less on day  360  than on day  0.

     These  results  indicate that soil degradation can  have  a  significant
impact  on  the  mutagenic  potential  of  hazardous waste   constituents.
Alexander (1981)  states  that biodegradation may increase the  toxicity of
some hydrocarbons.  The increases in the mutagenic activity  of soil-waste
extracts  observed  in  the  present study  may  have  been  a  result  of
hydrocarbon  oxidation or  a  result of  the  reduction in  the number  of
different   residual   waste   constituents   in  the  soil.   The   initial
reactions   involved   in   the  oxidation   of  aromatic  hydrocarbons  are
believed  to  result  in   the   formation  of  dioxetanes  and  epoxides  in
microbial and mammalian  systems, respectively,  with subsequent reactions
producing  dihydrodiols  in both  systems  (Gibson, 1972).   Although  the
epoxide  and not the  dihydrodiol  form  is  mutagenic  (Huberman et^ al.,
1971),   it   appears   from  the  results   of  the  present   study   that
biodegradation can  increase  the  mutagenic  potential  of hydrocarbons  in
the  soil.   In  addition,  mixed  function  oxygenases  are  the  enzymes
believed to account  for  numerous mammalian activation reactions  (Miller
and  Miller,  1974)  and   have  also been  found   in  plants  (Higashi  et_
al.,  1981)  and  bacteria   (McKenna,   1972;  Sokatch, 1969).   However,  Sims
and  Overcash  (1981)  observed   that  the  products   of  soil  incubated
benzo(a)pyrene (B[a]P) are much less mutagenic  than the  parent compound;
and  in  the  the present   study,  the degradation products  of  dimethyl
phenanthrene  appeared to  be  less mutagenic  than  the original  components
of  the neutral  fraction  of the COMBO waste.   Thus,  the major  impact  of
degradation  on   the  mutagenicity  of a complex mixture may be  its  affect
on the composition of  the  mixture.

     The  components  of   a  complex  mixture   may   have   synergistic,
antagonistic,  or  additive  effects on  the  mutagenic potential  of  the
mixture  as   a whole.  Hass   et  al.  (1981)  suggest  that even  a  very
slight  shift  in  the  concentration  of  one  of  the nonmutagenic  chemical
species  can drastically   alter  the response  of  the  mutagenic  species.
Hermann  (1981)   observed  that several  nonmutagenic hydrocarbons  enhanced
the  mutagenic   activity   of  B(a)P,  while  most mutagenic   polycyclic
aromatic   hydrocarbons   (PAH)   produced    a   large    decrease  in   the
mutagenicity  of  benzo(a)pyrene.   When  Penalva  (1983)   examined  the
interactions  of   the  vapors  and aerosols emitted by  road coating  tar,
they  found  enhancement at low levels and inhibition  at high  levels  for
                                 278

-------
indirect-acting mutagens.   However, only  the inhibition effect  appeared
for  direct  acting  mutagens   (Penalva,  1983).   This  may  explain  the
inhibition  of  direct-acting  mutagenicity   that  was   observed   in  the
initial extracts from the COMBO waste amended soil.

     The  data  of   Shahin  and  Fournier  (1978)  indicate  that  the  PAH
fraction   of   Athabasca   tar-sand  suppressed   the   mutagenicity   of
2-aminoanthracene.   In  a  study  by Kaden  e_t  al.  (1979)  the mutagenic
activity of  a  kerosene  soot extract was 10 to  20 times  higher  than  could
be  accounted  for  by the  amount  of B(a)P  present.   By evaluating  the
mutagenic  activity  of   the  70   PAH  identified  in  the soot,  Kaden  et
al.  (1979)  were able  to account for the mutagencity  of  the  whole  PAH
fraction in  terms   of  the  additive mutagenic  activity of  the  individual
components.   Haugen and Peak  (1983) observed  that  a complex mixture  of
aromatic hydrocarbons   isolated   from a  coal-derived  oil suppressed  the
mutagenic  activity  of  indirect   mutagens   but  had  no  effect  on  the
activity  of   direct-acting   mutagens.    Haugen  and   Peak  (1983)   also
demonstrated  that   this  suppression  was  produced  by  inhibition of  the
microsomal  monooxygenase system.   Environmental  factors  may  have  also
affected the mutagenic  activity  of the  residual hydrocarbons  (McCoy  et
al.,   1979;   Claxton   and   Barnes,  1982).    The   information   in  the
literature indicates  that  the increased mutagenicity  observed  in some  of
the soil-waste  extracts from the present  study was probably a  result  of
degradation  reducing the  number of  compounds  in  the  complex mixtures.
This  reduction effectively  reduced  competition for  activating  enzymes
with a  resultant  increase  in the mutagenicity  of the  residual  compounds.
While  this   reduction  in  compounds appears  to  be the dominant  factor
affecting  the  mutagenic activity of hazardous  waste amended  soils,  the
increased   presence  of  direct-acting   mutagens  with  time   indicates
microbial oxidations may also have  played an  important role.

     The  results  of  the  present   study  and  those  in  the  literature
indicate  that   the  composition   of  a  complex  mixture  will   have  a
significant  influence  on  the mutagenic  potential  of  the  mixture.   The
composition  of the acid, base,  and neutral  fractions  from the PENT  S
waste  amended  Norwood   and   Bastrop  soils  are  given  in  Table 91  and
Figures  107  through  117.   Apparently  from  the  variety of  constituents
identified  in the  extracts,  the prediction  of the genotoxic  effects  of
these  samples  from chemical  analysis  alone  would be  difficult if  not
impossible.   However,    from   the  variety   of  identified   initiators,
promoters,   mutagens,   and   carcinogens,   chemical   analysis   evidently
provides  valuable  information pertinent  to  the  interpretation of  the
results   from  the  biological   testing.    A  number   of  alkanes   were
identified  in  the  base  and   neutral  fractions of  the soil  extracts.
These   included   the   promoting   agents   dodecane,    tetradecane,   and
octadecane;  the cocarcinogens  octadecane  and  eicosane;  and  hexadecane
which  is an inhibitor  (Lankas  £t al.,  1978;  Goldschmidt,  1981).   The
majority  of  the alkanes  detected  in the PENT  S soil extracts were also
present  in the extract  of the unamended soil.
                                  279

-------
                                           TABLE 91.  LIST OF COMPOUNDS DETECTED IN PENT S HASTE AMENDED SOIL
            Sample
                 Acid
   Compound (Peak Number)*
                                                                   Fraction
               Base
 Compound (Peak Number)*
                 Neutral
          Compound (Peak Number)*
            Norwood
            Day 0
  Not Determined
t-o
oo
o
            Norwood
            Day 360
Unknown (267)
Dimethyl nonane (303)
Unknown (377)
Methyl propyl pentanol (358)
Unknown (377)
Ethyl hexanol (399)
Pentachlorophenol (419)*HO; Cl
Dimethyl undecane (437)
Trimethyl octane (469)
Benzene dicarboxylic acid (492)*MO
Fluoranthene (S22)*H1; CO; CC
Pyrene (S38)*M1; CO; CC
Unknown (562)
Unknown (591)
Unknown (620)
Unknown (639)
Unknown (657)
Methyl napthalene (249)*M1; CO
Dimethyl napthalene (289)*HO
Dihydro acenaphthylene (314)*M1
Hexene (332)
Dimethyl butane (358)
Unknown (377)
Epoxy-methyl-pentane (397)
Unknown (435)
Unknown (461)
Trifluoro methane (472)*M1
Unknown (496)
Unknown (523)
Unknown (541)
Unknown (570)
Unknown (590)
Unknown (616)
Unknown (646)
Unknown (676)
Unknown (277)
Unknown (303)
Ethyl heptane (318)
Unknown (339)
Dimethyl nonane (359)
Unknown (378)
Dimethyl hexane (399)
Trimethyl heptane (469)
Propyl aziridine (492)
Fluoranthene (523)*H1; CO; CC
Pyrene (539)*M1; CO; CC
Unknown (586)
Unknown (619)
Unknown (650)
Unknown (681)
Unknown (238)
Methyl napthalene (251) (257)*M1; CO
Biphenyl (281)*MO; Cl
Dimethyl napthalene (291) (295)*MO
Dihydro acenaphthylene (321)*M1
Dibenzofuran (334)
Fluorene (359)*MO; CO
Unknown (384)
Unknown (406)
Dibenzothiophene (424)*MO
Phenanthrene (432)*MO; CO
Unknown (462)
Unknown (478)
Unknown (503)
Fluoranthene (531)*M); CO; CC
Pyrene (547)*M1; CO; CC
Unknown (589)
Unknown (615)
Unknown (637)

Unknown (237)
Unknown (271)
Unknown (281)
Alkane (308)
Dihydro acenaphthylene (324)*M1
Unknown (334)
Trimethyl naphthalene (347)*MO
Unknown (375)
Dimethyl octane  (384)
Dimethyl biphenyl (407)
Unknown (421)
Methyl propyl pentanol (445)
Unknown (462)
Trimethyl octane (476)
Cyclopenta phenanthrene (481)*MO
Unknown (499)
Dimethyl undecane (508)
Fluoranthene (529)*M1; CO; CC
Pyrene (544)*M1; CO; CC
Unknown (568)

-------
                                                                 TABLE 91 CONTINUED
                                                                 Fraction
          Sample
                             Acid
               Compound (Peak Number)*
              Base
Compound (Peak Number)*
                                                        Neutral
                                                 Compound (Peak Number)*
Methyl napthalene (240)*M1; CO
Dimethyl napthalene (285) (299)*MO
Dihydro acenaphthylene (317)*M1
Methyl ethyl napthalene (326)
Dibenzofuran (331)
Unknown (343)
Phenalene (352)*M1
Trimethyl napthalene (363)*MO
Unknown (365)
Alkane (405)
Dibenzothiophene (424)*MO
Methyl dibenzothiophene (461)*M1
Methyl phenanthrene (478)*M1
Phenyl napthalene (504)
Fluoranthene (533)
Pyrene (550)
Unknown (627)
Unknown (679)
Unknown (730)
Unknown (775)
Unknown (822)
Unknown (876)
                                                   Dimethyl hexane (277)
                                                   Unknown (303)
                                                   Dihydro acenaphthylene (321)*M1
                                                   Unknown (343)
                                                   Unknown (361)
                                                   Trimethyl octane (397)
                                                   Unknown (456)
                                                   Cyclopenta phenanthrene (476)*MO
                                                   Unknown (502)
to
00
Bastrop     Methyl napthalene (239)*M1; CO
Day 0       Unknown (246)
            Dimethyl napthalene (282) (292)*MO
            Dihydro acenaphthylene O19)*M1
            Alkane (326) (367) (407)
            Dibenzofuran (332)
            Trimethyl napthalene (346)*MO
            Phenalene (353)*M1
            Pentachlorophenol (429)*MO; Cl
            Unknown (481)
            Unknown (515)
            Fluoranthene (535)*M1; CO: CC
            Pyrene (553)*M1; CO: CC
            Unknown (635)
            Unknown (691)
            Unknown (728)
            Unknown (770)
            Unknown (807)
            Unknown (846)
            Unknown (884)
          Baatrop     Unknown (267)
          Day 360     Ethyl methyl pentanol (277)
                      Unknown (303)
                      Dihydro acenaphthylene (323)*M1
                      Trimethyl napthalene (345)*HO
                      Dodecane (358)*P; CC
                      Dimethyl octane (376)*P
                      Dimethyl undecane (398)
                      Pentachlorophenol (422)*C1
                                      Unknown (220)
                                      Methyl naphthalene (244) (250)*M1; CO
                                      Unknown (277)
                                      Dimethyl naphthalene (287) (293)*MO
                                      Dihydro acenaphthylene (319)*M1
                                      Alkane (323)
                                      Dibenzofuran (332)
                                      Trimethyl naphthalene (337) (343)*MO
                                      Phenalene (358)
                                      Alkane (364)
                                      Unknown (378)
                                      Unknown (392)
                                      Methyl fluorene (405)
                                      Dibenzothiophene (422)*MO
                                      Unknown (438)
                                      Methyl dibenzothiophene (467)*MO
                                      Methyl phenanthrene (477)*MO
                                      Cyclopenta phenanthrene (482)*MO
                                      Phenyl napthalene (501)
                                      Unknown (511)
                                      Fluoranthene (531)*M1; CO
                                      Pyrene (548)*M1; CO
                                      Unknown (561)
                                      Unknown 578)

                                      Unknown (276)
                                      TetradeCane (287)*P
                                      Unknown (314)
                                      Dihydro acenaphthylene (33S)*M1
                                      Trimethyl naphthalene (359)*MO
                                      Unknown (385)
                                      Hexadecane (400)*A
                                      Trimethyl octane (417) (447)
                                      Heptadecane (429)

-------
                                                                  TABLE 91 CONTINUED
                                                                  Fraction
           Sample                       Acid                                 Base                                      Neutral
                          Compound  (Peak  Number)*              Compound  (Peak Number)*                          Compound  (Peak  Number)*

                       Methyl propyl nonane  (432)  (467)  (498) Dimethyl phenanthrene  (514)*H1
                       Phenyl naphthalene  (452)               Fluoranthene  (52l)*Hl; CO; CC           Octadecane (450)*P;  CC
                       Cyclopenta phenanthrene  (473)*MO       Pyrene  (537)*M1; CO; CC                 Unknown  (467)
                                                                                                      Nonadecane (479)
                       Unknown  (510)                                                                  Cyclopentaphenanthrene (487)*MO
                       Fluoranthene  (519)*M1; CO;  CC                                                  Eicosane (510)  *CC
                       Pyrene (534)*H1; CO;  CC                                                        Fluorantbene  (531)*M1; CO;  CC
^j                     Unknown  (558)                                                                  Heneicosane (541)
00                                                                                                    Pyrene  (547)*M1;  CO; CC
^                                                                                                    Docoaane (571)
                                                                                                      Unknown  (601)  (630)


           *   Potential  genetic  toxicity:  I  - initiator;  P - promoter;  A -  antagonist;  CC =  cocarcinogen(aynergiat); HO  -
               nonmutagenic;  HI  *• mutagenic; CO • non-carcinogen;  Cl " carcinogen; all others  • no information.   The  references
               used  in  determining  these  factors include  HcCann  e£  al   (1975);  Kaden e£ al_  (1979); Goldschmidt  (1981) and
               DHEW  (1969).

-------
1-0
00
LO
RIG
                                                                 NORWOOD

                                                                 RENTS BASE

                                                                 DAY 0
2<

DO
i
300
400
500
600
700
                                                   RT
                 Figure  107.  GC/MS chromatograph of  base  fraction of PENT S amended Norwood
                             soil collected on day 0.

-------
                                                                   NORWOOD

                                                                   RENTS NEUTRAL

                                                                   DAY 0
00
         RIC
            200
300
400
500
600
                                                 RT
                Figure  108.  GC/MS chromatograph of neutral fraction of PENT S amended
                            Norwood  soil collected on day 0.

-------
ro
oo
Ln
        RIG
                                                                 NORWOOD


                                                                 RENTS ACID


                                                                 DAY 360
          200
300
400
500
600
700
                                              RT
              Figure 109.  GC/MS  chromatograph of acid fraction of PENT S amended Norwood

                          soil collected on day 360.

-------
                                                                NORWOOD

                                                                RENTS BASE

                                                                DAY 360
IsJ
cn
            200
600
700
                                                RT
                Figure 110.   GC/MS chromatograph of base fraction of PENT S amended Norwood
                            soil collected on  day 360.

-------
                                     NORWOOD
                                     RENTS NEUTRAL
                                     DAY 360
(•o
oo
RIG
              200
                      i
                    300
400
RT
500
                                                                                      600
                  Figure 111.   GC/MS chromatograph of neutral fraction of PENT S amended
                              Norwood soil collected on day 360.

-------
oo
00
           RIC
                                                                 BASTROP


                                                                 RENTS ACID

                                                                 DAY  0
                                                                                   r^  
-------
N>
OO
VO
RIG
                                                               BA3TROP

                                                               PENTS BASE

                                                               DAY 0
                                                                      r.  I-    oo    oo
                         ZOO
                                   400
600
800
                                                RT
            Figure 113.  GC/MS chromatograph of base fraction  of PENT S amended  BasCrop
                        soil collected on day 0.

-------
                                                                      BASTROP


                                                                      RENTS  NEUTRAL


                                                                      DAY  0
to
vo
o
RIC
            200
                     300
400
                                                  RT
500
600
               Figure 114.   GC/MS chrotnatograph of neutral fraction  of PENT S amended Bastrop

                            soil collected on day 0.

-------
                            BASTROP

                            PENT3  ACID

                            DAY 360
hO
VO
      RIG
200
                           300
400

 RT
500
600
            Figure 115.   GC/MS chromatograph of acid  fraction of PENT S amended Bastrop soil
                        collected on day 360.

-------
                                                                       BASTROP

                                                                       PENTS BASE

                                                                       DAY 360
tv>
VO
1x3
            200
600
700
                                                 RT
               Figure 116.  GC/MS chromatograph of base fraction of  PENT S amended Bastrop soil
                           collected on day 360.

-------
                                                                             BASTROP

                                                                             RENTS NEUTRAL

                                                                             DAY 360
N>
VO
OJ
             RIG
               250
350
450
                                                    RT
550
 i
650
                   Figure  117.  GC/MS chromatograph of neutral fraction of PENT S amended Bastrop
                               soil collected on day 360.

-------
     Several polycyclic  aromatic  hydrocarbons (PAH) were also  identified
in   the   extracts  of   the  PENT   S  amended   soils.   These   included
methylnapthalene, dimethyl  napthalene,  trimethyl napthalene, and dihydro
acenapthylene.  Of  the  methylated napthalenes,  only methylnapthalene  has
been  found  to be  mutagenic  (Kaden  et_  a_l. ,   1979).   Although  dihydro
acenapthylene  was  not mutagenic  in  the  standard reverse mutation  assay
(Gatehouse,  1980),  it was  positive when  tested in the forward  mutation
assay  (Kaden  e£  al. ,  1979).  Non-mutagenic   PAH  with  three  or more
aromatic  rings were  identified  in  the  soil-waste extracts and  included
anthracene,  phenanthrene,  and  cyclopentaphenanthrene  (McCann  et al.,
1975;  Kaden et^  al.,   1979).   Of  these  compounds,  only  anthracene  has
been   tested  in   a   whole  animal   bioassay   and   was   found   to   be
non-carcinogenic   (DHEW,   1969).   Identified   mutagenic   PAH   included
methylphenanthrene,   dimethyl   phenanthrene  (La  Voie  et  al.,  1983),
and  pyrene   and   fluoranthene  (Kaden   et   al.,   1979)  which  are  not
carcinogens   (DHEW,   1969).   Pyrene  and  fluoranthene  have,   however,
displayed  cocarcinogenic  activity  (Hoffman  et  al. ,  1982).  A  study by
La   Voie   e£   al.    (1981)    found   that    methylphenanthrene    and
dimethylphenanthrene  were  mutagenic  toward  Salmonella  and  that  only
dimethyIphenanthrene  acted  as  a  tumor  initiator  on  mouse  skin.  Two
polycyclic   aromatic    sulfur   heterocycles   were   identified   in  the
soil-waste  extracts.   Both  of  these  compounds  have  been  tested in  the
Salmonella  assay,  and  dibenzothiophene  and methyldibenzothiophene were
not   mutagenic    (Pelroy    et   al. ,   1983).    The   only   chlorinated
hydrocarbon  identified  in  the waste-soil  extracts  was pentachlorophenol.
Pentachlorophenol  is  not   mutagenic  in  the Salmonella  assay  (Anderson
e_t  al. ,  1972) but has  been found  to  induce  mitotic  gene  conversion
in  J5.  cerevisae   (Fahrig,   1974).   In   addition,  Schmid  ejt  a_l  (1983)
observed  an increased  incidence  of  chromosome  damage in workers  from a
pentachlorophenol  plant. Thus,  chemical analysis  of  the PENT  S amended
soils  identified  more  than  fourteen polycyclic aromatic  hydrocarbons,
including  four that were mutagenic  and two animal carcinogens.

     Although  a  large number of  compounds were identified in  the PENT S
soil extracts, there were many additional  compounds that were  detected
but  not identified.   These included  a  large number  of higher molecular
weight  compounds  that  were possibly  three  to  five ring PAH.  The source
of  the waste  and  some of the  potential  soil metabolites can provide
information  as to  the  identity of these minor constituents.   Technical
grade  pentachlorophenol  is  known  to  contain   a  number  of  impurities
including    tetrachlorophenol,   dibenzo-p-dioxins,    and    dibenzofurans
(Fishbein,  1979).   Of these compounds,  only dibenzofuran was  detected in
the  waste-soil  extracts  from  the greenhouse  study.  Creosote oil  is
composed  of a variety of  aromatic  hydrocarbons and has been  shown to be
an  indirect-acting  mutagen  (Bos  e£ al. ,   1983).   Since   this  oil  was
used   in   the    process   that   generated  the  PENT  S,   the  aromatic
hydrocarbons  which  compose  creosote oil would  be  anticipated in  the
soil-waste   extracts.   The  biodegradation  of  some  of  the   organic
compounds   present  in   waste   fractions   would   be  expected  to  produce
metabolites  such  as hydroxylated napthalenes  (Higgins and  Gilbert,  1978)
                                 294

-------
and catechol  (Gibson,  1972).   Catechol is  not mutagenic for  Salmonella
but is  a  co-mutagen  (Yoshida  and  Fukuhara,  1983)  and  a  co-carcinogen
(Van Duuren  and Goldschmidt,  1976).   Thus,  the extracts  of the PENT  S
amended soil  contain a complex mixture of chemicals,  including mutagens,
carcinogens,   teratogens,   promoters,   initiators,   inhibitors,    and
co-carcinogens.

     A comparison  of the GC/MS chromatograms  of  the  PENT  S  soil  extracts
from  day  0  and  360  does  not indicate  any significant  loss of  organic
compounds  nor  any  appreciable   gain  in  metabolic  products  from  soil
degradation   (Figures  107  to   117).   Methylnapthalene  was  the   only
mutagenic compound  present in day 0 samples  that was  not  also  identified
in  the  soil  from  day  360.   Potential  biodegradation products that  were
identified  in  the  soil  extracts   from  day  360  include  methyl  propyl
pentanol,  ethyl   methyl  pentanol,   and  ethyl  hexanol.    The   enzymes
responsible   for  the  formation   of  these  compounds   are  mixed  function
oxygenases  (McKenna,  1972).   If  these compounds  are  products   of  soil
degradation,  these  results  indicate  that  the  enzymes  responsible  for
activating promutagens may be present  in  the soil.   Thus,  the  increased
activity  observed  in  some of the incubated  soil samples was  possibly  a
result  of soil activation or a  result of  decreased  competition  for the
activating enzymes used in the mutagenesis bioassays.

     The  GC/MS analysis  was  unable  to conclusively  identify any of the
components of the  acid, base, and neutral  fractions  of  the SWRI  waste or
the  day  0  extracts.   Additional   concentration  of  the  day  360  soil
samples  allowed the  identification  of  seven compounds and  the  detection
of  25  additional  unknown  compounds.  The compounds identified  in the day
360   extract  from   the  SWRI   waste   amended  Bastrop   soil   included
heptadecane,  nonadecane,  dihydro acenapthylene, dimethyl  octane,  ethyl
propyl hexanol,  trimethyl decane, and  pyrene (Figures 118,  119 and 120).
Only  two  of  these  compounds,   dihydro  acenapthylene  in  the  base  and
pyrene  in  the  neutral  fraction,   are potential  sources   of mutagenic
activity   (Kaden   et_  al. ,   1979).   Kaden  ejt  a_l.  (1979)  indicate  that
the  mutagenic  potential  of  acenapthylene and  pyrene are  approximately
equal.   However,  biological  analysis   demonstrated   that  the mutagenic
potential  of  the  base fraction was   three  to  four  times  that of the
neutral   fraction.    An  evaluation   of the   combined  results  from  the
chemical  and biological  analysis of the  day  360  samples  from  the  SWRI
waste   amended  Bastrop   soil  indicate  that  the  decreased  mutagenic
activity  observed   in  the   neutral fraction  may  have  resulted  from
inhibition   produced  by  the  non-mutagenic   components  of  the  neutral
fraction.

     A  list   of  the   compounds detected in  the COMBO  waste  amended  soils
is  provided  in  Table  92,   and  the   GC/MS  chromatograms  are given  in
Figures  121   through to 131. Unlike the PENT S waste,  a review of the
GC/MS  chromatograms  from  the COMBO  waste amended soil does indicate that
significant   quantities  of organic  compounds are  degraded   in the  soil.
The  GC/MS   chromatograms   of  the   acid  fraction  of  the   Norwood  soil


                                  295

-------
                                                              BASTROP

                                                              SWRI ACID

                                                              DAY 360
to
         200
300
400
                                              RT
             Figure  118.  GC/MS chromatograph of acid fraction of SWRI amended Bastrop
                         soil collected on day 360.

-------
                                                                            BASTROP

                                                                            SWRI BASE

                                                                            DAY 360
               RIG
NJ
VO
-J
                 200
300
400


 RT
500
600
                     Figure  119.  GC/MS chroraatograph of base  fraction of SWRI  amended Bastrop
                                 soil collected on day 360.

-------
10
10
              RIG
                                  BASTROP
                                  SWRI  NEUTRAL
                                  DAY 360
                 250
350
450
 RT
550
650
                           Figure  120.  GC/MS chromatograph of neutral fraction of SWRI amended
                                       Bastrop  soil collected on  day 360.

-------
                                     TABLE 92. LIST OF COMPOUNDS DETECTED IN COMBO WASTE AMENDED  SOIL
     Sample
                                                            Fraction
                             Acid
               Compound (Peak Number)*
              Base
Compound (Peak Number)*
       Neutral
Compound (Peak Number)*
t-o
<£>
10
Norwood        Unknown (226)
Day 0          Trimethyl octane (233)
               Unknown (245)
               Phenyl cyclopentanol (257)
               Methyl napthalene (263)*M1; CO
               Trimethyl dodecane (280)
               Unknown (295)
               Dimethyl napthalene (300)(305)(313)*MO
               Propyl heptanol (318)
               Methyl ethyl napthalene (339)
               Trimethyl napthalene (350)(356)(364)*HO
               Methyl propyl napthalene (377)
               Unknown (386)
               Undecane (396)
               Methyl (Meth) napthalene (405)
               Ethyl tridecane (418)
               Dimethyl undecane (457)
               Unknown (477) (492)

Norwood        Unknown (335)
Day 360        Unknown (357)
               Unknown (376)
               Methyl decane (397)
               Unknown (468)
               Unknown (492)
               Unknown (527)
               Unknown (548)
               Unknown (576)
   Dimethyl decane (272)           Unknown (227)
   Dimethyl undecane (300)         Methyl napthalene (251)*H1; CO
   Unknown (347)                   Unknown (258)
   Unknown (385)                   Trimethyl octane (273)
   Unknown (406)                   Dimethyl napthalene (288) (299)*MO
   Unknown (437)                   Unknown (303)
   Unknown (470)                   Unknown (322)
   Unknown (517)                   Methylethyl napthalene (329)
   Unknown (549)                   Trimethyl napthalene (339) (347) (352)*MO
   Unknown (583)                   Propylmethyl napthalene (367)
   Unknown (609)                   Unknown (375)
   Unknown (643)                   Methyl ethyl decane (386)
   Unknown (675)                   Unknown (395)
   Unknown (708)                   Methyl fluorene (408)
                                   Unknown (446)
                                   Methyl phenanthrene (480)*M1
                                   Unknown (505)
                                   Dimethyl phenanthrene (519)*M1; Cl
                                                             Tridecane  (236)
                                                             Unknown  (258)
                                                             Tetradecane  (279)*P
                                                             Dimethyl napthalene (295)*HO
                                                             Unknown  (308)
                                                             Pentadecane  (319)
                                                             Unknown  (331)
                                                             Fluorene (355)*MO;  CO
                                                             Hexadecane (360)*A
                                                             Dimethyl undecane  (379)
                                                             Heptadecane  (399)
                                                             Phenanthrene (428)*MO;  CO
                                                             Octadecane (436)*P; CC
                                                             Unknown  (456)
                                                             Nonadecane (471)
                                                             Benzene  dicarboxylic acid (493)*MO;  CO
                                                             Eicoaane (505)*CC
                                                             Fluoranthene (525)*Ml;  CO
                                   Unknown (330)
                                   Unknown (353)
                                   Unknown (353)
                                   Unknown Branched Alkane (399)
                                   Dimethyl nonane (415)
                                   Unknown (429)
                                   Unknown (468)
                                   Dimethyl decane (479)
                                   Unknown (489)
                                   Unknown (510)
                                   Unknown (533)
                                   Unknown (572)

-------
                                                                   TABLE 92 CONTINUED
                                                                   Fraction
(-0
O
O
            Sample
            Norwood
            Day  360
            Bastrap
            Day 0
             Bastrop
             Day  360
              Acid
Compound (Peak Number)*
              Base
Compound (Peak Number)*
                  Neutral
           Compound (Peak Number)*
Unknown (224)
Hethylnapthalene (249)(255)*M1; CO
Alkane (272)
Dimethyl napthalene (291)(297)(305)*MO
Dihydro acenaphthylene (323)*Ml
Methyl ethyl napthalene (331)

Trimethyl napthalene (341)(349)(355)*MO
Propenyl napthalene (369)
Unknown (377) (388) (396)
Methyl fluorene (409
Dimethyl fluorene  (433)
Methyl phenanthrene (481)*M1
Unknown (507) (527) (606) (641) (683)

Unknown (327)
Dimethyl napthalene (341)*MO
Dihydro acenapthylene  (356)*M1
Phenalene (380)"Ml
Unknown (395)
Dimethyl undecane  (407)
Unknown (457)
Trimethyl decane  (467)(498)
Unknown (476) (520) (536) (558) (587)
     Heneicosane (536)
     Pyrene (541)*M1; CO
     Docaaane (566)
     Unknown (577)(596)

     Methyl napthalene (253)*M1
     Dimethyl napthalene (295)*MO
     Ethyl napthalene (303)
     Alkane (309)
     Methyl ethyl napthalene (328)
     Trimethyl napthalene (338)(344)
     (351)*HO
     Methyl propyl napthalene (364)
     Unknown (405) (479) (513) (555)
       (592) (657) (697) (755)
       (795) (838) (877)
                                                                      Not  determined
Methyl napthalene (245)*M1
Alkane (271)
Dimethyl napthalene (285)(291)*MO
Propyl heptanol (303
Methyl ethyl napthalene (327)
Trimethyl napthalene (338H346)(352)*MO

 Propenyl napthalene (367)
 Unknown (387)
 Dimethyl biphenyl (408)
 Methyl phenanthrene (481)*M1
 Unknown (526) (600) (689)  (736)  (801)
       (847)
                                      Unknown  (289)
                                      Benzene  dicarboxyllc acid  (484)*MO;CO
                                      Unknown  (543)
             *  Potential genetic  toxicity:  I  *  initiator;  P  « promoter;  A  " antagonist;  CC  »  cocarcinogendynergiat); MO  -
                nonmutagenic;  Ml  » mutagenic; CO  -  non-carcinogen;  Cl • carcinogen; all  others • no  information.   The  references
                used  in  determining  these  factors  McCann   et_ a_l   (1975);  Kaden  et_  a±  (1979);  Goldachmidt  (1981)  and  DHEU
                (1969).

-------
CO
o
              RIG
                                                                            NORWOOD


                                                                            COMBO ACID


                                                                            DAY 0
                200




                   Figure  121.
        300
400
                                                        500
                      RT
GC/MS chromatograph of acid fraction of COMBO amended Norwood

soil collected  on  day 0.

-------
OJ
o
S3
RIG
                                                                              NORWOOD


                                                                              COMBO BASE

                                                                              DAYO
                                                                                  O*  CO
                                                                              Is*   ••»  00   O\  **>  tf\    tO
                                                                              »H   tt\  tfl   O  •*  I-*    O
                                                                              t/\          vo  \o  »o    r*»
                               100




                          Figure 122.
                         200
300
400
500
600
700
                                           RT
                       GC/MS chromatograph of base fraction  of COMBO amended Norwood

                       soil collected on day 0.

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                                                                    NORWOOD

                                                                    COMBO NEUTRAL

                                                                    DAY 0
LO
o
U)
         RIG
           200
                                 300
                        400
500
                                                 RT
                 Figure 123.
GC/MS chromatograph of neutral  fraction of COMBO amended Norwood

soil collected on day 0.

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                                                                   NORWOOD


                                                                   COMBO ACID


                                                                   DAY 360
         RIC
u>
o
.p-
            200
300
500
                                                                                     600
                                                 RT
             Figure 124.  GC/MS  chromatograph of  acid fraction of COMBO amended Norwood soil

                          collected on day 360.

-------
              RIC
U)
o
Cn
                                                                        NORWOOD


                                                                        COMBO  BASE


                                                                        DAY 360
                200
 300
40O


 RT
                                                                500
                                                 600
                  Figure 125.
GC/MS chromatograph of base fraction of COMBO amended

Norwood soil collected on day 360.

-------
                   RIG
LO
O
                                                                             NORWOOD

                                                                             COMBO NEUTRAL

                                                                             DAY 360
                                300
400
500
600
                                                           RT
                      Figure 126.  GC/MS chromatograph of neutral fraction of COMBO amended Norwood
                                  soil collected on day 360.

-------
                                                 BA8TROP
                                                 COMBO ACID
                                                 DAYO
                             300
400
500
600
700
                                    RT
Figure  127.  GC/MS chromatograph of acid fraction  of COMBO amended Bastrop soil
            collected on day  0.

-------
                                                                  BASTROP
                                                                  COMBO BASE
                                                                  DAY 0
Lo
O
oo
RIG
                                                        o>    n  
-------
LO
o
V0
                 RIG
                                                                           BASTROP


                                                                           COMBO NEUTRAL


                                                                           DAYO
                                                                                o\
                                                                                CO
                                                                                
-------
u>
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RIG
                                                                          BASTROP


                                                                          COMBO ACID


                                                                          DAY  360



2(

\ f^ .H »o o m o l\ to*of^ ••* in in
X^^ M •» ir> eo o< «» 11 •«•»•«
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I 1 1
)0 300 400 500
RT



600

                        Figure 130.  GC/MS chromatograph of acid fraction  of  COMBO amended Bastrop

                                     soil collected on day 360.

-------
RIG
                                                          BASTROP

                                                          COMBO NEUTRAL

                                                          DAY 360
         200
300
400
500
600
700
                                       RT
      Figure 131.  GC/MS  chromatograph  of neutral fraction of COMBO  amended Bastrop
                  soil collected on day 360.

-------
indicates  that  on day  0  there were  twelve  compounds identified with  an
additional six  unknown compounds  detected  (Figure  118).   Of the  twelve
compounds  identified,  only methylnapthalene is  mutagenic  (Kaden,  1979).
The acid  fraction  from day 360 contained only one identifiable  and eight
unknown detectable  compounds  (Figure 118).  However,  the bioassay  of  the
acid  fractions  from day  0 and  360  did not reflect a  reduced  level  of
mutagenic  activity  (Table 85).   Similar results  were  obtained  from  the
neutral  fraction from  day 0  with  ten compounds identified plus  eight
unknown  detected  (Figure  119).   While  three  of  the   ten   compounds
identified in the  day  0 sample were mutagenic, none  of  the mutagens were
also detected in the  extract from day  360 (Table 90).   The reverse trend
seemed  to  occur in  the base fraction  with  the  GC/MS chromatograph from
day 360  (Figure 125)  appearing  more complex than the  sample from day 0
(Figure  122).    The  base  fraction from  COMBO  waste amended soils  also
showed  a  corresponding   increase  in  mutagenic  activity  on  day  360.
(Figures  101 and 104). The results from chemical and biological analysis
of  the  acid  fraction  of  the   COMBO waste  amended  soils  appear  to
contradict  each  other,  while  the   chemical  analysis  of the  base  and
neutral  fractions  provides confirmation of  the  respective increased  and
decreased mutagenic activity that  was observed in  the bioassays.

     Neither  chemical  analysis   of  the  soil  extracts  nor  biological
analysis   of   residual   hydrocarbons  have  been   capable  of  clearly
demonstrating  treatment  of  soil applied  waste.    The  results  already
presented  in  Figures  83  through 106  describe  the  mutagenicity  of  the
residual  hydrocarbons  in  waste  amended soil.   The   results  presented  in
Figures  107 through  131 identify  the major  organic  constituents residual
in  the  soil.   However, in order  to determine if a waste is rendered less
or  non-hazardous by soil  incorporation,  it is  necessary  to compare  the
mutagenic  potential  of  equal volumes of  waste-amended  soil.   In  the
Salmonella  assay,  the  mutagenic potential  (Figures   132  to   134)  was
determined by  calculating the mutagenic  activity ratio  (Commoner, 1976)
of  two non-toxic  dose  levels  from  a  five member  dose-response  curve
(Table  73 through  90  and Figures  83  through  106)  and  adjusting this
ratio   by  the   rate-  of  hydrocarbon   degradation.    While   in  the
Aspergillus  methionine   assay   (Figures   135,  136  and  137)  equivalent
volumes of soil were compared by evaluating the total mutation frequency
induced  by the   soil-waste extract.   The  concentration of  extract tested
in  each  assay  was adjusted according to  the rate of degradation.  Thus,
the  data  presented  in  Figures  132  through  137   is  not  an  accurate
representation  of  the mutagenic  activity  of  soil-waste  extracts.   The
utility   of   these  data  is  their  ability  to  define   the   hazardous
characteristics  of  equal volumes  of   waste-amended soil.   The  volume
tested   from   the  acid   and  base   fractions   of   the   SWRI  and  COMBO
waste-amended soils  was the equivalent of 1 gram.   However, the neutral
fraction  from  the SWRI and COMBO soils, and all  three  fractions from the
PENT  S  soils  were  tested in  the  Aspergillus  assay  at  a  level twice
that  tested  in  the   Salmonella  assay.   While  it   is  unfortunate  that
equal  volumes were not tested in all assays,  these  results do  allow some
general  comparisons  to be made.   By  comparing the mutagenic  potential of
                                312

-------
equivalent volumes  of waste  amended soil  over time,  it  is possible  to
determine  if   a   waste   is  rendered   less  or  non-hazardous   by   soil
incorporation.

     The  results  from evaluating  the affect of  soil degradation on  the
mutagenic potential  of  PENT S amended soils are presented  in Figures  132
and  135.   In the  Norwood  soil,  the mutagenic  potential of the  base  and
neutral  fractions  decreased  to  below  the significant  level  (two  times
solvent   control),   in   both  bioassays.   In  the   acid   fraction,   the
mutagenic  potential  with  metabolic  activation was  reduced  to below  a
level  at  which  the  sample  would  be  considered  mutagenic   in   both
bioassays, although  the response  without  activation in Aspergillus  was
increased by more than  50% from day 0  to 360.  The mutagenic  potential
of  the  neutral  fraction   from  PENT  S amended  Bastrop   soil  was  also
decreased  to below  significant  levels  in both bioassays.   In  the  acid
and  base  fractions   from   PENT  S  amended Bastrop   soil,  the  mutagenic
potential was  increased on day  180.   The responses in Aspergillus  from
both  fractions  were  reduced by  day  360  to less than  that  observed on day
0;  and in Salmonella  the   mutagenic  potential  of  the  base fraction  was
reduced  by  day  360  while  the  response  from  the acid  fraction did  not
decrease  until  day 540.   Thus,  both bioassays  detected  constituent(s) of
the  acid  fraction of  the  PENT  S waste  amended soil that  were  resistant
to  degradation  and highly  mutagenic.   The bioassays also  indicated  that
the   bulk   of   the   total   extractable  hydrocarbons   were   rendered
non-hazardous by land treatment.

      The  mutagenic  potentials of the extracts  of SWRI amended  soils  are
presented  in Figures  133  and 136.   In  the  Norwood soil,  the  mutagenic
potential  of the  acid  and  base fractions was  not  reduced to  below the
significant  level  in  either of   the   bioassays  360  days  after  waste
application.    Although   there  was  an  appreciable  reduction  of  the
mutagenic  potential  of  these  two  fractions   in  the Aspergillus  assay,
the  mutagenic potential of the acid  and  base fractions  on day 360,  as
measured  with  J5.   typhimurium,  was approximately   twice  the  mutagenic
potential  of   an  equivalent  volume   of  soil  from  day  0.    In  both
bioassays, the  mutagenic potential  of  the neutral fraction from day 360
was  approximately  25% that  of the  sample  from day 0.   The acid fraction
of  the SWRI  waste amended  Bastrop  soils induced a  lower  response on day
360  than on  day  0;  however,  in both  bioassays  the response  induced by
the   sample  collected  on   day  360  would  be  considered  mutagenic.  The
response  induced by  the base fraction   from SWRI  waste amended Bastrop
soils   increased   from   day  180  to  360  in   both   the  Salmonella  and
Aspergillus  assays.    Although  the  response  induced by the sample  from
day   360  was  below  a  level  at   which  a sample  would  be  considered
mutagenic  in  Salmonella,   in Aspergillus  the  response   from   the  base
fraction  collected on day  360 was  slightly greater  than this  level.  The
response  induced by  the neutral  fraction extracted from  the  SWRI  waste
amended  Bastrop soil collected  on  day  360 was less  than  the  significant
level   in  both  bioassays.   A  comparison  of   the  results  from  the  two
bioassays  indicates  that  degradation did  not  render  the  acid  and  base
                                313

-------
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                                                        1-89 0
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   Figure 132.   Total extractable hydrocarbons and mutagenic potential of equivalent
                volumes of PENT S amended Norwood (NW) and^pastrop  (BA) soils as
                measured with S. typhi'murium strain TA98 with and without metabolic
                activation. Dashed line  (	) is equal to 2.5 times solvent control.

-------
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                                                                       180	•> ••	360"



                                                                          TIUE(D*yi)
                                                                                                           540
                      Figure 133.
                    Total extractable hydrocarbons and mutagenic  potential of equivalent

                    volumes of SWRI amended  Norwood (NW) and  Bastrop (BA) soils as measured

                    with j>. typhimurium  strain TA98 with and  without metabolic activation.

                    Dashed line  (	) is equal to 2.5 times solvent control.

-------
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                       Figure 134.   Total extractable hydrocarbons and mutagenic potential  of equivalent
                                    volumes of COMBO amended Norwood  (NW) and Bastrop  (BA)  soils as measured
                                    with S^ typhimurium strain TA98 with and without metabolic activation.
                                    Dashed line (	) is equal to 2.5 times solvent control.

-------
                                RENTS
X
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ACID  CZOOmg)
       SO-.
                                                  NEUTRAL C20mg)
                               TIME  (Days)
           Figure 135.   Total induced mutation frequency of equivalent
                        volumes of PENT S amended Norwood  (NW) and
                        Bastrop (BA) soils as measured  in A. nidulans
                        methionine system with and without metabolic
                        activation. Dashed line (	) is equal to total
                        induced mutation frequency of 5.0/10^ survivors.
                                317

-------
                           SWRI
 50-
 I 0-
                BA
       NW
                         NW
     + S9  £2
     -S9  D
          ACID (10)
BA                BA
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                                   ^
                   i
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                       TIME (Days)
   Figure 136.   Total induced mutation frequency of  equivalent
                volumes of SWRI amended Norwood (NW)  and
                Bastrop (BA) soils as measured in A.  nidulans
                methionine system with and without metabolic
                activation. Dashed line (	)  is equal  to total
                induced mutation frequency of  5.0/10^ survivors.
                          318

-------
                                  COMBO
CO
V
a.
2
                                                      NEUTRAL  C.lg)
                               TIME (Days)
   Figure 137.   Total  induced mutation frequency of equivalent
                volume of COMBO amended Norwood (NW) and Bastrop
                (BA) soils as measured in A. nidulans methionine
                system with and without metabolic activation.
                Dashed line (	) is equal to total induced
                mutation frequency of 5.0/10^ survivors.
                               319

-------
fractions  less or  non-hazardous.   However,  the  results  also  indicate
that  the neutral  fraction, which  represents  greater  than 90%  of  the
total   extractable   hydrocarbons,   was    rendered   non-hazardous    by
degradation in the soil.

     The average  rate  of  degradation of the  COMBO  waste in the  Bastrop
and  Norwood  soils  was  the maximum  rate  observed  in  the  three  wastes
studied.  This   degradation  rate  was  also  reflected  in  the  mutagenic
potential of  the  soil  extracts as  measured in  the  biological  systems.
The response induced  by the acid, base,  and neutral fractions  extracted
from  the COMBO waste  amended Norwood  soil  collected on  day  360 was  less
than  a  level  at which  the sample would  be considered mutagenic  in  both
the   Salmonella  and   Aspergillus   assays   (Figures    134   and   137).
Similarly, in  the waste amended Bastrop  soil  the  response  induced by the
fractions of the  samples collected on day  360 was less  than that induced
by  the  samples collected  on day  0.  In addition,  except  for  the  acid
fraction  from  the Bastrop  soil in  the   Salmonella  assay,   the  mutagenic
potential of  the  three waste  fractions   from  day  360  were  less  than the
significant  level  in  both bioassays.   Thus,  if  the   response in  the
eukaryotic assay  is  assumed to provide a more accurate  prediction of the
mutagenic  response  in  a  mammalian   system,  all  three  fractions of  the
COMBO waste were rendered non-hazardous by  land  treatment.

     The  major  factors  influencing  the   mutagenic  potential  of  the
hydrocarbons residual  at a land treatment  facility  include  the number of
different compounds  present, the  concentrations of those compounds,  and
the  toxic effects  and  interactions of  those compounds.  Biodegradation
will  influence the mutagenic  potential  as  it reduces  the  concentration
of  certain compounds  and alters the  reactivity  of others.   Oxidation or
substitution   at   specific  sites  have   been  shown   to   increase   the
reactivity  of  PAH   (LaVoie  et_  al.,  1981;  Hubermann £it  al. ,  1978;
Ho  et  al.,  1981).   The  rate  of  biodegradation may  increase as  soil
bacteria  adjust  to  the  types  of  hydrocarbons   in  the   soil.   Poglazova
et   al.   (1967),   Shabad  e£   al,.    (1971)   and   Khesina   et^   al..
(1969)  observed that  the  degradation of PAH by soil microorganisms was
significantly  increased in a soil previously  exposed  to these  compounds.
It  is  also  anticipated  that  bacteria  capable  of degrading  the  more
complex  PAH  will occur in nature,  since  compounds  such as  napthalene,
phenanthrene,     fluoranthene,     dibenzothiophene,     carbazole,     and
dibenzofuran  are  components  of  coal (Sims and  Overcash,  1983).   Soil
microorganisms  possess a  broad  range  of  enzymatic  capabilities  and
should  be  capable   of  degrading  an  assortment  of  hazardous  compounds
(Clark   et_   al.,    1979;   Patil    et   al.   1970;   Chacko   et_   al,.,
1966;   Bixby   e±   al.,    1971).     The   results   of   this   research
demonstrate  that  land  treatment can  reduce the  hazardous characteristics
of  a waste by transformation  or  degradation.  Thus, land  treatment can
render  a waste less or  non-hazardous  if  it can  also  be  demonstrated that
hazardous constituents  are  immobilized in the  soil.
                                  320

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                               SECTION 10

        SOIL MOBILITY AND DEGRADATION OF MUTAGENIC CONSTITUENTS
                 FROM A WOOD-PRESERVING BOTTOM SEDIMENT
INTRODUCTION

     The  interaction  of  environmental  parameters with  soil  and waste
components  will  greatly  influence the  rate  at which  hazardous  organic
constituents  are   transformed,   degraded,  or  immobilized  at   a   land
treatment   facility.    While   the   majority   of  hazardous   organic
constituents  will   apparently  be  retained and  degraded  in  the  surface
layer of  soil,  there  is  concern  about  the  environmental  fate of those
constituents  which  may  be  mobile  in  soil.   Mobile  compounds  may  be
soluble  in  water  and  move  with the  wetting   front  or  they  may  be
hydrophobic  and move  ahead  of   the  wetting  front.   In  addition,   the
mobility  of  a  compound  may  be  modified  by  chemical  and   biological
reactions occurring in  the soil.

     In  order  for  land  treatment  to  be   an   environmentally sound
alternative  for hazardous  waste  disposal,   there is  a  need   to  develop
procedures  for  sampling  and  techniques  for  monitoring mobile compounds
in  soil.   Two  procedures   have   been  recommended  for  sampling mobile
compounds  at  a hazardous  waste  land  treatment   facility  (EPA,  1982).
Soil core  samples  are  intended to provide information  on  the movement of
"slower  moving"  constituents, whereas soil-pore samples are intended to
provide   information   on   the   movement   of   fast-moving    hazardous
constituents  that  may  be missed  by  a soil-core  sample.   This  research
project was  designed to provide information  as  to the  utility  of the two
sampling  procedures and  to  monitor the mobility  of  the components  of a
complex mixture in  soil using  both biological  and  chemical  analysis.

MATERIALS AND METHODS

Soil

     Undisturbed  soil  monoliths  of  the Norwood silt   loam  were  used in
this  study.  The  properties  of  this  soil  are  discussed  in  detail in
Section  6,  and  the  chemical and  physical  properties with  depth  are
provided  in Table  93.  The  soil monolith  was  obtained  from a virgin  area
that had not  received  waste  applications of any kind.
                                321

-------
      TABLE 93a. CHEMICAL PROPERTIES OF THE NORWOOD  SOIL  SERIES
Exchangeable Cations
Depth
(cm)
0.0-15.2
15.2-30.5
30.5-61.0
61.0-91.5
91.5-119.0
119.0-122.0
122.0-152.0
pH CEC*
(meq/100 g)
7.69
7.73
7.74
7.86
7.75
7.75
7.95
19.6
21.1
22.9
17.8
16.2
30.0
13.2
Ca++

20
20
20
20
20
20
20
++
Mg
I/ 100 g -
4.0
4.0
4.0
4.0
4.0
4.0
4.0
K*

0.8
0.8
0.8
0.8
0.8
0.8
0.8
*CEC = cation exchange capacity.
     TABLE 93b.  PHYSICAL APROPERTIES OF THE NORWOOD  SOIL  SERIES
Particle Distribution
Depth
(cm)
0.0-15.2
15.2-30.5
30.5-61.0
61.0-91.5
91.5-119.0
119.0-122.0
122.0-152.0
* sc = sandy clay,
Texture
(USDA)
sc*
scl
c
cl
cl
c
scl
scl = sandy
Sand

48^2
49.6
36.0
40.5
42.0
23.1
49.1
clay loam,
Silt
	 	 /yv
— 	 \h) —
15.2
15.1
18.4
22.3
25.0
20.5
15.8
c = clay, cl =
Clay

36.6
35.3
45.6
37.2
33.0
55.6
35.1
clay loam
                                 322

-------
Waste

     The  waste  used  in  this   segment   of  the  research  was  a  wood-
preserving  bottom  sediment.   A  detailed  description of  this waste  is
given in Section 5  and the characteristics  summarized  in  Table 50.

Lysimeters

     Six  undisturbed soil monolith  lysimeters  were used in  this  portion
of  the  study.   A detailed  description of   the   procedures  for  the
collection  and  installation  of  lysimeters   is given  by  Brown  e_t  al.
(1974).   Briefly,  the  technique  is  as  follows:  Casings (28  cm x 90 cm)
were obtained from  the  Sharney  Container Corp. (Houston,  Texas).  These
55  gal  straight-walled  barrels  were  cleaned  and  coated  with an  epoxy
based  heavy metal  free  paint  (Shertar,  Sherwin-Williams Co).  Using  an
iron  frame  for  support,  the  casings  were forced  into  the  ground with
pressure  applied  by  a  backhoe.   As  the casing  was  pushed into  the
ground,  the soil was removed  around the  outside to  relieve  the pressure.
The  backhoe was  used  to  lift the  soil  monolith and  to roll  it  upside
down.   Sufficient  soil  was  removed from  the  bottom  of the  profile  to
install  three porous ceramic  suction  cups at   the bottom of the profile.
The  nylon  tubes  that  were used  to conduct  the leachate to  the  surface
were  threaded through  a 1.27  cm diameter PVC tube  installed along the
inside  of  one wall.  A  barrel gasket  was sealed in place,  and the bottom
was  clamped on the  barrel.  The  lysimeters were then  turned upright and
installed  in  a location  to facilitate  leachate  collection.

Leachate 'Sample  Collection

     A  schematic diagram  of   the  leachate collection system  is shown in
Figure  138.  Leachate  from  the  bottom of each lysimeter  was collected
through  3  porous  cups   (Coors  Type #70001-P-6-C).   Each_?had  a_.bubbling
pressure   of  0.5  bars,  a  conductivity  of   1.2  ml  cm   min    bar   ,
and a surface area  of 38.8 cm  .

     Plexiglass  caps were sealed   to  the open end of  the  cups with a
water  proof  two part  epoxy  (Armstrong   #34).   Nylon  tubes  .159  cm in
diameter  were cemented  into   the  plexiglass  caps  with  another two part
epoxy  (Armstrong #6) that adhered  well to nylon.   The three tubes passed
through   the   1.27   cm   PVC   pipe  to   a  plexiglass  collection  manifold
approximately 7.5  cm above  the soil  surface.  Nylon  tubes  of  0.32  cm
diameter  were used to   convey  the   leachate to amber glass  bottles in a
refrigerator  at  4  C.    A  continuous  vacuum was  maintained  on all  six
bottles.  Each bottle was equipped  with  an outflow tube connected to a
trap bottle.   A glass tube 0.64  cm in diameter was placed in the center
of  a rubber  stopper in  the  trap  bottle and connected to a vacuum pump by
rubber   tubing.     Leachate   samples  were  collected  as   necessary  by
replacing  the amber glass bottles.   Leachate  samples from each lysimeter
were  composited  for the  thirty  days prior to  waste application, day 0 to
30  after application, and day 30 to 90 after  application.  All containers
                                 323

-------
U)
to
•p-
                   LYSIMETER
                                                                   •CAMBER GLASS
                                                                    COLLECTION
                                                                      BOTTLE
                          PLEXIGLASS MANIFOLD
                 SOIL  SURFACE       POROUS CUPS ^^-1/16" TUBES
        Figure 138.  Schematic diagram of  leachate collected system used in the lysimeter
                     study.

-------
were cleaned with  soap and water and sequentially rinsed with  tap  water,
acetone,  and  distilled water  to remove  all  organics prior to  sampling.
All samples were stored at 4 C after arrival  at  the  laboratory.

Soil Sample Collection

     Surface  soil  samples,  0  to  15   cm,  were   collected   from  each
lysimeter prior  to  and immediately after waste  application.  Ninety days
following  waste  application,   the  lysimeters  were  dissected  using  a
circular  saw   equipped  with   an  abrasive  blade.    Four of  the  six
lysimeters  were sacrificed  in  order   to  collect  the amount  of  sample
needed.   Sufficient  soil  was   collected to conduct  a  biological  and
chemical  analysis  on  the soil  extract, as well as  to provide  a  reserve
sample  for  future  use.   Soil samples  were  collected from the  center of
each  lysimeter  at  depths of 0  to 15  cm,  15 to 45  cm,  and 45  to  90  cm.
Precautions were taken  to  prevent cross-contamination  of cores.   These
included  collecting the  soil-cores  from the center of the lysimeter to
avoid  any  influence  due to  side-channel  flow,  cleaning the  sampling
device   between   corings,   collecting   samples   from  control   before
waste-amended   lysimeters,  and  collecting  multiple  composited  samples
from each lysimeter at  each  depth.

Biological Analysis

     The  ability  of  the  organic  extract of soil  and  water   samples  to
induce  genetic  damage  was  measured in a prokaryotic  system  capable  of
detecting    compounds     which    induce    point     mutations.      The
Salmonella/microsome   assay*  of   Ames   et^  al.    (1975)  utilizes   a
prokaryotic  organism  to  evaluate  the  capacity of  a sample   to  induce
reverse  mutations  to  histidine  prototrophy.  Salmonella   strain  TA98 (a
frameshift  mutant)  was   supplied  by   Dr.   B.  N.  Ames   (University  of
California, Berkeley,  CA).   The procedural methods  were  the  same  as Ames
e£   al.   (1975),  except   that   overnight   cultures  were prepared   by
inoculation  into  10  ml  of Nutrient   Broth #2  (KC  Biological,  Inc.,
Lenexa,  KS).  Soil  extracts  were tested  on   duplicate   plates  in  two
independent  experiments  in  the  standard plate  incorporation  assay at a
minimum   of  4   dose   levels  of  the   sample with   and   without   enzyme
activation  (0.3 ml rat  liver/ml  S-9  mix).  Aroclor 1254  induced  rat
liver  was  obtained  from Litton  Bionetics   (Charleston,   SC).   Positive
controls  included  25  ug/plate  2-nitrofluorene  (Aldrich  Chemical Co.,
Milwaukee,  WI),  and  10  jag/plate 2-aminoanthracene  (Sigma)  which  was
used  to  verify  the functioning  of  the metabolic activation system.  All
reagents  and extracts  were  tested for sterility;  DMSO  was  used as a
negative  control.

RESULTS AND DISCUSSION

     The  chemical  and biological  analysis  of  soil  and  leachate  water
from   control    and  waste   amended  lysimeters   indicate   that  certain
constituents  of  the   wood-preserving   bottom   sediment  are  capable  of
                                 325

-------
 migrating  through   the  soil.   The  analysis  of  soil-core  samples  from
 control and  waste-amended lysimeters over various  depths indicated that
 greater quantities  of residual hydrocarbons  and  mutagenic activity were
 present in  waste  amended  samples  up to  a depth of 45  cm (Figure 139).
 There was  no appreciable  difference in  the  mutagenic  potential  of the
 soil from control  and waste amended lysimeters at the 45  to 90 cm depth,
 although greater quantities  of residual hydrocarbons were recovered from
 the  waste  amended  soil at  this  depth.  The  mutagenic  potential  of the
 soil-core sample from a depth of 0 to 15 cm was greatest  in the presence
 of  metabolic  activation;  whereas,  the  soil  at  15   to  45  cm  gave
 approximately  the   same  response  with  or  without  metabolic  activation
 (Figure 139).

      The  results   from  the chemical  analysis of soil-core  samples from
 control and  waste   amended  lysimeters are  provided in  Tables  94 and  95
 and  Figures  140,  141,  142,  and  143.  The  compounds  identified  in the
 soil-core sample from the unamended lysimeter  (Table  94 and Figure 140)
 were  predominantly the  same  as  those  identified  in   the  Norwood soil
 (Table  45  and Figure  52).   Two  compounds  of  an unknown  origin were
 identified  including  1,2-dichlorobenzene  and   trimethyl-hexadione.    A
 larger number  of compounds were identified in  the  waste  amended  soil  at
 all  depths  than  were  identified  in  the  unamended soil  (Table  95 and
 Figures  141,  142, and  143).   These  included  several  high molecular
 weight polycyclic  aromatic hydrocarbons.   Mutagenic compounds identified
 in   the  surface   soil  sample  (Figures   135,  136,  and 137)   included
 methylnapthalene,   dihydro  acenapthylene,   fluoranthene,  pyrene,  and
 benzanthracene  (Kaden  et^ al.,  1979;   McCann   et^ al.,  1975).    Other
 compounds with  a. potential influence on  the  genetic activity  of  the soil
 extract   included   pentachlorophenol,    several   alkane  promoters  and
 cocarcinogens,  and hexadecane which is an  inhibitor.   Only  one  compound,
 dihydro acenapthylene,  was consistently  identified  in  the waste  and soil
 core samples at all depths  (Figure 94).

      When  compared to  the soil-core samples,  the analysis of  soil-pore
^samples  provides   a  slightly  different  perspective on the capacity  of
 PENT  S waste  samples to  migrate  through the soil.  Biological  analysis
 indicated  that there was  no  mutagenic  activity,  as   measured  with  J3.
 typhimurium  strain TA98,  detected  in  the  leachate water collected from
 control  and waste amended  lysimeters  prior  to  waste   application.  The
 mutagenic  potential  of the  soil-pore  sample  collected  on day  30 was
 approximately  seven  times  greater  than  the  control,  whereas the  sample
 collected  on day  90  had  a  mutagenic potential  approximately ten  times
 the  control  (Figure  144).   Thus,   the bioassays detected  significantly
 greater quantities of mutagenic activities in  the  soil-pore samples from
 the  PENT S  lysimeters both on  day 30  and  on day 90.

      Nine  compounds  were  detected  in  the soil-pore  liquid sample from
 the   unamended  lysimeters    (Table   96   and    Figure   145)    including
 benzene-dicarboxylic  acid  and chloro-octane.   Neither  of these  compounds
 is  known  to  have any genotoxic  activity.    There were  ten  compounds
                                  326

-------
1200-

1000
60
40
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UT51METER SOIL
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                                       4S-9O
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                      IS— »3
                                     49-30
                                                   WASTE
 Figure  139.   Extractable hydrocarbons and mutagenic
               activity from soil core samples  collected
               at various depths  on day 90.
                             327

-------
TABLE 94. LIST OF COMPOUNDS DETECTED IN SOIL CORE
           SAMPLE COLLECTED ON DAY 90 FROM CONTROL
                 NORWOOD SOIL AT 0-15 CM DEPTH
      Compound (Peak Number)*   Genetic Toxicity

      Pentadecane (324)X
      Unknown (351)                     X
      Hexadecane (367)                  A
      Unknown (388)                     X
      Heptadecane (411)                 X
      Octadecane (443)                  P; CC
      Unknown (463)                     X
      Nonadecane (475)                  X
      Unknown (496)                     X
      Eicosane (507)                    CC
      Heneicosane (538)                 X
      Unknown (550)                    °X
      1,2-dichlorobenzene (564)         Ml
      Trimethyl-hexanedione (599)       X
      Unknown (614)                     X
      Unknown (663)                     X
      Unknown (684)                     X

*  Potential genetic toxicity: I = initiator;
   P = promoter;  A = antagonist; CC = cocarcinogen
   (synergist);  MO = nonmutagenic; Ml = mutagenic;
   CO = non-carcinogen; Cl = carcinogen; all others
   = no information.  The references used in determining
   these factors  are listed in the text.
                          328

-------
TABLE 95.
LIST OF COMPOUNDS DETECTED IN SOIL CORE SAMPLES COLLECTED ON DAY 90 FROM PENT S WASTE AMENDED NORWOOD SOIL AT
                                         VARIOUS DEPTHS
                                                       Fraction
Sample
                  Acid
    Compound (Peak Number)*
           Base
Compound (Peak Number)*
           Neutral
Compound (Peak Number)*
0-15 cm        Unknown (222)
               Tridecane (236)
               Methyl napthalene (243)*M1; CO
               Unknown (262)
               Tetradecaiie (2B3)*P
               Dimethyl napthalene (290)*MO
               Dihydro acenaphthalene O17)*M1
               Pentadecane (330)
               Fhenalene (369)*Ml
               llexadecane  (379)*A
               Unknown (396)
               Heptadecane (409)
               Pentachlorophenol (437)*HO; Cl
               Methyl dibenzothiophene  (461)*MO
               Nonadecane  (472)
               Eicosane (503)*CC
               Fluoranthene  (525)*M1; CO; CC
               Pyrene (540)*M1; CO; CC
               Docosane (563)
               Unknown (592)
               Unknown (620)
               Unknown (642)
               Unknown (671)
                                            Tridecane (249)
                                            Dimethyl napthalene (296)*HO
                                            Tetradecane (3!l)*P
                                            Dihydro acenaphthalene (323)*M1
                                            Unknown (337)
                                            Pentadecane (353)
                                            Phenalene (366)*t(l
                                            Hexadecane (384)*A
                                            Carbazole (402)*MO; CO
                                            Heptadecane (414)
                                            Octadecane (445)*P; CC
                                            Unknown (457)
                                            Nonadecane (477)
                                            Cyclopentaphenanthrene (485)*MO
                                            Eicoaane (509)*CC
                                            Fluoranthene (530)*M1; CO; CC
                                            Heneicosane (540)
                                            Pyrene (545)*Ml; CO; CC
                                            Docosane (569)
                                            Unknown (599)
                                            Unknown (628)
                                    Unknown (242)
                                    Unknown (304)
                                    Pentadecane (338)
                                    Dimethyl napthalene (3S1)*MO
                                    Dihydro acenaphthylene (366)*Ml
                                    Dibenzofuran (375)
                                    Trimethyl naphthalene (385)*MO
                                    Heptadecane (401)
                                    Methyl dibenzofuran (416)
                                    Octadecane (437)*P; CC
                                    Dibenzothiophene (455)*MO
                                    Nonadecane (472)
                                    Eicosane (506)*CC
                                    Ethyl undecane (520)
                                    Methyl hexadecane (540)
                                    Docoaane (569)
                                    Branched alkane (595)
                                    Tricosane (620)
                                    Tetracosane (639)
                                    Benzophenanthrene (659)
                                    Benzanthracene (680)*M1; Cl

-------
                             TABLE 95 CONTINUED
    15-45 cm (crude)
Compound (Peak Number)*
    45-90 cm (crude)
Compound (Peak Number)*
Unknown (213)
Tridecane (234)
Unknown (267)
Tetradecane (277)*P
Unknown (303)
Dihydro acenaphthylene (311)*M1
Pentadecane (319)
Unknown (338)
Fluorene (351)*MO; CO
Hexadecane (358)*A
Trimethyl octane (378)
Heptadecane (398)
Octadecane (435)*CC
Unknown (450)
Nonadecane (470)
Benzene dicarboxylic acid  (492)*MO
Eicosane (502)*CC
Unknown (514)(523)(554)(592)
Unknown (230)
Unknown (257)
Dihydro acenaphthylene (307)*Ml
Dimethyl nonane (314)
Unknown (339)
Trimethyl octane (354)
Unknown (373)
Tetrazolamine (393)
Unknown (475)
Benzenedicarboxylic acid (487)*MO
Methyl hexene (521)
Unknown (563) (589)
Ethyl methyl pentanol (604)
Ethyl methyl heptane (610)
Unknown (636)
Methyl heptanol (651)
Unknown (685) (716)
Methyl propyl pentanol (738)
Unknown (755) (780)
   Potential genetic toxicity:  I = initiator; P = promotor; A  =  antagonist;
   CC = cocarcinogen(synergist); MO = nonmutagenic; Ml = mutagenic;
   CO = non-carcinogen; Cl = carcinogen; all others = no information.
   The references used in determining these factors are listed in  the  text.

-------
                                                     o
                                                     o
                                                     m
RIG
                                                              LYS.  CONTROL


                                                              SOIL  - CRUDE


                                                              DAY 90
                                                               oo
                                                               u>
                                                               •n
          200
300
400
                                       RT
500
600
                                       111

   Figure 140.   GC/MS  chromatograph of crude extract  of  soil core sample

                collected on day 90 at a depth of 0 to  15 cm from unamended

                Norwood  lysimeter.

-------
OJ
CO
ho
             RIG
                                                                      LYS.  0-6"


                                                                      PENTS ACID


                                                                      DAY 90
                                                                                  o
                                                                                  r4
                                                                                  vO
                200
300
400
5dO
600
                                                     RT
                   Figure 141.  GC/MS  chromatograph of acid fraction of soil core sample collected on

                                day 90 at a depth of 0 to  15 cm from PENT S  amended Norwood lysimeter.

-------
                                                                               LYS. 0-6"

                                                                               RENTS BASE

                                                                               DAY 90
CO
                RIG
                   200
 300
400
500
600
                                                       RT
                      Figure 142.
GC/MS chromatograph of base fraction of  soil core sample  collected
on day 90 at a depth of 0  to 15 cm from  PENT S amended Norwood
lysimeter.

-------
                                                                            LYS.0-6"


                                                                            RENTS NEUTRAL


                                                                            DAY 90
             RIG
OJ
CO
               200
300
400
500
600
                                                                                  700
                                                  RT
                   Figure  143.  GC/MS chromatograph of neutral fraction of soil core sample

                               collected on day 90 at a depth of 0 to 15cm from PENT S
                               amended Norwood lysimeter.

-------
U)

U)
                          600
                        1 400
                        O
                        to
                        00

                        CD

                        <
                          zoo
                                                         I — C — i    i — PS— i
                                     LYSIMETER LEACHATE
                                     {"I CONTROL    C
 O PENTS


-89
                                                 PS
+89
                              — C — i  i — PS
                                      1  V//A

                                BACKGROUND
                        DAY 30
                                                                                       C — i   '— P
                                                            i
                                                                                         DAY 90
                              Figure  144.   Mutagenic  activity of  leachate water  from control  and

                                            PENT S waste amended lysimeters.

-------
TABLE 96.  LIST OF COMPOUNDS DETECTED IN SOIL PORE SAMPLES COLLECTED ON DAY
                        90 FROM PENT S WASTE AMENDED NORWOOD SOIL

        Compound (Peak Number)*                  Compound (Peak Number)*

PENT SUnknown (164)
        Hydroxyl methyl pentanone (185)     CONTROL:Unknown (298)
        Unknown (212)                               Unknown (391)
        Unknown (226)                               Unknown (417)
        Unknown (251)                               Benzene dicarboxylic
                                                        acid(491)*MO
        Unknown (278)                               Unknown (542)
        Octanedione (287)                           Unknown (572)
        Unknown (308)                               Unknown (602)
        Unknown (325)                               Chloro-octane (632)
        Tetrachlorophenol (338)#MO                  Unknown (661)
        Phenyl butanone (362)
        Phenalene (376)*M1
        Anthracene (402)*MO
        Pentachlorophenol (415) (429)*MO; Cl
        Benzene dicarboxylic acid (491)*MO

*  Potential genetic toxicity: I = initiator; P = promoter; A = antagonist;
   CC = cocarcinogen(synergist); MO = nonmutagenic; Ml = mutagenic;
   CO = non-carcinogen; Cl = carcinogen; all others = no information.
   The references used in determining these factors are listed in the text.

-------
u>
            RIG
                                                                  LEACHATE


                                                                  CONTROL


                                                                  DAY 90
                                                                             «  IN
                                                                             r-  o
                                                                                       VO
                                                                                       t>
                                    200
                                        400
600
                                                   RT
Figure  145.
                              GC/MS chromatograph of soil pore liquid sample collected from

                              unamended Norwood lysimeter on day 90.

-------
identified  in   the   soil-pore  samples  from  the  PENT  S   lysimeters,
including anthracene  and pentachloraphenol  which were  also  detected  in
the 0  to 15 cm  soil-core sample  from day 90  (Table  96 and Figure  146).
Anthracene,   a  non-mutagenic  hydrocarbon,  has  been  found   to   produce
significant  enhancement  when  in  mixture with  other  polycyclic  aromatic
hydrocarbons  (Hermann,  1981);   at high  concentrations,  anthracene caused
significant    enhancement  of  2-aminoanthracene   (Kawalek  and   Andrews,
1981).  Phenalene,  another compound identified  in a leachate  sample,  was
also  present  in the  waste  but was not  detected  in any of the soil-core
samples.  Tetrachlorophenol, a degradation  product of  pentachlorophenol
(Fishbein,  1977),  was also  detected  in  the  90  day leachate sample.  This
compound  was  not  present  in  waste  or  soil-pore  samples.   As a result,
the  tetrachlorophenol may  have been  transformed from  pentachlorophenol
at  the  soil   water   interface and  was  subsequently  leached  into  the
soil-pore   water  90   cm  below   the   soil   surface.   The   absence   of
tetrachlorophenol  in  the 0 to 15 cm  soil  sample makes it unlikely that
the  compound  reached  the soil-pore  sample  as a result of  side channel
flow.

      This   analytical  protocol,   using  both  biological   and   chemical
analysis,   has   demonstrated   that   soil-core   and    soil-pore  liquid
monitoring   can  be  used   to  detect  different  types   of   compounds.
Mutagenic activity was detected  in  both soil-core and soil-pore  samples,
although no  activity  was detected in  the 45  to   90 cm soil-core sample.
Saturated   alkanes,  branched  alkanes,   and  alkanols   were  identified  in
soil-core  samples, while  the  more  complex  compounds  such as tetra- and
pentachlorophenol,  phenalene, and   anthracene  were   identified   in  the
soil-pore   samples.   In  addition, the  results  from   utilizing  bioassay
directed chemical analysis   indicated  that  compound(s) such as anthracene
may  have served  to  enhance the  activity of mutagenic compounds present
in  the leachate in trace quantities.   This  combined  testing  protocol has
demonstrated  that both  soil-core  and soil-pore  samples are  necessary to
provide an accurate  evaluation  of   the  potential  for hazardous  waste
constituents  to  migrate  below  the  zone   of  incorporation  at   a  land
treatment   facility.   The  analysis  of  samples  from   lysimeters  amended
with   a  wood-preserving bottom   sediment   indicated   that  mutagens  and
potential carcinogens are capable of  migrating to a  depth  of 75  cm below
the  zone of  incorporation  within 90  days  following  waste  application.
These  results  indicate that  land treatment  of  a wood-preserving waste
should proceed  with  caution,  and  that pretreatment  options  or  in-plant
process controls  might  be  used  to  reduce the  concentration of mobile
constituents  in the waste prior to land application.
                               338

-------
                                                      P3  LEACHATE
                                                          DAY90
RIC
   150
Figure 146.
                                                                            550
                     GC/MS chromatograph of soil pore liquid sample collected from
                     PENT S amended lysimeter on day 90.

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                                  SECTION 11

                               LITERATURE CITED
1.     Abrams, E. F. ,  D.  K.  Guinan, and  D.  Derkics.  1976.  Assessment of
      Industrial   Hazardous   Waste   Practices.    Textiles   Industry.
      PB-258-953.

2.     Abbondanolo,   A.,   S.  Bonatti,  C.  Corsi,  G.  Corti,  R.  Fiorio, C.
      Leporini,  R.  Barale,  and  N. Loprieno.  1980.   The  use  of organic
      solvents in mutagenicity testing. Mutat. Res. 79:141-150.

3.     Adler,  B.,  R.  Braun,  J.   Schoneich,  and H.  Bohme.   1976.   DNA
      repair assay using P. mirabilus. Biol. Zentrabl.,  95:463-469.

4.     Aeschbacher,  H.U.,  P.A. Finet,  and  U.  Wolleb  1983.  Interactions
      of  histine-containing  substances  and extraction  methods  with  the
      Ames mutagenicity  test.  Mutat.  Res.  113:103-116

5.     Alderson,  T.  and  J.   Hartley.  1969.  Interlocus  specificity  for
      chemical   mutagens    in    Aspergillus   nidulans.   Mutat.    Res.
      8:255-264.

6.     Alderson,  T.,  and  B.  R.   Scott.  1970. The photosensitizing  effect
      of   8-methoxy-psoralen  on   the  inactivation   and  mutation   of
      Aspergillus   conidia    by   near  ultraviolet   light.  Mutat.   Res.
      9:569-578.

7.     Alexander, M.  1981.   Biodegradation of chemicals  of environmental
      concern.   Science  211:132-138.

8.     Ames,  B.  N.,  W.   E.  Durston,  E.   Yamasaki and  F.  D.  Lee.  1973.
      Proc.  Nat. Acad.  Sci. USA  70(8)2281-2285.

9.    Ames,  B.  N.,  J.  McCann   and   E.  Yamasaki.    1975.   Methods  for
      detecting  carcinogens  and  mutagens  with   the  SaImone11a/mamma1ian
      microsome  mutagenicity  test. Mutat.  Res. 31:347-364.

10.   Ames,  B.  N.  1979.  Identifying  environmental  chemicals   causing
      mutations  and cancer.   Science  204:587-593.
                                 340

-------
11.    Anderson,  K.  J. ,   E.  G.  Leighty  and  M.  T.  Takahashi.^   1972.
      Evaluation  of  herbicides  for  possible  mutagenic  properties.   J.
      Agric. Food Chem. 20(3)649-656.

12.    Anderson,   D.   and    A.   Styles.   1978.    An  evaluation  of   six
      short-term   tests   for   detecting  organic   chemical  carcinogens.
      Appendix   II.    The  bacterial   mutation  test.   Br.   J.   Cancer
      37:924-930.

13.    Anderson, D.  and E. Longstaff. 1981.  An appraisal  of mutagenicity
      test systems.  The Analyst. Vol.106, No. 1258:1-22.

14.    Anon.  1975.  Industry's   problems  with  cancer  aired.   Chem. Eng.
      News. 53:4.

15.    Ashby,  J.  1981.  Results of reverse mutation  assays.  Iji F.  J.  De
      Serres   and  J.  Ashby   (eds.).   International  Program  for  the
      Evaluation   of   Short-Term  Tests   for   Carcinogenicity.   Elsevier,
      Amsterdam.

16.    Baker,  R.S.U.,   A.  M. Bonin,  I.   Stupans  and  G.  M. Holder.  1980.
      Comparison  of rat  and guinea pig  as  sources  of the S9  fraction in
      the   SaImone1la/Mamma Han  Microsome  Mutagenecity   Test.    Mutat.
      Res., 71:43-52.

17.    Barber,  E.  D.,  W.  H.   Donish   and  K.  R.  Mueller.   1983.   The
      relationship  between growth  and  reversion in  the  Ames  Salmonella
      plate incorporation  assay.  Mutat.  Res.,  113:89-101.
        i
18.    Barnes,   W.S.   and  E.J.   Klekowski,  Jr.   1978.    Testing   the
      environment  for dispersed  mutagens:  use of  plant  bioconcentrators
      coupled  with microbial  mutagen assays.  Environ. Health  Perspective
      27:  61-67.

19.    Bartsch,  H., C. Malaveille,  A.   M.  Camns,  G. Martel-Planche,  G.
      Brun,  A.   Hautefuille,   N.   Sabadie,  A.,  Barbin,  T.  Kuroki,   C.
      Drevon,  C.   Piccoli,  and   R.  Montesano.  1980.    Validation  and
      comparative   studies   on  180   chemicals   with    j>.   typhimurium
      strains  and  V79 Chinese hamster  cells  in the presence  of  various
      metabolizing systems.  Mutat.  Res.  76:1-50.      N

20.   Beck,  D. B.  1978.   Miscellaneous cyclic and acyclic  chemicals,  p.
      293-305.   In   Synthetic   Organic  Chemicals.  U.S.  International
      Trade  Commission  Publication  1001.  U.S. Govt.  Printing  Office,
      Washington,  D.C.

21.   Belinki,  B.  R.  1980.    Improved  resolution  in  high  performance
      liquid    chromatography    analysis   of    polynuclear    aromatic
      hydrocarbons using  ternary  solvent systems,  p.  149-168. In D.  D.
                                 341

-------
      Dollberg  and A.  W.  Verstuyft  (ed.).  ACS  Symposium  Series  120.
      American Chemical Society, Washington, DC.

22.    Belser, Jr.,  W.  L.,  S.  D.  Shaffer,  R.  D. Bliss,  P.  M. Hynds, L.
      Yamamoto,  J.  N.  Pitts,  Jr.,  and J. A. Wine.  1981.  A  standardized
      procedure      for       quantification      of       the      Ames
      Salmonella/mammalian-microsome    mutagenicity    test.     Environ.
      Mutagen.,  3, 123-139.

23.    Bernstein,  L.,  J.  Kaldor,  J.  McCann, and M.  C.  Pike.  1982.  An
      empirical approach to  the statistical analysis of mutagenesis data
      from the Salmonella test. Mutat. Res. 97:267-281.

24.    Bertoldi,  M.,  M.  Griselli,  and  R.  Barale. 1980.   Different test
      systems  in  Aspergillus   nidulans  for  the  evaluation  of mitotic
      gene conversion,  crossing-over and  non-disjunction.  Mutat.  Res.,
      74:303-324.

25.    Bigani, M. ,  G. Morprugo, R. Pagliani, A.  Carere,  G. Conte, and G.
      DiGuiseppe.   1974.   Non-disjunction  and   crossing  over induced by
      pharmaceutical   drugs   in  Aspergillus   nidulans.   Mutat.   Res.
      26:159.

26.    Bignami,  M. , G.  Conti,  L. Conti, R.  Crebelli,  F. Misuraca, A. M.
      Puglia,   R.   Randazzo,   G.  Sciandrella   and   A.   Carere.    1980.
      Mutagenicity  of  halogenated  aliphatic hydrocarbons in  Salmonella
      typhimurium.     Streptomyces     coelicolor     and     Aspergillus
      nidulans Chem. Biol. Interactions, 30:9-23.

27.    Bignami,   M. ,   G.   Couti,  R.  Crebelli,   and  A.  Carere.   1981.
      Growth-mediated    metabolic    activation    of    promutagens   in
      Aspergillus  nidulans. Mut. Res. 80:265-272.

28.    Bixby,  M.  W. ,  G. M.  Boush, and F. Matsumura.  1971.  Degradation of
      dieldrin   to  carbon   dioxide   by   a   soil   fungus   Trichoderma
      koningi.  Bull. Environ.  Contam. Toxicol.  6(6):491-495.

29.    Bos,  R.  P.,  C.T.J.  Hulshof,  J.L.G. Theuws  and  P.T.  Henderson.
      1983.   Mutagenicity   of  creosote  in  the   Salmonella  microsome
      assay.  Mutation Research,  119:21-25.

30.    Bourquin, A.  W.  and D.  T. Gibson.  1978.  Microbial degradation of
      halogenated  hydrocarbons, ^n  R.  L.  Jolley, H.  Gorchev, and D. H.
      Hamilton,  Jr.  (eds).  Water  Chlorination:Environmental  Impact and
      Health  Effects, Vol.2.   Ann Arbor  Science, Ann Arbor, MI.

31.    Bridges,  B.  A.,  D.  MacGregor,  E.  Zeiger,  A.  Bonin, B.  J. Dean, F.
      Lorenzo,  R. C.  Garner,  D. Gatehouse,  S.  Hubbard,  D.  Ichinobutso,
      D.  MacDonald,  G. Martire,  T.   Matshumisha,  G. Mohn,  M. Nagao, M.
      Richold,  I.  Rowland,  V.  Simmon,  T.  Skopek,  R.  Truman,  and S.
                                   342

-------
      Venih.  1981.   Summary Report  on Bacterial  Mutation Assays. In F.
      J.  de  Serres  and  J.  Ashby (eds.).  Evaluation  of Short-Term Tests
      for Carcinogens,  pp.  49-67.  Progress in Mutation Research Vol. 1.
      Elsevier/North Holland.

32.    Brookes,  P. and  F.  J. de Serres.  1981.   Overview of Assay  Systems
      Performance.  In  F. J.  de  Serres  and  J.  Ashby  (eds.). Evaluation
      of  Short-Term  Tests  for  Carcinogens,  p.  96-111.   Progress  in
      Mutation Research Vol. 1. Elsevier/North Holland.

33.    Brown,    J.    P.   and   P.  S.   Dietrich.    1979.   Mutagenicity  of
      anthraquinone    and    benzantraquinone    derivatives     in    the
      Salmonella/microsome  test:activation  of   anthraquinone glycosides
      by enzymaic extracts of rat cecal bacteria. Mutat. Res.  66:9-24.

34.    Brown,  K.  W., C.  Woods,  and  J.  F. Slowey.  1975.   Fate of metals
      applied  in  sewage  at  land  wastewater disposal sites.   Final Report
      ADAO 43363 to US Army Medical Research and  Development  Command.

35.    Brown,  K.  W.  L.  E.  Deuel,   Jr.,   and  J.   C.  Thomas.  1982.   Soil
      disposal  of  API  pit  wastes.   Final  report  of a  study  for  the
      Environmental Protection Agency. (Grant No.  R805474013). 209p.

36.    Brown,  K.  W.  and  K.  C.  Donnelly. 1983.   The  influence of  soil
      environment  on  biodegradation  of  a refinery and  a petrochemical
      sludge.  Environ. PolKSeries 8)9(2)119-132.

37.    Brown,  K.  W.  and  K.  C.  Donnelly. 1982.   Mutagenic  potential of
      water  concentrates  from the  effluent of a  waste oil storage  pond.
      Bull.  Environm.  Contam. Toxicol. 28:424-429.

38.    Brown,  K.  W., K.  C.  Donnelly  and B.  Scott.   1982b.   The  fate of
      mutagenic  compounds  when  hazardous  wastes are  land  treated,  pp.
      383-397.    In:  Land  Disposal  of  Hazardous  Waste  Proceed.   8th
      Annual Res. Symp. EPA-600/9-82-002.

39.    Brusick,  D.   1983.   Mutagenicity  and  carcinogenicity  correlations
      between  bacteria  and  rodents,  ^n G.  M.   Williams,  V. C.  Dunkel,
      and  V.  A.  Ray   (eds.).  Cellular  Systems  for  Toxicity  Testing.
      Annals of  the New York Academy of  Sciences  Vol. 407. pp.  164-176.

40.    Brusick,  D.   J.   1980.   Principles of Genetic  Toxicology. Plenum
      Press,  Inc. New  York.

41.    Carere,  A.,  G.  Morpurgo, G.   Cardamone, M.  Bignami,  F.  Aulicino, G.
      DiGuisepie,   and   C.  Conti.   1975.   Point  mutations   induced by
      pharamaceutical  drugs. Mutat.  Res.  29:235.
                                  343

-------
42.   Chacko,  C.  I.,   J.  L.  Lockwood,  M.  Zabick.  1966.   Chlorinated
      hydrocarbon   pesticides  -   degradation   by  microbes.    Science
      154:893-894.

43.   Cheli,  C.,  D.  DeFrancesco,  L. A.  Petrullo, E. C. McCoy,  and  H.  S.
      Rosenkranz.     1980.    The    Salmonella    mutagenicity   assay:
      reproducibility.  Mutat. Res. 74:145-150.

44.   Chu,  K. C., K.  M.   Patel,  A. H. Lin,  R.  E.  Tarone, M.  S.  Linhart
      and  V.  C.  Dunkel.  1981.   Evaluating  statistical  analyses  and
      reproducibility  of  microbial mutagenicity assays. Mutat. Res.  85,
      119-132.

45.   Cifrulak,  S.  D.   1969.   Spectroscopic evidence  of phthalates  in
      soil organic matter..   Soil Science,  Vol.  107 No.  1:63-69.

46.   Clark,   R.   R.,   E.  S.  K.   Chian,   and  R.  A.   Griffin.  1979.
      Degradation   of  polychlorinated   biphenyls   by  mixed  microbial
      cultures.  Appl.  Environ. Microbiol.  37(4):680-685.

47.   Clayson, D.  B.  1962.  Chemical  carcinogenesis.  Churchill, London.

48.   Claxton,  L.  D.  and  H.  M.  Barnes.   1981.   The  mutagenicity  of
      diesel-exhaust  particle   extracts   collected  under  smog-chamber
      conditions   using   the   Salmonella   typhimurium   test   system.
      Mutat.  Res.  88:255-272.

49.   Clive,  D.  1982.  Can  we make  risk  estimates?   pp.  1114-1176.  Jin
      F.   D.   deSerres  and   M.   S.  Shelby   (ed.).  Comparative  Chemical
      Mutagenesis.  Plenum Press,  New  York.

50.   Committee   17.    1975.   Environmental  Mutagenic   Hazards,  Science,
      187:503-514.

51.   Commoner,    B.   1976.    Reliability   of   bacterial   mutagenesis
      techniques   to   distinguish   carcinogenic   and   noncarcinogenic
      chemicals.  EPA-600/1-76-022.

52.   De  Flora,  S.  1981.  Study  of  106 organic and  inorganic compounds in
      the  Salmonella/microsome  test.   Carcinog.  2(4)283-298.

53.   De  Serres,  F.  L. and  J.  Ashby.  1981.  International  Program for
      the  Evaluation of  Short-Term Tests  for  Carcinogenicity, Elsevier,
      Amsterdam.

54.   Department  of Health,  Education  and  Welfare.   1969.   Survey  of
      Compounds   Which  Have  Been   Tested  for  Carcinogenic  Activity.
      United  States  Public  Health Service  Publication  149, 1968-1969.
      Vol.,  1972; 1961-1967 Vol.,  Sect.  I and  Sect. II,  1973; 1970-1971
                                  344

-------
      Vol., 1974;  1972-1973  Vol.,  1975; Suppl.  1,  1967;  Suppl. 2,  1969.
      Washington, B.C., United States Government Printing Office.

55.   Donahue,  E.,  J.  McCann,  and  B.  N..  Ames.   1978.    Detection  of
      mutagenic   impurities   in  carcinogens   and   noncarcinogens   by
      high-pressure  liquid  chromatography  and  the  Salmonella/microsome
      test.  Cancer Res. 8:431-438.

56.   Donnelly,  K.  C.  and  K.  W.  Brown.  1981.    The  Development  of
      Laboratory  and Field  Studies  to  Determine   the  Fate  of Mutagenic
      Compounds  from Land  Applied  Hazardous Waste,  p.  224-239.   In  D.
      W.  Shultz  (ed.). Land disposal;   Hazardous Waste.   Proceedings  of
      the Seventh Annual Research Symposium.  EPA-600/9-81-002b.

57.   Donnelly,  K.  C.,  K.  W. Brown  and R.  M. Saltarelli. 1983.   The use
      of  a  B_.  subtilis   in a  pre-incubation  assay  for  the detection
      of  DNA-modifying  agents.   Res.  Comm.  in  Chem.   Path.   Phara.
      42(1)135-143.

58.   Donnelly,  K.  C.,  K.   W.  Brown   and  B.  Scott.  1983.  pp.  58-78.
      Short-Term  Bioassays   in  the  Analysis  of   Complex   Environmental
      Mixtures III.  (Waters,  M.  D.,  S.  S. Sandhu, J.  Lewtas,  L.
      Claxton,  and N. Chernoff  and S.  Nesnow (eds). The Application of
      Short  Term Bioassays  in the  Fractionation and Analysis  of  Complex
      Environmental Mixtures. Plenum, New York.

59.   Dunkel,    V.   C.     1979.     Collaborative   studies   on    the
      Salmonella/microsome   mutagenicity assay,  J.  Assoc.   Off.   Anal.
      Chem., 62, 874-882.

60.   Dunkel,  V.  C.  1983.   Biological  Significance  of  End-points.  J[n
      G.M.  Williams,  V.   C. Dunkel,   and  V.  A.   Ray  (eds.).  Cellular
      Systems  for  Toxicity  Testing.   Annals  of the New York  Academy of
      Science  Vol. 407. pp.  34-41.

61.   Environmental  Mutagen  Information Center. 1978.  Literature Search
      -  Salmonella.  December,  1978.  Oak Ridge  National Laboratory. Oak
      Ridge, TN.

62.   Environmental  Mutagen  Information Center. 1982.  Literature Search
      -  Salmonella.  December,  1982.  Oak Ridge  National Laboratory. Oak
      Ridge, TN.

63.   EPA.   1982.     Hazardous   Waste   Management    Systems;   Permitting
      Requirements  for Land Disposal  Facilities.    Federal  Register Vol.
      47, No.  143:  32274-32388.  July 26, 1982.

64.   EPA.    1983.    ES&T   Currents.    Environ.   Sci.    and   Technol.
      17(10)461A.
                                   345

-------
65.   EPA.    1980   Hazardous   waste   land   treatment.    United   States
      Environmental Protective Agency.  SW874.

66.   Epler,  J.  L.,  J.  A.  Young,  A.  A.  Hardigree,  T.  K.  Rao,  M.  R.
      Guerin.  I.  B.  Rubin,  C.  H.  Ho, and B.  R.  Clark. 1978. Analytical
      and Biological  Analyses of Test Materials  from the Synthetic  Fuel
      Technologies.  I.  Mutagenicity  of  Crude  Oils  Determined  by  the
      Salmonella   typhimurium/microsomal   Activation   System.    Mutat.
      Res.  57:265-276.

67.   Epstein, S.  S.   1974.   Environmental Determinants of  Human  Cancer.
      Cancer Res.  34:2425-2435.

68.   Fahrig,   R.   1974.    Comparative   Mutagenicity    Studies    with
      Pesticides.   In   Montesano   and   L.    Tomatis   (eds.).   Chemical
      Carcinogenesis  Assays. Vol.  10.  International Agency  for  Research
      on Cancer, Lyon. pp. 161-168.

69.   Felkner,  I.  C.  1977.  In A.  Portoles,  R.  Lopez  and M.  Espinoza
      (eds.).    Modern   Trends    in   Bacterial    Transformation   and
      Transfection, North-Holland,  amsterdam,  pp.  293-298.

70.   Felkner,  I.C.,  K.  M.  Hoffman,  and  B.  C.  Wells.  1979.   DNA-damaging
      and mutagenic effect of 1,2-Dimethylhydrazine  on
      Bacillus    subtilis     repair-deficient    mutants.    Mutat.    Res.
      28:31-40.

71.   Felkner,  I.  C.  1981.   Microbial  Testers:   Probing  Carcinogenesis.
      Marcel  Dekker,  Inc., New York.

72.   Fishbein,  L.  1977.  Potential  Industrial  Carcinogens and Mutagens.
      EPA-560/5-77-005.

73.   Fishbein,   L.     1979.    Potential   industrial   carcinogens   and
      mutagens.    Studies    in   Environmental    Science   4.    Elsevier
      Scientific Publ. Co. Amsterdam.

74.   Friederich,  U.,   H.   U.   Aeschbacher,   J.   P.   Sieler,  and  F.  E.
      Wurgler.   1982.    The   Salmonella/microsome   assay;   some  possible
      causes  for interlaboratory variations,  Mutat.  Res.  103:133-140.

75.   Garner,  R.  C.,  E.   C. Miller,  and  J.  D.  Miller.   1982.   Liver
      microsomal  metabolism of Aflatoxin  B,  to a reactive  derivative
      toxic    to   Salmonella   typhimurium   TA1530.   Cancer  Res.   32,
      2058-2066.

76.   Gatehouse,, D.  1980.   Mutagenicity  of 1,2 ring-fused  acenaphthenes
      against  £._  typhimurium  TA1537   and   TA1538:   structure-activity
      relationships. Mutat.  Res.,  78:121-135.
                                    346

-------
77.   Gehrs,  C.  W. ,   B.   R.  Parkhurst   and   D.   S.  Shriner.    1978.
      Environmental  testing.  In:  Symposium on  the  Application of  Short
      Term  Bioassays  in  the  Fractionation  and  Analysis  of   Complex
      Mixtures, Williamsburg, Va.

78.   Gibson,  D.  T.  1972.   Initial  Reactions  in  the  Degradation  of
      Aromatic   Hydrocarbons.    In   Proceedings   of    Conference   on
      Degradation  of  Synthetic  Organic   Molecules   in   the   Biosphere.
      National Academy of Sciences. Washington,  D.C. pp. 116-136.

79.   Goggelmann,  W. ,  and  P.   Spitzauer.   1982.   Mutagenic   activity,
      content  of  polycyclic aromatic  hydrocarbons  (PAH) and  humus  in
      agricultural soils.  Mutat. Res. 89:189-190.

80.   Goldschmidt,  B.  M.  1981.  Nonnitrogenous Carcinogenic  Industrial
      Chemicals.  In  J.   M.   Sontag  (ed.).  Carcinogens in  Industry  and
      the Environment, pp. 283-343. Marcel Dekker,  Inc., New  York.

81.   Grabow,  W.  0.  K.,   J.  S.  Burger,  and C.   A.   Hilner.    1981.
      Comparison  of Liquid-Liquid  Extraction  and  Resin  adsorption  for
      concentrating  mutagens   in  Ames   Salmonella/Microsome  assays  on
      water.  Bull Environ.  Contain. Toxicol,  27:442-449.

82.   Grafe,  A.,  I.  E.  Mattern,  and   M.   Green.   1981.    A  European
      collaborative  study  of  the  Ames  assasy. I.  Results  and  general
      interpretation.  Mutat.  Res. 85,  391-410.

83.   Grant,  W.  F.   1979.   The genotoxic effects of 2,4,5-T.  Mutat. Res.
      83-119.

84.   Green,  M. ,  A.  Grafe,   and   I.  E. Mattern.    1981.   A  European
      collaborative  study  of  the  Ames  assay.   I.   Results  and  General
      Information. Mutat.  Res.  85:391-410.

85.   Green,  M.  H.  L.  and  W.  J.  Muriel.  1976.  Mutagen testing  using
      TRP   reversion in  Escherichia coli. Mutat. Res.  38:3-32.

86.   Greim,  H.,  W.  Gogglemann,  K.   H.  Summer,  and T.  Wolff.  1980.
      Mutagenicity   testing  with   Salmonella   microsome   test.  Arch.
      Toxicol. 46,  31-40.

87.   Hamaker,  J. W.   1971.   Decomposition:  quantitative aspects.  pp.
      253-434.    Iji  C.A.I.   Goring   and  J.W.   Hamaker  (ed.).  Organic
      Chemicals  in  the  Soil Environment. Vol.  2.  Marcel Dekker,  Inc.,
      New York.

88.   Hartley,  M. J.  1969.   Reversion  of non-nitrate utilizing  (NIA D)
      mutants  of Aspergillus nidulans.  Mutat. Res.  7:163-170.
                                   347

-------
89.   Hass, B. S.,  E.  E.  Brooks, K.  E.  Schumann, S. S. Dornfield.  1981.
      Synergistic,  additive,  and  antagonistic  mutagenic  responses   to
      binary  mixtures  of benzo(a)pyrene  and benzo(e)pyrene as detected
      by strains  TA98  and  TA100 in  the  Salmonella  assay.  Environ. Mut.
      3:159-166.

90.   Haugen, D.A.  and  M.  J. Peak. 1983. Mixtures of polycyclic aromatic
      compounds  inhibit  mutagenesis   in  the  Salmonella/microsome  assay
      by inhibition of metabolic activation.  Mutat. Res.  116:257-269.

91.   Hertlein,  M.  W., D.M.  DeMarini, A.  J.  Katz,  J.  C.  Means, M.  J.
      Plewa,  and  H.  E.  Brockman.   1981.  Mutagenicity of  municipal  water
      obtained from an agricultural area.  Environ. Mutagen.  3:519-530.

92.   Hermann, M.  1981.   Synergistic effects  of  individual  polycyclic
      aromatic  hydrocarbons  on  the  mutagenicity  of  their mixtures.
      Mutat.  Res. 90:399-409.

93.   Higashi,  K.,  K.  Nakashima,   Y.   Karasaki,  M.   Fukunaga   and   Y.
      Mizuguchi.   1981.   Activation of  Benzo(a)pyrene  by  microsomes  of
      higher   plant  tissues   and   their   mutagenicity.     Biochemistry
      International Vol. 2,  No. 4 pp.  373-380.

94.   Higgins,  I.  J.  and  P.  D.  Gilbert.   1978.   The biodegradation  of
      hydrocarbons.   Ch.  7.  jn  K.  W.  A.   Chater  and  H.  J.  Somerville
      (eds.).  The  Oil  Industry  and  Microbial  Ecosystems, pp.   80-117.
      Heyden  and  Son, London.

95.   Higginson,   J.   1980.   Multiplicity of  factors  involved in cancer
      patterns and  trends.   J. Environ. Pathol. Toxicol.   3:113-125.

96.   Ho,  C-H.,   B.  R.  Clark,  M.  R.   Guerin,  B.  D.  Barkenbus, T. K.  Rao
      and  J.  L.  Epler.  1981.  Analytical and biological analyses  of test
      materials   from  the  synthetic   fuel   technologies   IV.  Studies  of
      chemical  structure-mutagenic  activity  relationships  of  aromatic
      nitrogen compounds native  to  synfuels.  Mutat.  Res. 85:335-345.

97.   Hoffman, D.,  E.  J.  La Voie,  and  S.  S.  Hecht. 1982.  Polynuclear
      Aromatic    Hydrocarbons:    Effects   of   Chemical    Structure   on
      Tumorigenicity.   Iji  M.  Cooke,  A.  J.   Dennis  and   G.  L.   Fisher
      (eds.).  Polynuclear Aromatic Hydrocarbons: Physical and Biological
      Chemical.  Batelle  Press,  Columbus.  Richland  and Springer-Verlag;
      New  York pp.  1-9.

98.   Horn,   L. ,   J.  Kaldor,  and   J.  McCann.    1983.   A   comparison  of
      alternative  measures   of   mutagenic   potency   in  the  Salmonella
      (Ames)  test. Mutat. Res. 109, 131-141.

99.   Huberman,  E., L.  Aspiras,  C.   Heidelberger,  P.  L.  Grover and  P.
      Sims.  1971.  Mutagenicity  to mammalian cells  of epoxides and  other
                                 348

-------
      derivatives  of  polycyclic  hydrocarbons.   Proc.  Nat.  Acad.  Sci.
      (USA) Vol.  68, No. 12 pp. 3195-3199.

100.   Ishio,  S.,  J.  C.  Chen, Y.  Kawasaki,  and N.  Ohba.  1977.   Cell
      division of  Gyrodinium  sp.   and  mitotic  delay  induced by causal
      substances  of  algal tumor and  carcinogens. Bull.  Japan Soc. Sci.
      Fisheries 43(5)507-516.

101.   Kada, T.,  M.  Morija,  and Y.   Shirasu. 1974. Screening  of pesticides
      for  DNA  interactions  by  REC assay  and  mutagenic   testing   and
      frameshift mutagens detected. Mut. Res. 26:243.

102.   Kada,   T.,   K.   Hirano  and  Y.   Shirasu.    1978.     Screening   of
      environmental  chemical  mutagens   by  the   REC  assay  systems with
      Bacillus   subtilis.    In:    Hollaender,    A.    (ed.).    Chemical
      Mutagens. Vol. 6.

103.   Kada, T.  1981.   An  evaluation of  test  using  DNA repair deficient
      bacteria  for  predicting  genotoxicity and  carcinogenicity. Mutat.
      Res, 87:211-297.

104.   Kaden,  D.  A., R.  A.  Kites,   and  W.  G.  Thilly.  1979.   Mutagenicity
      of   soot  and   associated   polycyclic  aromatic  hydrocarbons   to
      Salmonella typhimurium.  Cancer Research 39, 4152-4159.

105.   Kafer,  E.,  B.   R.  Scott,   G.   L.  Dorn  and  R.  Stafford.   1982.
      Aspergillus   nidulans:   Systems    and   Results   of   Tests    for
      Chemical Induction  of  Mitotic Segregation  and  Mutation. I. Diploid
      and  Duplication  Assay  Systems. A  Report of the U.S.E.P.A.  Gene-Tox
      Program. Mutat.  Res. 98:1-48.

106.   Kanematsu,   N.,   M.  Hara,  and   T.  Kada.  1980.    REC  assay   and
      mutagenicity  studies on metal compounds. Mutat. Res.  77:109-116.

107.   Katz,   A.  J.    1979.    Design   and  analysis  of   experiments   on
      mutagenicity  II.   Assays involving microorganisms.   Mutat.  Res.
      64:61-77.

108.   Kawalek,  J.   C.   and  A.  W.  Andrews.   1981.   Effect of  aromatic
      hydrocarbons  on  the  metabolism  of  2-aminoanthracene  to mutagenic
      products in  the  Ames assay.   Cacinogenesis  2(12)1367-1369.

109.   Khesina,   A.  Ya.,  N.   P.  Shcherback,  L.  M.  Shabad,  and  I.   S.
      Vostrov. 1969.   Benzpyrene  breakdown by soil microflora. Byulleten
      Eksperimental'noi Biologii i  Meditsiny 68:70.

110.   Kier,  L.  D.,  E.  Yamasaki,   and  B.  N.  Ames.  1974.   Detection of
      mutagenic  activity  in  cigarette  smoke  condensates.  Proc.   Natl.
      Acad. Sci. USA.  71(10)=4159-4163.
                                  349

-------
111.   Lankas,   G.  R.,  C.  S.  Baxter,  R. T.  Christian.  1978.   Effect of
      alkane tumor-promoting  agents  on chemically induced mutagenesis in
      cultured  V79   Chinese  hamster   cells.   J.   of   Toxicology  and
      Environmental Health,  4:37-41.

112.   La  Voie,  E.  J. ,  L.  Tulley-Freiler,  V.  Bedenko  and  D. Hoffmann.
      1981.  Mutagenicity,  tumor-initiating activity,  and metabolism of
      methylphenanthrenes. Cancer Research 41, 3441-3447.

113.   La  Voie,  E.  J.,  L.  Tulley-Freiler,  V.  Bedenko,  and  D. Hoffman.
      1983.   Mutagenicity  of  substituted  phenanthrenes  in   Salmonella
      typhimurium.  Mutat. Res. 116:91-102.

114.   Leifer,   Z. ,  T.  Kada,  M. Mandel,  E.  Zeiger,  R. Stafford, and  H. S.
      Rosenkranz.   1981.     An   evaluation   of    tests   using    DNA-
      repair-deficient   bacteria   for   predicting   genotoxicity   and
      carcinogenicity.   A  report  of  the  U.S.EPA's  Gene-Tox Program.
      Mutat. Res. 87:211-297.

115.   Levin,  D.   E.,  M.  Hollstein,  M.  F.   Christman,  E.A.  Schwiers and
      B.N.  Ames.   1982a.   A  new  Salmonella tester  strain (TA102)  with
      A-T  base  pairs  at the  site of mutation detects oxidative mutagens.
      Proc. Natl. Acad. Sci.  79:7445-7449.

116.   Levin,   D.E.,   E.  Yamasaki   and  B.  N.   Ames.   1982b.   A new
      Salmonella  tester  strain,  TA97,  for the  detection of  frameshift
      mutagens.   Mutat. Res.  94:315-330.

117.   Lilienfield,  A.  M. ,  M.  L.  Levin, and Kessler II.   1972.   "Cancer
      in  the  United States."   Cambridge,  MA.   Harvard  University  Press.
      215-232.

118.   Lilly,  L.   J.   1965.   An investigation  of  the suitability of  the
      suppressors  of Meth  1  in  Aspergillus  nidulans  for  the study  of
      induced  spontaneous mutation.  Mutat.  Res.  2:192-195.

119.   Lippens,  R.,  M.  Claeys,  C. Wildemauwe and N. Van Larebeke.  1983.
      Mutagenicity  studies  on  10 pesticides, on  trichloroethane and  on
      diaminobenzidine. Mutat.  Res., 113:277-278.

120.  Lowenbach,  W.  and J.  Schlesinger. 1978.  Acrylonitrile  manufacture
      pollutant  prediction  and  abatement.  Mitre  Technical   Report, MTR
      77752.

121.  MacPhee,  D. G. and J.  A.  Pallister.  1983.   Frameshift  mutagenesis
      by   2,4-dinitrophenylhydrazine   in  Salmonella:  unexpected   effect
      of  inoculum size  on mutation yield.   Mutat.  Res.,  119:  255-258.
                                   350

-------
122.  MacPhee,   D.   G.   and   F.   P.   Imray.    1974.    Mutagenesis   by
      photoactivation   of   chlorpromazine,   a   tranquilizer   of    the
      phenothiazine group, Austral. J. Biol. Sci., 27, 231-234.

123.  Margolin,  B.   H. ,   N.  Kaplan,  and E.  Zeiger.  1981.    Statistical
      analysis  of   the   Ames   Salmonella/microsome  test.   Proc.   Natl.
      Acad. Sci (USA), 78, 3779-3783.

124.  Maron,  D.  M.   and  B.  N.  Ames.  1983.    Revised  methods  for  the
      Salmonella mutagenicity test. Mutation Research 113:173-215.

125.  Maron,   D.,   J.    Katzenellenbogen,   and  B.   N.   Ames.   1981.
      Compatibility  of  organic solvents  with  the  Salmonella/microsome
      test. Mutat. Res. 88:343-350.

126.  Matney,  T.  S.  1981.   Mutagenic assays  in gram-negative  bacteria
      for   the  detection   of   potential   carcinogens:   activation   by
      mammalian  microsomal   fractions,  pp.  121-129. In:  Felkner,   I.  C.
      (ed.).  Microbial Testers:  Probing  Carcinogenesis.  Marcel Dekker,
      Inc.. New York, New York.

127.  Matney,  T.  S.,  B. R.  Scott,  A.  Hollaender, and  M.   S.  Legator.
      1979.   Intensive  laboratory  training course on microbial  tests  for
      detecting  and  characterizing  mutagens  and potential  carcinogens.
      University  of  Texas  System  Cancer  Center.    Smithville,  Texas.
      April,  1979.

128.  McCann,  J.,  R.  Choi,  E.   Yamasaki  and B.  N.  Ames.   1975.  Detection
      of   carcinogens  as  mutagens   in  the   Salmonella/microsome   test:
      assay of  300 chemicals. Proc. Nat. Acad.  Sci.  72(12):5135-5139.

129.  McCann,   J.  and  B.  N.  Ames.    1977.    The  Salmonella/microsome
      mutagenicity  test:  predictive  value for  animal  carcinogenicity.
      In:  H.  H. Hiatt  (ed.). Origins  of  Human  Cancer. New York.

130.  McCann,   J. ,  N.  E.   Spingarn,  J.  Kobori,   and  B.  Ames.   1975.
      Detection  of  carcinogens  as mutagens:Bacterial tester  strains with
      R  factor   plasmids.   Proc.  Natl.   Acad.   Sci.  USA  Vol  72,  No.
      3:979-983.

131.  McCoy,  E.  C.,  J. Hyman and  H.  S.  Rosenkranz. 1979.   Conversion of
      environmental  pollutant   to  mutagens by  visible  light.   Environm.
      Mutagens. 89(2):729-734.

132.  McFall,  T. , G.  M.  Booth, M.  L.  Lee,  Y.  Tominaga,  R. Pratap,  M.
      Tedjamulia   and  R.   N.   Castle.   1984.   Mutagenic   activity   of
      methyl-substituted    tri-   and    tetracyclic   aromatic    sulfur
      heterocycles. Mutat. Res., 135:97-103.
                                   351

-------
133.   McGill,  W.   B.,  and  M.  J.  Rowell.  1980.   Determination  of oil
      content of oil contaminated soil.  Sci. Total Environ. 14:245-253.

134.   McKenna,  E.   J.   1972.    Microbial   Metabolism   of  Normal  and
      Branched  Chained   Alkanes.   In  Proceedings   of   Conference   on
      Degradation  of  Synthetic  Organic  Molecules   in  the   Biosphere.
      National Academy of Sciences. Washington, D.C.   pp. 73-97.

135.   Meyers,  V.  K. and  R.  E.  Beyler.  1981.  How to make an  "educated
      guess"   about  the  teratogenicity   of  chemical  compounds.  In:
      Samani,  S.  M.  and  F.  L. Cavender  (eds.).  Environmental  Toxicology
      Principles and Polices.

136.   Miller,  J.  A. and  E.  C.  Miller.   1975.   Metabolic  and  reactivity
      of chemical carcinogens.  Mutat. Res.   33:25.

137.   Miller,  E.  C. and  J.  A.  Miller,  1974.  Biochemical Mechanisms  of
      Chemical   Carcinogenesis.    In   H.  Busch   (ed.).    The   Molecular
      Biology  of  Cancer, Academic  Press, N.Y.,  pp.  377-402.

138.  Moore,  D.  and  J.   S.  Felton.  1983.   A  microcomputer program  for
      analyzing Ames test data.  Mutat. Res.  119,  95-102.

139.  Morin,   J. ,   D.   Goldberg,  and   I.   Seginer.   1967.   A  rainfall
      simulator with a rotating  disk.  Trans.  ASAE  1967:74-77.

140.  Morrison and W. Bick.  1967.  The  wax fraction  of  soils:separation
      and   determination  of  some   components.   J.  Sci.  Fd.   Agric.,
      18:351-355.

141.  Muller,  D.,  J.   Nellas,  E.   Deparade,   and  P.  Ami.  1980.   The
      activity  of  S9-liver   fractions  from   seven  species   in  the
      Salmonella/Mammalian  microsome  mutagenicity  test.   Mutat.  Res.
      70:279-300.

142.  Munson,  R.  J. and D. T.  Goodhead. 1977.   Relation between induced
      mutation frequency and  cell survival: A theoretical approach  and
      an  examination  of experimental  data  for  eukaryotes. Mutat.  Res.
      42:145-160.

143.  Myers,  L.  E.,  N.  H.  Sexton,  L.  I.  Southerland,  and T.  J.  Wolff.
      1981.   Regression  analysis of Ames test  data.  Environ.  Mutagen,  3,
      575-586.

144.  National Cancer   Institute.   1976.   Fourth  Annual   Collaborative
      Conference,  Carcinogens is  Program. Orlando,  Fla.,  Feb.  22-26.

145.  Ogner,  G.  and M.  Schnitzer.  1970a.   The occurence  of   alkanes  in
      fulvic  acid,  a  soil  humic  fraction.   Geochimica et Cosmochimica
      Acta,  Vol.  34:921-928.
                                  352

-------
146.   Ogner,  G.  and  M.  Schnitzer.  1970b.  Humic  substances:  Fulvic
      Acid-Dialkyl  phthalate  complexes  and  their  role  in  pollution.
      Science, Vol. 170:317-318.

147.   Omori,  Y.  1976.    Recent  progress  in  safety evaluation studies  on
      plastisizers  and  plastics  and  their  controlled  use   in  Japan.
      Environ. Health Perspect. 17:203-209.

148.   Patil,  K.  C.,  F.  M.  Matsumura, and G. M. Boush. 1970.  Degradation
      of  endrin,  aldrin,  and DDT  by soil  microorganisms.  Appl.  Micro.
      19(5):879-886.

149.   Peak, M.  J.  S.  Dornfield and  D.  Venters.   1982.   Liver-microsome
      S9  enzyme increases  spontaneous  background mutation frequency  in
      the  Ames  Salmonella  test  system  in  the  absence  of  any  added
      mutagen.  Mutat. Res. 103:263-265.

150.   Pelroy,  R.  A.,  D.  L. Stewart,  Y.  Tominaga,  M. Iwao,  R. N.  Castle,
      and  M.   L   Lee.   1983.   Microbial  mutagenicity  of  3-  and  4-ring
      polycyclic aromatic sulfur heterocycles'. Mutat. Res.  117,  31-40.

151.   Penalva,  J.  M. ,  J. Chalabreysse, M. Archimbaud, and  G. Bourgineau.
      1983.   Determining the  mutagenic activity of  a tar,  its'  vapor  and
      aerosols.  Mutat.  Res.,  117:93-104.

152.   Plewa,  M.  J.  1981.    Chemical mutagens  and  carcinogens  in  the
      environment.   p.  115-123.  Jin  S.  M.  Somani  and F.  L.  Cavender
      (ed.).  Environmental Toxicology.  Charles  C.  Thomas,  Springfield,
      111.

153.   Plewa,  M.  J. , D.  L.  Weaver,  L. C. Blair and  J.  M.  Gentile.  1983.
      Activation  of  2-aminofluorene  by  cultured  plant  cells.  Science
      219:1427-1429.

154.   Poglazova,  M. N.,  G.  E. Fedoseeva, A.  J.  Khesina, M. N. Meissel,
      and  L.   M.  Shabad.   1967.   Destruction of  Benzo(a)pyrene  by  soil
      bacteria.   Life  Sciences.  Vol.  6, No. 10:1053-1062.

155.  Purchase,   I.  F.  H.,  E.  Longstaff,   J.  Ashby,  J.  A.  Styles,  D.
      Anderson,  P. A.  Lefevre and  F.  R.  Westwood. 1976.   Evaluation of
      six  short  term  tests  for  detecting  organic chemical  carcinogens
      and  recommendations  for  their  use. Nature 264:624-627.

156.  Rao,  T.  K., J.  A.   Young,  C.  E.  Weeks,  T.  J.   Slaga,  and  J.  L.
      Epler.  1979.  Effect  of  the Cocarcinogen benzo(e)pyrene  on
      microsome    mediated    chemical    mutagenesis    in    Salmonella
      typhimurium.  Env.  Mut.  1:105-112.
                                  353

-------
157.   Rao. T.  K.,  J.  A.  Young, A.  A. Hardigree,  W.  Winton,  and J.  L.
      Epler.     1978.    Analytical   and   biological   analysis   of   test
      materials from the synthetic fuel technologies.  II Extended
      genetic and  biochemical  studies with  mutagenic fractions.  Mutat.
      Res. 54:185-191.

158.   Rinkus, S.J. and  M.S.  Legator. 1979.  Chemical  characterization  of
      465  known  or   suspected  carcinogens  and  their  correlation  with
      mutagneic   activity   in   the   Salmonella   typhimurium   system.
      Cancer  Res.  39:3289-3318.

159.   Roper,   J.   A.    1971.    Aspergillus.   In   A.  Hollaender   (ed.).
      Chemical  Mutagens,   Principles  and  Methods   for  their  Detection.
      Plenum Press, New York. Vol.2:343-365.

160.   Rosenkranz,   H.   S.  and  L.  A.  Poirier.   1979.  Evaluation  of  the
      mutagenicity   and  DNA-modifying   activity   of  carcinogens   and
      non-carcinogens   in  microbial  systems.   J.  Natl.   Cancer  Inst.
      62:873-892.

161.   Rowell, M.  J.    1977.  The Effect  of Crude  Oil  Spills on Soils.  A
      Review of  Literature.   In J.   A. Toogood  (ed.).  The Reclamation  of
      Agricultural   Soils   After   Oil    Spills.    Part.   1:   Research.
      Department  of  Soil  Science.   The  University of Alberta,  Edmonton,
      A.I.P.  Pub.  No. M-77-11.  pp. 1-33.

162.   Salmeen,  I.  and  A.  M. Durison.  1981.    Some  effects  of  bacterial
      population   on   quantitation    of   Ames   Salmonella-histidine
      mutagenesis assays.

163.   Santos, E.,  D. Martin-Zanca,  E. P.  Reddy, M.  A.  Pierotti, G.  D.
      Porta,   and   M.   Barbacid. 1984.  Malignant  activation of  a  K-ras
      oncogene  in  lung  carcinoma   but  not  in  normal  tissue  of  same
      patient.  Science 223(4637)661-664.

164.   Sax, N.  I.  1975.   Dangerous  Properties  of  Industrial  Materials.
      Van Nostrand Reinhold  Co., New York.

165.   Schmid, E.,  M.  Bauchinger and J.  Dresp.  1983.  Chromosome analysis
      of  workers  from  a  pentachlorophenol  plant.  Mutat.  Res.,   133:
      304-305.

166.   Schram, S.  B.  1980.   The LDC  Basic  Book  on Liquid  Chromatography.
      Milton Roy Co.,  St. Petersburg,  Fla.

167.   Scott,   B.  R.,   A.  H.   Sparrow,  S.  S.  Lamm and  L. Schairer.   1978.
      Plant metabolic activation of EDB to a mutagen  of greater potency.
      Mutat.  Res. 49:203-212.
                                   354

-------
168.   Scott,  B.  R.,   G.  L.  Dorn,  E.  Kafer,  and  R.   Stafford.   1982.
      Aspergillus   nidulans:   systems   and   results   of   tests    for
      induction  of  mitotic  segregation  and  mutation II.  Haploid  assay
      systems  and  overall  response  of  all  systems.   A report  of  the
      USEPA Gene-Tox Program. Mut. Res. 98:49-94.

169.   Scott, B.  R.,  and  T.  Alderson. 1971.  Features  of  radiosensitivity
      and  mutation  in  Aspergillus  nidulans,  Aspergillus   Newsletter,
      11:14-19.

170.   Scott, B.  R.,  T.  Alderson, and D.  G.  Papworth. 1972.  The effect
      of   radiation   on   the   Aspergillus   conidium.   I.    Radiation
      sensitivity and a "germination inhibitor," Radiat.  Bot., 12:45-50.

171.   Scott, B.,  R., T.  Alderson and D.  G.  Papworth. 1973.  The effect
      of  plating densities  on  the  retrieval of  methionine suppressor
      mutations  after  ultraviolet  or gamma  irradiation of  Aspergillus.
      J. Gen. Microbiol., 75:235-239.

172.   Shabad,  L. M. ,  Y. L.  Cohan,  A.   P.  Ilnitsky, A.  Ya Khesina,  N.
      Pshcherbak,   and   G.    A.    Smirnov.     1971.    The   carcinogenic
      hydrocarbon  Benzo(a)pyrene  in  the  soil.   J.  of  the Natl. Cancer
      Inst. Vol. 47, No. 6:1179-1191.

173.   Shahin,  M.  M.   and  F.  Fournier.   1978.  Suppression  of  mutation
      induction  and  failure to  detect  mutagenic activity with  Athabasca
      tar sand  fractions. Mut. Res. 58:29-34.

174.   Shiau,  S. Y.,  R.  A.  Huff,  B.C.   Wells and  I.C. Felkner.   1980.
      Mutagenicity  and  DNA-damaging  activity  for   several  pesticides
      tested with Bacillus subtilis mutants.  Mutat.  Res.  71:169-179.

175.  Sims,  R.  C.  and  M.   R.  Over cash.  1981.  Land Treatment of Coal
      Conversion  Wastewaters.    In EPA  Symposium:  Environmental  Aspects
      of  Fuel   Conversion   Technology  VI.  Denver,   CO.  October,  1981.
      EPA-600/9-82-017 pp. 218-230.

176.  Sims,  R.  C.  and M. R. Overcash. 1983.  Fate  of  polynuclear aromatic
      compounds  (PNA's)  in soil-plant  systems. Residue Reviews,  88:1-68.

177.  Skopek,  T. R.,  J. L. Liber,  J.  J.  Krowleski, and  W. G.  Thilly.
      1978.     Quantitative   forward   mutation   assay   in   Salmonella
      typhimurium  using  8-azaguanine  resistance  as a genetic  marker.
      Proc.  Nat'l Acad.  Sci. 75:410.

178.  Slater,  E.,  M.  D.  Anderson,  and  H.  S.  Rosenkranz.   1971.  Rapid
      detection of mutagens  and  carcinogens.  Cancer Res. 31:970.

179.  Snee,   R.  D.   and  J.  D.  Irr.   1981.   Analysis  of  Salmonella
      histidine reversion data.   Paper  presented  at the  NIEHS Workshop

                                  355

-------
      on  Statistical  Analysis  of  In  Vitro  Tests  for  Mutagenicity.
      Chaptel Hill, N.C., April 20-28, 1981.

180.   Sokatch,  J.   R.   1969.   Bacterial   Physiology  and  Metabolism.
      Academic Press. New York.

181.   Spizizen,  J.  1958.    Transformation  of  biochemically  deficient
      strains  of   Bacillus   subtilis  by  deoxyribonucleate.  Proc.  Nat'l
      Acad. Sci.,  USA, 44:1072-1078.

182.   Stead, A. G.,  V.  Hasselblad, J. P.  Creason,  and L.  Claxton.  1981.
      Modeling the Ames test. Mutat. Res. 85, 13-27.

183.   Steel,   R.   G.   D.   and  J.   H.  Torrie.  1976.    Introduction   to
      Statistics.  McGraw-Hill Book Company, New York.

184.   Stoltz,  D.  R., L. A.  Poirier,  C.  C. Irving,  H.  F.  Stitch,  J.  H.
      Weisburger,   and  H.   C.  Grice.   1974.   Evaluation  of  short-term
      tests for carcinogenicity.  Toxicol. Appl. Pharmacol.,  29:157-180.

185.   Sugimura, T.,  S.  Sato, M.  Nagao,  T.  Yahagi,  T.  Matsushima,   Y.
      Seino,   M.   Takeuchi,  and  T.  Kawachi.   1976.   Overlapping   of
      carcinogens  and mutagens.  In  Fundamentals   in  Cancer  Prevention.
      P.  N.  Magee,  S.  Takayoma,  T.  Sugimura,  and T. Matsushima  (eds.).
      University Park Press. Baltimore, MD. pp. 191-195.

186.   Suter, W. and I.  Yeager. 1982. Comparative  evaluation  of different
      pairs  of DNA-repair  deficient  and  DNA-repair proficient bacterial
      tester   strains  for   rapid  detection  of   chemical  mutagens  and
      carcinogens.  Mutat. Res,. 97:1-18.

187.   Tanooka,  H.    1977.   Development   and  applications  of  Bacillus
      subtilis   test   systems    for   mutagens    involving    DNA-repair
      deficiency  and  suppressible  auxotrophic  mutations.  Mutat.  Res.,
      12:19-32.

188.   Tikkanen, L. , T.  Matsushima and S.  Natori.   1983.  Mutagenicity of
      anthraquinones  in  the Salmonella preincubation  tests.  Mutat.  Res.,
      116:297-304.

189.   USDA.    1980.   The    Biologic    and   Economic   Assessment   of
      Pentachlorophenol,  Inorganic  Arsenicals,  Creosote.  Vol.   1: Wood
      Preservatives.  Technical Bulletin No. 1658-1. 433  pp.

190.   U.S.  Tariff   Commission.   1974.   "Synthetic  Organic  Chemicals," U.
      S.   Production  and   Sales,  Annual,  Government  Printing   Office.
      Washington,  D.  C.
                                 356

-------
191.   Van Duuren, B.  L.  and B. M. Goldschmidt.  1976.  Cocarcinogenic and
      tumor-promoting agents in  tobacco  carcinogenesis. J. Nat'l. Cancer
      Inst., 56:1237-1242

192.   Venitt,   S.   1980.    Bacterial  mutation   as   an   indicator   of
      carcinogenicity. Br. Med. Bull., 36, 57-62.

193.   Withrow, W. A.   1982. Mutagenicity of  Roadside  Soils.   Thesis for
      Master of  Science  in  Environmental  Engineering,  Illinois  Institute
      of Technology. Chicago, 111.

194.   Yergey,  J. A.,  T.  H.  Risby  and  S.   S.  Lestz.   1982.   Chemical
      characterization  of   organic   adsorbates   on  diesel  particulate
      matter.  Anal. Chem. 54:354-357.

195.   Yoshida,   D.   and    Fukuhara,    Y.    1983.    Mutagenicity   and
      co-mutagenicity   of   catechol   on    Salmonella.   Mutat.    Res.,
      120:7-11.

188.   Yost,  R.  W.,  L.  S.   Ettre,  and  R.  D.  Conlon.  1980.    Practical
      Liquid  Chromatography-An  Introduction.  The  Perkin-Elmer  Corp.,
      Norwalk, Conn.
                                 357

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