DEVELOPMENT DOCUMENT FOR FINAL EFFLUENT LIMITATIONS
GUIDELINES, NEW SOURCE PERFORMANCE STANDARDS AND PRETREATMENT STANDARDS
                             FOR THE
                  PHARMACEUTICAL MANUFACTURING
                      POINT SOURCE CATEGORY
                     William D. Ruckleshaus
                          Administrator
                        Rebecca W. Hanmer
                 Acting Assistant Administrator
                            for Water
                         Steven Schatzow
                            Director
            Office of Water Regulations and Standards
                        Jeffery D. Denit
             Director, Effluent Guidelines Division
                       Robert W.;Dellinger
          Acting Chief, Wood Products and Fibers Branch.
                       Frank H.  Hund,  Ph.D
                         Project Officer
                  Effluent Guidelines Division
                         Office of Water
              U.S.  Environmental Protection Agency
                     Washington, D.C.  20460
                         September 1983

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                            ABSTRACT


This  document  presents  the  findings  of  a   study   of   the
Pharmaceutical   Manufacturing  Point  Source  Category  for  the
purpose  of  finalizing  effluent  limitations   guidelines   for
existing  and  new  point  sources  and to establish pretreatment
standards for existing and  new  dischargers  to  publicly  owned
treatment  works  to  implement Sections 301, 304, 306, 307, 308,
and 501 of the Clean  Water  Act  (the  Federal  Water  Pollution
Control  Act Amendments of 1972, 33 USC 1251 et.. seq., as amended
by the Clean Water Act of 1977, P.L. 95-217  (the  "Act")).   This
document   was  also  prepared  in  response  to  the  Settlement
Agreement in Natural Resources ,Defense Council,  Inc.  v.  Train,
8 ERC 2120  (D.D.C.  1976),   modified, 12 ERC 1833 (D.D.C. 1979),'
modified by Orders dated October 26, 1982, and August 2, 1983.

The information presented supports  final  regulations  based  on
best practicable control technology currently available (BPT) and
best available technology (BAT), new source performance standards
(NSPS)  and  pretreatment  standards for new and existing sources
(PSNS and PSES) for the Pharmaceutical Manufacturing Point Source
Category.  The  report  presents  and  discusses  data  gathering
efforts,  consideration of subcategorization, characterization of
wastewaters,  selection  of  pollutant  parameters,   review   of
treatment  technology,   cost  and nonwater quality considerations
and development of regulatory options and effluent limitations.

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                        TABLE OF CONTENTS
Section
                     Title
          EXECUTIVE SUMMARY
II
III
IV
V
VI
A.   Summary                                            1
B.   S u b c a te gor i zra t i on                                  2
C.   Effluent Limitations Guidelines                    2
D.   Impact of Regulation                               6

INTRODUCTION?                                            7

A.   Purpose and Legal Authority                        7
B.   Prior EPA Regulations                              9
C.   Scope of this Rulemaking                           9
D.   Definition of the Industry                         9
E.   Summary of Methodology                            12
F.   Data and Information Gathering Program            13
G.   Processing of Data and. Information                15

DESCRIPTION OF THE INDUSTRY                            17

A.   Introduction                                      17
B.   Detailed Industry Profile                         17
C.   Manufacturing Processes                           21
D.   Raw Materials and Products                        31
E.   Current Discharger Status and BPT Compliance      33

INDUSTRY SUBCATEGORIZATION                             37

A.   Introduction                                      37
B.   Basis for BPT Subcategorization                   37
C.   Selected Subcategories                            38
D.   Subcategory Characteristics                       38
E.   Subcategorization Analysis                        40
F.   Conclusions of Subcategory Analysis and
     Decision to Maintain the Existing Subcategori-
     zation Scheme                                     47

WASTE CHARACTERIZATION                                 49

A.   Introduction                                      49
B.   Traditional Pollutants                            49
C.   Priority Pollutants                               54
D.   Wastewater Flow Characteristics                   75
E.   Precision and Accuracy Program                    75

SELECTION OF POLLUTANT PARAMETERS                      81

A.   Introduction                                      81
B.   Traditional Pollutants                            81
C.   Priority Pollutants                               83

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Section
             TABLE OF CONTENTS (Continued)

                     Title
Paqe
VII
VIII
IX
X
XI
XII
CONTROL AND TREATMENT TECHNOLOGY

A.   Introduction
B.   In-Plant Source Control
C.   In-Plant Treatment
D.   End-of-Pipe Treatment
E.   Ultimate Disposal

ANALYSIS OF LONG TERM DATA FOR POLLUTANTS
OF CONCERN

A.   Description and Technical Analysis of Data
B.   Effluent Variability Analysis

EFFLUENT REDUCTION ATTAINABLE THROUGH THE APPLI-
CATION OF THE BEST PRACTICABLE TECHNOLOGY CURRENTLY
AVAILABLE-EFFLUENT LIMITATIONS GUIDELINES

A.   General
B.   Regulated Pollutants
C.   Identification of the Best Practicable
     Control Technology Currently Available
D.   BPT Effluent Limitations
E.   Rational for the Selection of the Technology
     Basis of BPT
F.   Methodology Used for the Development of BPT
     Effluent Limitations
G.   Cost of Application and Effluent Reduction
     Benefits
H,   Nonwater Quality Environmental Impacts

BEST CONVENTIONAL POLLUTANT CONTROL TECHNOLOGY
CURRENTLY AVAILABLE
          A.
     General
EFFLUENT REDUCTION ATTAINABLE THROUGH THE APPLI-
CATION OF THE BEST AVAILABLE TECHNOLOGY
ECONOMICALLY ACHIEVABLE-EFFLUENT LIMITATIONS GUIDE-
LINES

A.   General
B.   BAT Effluent Limitations

NEW SOURCE PERFORMANCE STANDARDS
          A.
          B.
     General
     NSPS
103

103
103
105
137
149
                                                               151

                                                               151
                                                               169
175

175
175

176
176

177

177

179
179


181

181
 183

 183
 184

 185

 185
 185
                                 VI

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Section
             TABLE OF CONTENTS  (Continued)

                     Title
                                                               Paqe
XIII
XIV

XV

XVI
PRETREATMENT STANDARDS FOR NEW AND EXISTING
SOURCES

A.   General
B.   PSES and PSNS
C.   Cost of Application and Effluent Reduction
     Benefits
D.   Nonwater Quality Environmental Impacts

REFERENCES

LEGEND OF ABBREVIATIONS

ACKNOWLEDGEMENTS

APPENDICES

APPENDIX A.   COST, ENERGY,  AND NONWATER QUALITY
             ASPECTS

APPENDIX B.   GLOSSARY

APPENDIX C.   PHARMACEUTICAL INDUSTRY WASTEWATER
             DISCHARGE METHODS
187

187
190

190
191

193

205

209
                                                               21 1

                                                               237



                                                               251
                                vti

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                         LIST OF TABLES
Number

Section III
                       Title
III-l


III-2

III-3

III-4

Section
  Pharmaceutical Industry
  Geographical Distribution

  Subcategory Breakdown

  Production Operation Breakdown

  Comparision of Plant Performance vs.  1976 BPT
IV
IV-1      Flow and Pollutant Averages Used in Pharmaceutical
          Subcategorization Analyses

IV-2      Summary of Kruskel-Wallis and Van der Waerden
          Tests of Equality of the Four Subcategories

IV-3      Across Plant Mean Pollutant Levels for Unique
          Subcategory Plants Only

IV-4      Across Plant Mean Pollutant Levels for Defined
          "High" vs. "Low" Group Comparisons

Section V

V-l       Summary of Long-Term Data

V-2       List of EPA Designated Priority Pollutants

V-3       Summary of Priority Pollutant Information:
          PEDCo Reports

V-4       Compilation of Data Submitted by the PMA from
          26 manufacturers of Ethical Drugs:  RTP Study

V-5       Summary of Volatile Organic Compound Emission
          Data:  RTP Study

V-6       Summary of Major Priority Pollutants Identified
          from Multiple Sources of Information

V-7       Summary of Priority Pollutant Occurrence-
          Screening Plant Data

V-8       Analysis of Priority Pollutant Concentrations-
          Screening/Verification Data Base
Page




 18

 22

 23

 35
                                                        41


                                                        43


                                                        44


                                                        46



                                                        51

                                                        55


                                                        58


                                                        59


                                                        61


                                                        63


                                                        65


                                                        70
                                 IX

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                        LIST OF TABLES  (Continued)
Number

V-9

V-10


Section VI

VI-1



VI-2


VI-3


VI-4




VI-5
                     Title

Analysis of Wastewater Flow Characteristics

Comparison of Precision and Accuracy (P&A)
Data - Plant 12236
Priority Pollutants Excluded from Direct Dis-
charger Regulations Based on Control by Other
Limitation Technologies

Priority Pollutants Excluded from Direct Dis-
charger Regulations Based on Low Level Presence

Priority Pollutants Excluded from Direct Dis-
charger Regulations Based on Infrequent Occurrence

Priority Pollutants Excluded from Direct Discharger
Regulations Based on Presence in Amounts too Small
to be Effectively Reduced by Technologies Known to
the Administrator

Estimated Achievable Long - Term Average Effluent
Concentrations for the Priority Pollutant Metals
VI-6      Pollutants Excluded from Pretreatment Standards

VI-7      Pollutants Considered for Pretreatment Standards

Section VII
VII-1     Summary of In-Plant Treatment Processes

VII-2     Methylene Chloride Removal in Packed Column
          Steam Stripper at Plant 12003

VII-3     Toluene Removal in Steam Distillation Flash
          Tank at Plant 12003

VI1-4     Summary of End-of-Pipe Treatment Processes
          (Data Base:  308)

VI1-5     Summary of Wastewater Discharges
Page

 76


 77
 86


 87


 89





 91


 93

 96

 99



107


124


131


139

150

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                         LIST OF  TABLES  (Continued)
Number

Section VIII
                      Title
                                                      Page
VIII-1



VIII-2


VIII-3



VIII-4

VIII-5


VII1-6

VII1-7



VII1-8


VIII-9




Appendix A
Long-Term-Average Cyanide Concentrations
(LTAs) and Variability Factors  (VFs)  from
Cyanide Destruction Units

30-Day Maximum Average and Daily Maximum
Limitations and Standards for Cyanide

30-Day Maximum Average and Daily Maximum
Variability Factors Derived from End-of-Pipe
Data from Plant 12236

Alternate Cyanide Limitations and Standards

Average Concentrations and Variability Factors
Derived from Steam Stripping Data

Suggested TVO Limitations

Ratios of Effluent TSS (mg/1) to Effluent
BOD (mg/1) for Biological Treatment Plants without
Effluent Filtration

Summary of Median and Mean Ratios of  Effluent
TSS to Effluent BOD5 for Various Plant Groups

Comparision of Ratios of BPT 30-Day Maximum
Average Limitations for TSS (mg/1) and BOD
Ong/1) Established for Related Industrial
Categories Based on Biological Treatment
A-l

A-2


A-3


A-4

A-5
Cost Estimating Criteria

Incremental Cost Requirements for Achieving
BPT TSS Limitations

Design Criteria for CN Removal by Alkaline
Ch1orination

Cyanide Destruction Capital and Annual Costs

Design Criteria tor Steam Stripper
 154


 155



 157

 159


 161

 163



 165


 166




 167



213


216


217

219

222
                                 XI

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                        LIST OF TABLES (Continued)
Number
A-6
A-7

A-8

A-9

A-10
                     Title

Capital Itemized Costs for Batch Operation
Capital Itemized Costs for Continuous
Operation
Annual Itemized Costs for Batch Operation
Annual Itemized Costs for Continuous
Operation

BPT Cyanide Destruction Energy Requirements

BAT Steam Stripping Energy Requirements

PSES Cyanide Destruction Energy Requirements

PSES Steam Stripping Energy Requirements; for
Methylene Chloride Removal
Page

223

224
225

226

231

232

233


234
                                 xn

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                             LIST OF FIGURES
Number

Section III

III-l


Section VII

VII-1


VII-2


VII-3

VII-4


VII-5


VII-6


VII-7


VII-8

VII-9


VII-10

VII-11

Appendix A

A-l

A-2

A-3


A-4
               Title                            Page
Pharmaceutical Industry
Geographical Distribution
20
Cyanide Destruction System -
Chlorination                                    110

Cyanide Destruction System -
Alkaline Hydrolysis                             113

Chromium Reduction System                       116

Metals Removal System -
Alkaline Precipitation                          118

Typical Equipment for Steam Stripping
Solvents from Wastewater                        121

Packed Column Steam Stripper at
Plant 12003                                     130

Steam Distillation Flash Tank
at Plant 12003                                  134

Activated Carbon Adsorption Unit                138

Examples of Augmented Biological
Systems                                         144

Typical Clarifier Configurations                147

Filtration Unit                                 148
Cyanide Destruction Capital Costs               220

Cyanide Destruction Annual Costs                221

Capital Costs - Model Plant Steam Stripping
Batch vs. Continuous                            227

Annual Costs - Model Plant Steam Stripping
Batch vs. Continuous                            228
                                 xti i

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                            SECTION I

                        EXECUTIVE SUMMARY
A.  SUMMARY

This document  presents  the  technical  rationale  for  effluent
limitations  and  standards  for the pharmaceutical manufacturing
point source category as required by the Clean Water Act of  1977
(P.L.  95-217, "the Act") and the Settlement Agreement in Natural
Resources Defense Council, Inc. v.  Train,  8  ERC  2120  (D.D.C.
1976),  modified,  12  ERC 1833 (D.D.C. 1979), modified by Orders
dated  October 26,  1982,  and  August 2,  1983.   This  document
describes  the  technologies  which  form  the bases for effluent
limitations reflecting the best  practicable  control  technology
currently  available  (BPT)  and  the  best  available technology
economically achievable (BAT), new source  performance  standards
(NSPS),  and  pretreatment standards for new and existing sources
(PSNS and PSES).

EPA developed these limitations and standards after undertaking a
complex program utilizing industry data obtained under  authority
of  Section  308  of  the  Act,  supplemented  by additional data
collection programs for selected portions of the industry.

Plants in the pharmaceutical manufacturing point source  category
produce   biological  products,  medicinal  chemicals,  botanical
products  and  pharmaceutical  products   covered   by   Standard
Industrial  Classification  Code  (SIC)  Numbers  2831, 2833, and
2834,. and other commodities described within this report.

The industry is characterized by diversity of  product,  process,
plant  size,  and process stream complexity.   Subcategories based
on process characteristics were defined for purposes of technical
evaluation.  These subcategories were found to be appropriate for
regulatory purposes.
Section II
Sections  I
engineering
options.
technology
standards
limitations
are  to be
of this document summarizes  the  rulemaking  process.
II  through  VIII  describe  the  technical  data  and
 analyses used to develop  the  regulatory  technology
The  rationales  by  which  the  Agency  selected  the
options for  each  of  the  effluent  limitations  and
are  presented  in Sections IX through XIII.  Effluent
 guidelines based on the application of  BPT  and  BAT
achieved by  existing direct dischargers.  New  source

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performance   standards   (NSPS)  based  on  the  best  available
demonstrated  technology  are  to  be  achieved  by  new   direct
discharging  facilities.  Pretreatment standards for existing and
new sources (PSES and  PSNS)  are  to  be  achieved  by  indirect
dischargers  for  those pollutants which are incompatible with or
not susceptible to treatment in a publicly owned treatment  works
(POTW).   These effluent limitations and standards are required by
Sections 301,  304, 306, and 307 of the Act.
B.
SUBCATEGORIZATION
For the purpose of establishing BPT, BAT, NSPS,  PSES,  and  PSNS
EPA  subcategorized  the pharmaceutical manufacturing industry as
follows:
          Subpart A -
          Subpart B —
          Subpart C -
          Subpart D -
          Subpart E -
                - Fermentation Products
                — Extraction Products
                - Chemical Synthesis Products
                — Mixing/Compounding and Formulation
                - Research
This  subcategorization  scheme,  which  resulted  from  previous
Agency  rulemaking efforts in 1976, was reviewed based on current
information.  EPA considered various factors such as age and size
of plant, raw material  usage,  process  employed,  products  and
waste  treatability  in  reviewing  the  adequacy of the original
subcategorization scheme.

Based on the review, EPA excluded Subpart E, Research Only,  from
further regulation under BAT, NSPS, PSES, and PSNS.  In addition,
EPA  had  'considered  collapsing the remaining four subcategories
into a single subcategory.  The Agency, however, in  establishing
final rules, maintained the original subcategorization scheme.  A
detailed  discussion of subcategorization can be found in Section
IV.

C.  EFFLUENT LIMITATIONS GUIDELINES

1.   BPT Limitations

The 1976 BPT limitations on the discharge of BOD5. COD and pH  are
unchanged  and  remain  in effect.  These regulations require all
subcategories  of  plants  A  through  E  to   achieve   effluent
reductions  of 90 and 74 percent from raw waste for BOD!> and COD,
respectively.   Additionally,  these  regulations   require   all
subcategories of plants (A through E) to  maintain the pH of  the

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final  effluent  between  6.0 and 9.0 units.  In this rulemaking,
the Agency is amending BPT TSS limitations for subcategories B/ D
and E and establishing TSS limitations for subcategories A and  C
and   is   establishing   final   BPT   cyanide  limitations  for
subcategories A, B,  C  and  D.   In  addition,  the  Agency  has
reviewed the available influent and effluent BOD5_ and COD data in
the   light   of   our   decision   to   use   the  original  BPT
subcategorization scheme.  As a result, alternative  maximum  30-
day  average  concentrations are established for BOD5_ and COD for
three subcategories (B, D and E).   These alternative  limitations
reflect  the minimum attainable effluent BOD5_ and COD limitations
consistent with the technology basis of  BPT  as  established  in
1976 (41 FR 50178; November 17, 1976).  The newly established BPT
regulations are summarized below:
Parameter
TSS (mg/1)
Total Cyanide (mg/1)
     Alternate A
     Alternate B
   Maximum
30-Day Average

1.7 times the
equivalent
BPT BOD5_ Con-
centration
Limitation
  9.4
  9.4(.35)R
 Daily
Maximum
33.5
33.5(
18)R
Alternate  A:  Measure at effluent from cyanide destruction unit.
     Applies only when all cyanide-bearing wastes are diverted to
     a cyanide destruction unit and subsequently  are  discharged
     to a biological treatment system.

Alternate B: Measure at final effluent discharge point.

"R"  equals  the dilution ratio of the cyanide contaminated waste
streams to the total process wastewater discharge flow.

In addition, the BPT limitations applicable to subcategories B, D
and E would not require a plant in these subcategories to  attain
a  maximum  30-day  average  effluent limitation of less than the
equivalent of 45 mg/1 for BOD5_ and 220 mg/1 for COD.

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2.   BAT Limitations

Final BAT limitations which apply to subcategories A, B, C and  D
are summarized below:
Parameter

Total Cyanide
     Alternate A
     Alternate B

COD
   Maximum          Daily
30-Day Average     Maximum
  9.4              33.5
  9.4(,35)R        33.5(

      (Reserved)
18)R
Alternate  A:  Measure at effluent from cyanide destruction unit.
     Applies only when all cyanide-bearing wastes are diverted to
     a cyanide destruction unit and subsequently  are  discharged
     to a biological treatment system.

Alternate B: Measure at final effluent discharge point.

"R"  equals  the dilution ratio of the cyanide contaminated waste
streams to the total process wastewater discharge flow.

BAT  COD limitations are being reserved and will be   issued  at   a
later date.  Additional information on the identity  of pollutants
that contribute to COD and on applicable  COD  removal  technologies
is required  before EPA can fully  evaluate COD control options.

3.   BCT Limitations  (Reserved)

BCT  effluent limitations  are reserved pending issuance of  a final
BCT  methodology.

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4.
NSPS
Final NSPS limitations which apply to subcategories A, B, C and D
are summarized below:
Parameter

Total Cyanide
     Alternate A
     Alternate B
                        Maximum
                     30-Day Average
                       9.4
                       9.4(.35)R
 Daily
Maximum
33.5
33.5(
18)R
Alternate  A:  Measure at effluent from cyanide destruction unit.
     Applies only when all cyanide-bearing wastes are diverted to
     a cyanide destruction unit and subsequently  are  discharged
     to a biological treatment system.

Alternate B: Measure at final effluent discharge point.

"R"  equals  the dilution ratio of the cyanide contaminated waste
streams to the total process wastewater discharge flow.

NSPS COD limitations are being reserved  for  promulgation  at  a
later date.  Additional information on the identity of pollutants
that contribute to COD and on applicable COD removal technologies
is required before EPA can fully evaluate COD control options.

NSPS  BOD5_  and  TSS  limitations are being proposed concurrently
with promulgation of these  final  regulations.   These  proposed
limitations  are  discussed  in Proposed Development Document for
Effluent  Limitations  and  Standards  for   the   Pharmaceutical
Manufacturing Point Source Category,  (U.S.EPA, September 1983).
5.
PSES and PSNS
Final  PSES  and  PSNS which apply to subcategories A, B, C and D
are summarized below:                                      .
Parameter

Total Cyanide
     Alternate A
     Alternate B
                     Maximum 30-Day Average
                         9.4
                         9.4R
       Daily Maximum
           33.5
           33.5R
Alternate A: Measure at effluent from  cyanide  destruction  unit
     before  dilution with other streams.  Applicable only if all
     cyanide-containing  wastes  are  diverted   to   a   cyanide
     destruction unit.

Alternate B: Measure at final effluent discharge point.

"R"  equals  the dilution ratio of the cyanide contaminated waste
     streams to the total process wastewater flow.
                             5

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D.
IMPACT OF REGULATION
1.    BPT Regulation

BPT effluent limitations for cyanide are expected to prevent  the
discharge  of  127,000  pounds  of  cyanide  per  year to surface
waters.  The estimated total  annual  and  investment  costs  for
compliance  with  BPT  cyanide  limits  are $274,000 and $579,000
(1982 dollars), respectively.  Increases in energy consumption as
a result of these limitations are expected to be negligible  when
compared to the energy used in the manufacturing process.

The  final  BPT  TSS  limitations  are  expected  to  prevent the
discharge of 137,500 pounds per year of TSS.  The estimated total
annual  and  investment  costs  for  compliance  with   BPT   TSS
limitations   are   $140,000   and   $470,000   (1982   dollars),
respectively.

No implementation costs are attributable to the alternative  BOD5_
and COD limitations, because they are, in effect, a relaxation of
limitations  that previously applied to low raw waste load plants
in subcategories B, D and E.

2.   BCT Regulations (Reserved)
3.   BAT Regulations

No  incremental  costs,  removals  or  energy  requirements   are
attributable  to  the  BAT  cyanide  limitations  since  they are
identical to the BPT cyanide  limitations.

4.   PSES and PSNS Regulations

Final pretreatment standards  for existing sources  (PSES)   control
the  discharge  of  cyanide   to  POTWs.  EPA estimates that  these
standards will prevent the discharge of  148,000 pounds  per  year
of  cyanide  to  the  nation's  surface  waters.  Estimated  total
annual  and investment costs for compliance with  these  standards
are   $258,000   and   $415,000    (1982  dollars),   respectively.
Increases in energy use  resulting  from compliance with  these
standards  are  expected  to  be negligible when compared with the
total energy used in the manufacturing process.  Because PSNS are
equal to PSES, there is no incremental cost or non-water   quality
impact  resulting from compliance with PSNS.

5.   NSPS Regulation

Final NSPS for cyanide will not require  new  sources  to  reduce
their   discharge  of  cyanide beyond levels that  are required  of
existing sources.  Consequently, no incremental costs,  pollutant
removals  or  energy  requirements  are  expected   as a result  of
compliance with final NSPS.

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                           SECTION II

                          INTRODUCTION

A.  PURPOSE AND LEGAL AUTHORITY

The Federal  Water  Pollution  Control  Act  Amendments  of  1972
established  a  comprehensive program to restore and maintain the
chemical, physical, and  biological  integrity  of  the  Nation's
waters   [ Section 101(a) ].  By July 1, 1977, existing industrial
direct dischargers were required to achieve effluent  limitations
requiring   the  application  of  the  best  practicable  control
technology currently available (BPT) [  Section  301(b){l)(A)   ].
By  July 1,  1983,  these  dischargers  were  required to achieve
effluent  limitations  requiring  the  application  of  the  best
available  technology  economically  achievable (BAT), which will
result in reasonable further progress toward the national goal of
eliminating  the  discharge   of   all   pollutants   [   Section
301(b)(2)(A)  ].  New industrial direct dischargers were required
to comply with  Section  306  new  source  performance  standards
(NSPS)  based on best available demonstrated technology.  New and
existing dischargers to publicly  owned  treatment, works  (POTW)
were  subject to pretreatment standards under Sections 307(b) and
(c) of the 1972 Act.  .The  requirements  for  direct  dischargers
were   to  be  incorporated  into  National  Pollutant  Discharge
Elimination System (NPDES) permits issued under  Section  402  of
the  Act.   Pretreatment standards were made enforceable directly
against dischargers to POTWs (indirect dischargers).

Although Section 402(a)'(l)  of  the  1972  Act  authorized  local
authorities to set requirements for direct dischargers on a case-
by-case basis, Congress intended that, for the most part, control
requirements would be based on regulations promulgated by the EPA
Administrator.    Section   304(b)   of   the  Act  required  the
Administrator to  promulgate  regulatory  guidelines  for  direct
discharger  effluent  limitations  setting  forth  the  degree of
effluent reduction attainable through  the  application  of  best
practicable   control   technology   (BPT)   and  best  available
technology economically  achievable  (BAT).   Moreover,  Sections
304(c)  and  306  of the Act required promulgation of regulations
for NSPS,  and  Sections  304(f),  307(b),  and  307(c)  required
promulgation  of  regulations  for  pretreatment  standards.    In
addition to these regulations for designated industry categories,
Section  307(a)  of  the  Act  required  the   Administrator   to
promulgate  effluent  standards  applicable to all dischargers of
toxic pollutants.  Finally, Section 501(a) of the Act  authorized
the   Administrator   to  prescribe  any  additional  regulations
necessary to carry out his or her functions under the Act.

The EPA was unable to promulgate many of these regulations by the
dates contained in the 1972 Act.  In 1976 EPA was sued by several
environmental groups; in settlement of this lawsuit, EPA and  the
plaintiffs executed a Settlement Agreement, which was approved by

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the  Court.  This agreement required EPA to develop a program and
adhere to a schedule for promulgating, for 21  major  industries,
BAT  effluent limitations guidelines, pretreatment standards, and
new source performance standards for 65  "toxic"  pollutants  and
classes of pollutants.  (40)

On  December  27,  1977,  the President signed into law the Clean
Water Act of 1977.  Although this  law  makes  several  important
changes  in the Federal water pollution control program, its most
significant feature is its incorporating into the Act several  of
the  basic elements of the Settlement Agreement program for toxic
pollution control.  Sections 301(b)(2)(A) and 301(b)(2)(C) of the
Act now require the achievement by  July  1,  1984,  of  effluent
limitations  requiring  application  of BAT for toxic pollutants,
including the 65 priority pollutants and  classes  of  pollutants
which  Congress  declared  toxic under Section 307(a) of the Act.
Likewise, EPA's programs for new source performance standards and
pretreatment  standards  are  now  aimed  principally  at   toxic
pollutant  controls.   Moreover, to strengthen the toxics control
program, Congress added Section 304(e) to  the  Act,  authorizing
the  Administrator  to prescribe best management practices (BMPs)
to prevent the release of toxic  and  hazardous  pollutants  from
plant  site  runoff, spillage or leaks, sludge or waste disposal,
and drainage  from  raw  material  storage  associated  with,  or
ancillary to, the manufacturing or treatment process.

In keeping with its emphasis on toxic pollutants, the Clean Water
Act  of  1977 also revised the control program for "conventional"
pollutants  (including  biochemical  oxygen   demand,   suspended
solids,  fecal coliform, oil and grease, and pH) identified under
Section 304(a)(4).  Instead of BAT for  conventional  pollutants,
the new Section 301(b)(2)(E) requires by July 1, 1984 achievement
of  effluent  limitations  requiring  the application of the best
conventional pollutant control  technology  (BCT).   The  factors
considered  in  assessing  BCT  include the reasonableness of the
relationship between  the  costs  of  attaining  a  reduction  in
effluents  and  the  effluent reduction benefits derived, and the
comparison of the cost and level of reduction for  an  industrial
discharge  with  the  cost  and  level  of  reduction  of similar
parameters  for  a  typical  POTW  [Section  304(b)(4)(B)].   For
nontoxic,  nonconventional  pollutants, Sections 301(b)(2)(A) and
301(b)(2)(F) require  achievement  of  BAT  effluent  limitations
within  three  years  after  their establishment or after July 1,
1984 (whichever is later), but not later than July 1, 1987.

This document presents the technical rationale  for  revised  BPT
and   new   BAT  effluent  limitations,  new  source  performance
standards (NSPS), pretreatment  standards  for  existing  sources
(PSES), and pretreatment standards for new sources (PSNS) for the
pharmaceutical manufacturing point source category.

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B.  PRIOR EPA REGULATIONS

On  November  17,  1976,  the  EPA  promulgated interim final BPT
regulations for the  pharmaceutical  manufacturing  point  source
category  at 41 FR 50676, 40 CFR Part 439, Subparts A-E. (27) The
BPT regulations set monthly limitations for BOD5_ and COD based on
percent removals for all subcategories.  No daily  maximums  were
established  for these two parameters.  The pH was required to be
within the range of 6.0 to 9.0 at all times.  The rulemaking also
set a maximum allowable average  of  daily  TSS  values  for  any
calendar month for subcategories B, D, and E.  No TSS limits were
established  for  subcategories  A and C.  Subpart A (the section
applicable to the fermentation products subcategory) was  amended
on  February  4,  1977  (42  FR  6814),  to  improve the language
referring to separable mycelia and solvent recovery and to  allow
the  inclusion  of spent beers (broths) in the calculation of raw
waste loads for subcategory A in those instances where the  spent
beer is actually treated in the wastewater treatment system.  The
technical  basis  for  the  1976  BPT regulations was provided in
"Development Document  for  Interim  Final  Effluent  Limitations
Guidelines  and Proposed New Source Performance Standards for the
Pharmaceutical Manufacturing Point Source Category", published in
December 1976.  This report is henceforth referred to as the 1976
Development Document. (55) The 1976 BPT  regulations  were  never
challenged,  and  are still in effect.  On November 26, 1982, the
Agency proposed revised BPT and new BCT, BAT, NSPS, PSES and NSPS
limitations and standards for  the  Pharmaceutical  Manufacturing
Category (47 FR 53584).
C.
SCOPE OF THIS RULEMAKING
In EPA's initial rulemaking (August  1973  thru  November   1976),
emphasis  was  placed  on  the  achievement  of  BPT based  on the
control of familiar, primarily conventional pollutants,  such  as
BOD5_,  TSS,  and pH, and nonconventional pollutants, such as COD.
By contrast, EPA's efforts  in  this  round  of  rulemaking  were
directed  toward  finalizing  BPT  and  BAT effluent limitations,
NSPS,  PSES  and  PSNS,  with   a   special   emphasis   on   the
identification  and  quantitation  of  toxic pollutant discharges
from the pharmaceutical industry.

D.  DEFINITION OF THE  INDUSTRY

The pharmaceutical manufacturing point source category is defined
as  those  manufacturing  plants  producing  or   utilizing   the
following products, processes, and activities:
      (1)    Biological  products  covered
Classification  (SIC) Code No. 2831.
                                      by Standard Industrial
      (2)   Medicinal chemicals and botanical products covered  by
SIC Code No. 2833.

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     (3)   Pharmaceutical products covered by SIC Code No. 2834.

     (4)    All  fermentation, biological and natural extraction,
chemical synthesis, and formulation products which are considered
as pharmaceutically active  ingredients  by  the  Food  and  Drug
Administration,  but which are not covered by SIC Code Nos. 2831,
2833, or 2834.  (Products of these types which  may  not  contain
pharmaceutically  active ingredients will be included if they are
manufactured by  processes,  and  result  in  wastewaters,  which
closely   correspond   to  those  of  a  pharmaceutical  product.
Examples of ingredients which fall into this category are  citric
acid, benzoic aci'd, gluconic acid, fumaric acid, and caffeine. )

     (5)    Cosmetic  preparations  covered  by SIC Code No. 2844
which  function  as  a  skin  treatment.   (This  would   exclude
lipsticks,  eyeshadows,  mascaras, rouges, perfumes, and colognes
which enhance appearance or provide a pleasing odor, but  do  not
provide   skin   care.   In  general,  this  would  also  exclude
deodorants, manicure preparations, and shaving preparations which
do not primarily function as a skin treatment.)

     (6)    The portion of a product with multiple end uses which
is attributable to pharmaceutical manufacturing either as a final
pharmaceutical product, component of a pharmaceutical formulation
or a pharmaceutical intermediate.  (Products with  pharmaceutical
and  nonpharmaceutical  end  uses  will be entirely covered under
this point source category if the products are used primarily  as
Pharmaceuticals.)

     (7)    Pharmaceutical research  which  includes  biological,
microbiological,  and  chemical  research,  product  development,
clinical and pilot plant activities.  (This includes animal farms
at which pharmaceutical research is conducted or at  which  phar-
maceutically  active  ingredients are tested on the farm animals.
This does not include  farms  which  breed,  raise,  and/or  hold
animals for research at another site.  Also excluded are ordinary
feedlot   or   farm   operations   using   feed   which  contains
pharmaceutically  active   ingredients   since   the   wastewater
generated   from   these  operations  is  not  characteristic  of
pharmaceutical wastewater).
Products   or   activities   specifically   excluded
pharmaceutical manufacturing category are:
from   the
     (1)  Surgical and medical instruments and apparatus  covered
by SIC Code No. 3841 .

     (2)  Orthopedic,  prosthetic,  and  surgical  appliances  and
supplies covered by SIC Code No. 3842.
3843.
     (3)  Dental equipment and supplies covered by SIC  Code  No.
                              10

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     (4)  Medical laboratories covered by SIC Code No. 8071.

     (5)  Dental laboratories covered by SIC Code No. 8072.

      6)  Outpatient care facilities  covered  by  SIC  Code  No.
8081.

     (7)  Health and allied services,
covered by SIC Code No. 8091.
      not  elsewhere  classified,
     (8)  Diagnostic devices not covered by SIC Code No. 3841.

     (9)  Animal  feeds  which  include  pharmaceutically  active
ingredients such as vitamins and antibiotics.  (The major portion
of  the  product  is  nonpharmaceutical  and the wastewater which
results from the manufacture of feed  is  not  characteristic  of
pharmaceutical manufacturing.)

     (10) Foods and beverages which are fortified  with  vitamins
or other pharmaceutically active ingredients.  (The major portion
of  the  product  is  nonpharmaceutical  and the wastewater which
results  from  the  manufacture  of   these   products   is   not
characteristic of pharmaceutical manufacturing.)

In   the   1976  regulation  based  on  BPT,  the  pharmaceutical
manufacturing point source category was grouped into five product
or activity areas.  This subcategorization was based on  distinct
differences  in manufacturing processes, raw materials, products,
and wastewater characteristics and treatability.  The  five  sub-
categories that were selected are:
      (1)    Subcategory A
      (2)    Subcategory B

      (3)    Subcategory C
      (4)    Subcategory D
      (5)    Subcategory E
Fermentation .Products.
Biological and Natural Extraction
Products.
Chemical Synthesis Products.
Formulation Products.
Pharmaceutical Research.
For  the  purposes  of  the  1977-83  study,  EPA  decided to de-
emphasize    pharmaceutical     research     (Subcategory     E).
Pharmaceutical  research  does  not fall within the SIC Code Nos.
2831,  2833, and 2834, which were identified  in  the  Settlement
Agreement,  and  does  not appear to be a significant part of the
industry from the point of view of effluent.  In  addition,  this
activity does not involve production and wastewater generation on
a  regular  basis.   However,  in  cases where the pharmaceutical
research  activity  does  involve  the   production   of   active
ingredients  by processes generating wastewater which are similar
to those in the current study, the information contained in  this
development  document  may.  -be  used  by permit writers and other
interested parties.
                             11

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In  developing  the  November  1982  proposal,  this  subcategory
breakdown was utilized for evaluative purposes only.  In terms of
analyzing  raw  waste characteristics, wastewater flow, treatment
technology alternatives, etc., a breakdown  of  the  industry  by
product/process  (i.e.,  subcategories)  was  the most practical.
However,  as   explained   in   more   detail   below,   separate
subcategories   were  not  considered  necessary  for  regulatory
purposes at proposal because it appeared that one set  of  limits
could  be  met  by  all  pharmaceutical  plants.   Therefore, the
proposed  limitations  would  have  been  applicable  across  the
industry  irrespective of the process source of the waste.  Since
then, analysis of the data, including new data, and evaluation of
the  comments  on  the  November  1982  proposal,  indicate  that
different  limitations  may be appropriate for different types of
processes.  Therefore, as explained in more detail in Section  IV
of   this   document,  the  final  regulations  retain  the  1976
subcategorization scheme.

E.  SUMMARY OF METHODOLOGY

EPA first gathered  technical  and  descriptive  data  about  the
industry,  from  which  the Agency proceeded to develop the final
regulations.  EPA used four basic sources in  acquiring  data  to
support the new regulations.  These sources included:

     (1)  Data acquired from industry under Section  308  of  the
Act.   Using  this approach, questionnaires were distributed to a
representative sample of the industry.  This was  followed  by  a
screening  and  verification sampling program of candidate plants
chosen  after  review  of  the  questionnaire   responses.    The
analytical  procedures  for  pollutant  detection and measurement
were developed under section 304(h).   (See "Sampling and Analysis
Procedures for Screening of  Industrial  Effluents  for  Priority
Pollutants," U.S. EPA, April 1977.)

     (2)  Data acquired through  an  open  literature  search  of
publications relevant to the pharmaceutical industry.

     (3)  Data acquired from  EPA  regional  offices.  State  and
other government offices, and pharmaceutical plant visits.

     (4)  The Administrative Record from the  1976 rulemaking  for
the  pharmaceutical  industry,  including  the  1976  Development
Document.

EPA then studied the pharmaceutical industry  to determine whether
differences in such factors as  raw  materials,  final  products,
manufacturing   processes,   equipment,   water  use,  wastewater
constituents, and age and size of  the  manufacturing  facilities
required  the  development  of  separate effluent limitations and
standards for different segments of  the  industry.   This  study
required  the  identification  of  raw waste  and treated effluent
characteristics, including: (1)    the water  sources  and  volume
                               12

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used, (2) the manufacturing processes employed, (3)    the  loca-
tion  of  pollutant  and wastewater sources within the plant, and
(4)  the wastewater constituents  (including  toxic  pollutants).
After  tentatively designating subcategories, EPA then identified
the constituents of wastewaters which should  be  considered  for
effluent limitations and standards.

Next,  the  EPA identified several distinct control and treatment
technologies, including both in-plant  and  end-of-process  tech-
nologies,  which currently are in use or capable of being used to
control or treat pharmaceutical industry wastewater.  The  Agency
compiled and analyzed historical and newly acquired effluent data
from  plants  where  these  technologies are utilized.  Long-term
performance, operational limitations, and  reliability  for  each
treatment   and  control  technology  were  also  considered  and
statistical analyses of long-term data were performed in order to
derive   performance   standards   and    variability    factors.
Additionally,   the   EPA   evaluated   the   non-water   quality
environmental impacts of these technologies including impacts  on
air quality, solid waste disposal, and energy use.

The  EPA  developed base cases representative of each subcategory
(based on raw waste load  characteristics)  to  derive  treatment
processes  and  capital  and operating costs for each technology.
These costs were presented as  curve  functions  based  on  waste
loading and flow.  The technologies evaluated included biological
end-of-pipe  processes (e.g., biological enhancement), as well as
in-plant priority pollutant treatments (cyanide  destruction  and
steam  stripping).   The  annual  unit  costs  (including capital
amortization) were calculated for varying flows and waste  loads.
The  Agency  then evaluated the economic impact of these costs on
the  industry  as  a  whole.   Costs  and  economic   impacts  are
discussed   in  the  "Economic  Analysis of Effluent Standards and
Limitations for the  Pharmaceutical  Manufacturing  Point  Source
Category,"   (U.S.EPA,  September   1983).   Following  the  public
comment period for the proposal, EPA reviewed and  evaluated  the
comments  and  new  data, and made appropriate adjustments to the
earlier analyses.

Through  this  process,  EPA  identified  various   control   and
treatment   technologies as BPT, BAT, NSPS, PSES, and  PSNS.  These
regulations, however, do not  require  the   installation  of  any
particular  technology.   Rather,  they  require  achievement  of
effluent limitations representative of the proper application  of
these  technologies or equivalent  technologies.  A pharmaceutical
plant's existing controls should be fully evaluated,  and existing
treatment systems fully optimized  before making a  commitment  to
any  new or  additional end-of-pipe  treatment  technology.

F.   DATA AND INFORMATION GATHERING PROGRAM

The  data and information gathering program conducted  prior to the
publication  of  the proposed regulations on November 26,  1982 is
                              13

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discussed in  the  Development  Document  for  Proposed  Effluent
Limitations Guidelines and Standards for the Pharmaceutical Point
Source  Category, (U.S. EPA, November 1982).  Since the proposal,
the Agency has gathered data  and  information  for  purposes  of
adequately  responding  to  comments on the proposed regulations,
clarifying ambiguities and correcting errors in the Agency's data
base and providing adequate support for final regulations for the
pharmaceutical manufacturing point source category.   These  data
gathering  efforts  involved  a  sampling  program,  a 308 survey
questionnaire, 308 data requests and direct  communications  with
individual  plant personnel.  These areas of effort are discussed
below:

(1)  Post Proposal Sampling.

The Agency, in  response  to  comments  on  its  intended  policy
regarding  pretreatment  standards  for  toxic volatile organics,
sampled a POTW in order to determine whether or not pass  through
of  toxic  volatile  organics was occurring and whether this pass
through was  the  result  of  discharges  from  a  pharmaceutical
source.   This sampling episode is discussed in Section VI.  Also
in response to comments, the Agency sampled two  steam  strippers
operating  within  a pharmaceutical plant.  This sampling episode
is discussed in Section VII of this document.
(2)  308 Survey Questionnaire and
     Letters.
Individual  308  Data  Request
In  order to enable the Agency to evaluate correctly the need for
pretreatment  standards  for  toxic  volatile  organics  and   to
determine  the costs of complying with such standards, the Agency
sent a 308 survey  questionnaire  to  nine  indirect  discharging
pharmaceutical  plants.   This questionnaire and the responses to
it  are  discussed  in  Section  VII  of  this  document.   Other
individual  308  data  request  letters  were sent to plants that
commented on the proposed  regulations.   The  letters  requested
data   on   conventional  and  nonconventional  pollutants.   The
responses to these later requests  will  be  presented  when  the
Agency   finalizes   regulations  controlling  the  discharge  of
conventional and nonconventional pollutants.

(3)  Direct Communications with Individual Plants

Plants that had submitted data and comments in  response  to  the
proposed  regulations  were  contacted  whenever uncertainties or
ambiguities existed in  their  submissions.   Also,  plants  were
contacted  when  they  indicated  in their comments that they had
additional information which would  be  useful  to  the  Agency's
regulatory  effort.    Industry profile information obtained since
proposal is presented  in Section III.
                              14

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G. PROCESSING OF DATA AND INFORMATION

Stanford Research Institute  (SRI) was contracted to do a two-part
statistical analysis of the pharmaceutical  industry  data  base.
Long-term  effluent  data were evaluated to determine variability
of pollutant removal resulting  from  long-term  operation.   The
analysis  centered  on  effluent  data  from which SRI calculated
daily and monthly variability factors for each pollutant.

In the second part of the analysis,  screening  and  verification
data  were  evaluated to determine the frequency of occurrence of
each  priority  pollutant  occurring  in   the   manufacture   of
Pharmaceuticals.   A frequency ranking was prepared for groups of
priority pollutants and is discussed in Section V.  In  addition,
the  statistical  pattern  of  concentrations  of  each pollutant
present was analyzed.  Frequency of occurrence and  concentration
information  were two criteria on which the selection of specific
priority pollutants for regulation was based.  In  addition,  EPA
considered  whether  treatment  required  by existing regulations
would control these pollutants.  Section VI contains  a  detailed
discussion of this selection process in light of the criteria for
exclusion contained in paragraph 8 of the Settlement Agreement.

After  the  November  1982   proposal, SRI performed a statistical
analysis of  the  proposed   subcategorization  scheme  using  the
latest  available  data  including  data submitted with comments.
This analysis is discussed  in Section IV.  SRI also  performed   a
variability  analysis  on   the  cyanide  data used to develop the
final cyanide limitations.   This analysis  is discussed in  Section
VIII along with the analysis of the  data  obtained  through  the
direct sampling of steam strippers.
                                15

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                           SECTION III

                   DESCRIPTION OF THE INDUSTRY
    INTRODUCTION
In  order  to  establish  an  industry  data  base   upon   which
regulations  can  be promulgated, a comprehensive profile must be
developed  from  survey,  sampling  and  existing  data  sources.
Section   III  of  the  Proposed  Development  Document  presents
information  which  describes  the  pharmaceutical  manufacturing
industry in a quantitative and specific manner.  That information
was  obtained prior to publication of the proposed regulations on
November 26, 1982.  The information  presented  in  this  section
updates that information.


B.  DETAILED INDUSTRY PROFILE

The  objectives  of  the  308 Questionnaire were to obtain  infor-
mation  from  pharmaceutical  manufacturing  facilities  and   to
develop  an  industry  profile   that  includes  plant  size, age,
location, and production activities.  Appendix F of the  Proposed
Development  Document listed each of the 464 manufacturing  plants
contained in the comprehensive EPA data base by plant code  number
(assigned for identification purposes), applicable  manufacturing
subcategories,  manufacturing employment, and year of operational
startup.  Plants with code numbers in the 12000 series  are from
the  original   308  Portfolio  survey;  those  with  20000  series
numbers are from the Supplemental 308  Portfolio  survey.   Since
proposal,   four  pharmaceutical  plants  (11111, 33333, 44444, and
55555) not  in the original 308 survey supplied  the  Agency with
data.   The  Agency  also  learned that two facilities  (20153 and
12112) are  no longer manufacturing  Pharmaceuticals.   Therefore,
there  are now 466 plants  in the  comprehensive data base listed  in
Appendix C  by plant code  number.

Table  III-l  shows the  geographical distribution of the  industry
and  the number  of manufacturing  plants by state and  EPA   region.
Also  shown are the average number of manufacturing employees per
plant  and the average plant startup year.

Most of the pharmaceutical  industry  is   located   in  the   eastern
half  of  the   United   States   (See  Figure   III-l.)  Of   the 466
manufacturing plants  in the comprehensive data  base,   almost   80
percent  are  in the East.  New  Jersey  (with about  16 percent) and
Region  II   (with  approximately  36  percent)  are  the   largest
pharmaceutical   manufacturing  state  and  EPA region,  respectively.
The  data show that Regions  II,  III,  V,  and VII  (the  Northeast and
Midwest) have generally older  plants  than Regions  IV,   VI,   VIII,
and   IX   (the   South   and West).  This  is due to  the recent trend
toward building plants  in the  "Sun  Belt"  of   the   United   States.
                                17

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                           Table III-l
                     PHARMACEUTICAL INDUSTRY
                    GEOGRAPHICAL DISTRIBUTION
Location
EASTERN U.S.
Connecticut
Mai ne
Massachusetts
New Hampshire
Rhode Island
Vermont
REGION 1 Total
New Jersey
New York
Puerto Rico
Virgin Islands
REGION 2 Total
Del aware
Maryland
Pennsylvania
Virginia
West Virginia
District of Columbia
REGION 3 Total
Alabama
Georgia
Florida
Mississippi
North Carolina
South Carolina
Tennessee
Kentucky
REGION 4 Total
Illinois
Indiana
Ohio
Michigan
Wisconsin
Minnesota
Number of
Plants
369
8
0
7
0
1
1
17
75
43
46
2
166
2
7
27
7
2
0
45
3
6
8
2
12
3
10
5
49
38
18
14
14
4
4
Percent of
Total Plants
79.2
1.7
0.0
1.5
0.0
0.2
0.2
3.6
16.1
9.3
9.9
0.4
35.6
0.4
1.5
5.8
1.5
0.4
0.0
9.7
0.6
1.3
1.7
0.4
2.6
0.6
2.1
1.1
10.5
8.2
3.9
3.0
3.0
0.9
0.9
Average
Number
Employees
Per Plant
268
195
-
77
(2)
(2)
161
350
211
216
13
239
121
65
370
138
151
••
267
15
189
95
759
456
87
301
12
250
305
664
203
423
54
41
Average
Plant
Start-up
Year(l)
1952
1963
-
1961
(2)
(2)
1960
1950
1943
1970
—
1956
1965
1938
1950
1950
—
*™
1950
1958
1956
1967
1949
1971
1968
1940
—
1962
1951
1944
1929
1931
1957
-
REGION 5 Total
92
19.7
351
1943
                             18

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                                     Table III-l
                                       (cont'd)
                            PHARMACEUTICAL INDUSTRY
                           GEOGRAPHICAL DISTRIBUTION
Location
WESTERN U.S.
Arkansas
Louisiana
Oklahoma
Texas
New Mexico
REGION 6 Total
Iowa
Kansas
Missouri
Nebraska
REGION 7 Total
Colorado
Utah
Wyoming
Montana
North Dakota
South Dakota
REGION 8 Total
Arizona
California
Neva
Hawaii
REGION 9 Total
Alaska
Idaho
Oregon
Washington
Number of
Plants
97
2
2
0
13
0
17
3
4
17
4
28
5
1
0
0
0
0
6
1
38
1
0
40
0
0
2
4 ;
Percent of
Total Plants
20.8
0.4
0.4
0.0
2.8
0.0
3.6
0.6
0.9
3.6
0.9
6.0
1.1
0.2
0.0
0.0
0.0
0.0
1.3
0.2
8.2
0.2
0.0
8.6
0.0
0.0
0.4
0.9
Average
Number
Employees
Per Plant
152
1558
9
-
127
-
129
77
123
108
201
117
96
(2)
-
-
-
-
162
(2)
139
(2)
-
137
_
_
25
33
Average
Plant
Start-up
Year(l)
1962
1970
_
-
1968
-
1968
1963
1954
1943
1962
1951
1967
(2)
'
-
-
-
1968
(2)
1967
(2)
-
1967
_
-
-
-
       REGION  10 Total
1.3
30
1955
(1)   Since  data  concerning plant start-up year were not solicited
                                   19

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H
                                   20

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Puerto  Rico  has  close  to  10  percent  of the industry and is
becoming a major pharmaceutical manufacturing center.

Table  II1-2  breaks   down   the   industry   by   manufacturing
subcategory.   Subcategory D (formulating/mixing/ compounding) is
the most prevalent pharmaceutical manufacturing  operation,  with
80  percent  of  the  plants  in  the  industry  engaged  in this
activity.   Fifty-eight   percent   of   these   plants   conduct
Subcategory   D   operations   only.   The  remainder  also  have
operations in other subcategories.

Table III-3 summarizes the total number of batch, continuous, and
semi-continuous manufacturing operations by subcategory  for  the
entire  pharmaceutical  industry.   Batch-type  production is the
most common type of manufacturing technique for each of the  four
subcategories.

C.  MANUFACTURING PROCESSES

One of the most important generalizations which can be made about
the  wastewaters  produced  and  discharged by the pharmaceutical
industry is their extreme diversity.   Products,  processes,  and
the  materials to which wastewater  is exposed vary greatly.  With
the  goal  of  relating  discharged  wastewater  to  some  common
characteristics,   subcategories    based  on  unit  manufacturing
processes were defined.  The broad  manufacturing processing areas
considered were (a)  fermentation,  (b)  biological  and  natural
extraction, (c) chemical synthesis, and (d) formulation.

One  characteristic  of  processing  in this industry is that the
ratio of finished product  to  the  quantity  of  raw  materials,
solvents,  and  other processing materials is generally very low.
This is most apparent  in  natural  extraction   (Subcategory  B),
followed by fermentation (A), synthesis (C), and formulation (D),
respectively.
 1 .
Fermentation
Fermentation  is the usual method for producing  most   antibiotics
and  steroids.   The  fermentation  process   involves  three  basic
steps:   inoculum and seed preparation,  fermentation, and  product
recovery.

Production  of  a  fermentation pharmaceutical  begins  with spores
from the plant master  stock.   The  spores   are   activated  with
water,   nutrients,  and  warmth; they are  then  propagated through
the use  of agar plates,  test  tubes, and flasks  until enough  mass
is  produced  for  transfer   to the seed tank.    In  less critical
fermentations, a single  seed  tank may serve   several   fermenters.
In  this  type  of  operation,  the  seed  tank  is  never emptied
completely, so the seed  remaining will  serve  as the  inoculum  for
the  next  batch.   The  seed  tank is emptied, sterilized, and  re-
inoculated only when contamination occurs.
                              21

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Manufacturing
Subcategory
Combi nati on

A      only
AB
ABC
ABCD
ABD
AC
ACD
AD
B      only
BC
BCD
BD
C      only
CD
D      only
Not Available
Total Plants

Individual
Manufacturing
Subcategory

A
B
C
D
Not Available
                                      TABLE II1-2
                                 SUBCATEGORY BREAKDOWN
      Number of
      Plants

          4
          1
          2
          8
          4
          3
         10
          5
         21
         12
          9
         23
         49
         42
        271
          2
Number of Plants
in Subcategory

      37
      80
     135
     372
       2
Total  number  of  subcategon'es  626*
  Percent of
  Total  Plants
    10.
Percent of
Totals

    5.9
   12.8
   21.6
   59.4
    0.3
 * This  represents the total  number  of  subcategories covered by the 466
   manufacturing  plants.
                                  22

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                                      TABLE I IT-3
                             PRODUCTION OPERATION BREAKDOWN
Type of Operation
Batch
Continuous
Semi-continuous
Total Number of Operations
Percent of Total Operations
Percent of Subcategory
Which is Batch
                                               Number of Operations
A
32
3
11
46
6.7
B
76
0
9
85
12.4
Subcategory
C D
128
14
19
161
23.6
358
16
17
391
57.2
Total
594
33
56
683
100.0
Percent
of Total
Oper,
87.0
4.8
8.2
100.0

                             69.6   89.4    79.5   91.6
87.0
*  Since each individual  Subcategory within a plant may be comprised of more
   than one type of operation, this figure will  be greater than  the  total  number
   of subcategories.
NOTE:
The above data apply to 460 manufacturing plants.  For six plants  no
information was available on their subcategories and types of production
operations.
                                   23

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Fermentation is conventionally a large-scale  batch  process.   A
fermentation   cycle   begins   with   a  water  wash  and  steam
sterilization of the fermenter vessel".  Sterilized  nutrient  raw
materials   in   water   are   then  charged  to  the  fermenter.
Microorganisms are transferred to the  fermenter  from  the  seed
tank  and  fermentation  begins.   During  fermentation,  air  is
sparged into the batch and temperature is  carefully  controlled,
After  a  fermentation period of from twelve hours to a week,, the
fermenter batch whole broth is ready for filtration.   Filtration
removes  mycelia  (remains  of  the  microorganisms), leaving the
filtered aqueous broth containing product and residual  nutrients
ready to enter the product recovery phase.

There  are  three  common  methods  of product recovery:  solvent
extraction, direct precipitation, and ion exchange or adsorption.
Solvent extraction is a recovery  process  in  which  an  organic
solvent  is  used  to  remove the pharmaceutical product from the
aqueous broth  and  form  a  more  concentrated  solution.   With
subsequent  extractions,  the  product is separated from any con-
taminants.   Further removal of the product from the solvent  can
be  done by either precipitation, solvent evaporation, or further
extraction  processes.   Normally,  solvents  used  for   product
recovery  are recovered and reused.  However, small portions left
in the aqueous phase during the solvent "cut" can appear  in  the
plant's  wastewater stream.  The typical processing solvents used
in  fermentation  operations  are  methylene  chloride,  benzene,
chloroform, 1,1-dichloroethylene, and 1,2-trans-dichloroethylene.
(42)

Direct  precipitation consists of first precipitating the product
from the aqueous broth, then filtering  the  broth,  and  finally
extracting  the product from the solid residues.  Priority pollu-
tants known to be used in the precipitation  process  are  copper
and zinc. (42)

Ion-exchange  or  adsorption  involves the removal of the product
from the broth, using such solid materials as ion exchange resin,
adsorptive resin, or activated carbon.  The product is  recovered
from  the  solid  phase  with  the  use  of a solvent; it is then
recovered from the solvent.

Steam is used as the major sterilizing medium for most equipment.
However, to the extent that chemical disinfectants may  be  used,
they can contribute to priority pollutant waste loads.  Phenol is
a commonly used disinfectant.

Sometimes  a fermentation batch can become infested with a phage,
a virus that attacks microorganisms.  Although phage  infestation
is  rare  in  a  well-operated  plant, when it occurs, very large
wastewater discharges may be necessary in a short period of time.
Usually the batch is discharged early and its nutrient  pollutant
concentration is higher than that of spent broth.
                               24

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Another  fermentation  wastewater  source  is  the  air pollution
control  equipment  that  is   sometimes   installed   to   clean
fermentation  waste  off-gas.   The  air  and gas vented from the
fermenters  usually  contain  odoriferous  substances  and  large
quantities  of  carbon  dioxide.  Treatment is often necessary to
deodorize the gas before its release  to  the  atmosphere.   Some
plants  employ incineration methods; others use liquid scrubbers.
The blowdown from scrubbers may contain absorbed chemicals, light
soluble organic compounds, and heavier insoluble organic oils and
waxes.  However, wastewater  from  this  source  is  unlikely  to
contain priority pollutants.


The pollution contribution of the spent beer arises from the fact
that  the  beer contains food materials such as sugars, starches,
protein, nitrogen, phosphate, and other nutrients.   Methods  for
treating  the  fermentation  wastes  are  generally biological in
nature.  Although the spent beers, even in a highly  concentrated
form,  can  be  satisfactorily  handled  by  biological treatment
systems, it is less likely to upset the system if the wastes  are
first  diluted  with  other  wastewater to some degree.  Dilution
normally results from the  equalization  of  fermentation  wastes
with  the  other  waste  streams.   As  a  result, a satisfactory
biological reduction of the contaminants can be achieved.

The 308 data shows generally that wastewaters from Subcategory   A
plants  generally  are  characterized  by  high BOD, COD,  and TSS
concentrations, large flows, and a pH range of about 4.0 to 8.0.

2.   Biological and Natural Extraction

Many materials used as  Pharmaceuticals  are  derived  from  such
natural sources as the roots and leaves of plants, animal  glands,
and  parasitic  fungi.   These products have numerous and  diverse
pharmaceutical  applications  ranging  from   tranquilizers   and
allergy   relief  medications  to'  insulin  and  morphine.   Also
included in this group is blood fractionation, which  involves the
production of plasma and  its derivatives.

Despite their diversity, all extractive  Pharmaceuticals   have   a
common  characteristic;   they  are  too  complex  to  synthesize
commercially.  They are either very  large molecules and/or their
synthesis  results  in  the  production of several stereoisomers,
only one of which has pharmacological value.   Extraction   is  an
expensive  manufacturing process since  it requires the collection
and processing of very large  volumes  of  specialized  plant  or
animal matter to produce  very small  quantities of products.

The  extraction  process  consists of a series of operating steps.
In almost every step, the volume of  material  being  handled   is
reduced  significantly.   In  some processes,  the  reductions may be
in  orders  of  magnitude   and  the  complex  final   purification
operations may be conducted  on  quantities of materials only a few
                              25

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thousandths  of  the  volume  of  the material handled in earlier
steps.  Neither continuous processing  methods  nor  conventional
batch methods are suitable for extraction processing.  Therefore,
a  unique  assembly-line, small-scale batch processing method has
been developed.  Material is transported in  portable  containers
through  the plant in batches of 75 to 100 gallons.  A continuous
line of these containers is  sent  past  a  series  of  operating
stations.   At  each station, operators perform specific tasks on
each batch in turn.  As the  volume  of  material  being  handled
decreases,   individual   batches  are  continually  combined  to
maintain reasonable operating volumes and  the  line  moves  more
slowly.  When the volume is reduced to a very small quantity, the
containers   used   also  become  smaller,  with  laboratory-size
equipment used in many cases.

An extraction plant may produce one  product  for  a  few  weeks;
then,  by changing the logistical movement of pots and redefining
the tasks to be conducted at each station, a plant can convert to
the manufacture of a different product.

Residual wastes from an  extraction  plant  essentially  will  be
equal to the weight of raw material, since the active ingredients
extracted are generally present at very low levels.  Solid wastes
are  the greatest source of the pollutant load; however, solvents
used in the processing  steps  will  cause  both  air  and  water
pollution.

The  nature  of  the  products  of  the  pharmaceutical  industry
dictates that any manufacturing facility maintain a  standard  of
cleanliness   higher  than  that  required  for  most  industrial
operations.  Since most of these plants are  cleaned  frequently,
detergents   and   disinfectants   are   normally  found  in  the
wastewater.

As in the  fermentation  process,  a  small  number  of  priority
pollutants  were identified as being used in the manufacturing of
extractive Pharmaceuticals. (41) The cations of lead and zinc are
known to be used as precipitating agents.  Phenol was  identified
as  an  equipment  sterlizing  chemical  as  well  as  an  active
ingredient.  Otherwise, priority pollutants are found to be  used
only  as  processing  solvents.  Some identified as solvents were
benzene, chloroform, and 1,2 dichloroethane.

Solvents are used in two ways in extraction  operations.   First,
they  are used to remove fats and oils that would contaminate the
products.  These "defatting" extractions use  an  organic  liquid
that  dissolves  the  fat but not the product material.  Solvents
are also used to extract the product  itself.   Plant  alkaloids,
when  treated  with  an  alkali,  become soluble in such selected
organic solvents as benzene, chloroform, or 1,2 dichloroethane.

Ammonia is  used  in  many  extraction  operations  since  it  is
necessary  to  control the pH of water solutions from both animal
                               26

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and plant sources to achieve separation  of  valuable  components
from  waste  materials.   Ammonium  salts  are  used as buffering
chemicals  and  aqueous  or  anhydrous  ammonia  is  used  as  an
alkalizing  reagent.   The  high  degree  of  water solubility of
ammonium salts prevents unwanted  precipitation  of  salt;  also,
ammonia  does  not  react chemically with animal or plant tissue.
Such basic materials  as  hydroxides  and  carbonates  of  alkali
metals do not have these advantages.

The  principal  sources  of  wastewater  from  biological/natural
extraction operations are processes which generate (a) spent  raw
materials (waste plasma fractions, spent eggs, spent media broth,
plant  residues,  etc.);  (b) floor and equipment washwaters; (c)
chemical wastes (spent solvents and the like); and (d) spills.

In general, the bulk of the spent raw materials is collected  and
sent to an incinerator or landfill.  Likewise, the nonrecoverable
portions  of  the  spent  solvents are incinerated or landfilled.
However, in both cases, portions of the residual  materials  find
their  way  into  a  plant's  wastewater.    Floor  and equipment
washings  and  spills  also  contribute  to  the  ordinary  waste
discharge.

Pollutant   information  for  the  biological/natural  extraction
operations in the pharmaceutical data base was limited because of
the  relatively  small  number  of  plants  engaging   in   these
operations.   However,  the  available  data  did  allow for some
general conclusions to be  drawn.   Generally-,  wastewaters  from
Subcategory  B  plants are characterized by low BOD, COD, and TSS
concentrations; small flows; and pH values of  approximately  6.0
to 8.0.    "

3.   Chemical Synthesis

Most of the  .compounds  used  as  drugs  today  are  prepared  by
chemical  synthesis   (generally  by  a batch process).  The basic
major equipment item  is the conventional batch  reaction  vessel,
one of the most standardized equipment designs in industry.

Generally,  the  vessel  is equipped with a motor-driven agitator
and an internal baffle. It is made of either stainless  steel  or
glass-lined  carbon-steel and contains a carbon-steel outer shell
suitable for either cooling water or steam.  Vessels of this type
are made in many different sizes, with  capacities  ranging  from
0.02 to 11.0 m3 or more.

The  basic vessels may be fitted with many different attachments.
Baffles  usually  contain  temperature  sensors  to  measure  the
temperature  of  the  reactor contents.  An entire reactor may be
mounted on load cells to weigh accurately the  reactor  contents.
Dip  tubes  are  available to introduce reagents into the vessels
below the liquid surface.  One of the top nozzles may  be  fitted
with  a  floodlight   and  another with a glass cover to enable an
                               27

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operator to observe  the  reactor  contents.   Agitators  may  be
powered  by  two-speed  motors or by variable-speed motor drives.
Typically, batch reactors are installed with only the  top  heads
extending  above  the  operating  floor  of the plant in order to
provide the operator with easy access for loading and cleaning.

With other suitable accessories, these vessels  can  be  used  in
many different ways.  Solutions can be mixed, boiled, and chilled
in  them.   By  addition  of reflux condensation, complete reflux
operations are possible.  By application of a vacuum, the vessels
become vacuum evaporators.  Solvent extraction operations can  be
conducted  in them, and, by operating the agitator at slow speed,
they serve as crystallizers.

Synthetic pharmaceutical manufacture consists  of  using  one  or
more  of  these  vessels to perform in a step-by-step fashion  the
various operations necessary to make the  product.   Following   a
definite  recipe,  the  operator   (or, increasingly, a programmed
computer) adds reagents; increases or decreases the flow rate  of
cooling  water,  chilled  water,  or  steam; and starts and stops
pumps to transfer  the  reactor  contents   into  another  similar
vessel.   At  appropriate  steps   in  the   process, solutions  are
pumped through filters or centrifuges or are pumped into  solvent
recovery headers or waste sewers.

The  vessels  with an assembly of auxiliary equipment are usually
arranged  into independent process units; a  large  pharmaceutical
plant may contain many such units.  Each unit may be suitable  for
the   complete   or   partial   manufacture  of  many  different
pharmaceutical compounds.  Only with the highest volume  products
is  the  equipment  "dedicated" or modified  to be suitable for only
one process.

Each pharmaceutical  is usually manufactured in  a   "campaign"   in
which  one  or  more  process unit  is employed  for  a few weeks or
months to manufacture enough compound to   satisfy   its  projected
sales  demand.   Campaigns  are  usually   tightly scheduled, with
detailed  coordination extending  from procurement of raw materials
to packaging  and labeling of the product.   For  a variable   period
of  time,   therefore,   a  process   unit  actively   manufactures  a
specific  compound.   At  the  end  of  this   campaign,   another   is
scheduled   to follow.   The  same  equipment  and operating personnel
are used   to  make   a   completely   different  product,  utilizing
different   raw  materials,  executing   a   different recipe,   and
creating  different  wastes.

The synthetic Pharmaceuticals  industry  uses  a   wide   variety   of
priority  pollutants as  reaction  and purification  solvents.  (43)
Water was reported  to be  used more often  than would be   expected
in  an   industry   whose products are organic  chemicals.   However,
benzene  and toluene were  the most  widely   used   organic   solvents
since   they  are stable compounds  that  do  not easily  take  part in
chemical  reactions.   Similar six member ring   compounds   (xylene,
                              28

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cyclohexane,  pyridine,  etc.') also were reported as either being
used  in  the  manufacture  of  synthesized  Pharmaceuticals   or
resulting from unwanted side reactions.

Solvents  serve  several functions in a chemical synthesis.  They
dissolve gaseous,  solid,  or  viscous  reactants  to  bring  all
reactants into close molecular proximity.  They serve to transmit
heat to or from the reacting molecules.  By physically separating
molecules  from  each  other,  they slow down some reactions that
would otherwise take place too rapidly and that would  result  in
excessive temperature increases and unwanted side reactions.

There  are  other less obvious uses of solvents, however.  One of
these is the  use  of  a  .solvent  in  the  control  of  reaction
temperature.   It is common practice in a batch-type synthesis to
select a solvent whose boiling point is the same as  the  desired
reaction  temperature  and which is compatible with the reaction.
Heat is then applied to the reaction mass at a rate sufficient to
keep the mixture continuously boiling.  Vapors that rise from the
reaction vessel  are  condensed  and  the  liquefied  solvent  is
allowed  to  drain back into the reaction vessel.  Such refluxing
prevents both overheating and overcooling of the reactor contents
and can automatically compensate for variations in  the  rate  of
release or absorption of chemical energy.

Essentially   all  production  plants  operate  solvent  recovery
facilities that purify contaminated  solvent  for  reuse.   These
facilities  usually  contain  distillation  columns  and may also
include extraction facilities where still another solvent is used
to separate impurities.  Many of the wastes  from  the  synthetic
pharmaceutical  industry  will  be  discharged from these solvent
recovery facilities.  Aqueous wastes which may result  from  such
operations   include   residues   saturated   with  the  solvents
recovered.

Another cause of solvent loss is storage practices.  Bulk storage
is usually in  an  unpressurized  tank  that  is  only  partially
filled.   The  level of the liquid in the tank rises and falls as
liquid is added to or removed from the tank.  The  vapor  in  the
tank  above the surface of the liquid is therefore exhausted when
the liquid level is rising; as the level  falls,  fresh  air  (or
nitrogen from a padding system) is introduced.  Even if no liquid
is  added  or  removed,  the  tank  "breathes"  as  a  result  of
temperature and barometric pressure changes.  Each  time  a  tank
"exhales,"  the  released  vapor is saturated with solvent vapor;
rather large quantities of solvent can be lost to the  atmosphere
through this mechanism.

Chemical  synthesis  operations  also produce large quantities of
pollutants normally measured  as  BOD  and  COD.   Wastewater  is
generally  produced with each chemical modification that requires
the filling and emptying of the  batch  reactors.   These  waste-
                                29

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waters  can
solvents.
contain  the unreacted raw materials as well as some
The effluent from  chemical  synthesis  operations  is  the  most
complex  to  treat  because  of  the many types of operations and
chemical   reactions   (nitration,    amination,    halogenation,
sulfonation,   alkylation,   etc.).   The  production  steps  may
generate  acids,  bases,  cyanides,  metalsr   and   many   other
pollutants.  In some instances, process solutions and vessel wash
waters  may  also  contain  residual  solvents.   Sometimes, this
wastewater is incompatible  with  biological  treatment  systems.
Although  it is possible to acclimate the bacteria to the various;
substances, there may be instances where certain chemical  wastes
are  too  concentrated or too toxic to make this feasible.  Thus,
it may be necessary to equalize and/or chemically  pretreat  some
process wastewater prior to conventional treatment.

Primary  sources of wastewater from chemical synthesis operations
are  (a)  such  process  wastes  as  spent  solvents,  filtrates,
concentrates, etc.; (b) floor and equipment wash waters;  (c) pump
seal  waters;   (d)  wet  scrubber  spent  waters; and (e) spills.
Wastewaters from Subcategory C  plant  can  be  characterized  as
having  high  BOD,  COD, and TSS concentrations; large flows; and
extremely variable pH, ranging from 1.0 to 11.,0.

4.  Formulation

Although pharmaceutically active ingredients are produced in bulk
form, they must be  prepared  in  dosage  form  for  use  by  the
consumer.    Pharmaceutical  compounds  can  be  formulated  into.
tablets, capsules, liquids, or ointments.

Tablets are formed in a tablet  press  machine  by  blending  the
active  ingredient,  filler, and binder.  Some tablets are coated
by tumbling with a  coating  material  and  drying.   The  filler
(usually  starch,  sugar,  etc.) is required to dilute the active
medicinal ingredient to the proper concentration, a binder   (such
as  corn  syrup  or  starch)  is  necessary  to  bind  the tablet
particles together.  A lubricant  (such as magnesium stearate) may
be added for proper tablet machine operation.  The dust generated
during the mixing and tableting operation  is  collected  and   is
usually  recycled directly to the same batch.  Broken tablets are
generally collected and recycled to the granulation operation;   in
a  subsequent lot.  After the tablets have been coated and dried,
they are bottled and packaged.

Capsules are produced by first forming the hard  gelatine shell..
These  shells   are  produced by machines that dip rows of rounded
metal dowels into a molten gelatine solution and then  strip  the
capsules  from  the  dowels  after  the  capsules have cooled and
solidified.  Imperfect  capsules  are  remelted  and  reused,   if
possible,  or   sold  for  glue  manufacture.  Most pharmaceutical
companies purchase empty capsules from a few specialty producers1.
                               30

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The active ingredient and  any  filler  are  mixed  before  being
poured  by  machine into the empty gelatine capsules.  The filled
capsules are bottled and packaged.  As  in  the  case  of  tablet
production,  some  dust is generated.  Although this is recycled,
small amounts of waste dust must be disposed of.  Some glass  and
packaging  waste from broken bottles and cartons also result from
this operation.

Liquid preparations can be formulated for injection or oral  use.
In either case, the liquid is first weighed and then dissolved in
water.   Injectable  solutions  are  bulk  sterilized  by heat or
filtration and then poured into sterilized bottles.  Oral  liquid
preparations  may  be  bottled directly without the sterilization
steps.

Wastewaters are generated by general cleanup operations,  spills,
and  breakage.   Bad  batches  may  create a solid waste disposal
problem.

The   primary   objective    of    mixing/compounding/formulation
operations  is to convert the manufactured products into a final,
usable form.  The necessary production steps have typically small
wastewater flows because very few  of  the  unit  operations  use
water  in  a  way  that  would  cause wastewater generation.  The
primary use of water in the actual  formulating  process  is  for
cooling  water  in the chilling units and for equipment and floor
wash.

Sources   of   wastewater   from   mixing/compounding/formulation
operations  are   (a)  floor  and  equipment wash waters, (b) wet
scrubbers, (c) spills, and (d) laboratory  wastes.   The  use  of
water  to  clean  out mixing tanks can flush materials of unusual
quantity and concentration into  the  plant  sewer  system.   The
washouts  from  recipe  kettles may be used to prepare the master
batches of the pharmaceutical compounds and may contain inorganic
salts,  sugars,  syrup,  etc.   Other  sources  of   contaminated
wastewater  are  dust and fumes from scrubbers either in building
ventilation systems or on specific equipment.  In general,  these
wastewaters   are   readily  treatable  by  biological  treatment
systems.

An analysis of the pollutant information  in  the  pharmaceutical
data  base  shows  that  wastewaters  from  Subcategory  D plants
normally have low BOD, COD, and  TSS  concentrations;  relatively
small flows; and pH values of 6.0 to'8.0.

D.   RAW MATERIALS AND PRODUCTS

The  pharmaceutical  industry  utilizes  a  vast  array  of   raw
materials  and  processing agents.  The diversity of feedstock is
attributable to the variety of products and the number of process
variations common to the industry.  A number  of  materials  that
                              31

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can  be
below.
used  as  feedstocks and processing agents are discussed
Fermentation  operations  use  large   quantities   of   nutrient
materials  such  as carbohydrates and proteins.  Examples of some
raw  materials  are  meat  extractions  and  distillers  extract.
Materials   classified   as   priority   pollutants  which  enter
fermentation operations are mainly metals, as reaction  modifiers
and  processing  agents  in  the fermenter, and organic solvents,
which are employed as extractive agents  for  product  separation
and   purification.   The  residues  from  the  organic  starting
materials and mycelia  contribute  heavily  to  conventional  BOD
loadings.

Biological  and  natural  extraction  processes  can  have a wide
variety of feedstocks including roots, leaves of  plants,  animal
glands  or  parasite  fungi.   These substances contribute to BOD
loadings;  priority  pollutant  loadings  are  primarily  due  to
solvents  used  for extraction.  These solvents can be any number
of organic compounds with benzene and chloroform being among  the
most widely used.

Chemical  synthesis  presents  the  broadest spectrum of starting
materials.  Feedstocks can range from ox bile to dextrose.  Given
the appropriate starting material there are many common synthetic
processes (as many as several  hundred)  by  which  the  starting
material is transformed to the product.  A number of solvents and
additives  are  required to complete the synthesis.  Solvents are
usually  inexpensive  relative  to  the  product  and  are   used
liberally for this reason.  These solvents are almost exclusively
organic  and  may  be priority pollutants.  Additives are used to
control reactions and  many  contain  metals  that  are  priority
pollutants.

Product recovery and purification from most of the processes used
to  produce Pharmaceuticals including some formulation operations
expose a variety of solvents and extractive agents to wastewater.
These include hydrocarbons and other organic  compounds  such  as
methylene    chloride,   benzene,   carbon   tetrachloride,   and
chloroform.   Reaction  control,  and  in  some  cases   reaction
requirements,  call for the use of many metal compounds  listed as
priority pollutants.

Many of the 126 priority  pollutants  appear   in  the   industry's
wastewater.   Most of them have their source in the raw materials
and processing agents employed.  The organic  solvent  and  metal
pollutants  are almost completely accounted for by plant material
inputs.

In summary, chemical  materials  utilized  and  produced   in  the
pharmaceutical   industry are numerous and diverse.  They are used
as  reactants,  extractive   solvents,    catalysts,    inhibitors,
diluents,  and  for  other purposes.  In  addition, other chemical
                               32

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compounds may be identified as intermediates, products,  and  by-
products.   Many  of  these  materials  are among those listed as
priority pollutants.  Sections V and VI of this document  discuss
the usage and occurrence of priority pollutants in pharmaceutical
wastewater.

E.   CURRENT DISCHARGER STATUS AND BPT COMPLIANCE

1.   Discharge and Category Status

At proposal, there were 464 plants in the Agency's data base.  Of
these, 61 were direct dischargers, 270 were indirect  dischargers
and  133  were  zero dischargers.  Since proposal, the Agency has
become aware of changes in discharge and manufacturing status  in
the  industry.   Nine  plants  which  were formerly classified as
direct dischargers  (12239, 12030,  12194,  12267,  12281,   12057,
12261,   12264  and  12339)  have  now  been  classified  indirect
dischargers and one plant  (20402) has become a  zero  discharger.
The  Agency is also aware  that four new direct discharging  plants
(11111,  33333, 44444 and 55555) were not included in the 308 data
surveys.   In addition, two indirect dischargers (20153 and  12112)
are no longer manufacturing  Pharmaceuticals.   As  a  result  of
these    changes   there  are  now  466  plants  in  the  Agency's
pharmaceutical data base.  Of these, 55 are  direct  dischargers,
277  are  indirect dischargers and 134 are zero dischargers.  The
Agency is  also aware that  16 percent  of  these  plants  reported
both  direct  and   indirect discharges.  However, for purposes of
analysis and evaluation, the assigned discharge status was  based
on  the  manner  in  which  a  plant  disposed of the predominant
portion  of  its  process   wastewater.   Tables  III-l  and  II1-2
present  the  latest  information  on discharge and manufacturing
status.
                                               the  pharmaceutical
                                              dischargers   (12175,
                                              dischargers   (12247,
                                              portion  of the  total
                                                Consequently,   the
                                               representative   of
In addition, the Agency is  now  aware  that
manufacturing  operations  at  four  direct
12407, 20245 and 20297) and three  indirect
20312  and  20519)  contribute  only a small
process wastewater  flow  at  these  plants.
wastewater   at   these   plants   is   not
pharmaceutical manufacturing  and,  therefore,  data  from  these
facilities  were not used in the subcategorization analysis or in
other analyses.

2.   BPT Compliance

Direct discharger  wastewater  effluents  in  the  pharmaceutical
industry are currently subject to  1976 BPT regulations.  A plant-
by-plant   analysis  of  308  data  from  51  direct  dischargers
indicates that, although many plants are well within BPT  limits,
6 plants are not meeting either the BPT BOD5_  limitation requiring
90  percent  removal,  or  the  BPT  COD  limitation requiring 74
percent removal.  Another 12 plants are not meeting the 1976  BPT
TSS  requirements  for  Subcategory  B  and D plants.  Plants not
                                 33

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meeting one or more of the BPT requirements are listed
III-4.
in  Table
                             34

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                               TABLE  II1-4
Comparison of Plant Performance  vs.  1976  BPT

Direct Discharge Plants  Meeting  BPT  BOD5  and COD Limitations (BOD5
90% Removal and COD 74%  Removal)
12038
12026
12036
12132
12015
12117
12097
12294
12161
12053
12317
12462
12248
33333
44444
                         Total:   15
Direct Discharge Plants Meeting BPT  BOD5  Limitations But No COD Data
Available
12022
12463
12471
11111
55555
                                       Total
Direct Discharge Plants Not  Meeting  BPT  BODg  and/or BPT COD Limitations
12160
12338
12459
12236
20165
20257
                                       Total
Direct Discharge Plants Without  Percent  Removal Data:
12119
12256
12085
12187
12089
12098
12283
12287
12298
12307
20037
20201
20319
20246
12205
12001
12095
12406
20370
12073
20298
12006
12104
12308
12014
Total:   25
Direct Discharge B,  D Plants  Not  Meeting  1976 BPT TSS Limitations
(17.7 mg/1):
12085
12098
12160
12205
12248
12283
12298
12307
12338
12471
20037
44444
          Total:   12
                             35

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                           SECTION IV
                   INDUSTRY SUBCATEGORIZATION
A.   INTRODUCTION

This section describes the subcategorization scheme used for  BPT
and discusses the wastewater characteristics of each subcategory.
It  then  describes  the analyses performed as a result of public
comments on  the  proposal  to  collapse  four  of  the  original
subcategories  into  a single subcategory.  The section concludes
with an explanation of the decision to maintain the original  BPT
subcategorization   scheme .  for   regulations   controlling  the
discharge of conventional and nonconventional pollutants.

B.   BASIS FOR BPT SUBCATEGORIZATION

The existing BPT regulation divides the  pharmaceutical  industry
into  subcategories  based  on  the general type of manufacturing
process.   Process  method  is  an  easily  definable  basis  for
subcategorization  and   is well understood by those knowledgeable
of the  industry.  Characteristically only one process  is used for
a given  product  or  class  of  products' although   there   are
exceptions   in   the processing sequence.  Subcategorization based
on process,  therefore, provides   effective  subcategorization   by
product type as  well.

Both  plant  size and wastewater flow relate to process methods  in
the sense that some processing methods   (e.g.,   fermentation  and
synthesis) are generally undertaken only in large-scale  or highly
complex facilities.   More direct product-oriented methods,  such
as  biological extraction or product formulation  generally  involve
small and less complex manufacturing facilities   and   less  water
use.

The   wastewater   generated  by most plants in  the industry  results
from  more than one  kind  of  process.  Nonetheless,   the  existence
of    single    subcategory   plants    does    permit    wastewater
characterization according  to process   method.    Process  methods
are often distinct  from  one another  in  their  effect  on wastewater
 characteristics  (pollutant  identities,  loads  and flow) because  of
differences   in   the  production  modes  involved and the use of the
 campaign  operation.   Production  mode may be  batch  or  continuous
 and  in  some  cases   semi-continuous,   that  is, with part of the
 process being carried  out   on   a  batch  basis  (e.g.,   chemical
 synthesis)   and   the   other part of  the process being carried out
 continuously (e.g.,  product purification).    Campaign  operations
 involve  the use of the same equipment  train to produce different
 products  at different times.   Both approaches to  production  are
                               37

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employed  where  possible  to reduce unit operating costs and the
number of certification analyses.

Fermentation  and  chemical  synthesis  processes  are  generally
conducted  on a batch basis.  Fermentation usually involves large
batches, while the batch size  tends  to  vary  considerably  for
chemical   synthesis  processes.   Chemical  synthesis  involving
several steps is usually conducted using the  campaign  operation
method.  Biological extraction and product mixing and formulation
processes are generally carried out continuously.

The  use  of  differing  production  approaches  hot only affects
wastewater characteristics on a  plant-by-plant  basis  but  also
affects  the wastewater characteristics of individual plants on a
day-to-day basis.  The effect  of  this  induced  variability  on
wastewater   characteristics   and  the  resulting  influence  on
treatment efficiency can be ameliorated to some  extent  by  flow
equalization prior to treatment.
C.   SELECTED SUBCATEGORIES

The   pharmaceutical   industry   subcategories   selected
established for data analysis are:
                                         and
     Subcategory A
     Subcategory B
     Subcategory C
     Subcategory D
Fermentation
Biological Extraction
Chemical Synthesis, and
Mixing, Compounding, and Formulation
These  are  identical to four of the subcategories established in
the  original  BPT  rulemaking   (41  FR  50676).   An  additional
Subcategory  (Subcategory E - Research) was  identified earlier in
the 1976 Development Document.  However, since research does  not
fall  within  SIC  Codes  2831,  2833,  or 2834  (designated to be
studied by EPA in the Settlement Agreement)  and  does  not  have
wastewater   characteristics  warranting  the  development  of  a
national regulation, it is not  included in this study.

D.   SUBCATEGORY CHARACTERISTICS

There are discernable differences  among  the subcategories  when
viewed  in terms of effluent concentration averages or ranges and
wastewater   flow   rates.    These   differences   support   the
identification  and  use  of  these  subcategories for regulatory
purposes.

1.   Fermentation is the basic  processing   method  used   in  the
production  of most antibiotics and steroids.  The steps employed
are (a) preparation of a seed,  (b) innoculation of  the  nutrient
batch,  (c)  fermentation  of the  nutrient raw materials,  and (d)
recovery  of  the  product   by   such   means   as   extraction,
precipitation, or ion exchange.
                              38

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Fermentation  processes  are  typically  very  large water users.
Spent beers are the major source of characteristically high BODj^,
COD, and suspended solids levels in the wastewater.

2.   Biological or natural extraction is the  extractive  removal
of  therapeutic products from such natural sources as plant parts
(e.g., roots or leaves) animal parts (e.g., glands), or parasitic
fungi (e.g., molds).

In contrast to fermentation, biological extraction processes  are
normally  small-volume  water  users  with  lower  BOD!5, COD, and
suspended solids levels.

3.   Chemical synthesis is utilized widely in the manufacture  of
many  drugs  in  use today.  Most production is in batch reactors
which can be used for a wide variety of process  steps  (heating,
cooling,  mixing, evaporation, condensation, crystallization, and
extraction).   Generally,  these  vessels  are   constructed   of
glass-lined   or  stainless  steel.   Their  versatility  permits
multiple functions to produce many different compounds.

Chemical synthesis  processes  are  characterized  as  relatively
large  water  users  with  high pollutant loadings.  Also, a wide
variety of chemical pollutants can be expected.

4.   In  formulation  (mixing,  compounding,  and   formulation),
Pharmaceuticals  are  prepared  in such useable forms as tablets,
capsules,  liquids,  and  ointments.   Active   ingredients   are
physically  mixed with filler, formed into dosage quantities, and
packaged for distribution.
Formulation is normally a low-level water user (in many
dry operation) with low pollutant levels.
cases
5.   Variations in process routes employed by different producers
are common in the pharmaceutical industry.  Process variations in
chemical synthesis plants manufacturing the  same  product  occur
because  different  starting materials and reaction sequences are
used.  Two plants making the same  product  but  using  different
starting  materials  may use different reaction sequences.  It is
possible that once a common  intermediate  compound  is  derived,
that the remaining processing steps will mirror each other.  Even
if  the same starting material is used by different plants, it is
possible, due to the complexity  of  a  synthesis,  that  several
feasible  routes  to  an  end  product exist.  The decision as to
which route will be employed  can  depend  on  economics,  patent
coverage, corporate history or even personal preferences.

In  fermentation  and  material  extraction  processes, the major
differences  between  processes  will  occur  in  the  extraction
method.   In  many  cases, extractions can be accomplished by any
number  of  solvents.   Choice  of  a  solvent  will  depend   on
environmental  impact,  company  history,  economics, patents and
                              39

-------
other factors.  Due to the number of variables involved it is
surprising that such processes vary widely between companies.
                                                         not
E.
SUBCATEGORIZATION ANALYSIS
As explained in  the  preamble  to  the  regulation  proposed  in
November  of  1982 (47 FR 53584; November 26, 1982), EPA proposed
to collapse four subcategories into a single subcategory.   Along
with  comments on the November 1982 proposal, the Agency received
new plant data which was added to the existing data  base.   This
updated  data  base  is  presented  in  Table  IV-I.   The Agency
statistically  analyzed  these  data  on  influent  and  effluent
characteristics  of  all  direct  dischargers to determine if the
proposed  change  to  collapse  the  existing   four   production
subcategories  into  a  single  subcategory  was  appropriate.  A
discussion of the sources of data,  the  statistical  comparisons
employed, and the summary of results are presented below:
1 .
Sources of Data
The subcategorization analyses are  based  on  three  sources  of
data:

a.   the daily pollutant  specific  influent/effluent  monitoring
     data used in the November 1982 proposed rulemaking,

b.   pollutant  specific  long-term  influent/effluent   averages
     reported  to  EPA  on  the  308 Portfolio for Pharmaceutical
     Manufacturing, and

c.   pollutant   specific   influent/effluent   monitoring   data
     submitted   to   EPA   after   the  November  1982  proposed
     rulemaking.

The  following  rules  of  precedence  were  applied   for   data
utilization  if  a particular plant was included in more than one
data source: (a) plant specific pollutant long-term averages were
based on daily monitoring data rather than reported 308 long-term
averages when both sources of data were available; (b)  if  daily
monitoring data were not available for a specific pollutant, then
the  plant's  reported  "308" long term average was used; and (c)
daily pollutant specific monitoring data submitted after proposal
took precedence over earlier submitted daily monitoring data  and
reported "308" information.

2.   The Statistical Comparisons Employed

The   statistical   analyses   were   based   on    nonparametric
methodologies.   Nonparametric  procedures are typically utilized
when assumptions required in performing parametric  tests   (e.g.,
normality)  are either suspect, or not readily evaluated from the
available  data.   Nonparametric  procedures   do   not   require
specifying   a   particular   probability  distribution  for  the
                             40

-------
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underlying  data  to  utilize  the  methodology.   Because  plant
specific   long-term  flow  and  pollutant  level  averages  were
generated from different data sources  with  varying  degrees  of
supporting  daily monitoring data, a decision was made to rely on
nonparametric analysis procedures.  The nonparametric  procedures
utilized  were the k-sample Kruskal-Wallis test, k-sample Van der
Waerden  test,  and  Wilcoxon  2-sample   test   (or   equivalent
Mann-Whitney   U   test).   These  procedures  are  sensitive  to
differences in location  (i.e., shifts) in the pollutant  specific
distributions   of   plant   averages  being  compared,  and  are
equivalent to testing whether the.medians of plant  averages  for
the groups of interest are statistically different.

Three  types of statistical comparisons were performed to examine
the issue of subcategorization, and they are discussed below.

a.   Overall Test  of  Equality  of  Pollutant  Distributions  of_
     Subcategories A, B, C and D

For each sampling point  (i.e., influent or effluent) with respect
to  mass  (Ibs/day)  and  concentration  units  (mg/1), pollutant
specific averages and discharge flow values (thousand gallons per
day) were compared for those plants that  belong  exclusively  to
each of the four subcategories.  For example, the distribution of
influent  BOD5_  averages  (concentration units of mg/1) for those
plants participating exclusively in subcategory A  were  compared
simultaneously  to  the  distributions  of  averages  for  plants
exclusively in subcategory B, exclusively in subcategory  C,  and
exclusively  in  subcategory D.  Thus, this comparison represents
an overall test on a pollutant-specific basis that  distributions
of  averages  reported by plants exclusively within each of these
subcategories are statistically the same.  Rejection of this test
of equality indicates that at  least  one  of  the  subcategory's
distributions   differs   from   the   other  three  distribution
subcategories.    Table   IV-2   summarizes   results   of    the
Kruskal-Wallis  and  Van  der Waerden nonparametric procedures of
the above hypothesis that the four subcategories  are  the  same.
As  stated  earlier,  these two procedures are both nonparametric
methodologies.  While these procedures  test the same hypothesis,
the individual test statistics for these procedures are based  on
different  quantities  (i.e., the Kruskal-Wallis test is based on
rank scores while the Van der Waerden test is  based  on  inverse
normal  scores).   Table IV-2 summarizes the results of these two
test procedures on a pollutant specific  basis.   Flow,  influent
COD  (Ibs/day),  influent  TSS (mg/1), and influent TSS (Ibs/day)
were the only comparisons for which no significant difference was
detected.

For each unique subcategory, Table IV-3 presents  the  pollutant-
specific  arithmetic  average  of  the plant averages used in the
nonparametric analyses.  The table  illustrates  the  trend  that
subcategories  A and C tend to have greater pollutant levels than
subcategories B and D.
                               42

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                               TABLE IV-2

         Summary of Kruskal-WaVlis and Van der Waerden Tests of
                   Equality of the Four Subcategories
Pollutant

FLOWKGD = Discharge Flow (K gal/day)
IN80D = Influent BOD (mg/1)
EFBOD = Effluent BOD (mg/1)
INBODLB = Influent BOD (Ibs/day)
EFBODLB = Effluent BOD (Ibs/day)
INCOD = Influent COD (mg/1)
EFCOD = Effluent COD (mg/1)
INCODLB = Influent COD (Ibs/day)
EFCODLB = Effluent COD (Ibs/day)
INTSS = Influent TSS (mg/1)
EFTSS = Effluent TSS (mg/1)
INTSSLB = Influent TSS (Ibs/day)
EFTSSLB = Effluent TSS (Ibs/day)
K-W Test
            Van der Waerden Test
**
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**
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                        **
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     *Significant statistical difference exists among the four subcategories
for the cited pollutant variable.  Significant difference has a test statistic
whose probability p is between .01 and .05 (i.e. .01
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b.   Comparison of Distribution of Averages of "High" Subcategory
     Plants with Distribution of Averages  of  "Low"  Subcategory
     Plants

Having determined that at least one distribution for the averages
of  plants  operating  exclusively  in  one  of  the  four  cited
subcategories differed for the  majority  of  pollutant  variable
comparisons,  the four subcategories were grouped into "high" and
"low" raw waste subcategories.  The "high" group was  defined  to
include  plants that belonged to Subcategory A only, C only, or A
and C only.  Similarly, the "low" group was  defined  to  include
plants that belonged Subcategory B only, D only, or B and D only.
(That is, plants that operated in A and C only or in B and D only
were added to the plants used in the preceding overall analysis.)

Thus,  the  distribution  of  averages for plants assigned to the
"high" group was compared with the distribution of  averages  for
plants  assigned  to  the  "low"  group.   Again  a nonparametric
statistical procedure was used to compare the distributions.  The
Wilcoxon procedure was  used  for  these  pollutant-specific  two
group comparisons.  In general, the results of the tests indicate
that,  on a pollutant-specific basis, the "high" and "low" groups
of plants differ statistically.  In all cases the two groups were
determined to be significantly different (i.e.,  the  probability
associated  with the Wilcoxon test procedure was less than 0.05).
Each of the 13 pollutant-specific comparisons has  an  associated
test statistic probability considerably less than 0.05.

For each group, Table IV-4 presents pollutant-specific arithmetic
averages  of  the  plant  averages  used  in the two group (i.e.,
"high" vs. "low" comparisons) nonparametric analyses.

c.   Statistical Comparison of Distributions of Plants within the
     "High" Group and within the "Low" Group

To determine whether combining A and C  plants  into  the  "high"
group  and  B  and  D plants into the "low" group was reasonable,
statistical comparisons  were  performed  within  each  of  these
groups  using  single  Subcategory  plants  only.  That is, for a
specified pollutant, the distribution of averages  for  "A"  only
plants  was compared to the distribution of averages for "C" only
plants.  Similarly, pollutant-specific  distribution  comparisons
were  made  between  "B"  only  and "D" only plants.  Because the
number of plants involved in these analyses were smaller than  in
the  earlier  analyses,  the  decision  was  made  to utilize the
intermediate computer results produced for the Wilcoxon procedure
in  conjunction  with  a  set  of  referenced  tables   for   the
nonparametric  Mann  Whitney  U-test  to provide an exact test of
significance  rather  than   relying   on   the   normal   theory
approximation  produced  in the computer output.  Since the Mann-
Whitney U and Wilcoxon 2-Sample procedures  are  equivalent,  the
Wilcoxon  results can be utilized in this manner.  No differences
were detected between "A" only and "C" only plants.  For "B" only
                                45

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and "D" only plants influent BOD5_ (mg/1) and influent COD  (mg/1)
were  found  to  differ.   All other comparisons did not indicate
differences between "B" and "D" only plants.

3.    Summary of Results

The  results  of  the  overall  comparisons  of  the   individual
subcategories  substantiate  the  hypothesis  that,  in  general,
pollutant levels do differ by subcategory.  (134) In  general,  no
differences  were  found  between A only and C only plants, while
two influent pollutant variables (INBOD,  INCOD)  were  found  to
differ between B only and D only plants.  The remainder of B only
and  D only plant comparisons yielded no statistical differences.
Based on the above results and on the fact  that A  and  C  plants
tend  to  be  higher  than  B  and D plants on flow and pollutant
levels, "high" (A, .C, A/C) and "low" (B, D, B/D) groups of plants
were defined.   Comparisons  of  these  two  groups  consistently
indicated  significant differences for flow and pollutant levels.
A more detailed discussion of the statistical analyses  performed
is found in "Statistical Support for Pharmaceutical Rulemaking —
September 1983", a report that may be found in the record of this
rulemaking. (135)

F.    CONCLUSIONS OF SUBCATEGORY ANALYSIS AND DECISION TO MAINTAIN
     THE EXISTING SUBCATEGORIZATION SCHEME

The analyses of the most recent  data  discussed  above  indicate
that  the  subcategorization  scheme should separate fermentation
and chemical synthesis plants (subcategory A and C  plants)  from
extraction and formulation plants (subcategory B and D plants) in
so  far  as regulations controlling the discharge of conventional
and   the   nonconventional   pollutant   COD   are    concerned.
Specifically,  the  analyses  show that the influent and effluent
conventional pollutant concentrations and COD  concentrations  as
well as discharge flows of subcategory A and C plants are similar
and  that  these same characteristics for B and D plants are also
similar.  The analyses also indicate that the characteristics  of
the  subcategory  A  and  C  plant  group  are not similar to the
corresponding characteristics of the subcategory B  and  D  plant
group.    These  differences  indicate  that  different  effluent
discharge levels of conventional and  nonconventional  pollutants
would  be  expected when plants in these groups employed the same
control technology.  However,  the  existing  subcategory  scheme
accommodates these differences.  Since permitting authorities and
the   regulated   industry   are   familar   with   the  original
subcategorization scheme and the format in  the  Code  of  Federal
Regulations,  the  Agency  has  decided  to maintain the existing
subcategorization scheme.
                               47

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                             SECTION V

                      WASTE CHARACTERIZATION
A.
      INTRODUCTION
The Agency,  through   an   extensive  data   gathering  effort,   has
studied   qualitatively   and  quantitatively the wastewaters of the
pharmaceutical  industry.   This  effort  provided the baseline  data
necessary for  determining  the significant pollutants present in
the wastewaters of the pharmaceutical  industry and,  subsequently,
the regulatory  scope  for  the pharmaceutical  manufacturing point
source category.

As a result  of  earlier studies,  particularly the  1976 Development
Document,  the  EPA   had  available a limited amount of data which
characterized the wastewater discharges   of  the  pharmaceutical
manufacturing   industry.   However,  not   only were some  of these
data dated,  but for the most part  they were related only  to  such
 traditional"   pollutant  parameters  as   BOD5^   COD,  and  TSS.
Information  on  the 126  toxic  pollutants   or  classes of toxic
pollutants   was almost nonexistent.    In order to fill this void,
the Agency instituted a number  of   programs  aimed  at gathering
from  the pharmaceutical  industry additional data on both toxic
and traditional pollutants.
                                      addressed  considering   the
Wastewater characterization has been
following:

     (1)  Traditional pollutants
     (2)  Priority pollutants
     (3)  Wastewater flow

This section reviews  the  sources  of  data  and  describes  the
results   which   provide  the  basis  for  the  limitations  and
standards.

B.   TRADITIONAL POLLUTANTS

Traditional pollutants considered for regulation  are  BOD!>  COD,
TSS,  and  pH.   The  reasoning  behind  their  selection and the
omission of others is reviewed in Section VI.   Three  of  these,
BOD5., TSS, and pH are listed as conventional pollutant parameters
and one, COD, is listed as nonconventional.
1
     Sources of Data
     a.   Previous studies - The 1976 Development Document, which
supported the 1976 BPT regulations, comprises the main source  of
previously developed information.
                                49

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     b.   308 Survey - During 1978, the  pharmaceutical  industry
was   surveyed  to  obtain  wastewater  data  and  related  plant
information in support of this new rulemaking effort.  The  first
308   questionnaire   was   sent   to  member  companies  of  the
Pharmaceutical Manufacturers Association (PMA).  The  content  of
this   questionnaire  appears  as  Appendix  B  of  the  Proposed
Development Document.  The second phase of this survey was  aimed
at  the remainder of the industry, and the questionnaire employed
is  in  Appendix  D  of  the   Proposed   Development   Document.
Substantial  differences in both the form and question content of
these forms resulted from shifts of program emphasis between  the
times of their distribution.  Recipients are listed in Appendices
C  and  E  of the Proposed Development Document.  Survey/response
statistics are reviewed in Section II of the Proposed Development
Document.  Traditional pollutant (BOD5_, COD, and TSS)  levels  as
indicated in the 308 portfolio data, are summarized in Appendix  I
of  the  Proposed Development Document.  Flow data are summarized
in Appendix J of the Proposed Development Document.

     c.   Long-term data  -  Plants  were  selected  for  further
survey  of  long-term  plant  log  data  on end-of-pipe treatment
influents and effluents, with respect to BOD5., COD, "and TSS.  The
development of a long-term data base, covering at  least  a  full
year's data for representative plants, was necessary to allow EPA
to  establish  performance  averages  for  representive groups of
industry treatment plants in terms of both pollutant  levels  and
effluent  variability.   A summary of long-term data is presented
in Table V-l.

A brief description of ' plants  covered  by  the  long-term  data
program follows.  Some, but not all, of the plants also appear in
the  screening/verification  plant  list,  subsequently  used  in
priority pollutant analysis.

The flow values presented herein  are  long-term  daily  averages
developed  from  the log data submitted by each plant.  These may
differ from flows reported in the 308 questionnaires due  to  the
different  time  periods  in  which  they were established and/or
different modes of operation during those time periods.

Plant  12015 is a Subcategory D  plant  which  appears  among  the
screening plants and the long-term data plants.  Activated sludge
and  powdered  activated  carbon  are  used to treat 0.101 MGD of
wastewater from pharmaceutical manufacture.

Plant  12022 is a Subcategory A and C plant that  is  a  screening
plant  and  a  long-term data plant.  Plant 12022 discharges 1.45
MGD of wastewater from its  treatment  facilities  which  include
activated     sludge,     trickling     filters,    equalization,
neutralization, and primary clarification.

Plant  12026 is a Subcategory C plant which is a screening  plant,
a  long-term  data  plant,  and a verification plant.  This plant
                                 50

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discharges 0.161 MGD of pharmaceutical process  wastewater  after
treatment  by equalization, neutralization, activated sludge, and
a polishing pond.

Plant 12036 is a Subcategory A plant which is  both  a  screening
plant  and  a  long-term data plant.  This plant discharges 0.855
MGD of  wastewater  from  pharmaceutical  manufacture,  which  is
treated  by  activated  sludge,  trickling  filters,  an  aerated
lagoon, and a final stabilization lagoon.

Plant 12097 is a Subcategory C and D plant which is  a  screening
plant  as  well  as  a  long-term data plant.  The chemical waste
treatment  unit   consists   of   equalization,   neutralization,
physical-chemical    treatment,    filtration,    and    chemical
stabilization.  This plant discharges  0.640  MGD  of  wastewater
from pharmaceutical processes.

Plant  12098  is a Subcategory D plant.  Activated sludge is used
to treat pharmaceutical process wastewaters which amount to  0.005
MGD.
Plant  12117 is a Subcategory B and D plant.  Activated  sludge
used to treat 0.101 MGD of pharmaceutical process wastewater.
is
Plant   12123   is  a  Subcategory   C   and  D plant  which  uses  only
primary treatment   to   treat   0.932   MGD  of    wastewater    from
pharmaceutical manufacture.

Plant   12160   is  a  Subcategory. D plant.  Pharmaceutical process
wastewater   is treated   with   activated  sludge.    The   flow  of
wastewater  is  0.029  MGD.

Plant   12161  is an Subcategory  A,  C,  and D plant which appears as
both   a  screening   plant   and   a   long-term   data   plant.
Pharmaceutical process wastewaters are treated by neutralization,
primary  clarification,    equalization,  activated  sludge,   and
polishing ponds.  The amount of  wastewater   discharged   is  1.65
MGD.

Plant  12186 is a  Subcategory C  and D plant.   Activated  sludge and
an  aerated  lagoon  are  used to treat 0.370  MGD of pharmaceutical
process wastewaters.

Plant   12187  is   a   Subcategory  C   plant.    The  1.07   MGD   of
pharmaceutical  process   wastewaters  is treated with a trickling
filter.

Plant  12235 is a Subcategory C plant.  Primary treatment  is  the
only treatment used for  pharmaceutical process wastewater.    (This
plant   was  excluded from the variability analysis since it is not
 a direct discharger.)
                                  52

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Plant 12236, a Subcategory C  plant,  is  a  screening  plant,  a
verification plant, and a long-term data plant.  The 0.816 MGD of
pharmaceutical process wastewaters are treated .with equalization,
neutralization, primary sedimentation, and activated sludge.

Plant  12248  is a Subcategory D plant.  Activated sludge is used
to treat the 0.110 MGD of pharmaceutical process wastewater.

Plant 12257 is a Subcategory A, B, C, and D plant.  This plant is
both a screening plant and a long-term data plant.  The treatment
system components are equalization, neutralization, and activated
sludge.   The  amount  of   pharmaceutical   process   wastewater
discharged  is 0.755 MGD.

Plant  12294 is a Subcategory C and D plant.  Activated sludge is
used to treat the 0.118 MGD of pharmaceutical process wastewater.

Plant 12307 is a Subcategory D plant.  Two  biological  treatment
units,  an  activated sludge unit and an aerated lagoon, are used
to treat the 0.002 MGD of pharmaceutical process wastewater.

Plant 12317 is a Subcategory D plant.  Activated sludge  is  used
to treat the 0.740 MGD of pharmaceutical process wastewater.

Plant  12420  is  a  Subcategory  B  and  D plant.  This plant is
included in both the screening  plants  and  the   long-term  data
plants.   Activated  sludge  is  used  to  treat the 0.164 MGD of
pharmaceutical process wastewater.

Plant 12439 is a Subcategory C and D plant.  Plant 12439 is-  both
a  screening and a long-term data plant.  Process  wastewaters are
treated by  equalization, neutralization,  primary  sedimentation,
activated sludge, and an aerated lagoon.  Long-term flow data was
not available.

Plant  12459  is  a  Subcategory D plant with a discharge flow of
0.049 MGD.  The only method of wastewater treatment  utilized  is
an aerated  lagoon.

Plant  12462  is  a  Subcategory  A plant with an  average flow of
0.209 MGD.  The wastewater treatment employed includes  activated
sludge and  an aerated lagoon.

2.   Results and Bases for Limits

The Agency  analyzed all  traditional  pollutant  wastewater  data
submitted   to  the  Agency  in  order  to establish final BPT TSS
limitations for all subcategories  and  alternate  BOD5_  and  COD
limitations for  Subcategory B, D and E plants.   These data were
from 51 direct dischargers and consisted of 308  portfolio  data,
long-term   monitoring  submissions, and data obtained in comments
on the November 1982 proposal.  These data appear  in Table  IV-I.
Analysis of these data is discussed in Section VIII.

                                 53

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C. PRIORITY POLLUTANTS

The Settlement Agreement list of priority pollutants and  classes
of priority pollutants potentially includes thousands of specific
compounds.   However,  for  purposes  of  rulemaking,  the Agency
selected 126 specific pollutants for  consideration.   These  are
listed in Table V-2.

Thirty-three priority pollutants are present in the wastewater of
at least one of the plants sampled.  However, few of the priority
pollutants  are  individually  widespread  in their occurrence or
high in concentration.  The significance of these facts  as  they
affect  the  choice of pollutants to be regulated is discussed in
Section VI.

1.   Sources of Data

a.   308 Portfolio Survey -  The  308  Portfolio  Survey  was  an
invaluable  source  of information for developing profiles of the
pharmaceutical manufacturing industry.   Similarly,  this  survey
proved  to  be  a major source of data for waste characterization
purposes.  Not only did  it  provide  more  recent  and  detailed
information  on  traditional  pollutant parameters and wastewater
flow characteristics, but the 308 Portfolio was the  first  major
source   of  data  on  the  use  and/or  generation  of  priority
pollutants by this industry.

One purpose of the 308 survey was  directed  at  quantifying  the
nature  and  extent  of priority pollutants in the pharmaceutical
industry.  Of the 464 pharmaceutical manufacturing plants in  the
comprehensive  308.  Portfolio  Data  Base,  212  responded to the
questions concerning priority pollutants.  Of the   115  different
priority  pollutants  identified, chloroform, methylene chloride,
phenol, toluene,  and  zinc  were  reported  as  being  the  most
frequently  used  as  raw materials for manufacturing operations.
None of the priority pollutants were reported by even as many  as
ten  respondents  as  being intermediate or final products.  Some
priority pollutants  (such pesticide-related compounds  as  endrin
and  heptachlor) were reported as being analyzed in  the effluents
of the manufacturing plants (most probably due to the  mixing  of
pharmaceutical  and  nonpharmaceutical  wastewaters),  but not as
being  a  pharmaceutical  manufacturing  raw  material  or  final
product.

The  308  data  base  indicates that, although the  pharmaceutical
manufacturing industry uses and therefore might discharge a large
number of  priority  pollutants,  broad  occurrence of  specific
chemical  compounds   is  limited.  Priority pollutant information
submitted by the pharmaceutical manufacturing plants is presented
in Appendix H of the Proposed Development Document.
                                  54

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                            TABLE V-2
            LIST OF EPA-DESIGNATED PRIORITY POLLUTANTS
*No.   Compound
IB
2V
3V
4V
5B
6V
7V
8B
9B
10V
nv
12B
13V
14V
15V
16V
17B
18B
19V
2 OB
21A
22A
23V
24A
25B
26B
27B
28B
29V
30V
31A
32V
33V
34A
35B
36B
37B
38V
39B
40B
41B
42B
43B
44V
acenaphthene
acrolein
acrylonitrile
benzene
benzidine
carbon tetrachloride
chlorobenzene
1,2,4-trichlorobenzene
hexachlorobenzene
1,2-dichloroethane
1,1,1-trichloroethane
hexachloroethane
1,1-dichloroethane
1,1,2-trichloroethane
1,1,2,2-tetrachloroethane
chlofoethane
bis(chloromethyl) ether**
bis(2-chloroethyl) ether
2-chloroethylvinyl ether
2-chloronaphthalene
2,4,6-trichlorophenol
parachlorometa cresol
chloroform
2-chlorophenol
 ,2-dichlorobenzene
 ,3-dichlorobenzene
 ,4-dichlorobenzene
3,3'-dichlorobenzidine
 ,1-di ch1oroethy1ene
 ,2-trans-dichloroethylene
2,4-dichlorophenol
1,2-dichloropropane
1,3-dichloropropylene
2,4-dimethyIphenol
2,4-dinitrotoluene
2,6-dinitrotoluene
1,2-diphenylhydrazine
ethylbenzene
fluoranthene
4-chlorophenyl phenyl ether
4-bromophenyl phenyl ether
bis(2-chloroisopropyl) ether
bis(2-chloroethoxy) methane
methylene chloride
No.

7 OB
71B
72B
73B
74B
75B
76B
77B
78B
79B
BOB
81B
82B
83B
84B
85V
86V
87V
88V
89P
90P
91P
92P
93P
94P
95P
96P
97P
98P
99P
100P
101P
102P
103P
104P
105P
106P
107P
108P
109P
HOP
111P
112P
113P
Compound

diethyl phthalate
dimethyl phthalate
benzo(a}anthracene
benzo(a)pyrene
3,4-benzofluoranthene
bejizo (k) f luoranthane
chrysene
acenaphthylene
anthracene
benzo(gh i)pery1ene
fluorene
phenanthrene
dibenzo(a,h)anthracene
indenod , 2,3-C,D)pyrene
pyrene
tetrachlorethylene
toluene
trichloroethylene
vinyl chloride
aldrin
dieldrin
chlordane
4,4'-DDT
4,4'-DDE
4,4'-ODD
alpha-endosulfan
beta-endosu1f an
endosulfan sulfate
endrin
endrin aldehyde
heptachlor1
heptachlor epoxide
alpha-BHC
beta-BHC
gamma-BBC
delta-BHC
PCB-1242
PCB-1254
PCS-1221
PCB-1232
PCB-1248
PCB-1260
PCB-1016
toxaphene^
(lindane)
                        55

-------
45V    methyl chloride                114M
46V    methyl bromide                 115M
47V    bromoform                      116
48V    dichlorobromomethane           117M
49V    trichlorofluoromethane**       118M
50V    dichlorodifluoromethane**      119M
51V    chlorodibromomethane           120M
52B    hexachlorobutadiene            121
53B    hexachlorocyclppentadiene      122M
54B    isophorone                     123M
55B    naphthalene                    124M
56B    nitrobenzene                   125M
57A    2-nitrophenol                  126M
58A    4-nitrophenol                  127M
59A    2,4-dinitrophenol              128M
60A    4,6-dinitro-o-cresol           129B
61B    N-nitrosodimethylamine
62B    N-nitrosodiphenylamine
63B    N-nitrosodi-n-propylamine
64A    pentachlorophenol
65A    phenol                         *  V
66B    bis(2-ethylhexyl) phthalate       A
67B    butyl benzyl phthalate            B
68B    di-n-butyl phthalate              P
69B    di-n-octyl phthalate              M
antimony (total)
arsenic (total)
asbestos (fibrous)
beryllium (total)
cadmium (total)
chromium (total)
copper (total)
cyanide (total)
lead (total)
mercury (total)
nickel (total)
selenium (total)
silver (total)
thallium (total)
zinc (total)
2,3,7,8-tetrachloro-
 dibenzo-p-dioxin (TCDI
volatile organics
acid extractables
base/neutral extractab]
pesticides
metals
**   Deleted from the list of priority pollutants as per 46 FR 2264,
                             56

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b.   PEDCo Reports - Concurrent with the efforts to  profile  the
pharmaceutical  manufacturing  industry  using  the 308 Portfolio
survey, PEDCo Environmental, Inc. undertook a study to detail the
various  manufacturing  processes/steps  that  are  used  in  the
production   of   fermentation,   extractive,   and   synthesized
Pharmaceuticals.

In  their  studies,  PEDCo  examined  recent  industry  data  and
selected   those  products  that  comprise  the  major  areas  of
production for each  of  the  three  manufacturing  subcategories
(i.e.,  A,  B  and C).  With these major product lines as a base,
they then consulted all available literature describing the step-
by-step  procedures  to  be  used  in  the  production  of   each
substance.   As  a  result,  PEDCo  was  able to identify certain
priority  pollutants  that  were  known  to  be   used   by   the
pharmaceutical industry.  These pollutants are listed in Table V-
3.

Because of the size and complexity of the industry and the myriad
of  products  manufactured,  it  was not practical for a study of
this kind to identify every  priority  pollutant  that  could  be
used.

c.   RTP Study - In December 1978, EPA's Office  of  Air  Quality
Planning  and Standards at Research Triangle Park, North Carolina
published a document  (70) providing  guidance  on  air  pollution
control  techniques  for  limiting  emissions of volatile organic
compounds  from  the  chemical  synthesis  subcategory   of   the
pharmaceutical industry.

As   part   of   this  study,  the  Pharmaceutical  Manufacturers
Association (PMA)  surveyed  selected  pharmaceutical  plants  to
determine  estimates  of  the ten largest volume volatile organic
compounds that each company purchased and the mechanism by  which
they   leave  the plant  (i.e., sold as product, sent to the sewer,
or emitted as an air pollutant).

Table  V-4 presents a  compilation of the results of  this  survey.
Of  the  twenty-six   reporting companies, 25 indicated that their
ten largest volume volatile organics  accounted  for  80  to  TOO
percent  of  their  total plant usage.  (The other company stated
that the ten highest  volume  compounds  only  accounted  for  50
percent  of its total plant usage.)  These 26 companies accounted
for 53 percent of the domestic sales of  ethical  Pharmaceuticals
in 1975.

Included  in  the  list of 46 compounds presented in Table V-4 are
seven  priority  pollutants.   These  compounds   are   methylene
chloride,  toluene,   chloroform,  benzene,   carbon tetrachloride,
1,1,1-trichloroethane, and  1,2-dichlorobenzene.

Table  V-5 presents a  summary and analysis of the data outlined in
Table  V-4.   Priority  pollutants  represent  approximately   27
                                 57

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                             TABLE V-3
      SUMMARY OF PRIORITY POLLUTANT INFORMATION: PEDCo REPORTS

Priority Pollutants Identified As Used Int
Subcateqory AT

benzene
chloroform
1,1-dichloroethylene
1,2-trans-dichloroethylene
phenol
copper
zinc
Subcategory C3

benzene
carbon tetrachloride
chlorobenzene
chloroethane
chloroform
1,1-dichloroethylene
1,2-trans-dichloroethylene
methylene chloride
methyl chloride
methyl bromide
nitrobenzene
2-nitrophenol
4-nitrophenol
phenol
toluene
chromium
copper
cyanide
lead
zinc

Total No. of Pollutants:  23

1 Reference No. 42
2 Reference No. 41
3 Reference No. 43
Subcategory B2

benzene
carbon tetrachloride
1,2-dichloroethane
chloroform
methylene chloride
phenol
toluene
cyanide
lead
morcury
nickel
zinc
                            58

-------

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              60

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                            TABLE V-5
 SUMMARY OF VOLATILE ORGANIC COMPOUND EMISSION DATA:  RTF STUDY
                                                  Amount;
Item;


Amount purchased  (metric tons)

Amount discharged  (metric tons)

Amount recovered within the
  plant (metric tons)

Total amount used  in plant
  (sum of items 1 and 3)
  (metric tons)

Percent recovered

Percent of total used that is
  discharged

Percent of total used that is
  discharged to sewer

Percent of total discharged that
  is discharged to sewer
    Total
  Compounds
(total of 46)

  85,170

  86,142

 441,320


 526,490



   83.8%

     16%


    2.7%


   16.7%
   Priority
  Pollutants
(total  of 7)

   19,565

   19,595

  126,020


  145,585




    86.6%

    13.5%


     1.3%


     9.7%
                           61

-------
percent of the total volatile organic usage in the segment of the
industry  analyzed.   However, priority pollutants represent only
13 percent of the total mass discharge of  volatile  organics  to
the plant sewers.

Table  V-5  also  indicates  that  of  the  total quantity of all
volatile organic compounds  discharged,  only  a  fraction  (16.7
percent)  is  discharged  via wastewater.  The priority pollutant
volatile organics are discharged with the wastewater in  an  even
lower proportion (9.7 percent).

d.   RSKERL/ADA Study - The Robert S. Kerr Environmental Research
Laboratory  at  Ada,  Oklahoma  (RSKERL/ADA)  conducted  for  the
Effluent  Guidelines  Division  (EGD)  an  applied research study
entitled "Industry Fate Study" (90). The purpose of  this  report
was to determine the fate of specific priority pollutants as they
pass  through  a  biological  treatment system.  In the course of
this study, priority pollutants associated with  the  manufacture
of  Pharmaceuticals at two industrial facilities were identified.
The results of these wastewater analysis are reported in Appendix
K  of  the  Proposed  Development   Document.    These   priority
pollutants are listed in Table V-6 with similar data from the RTF
Study, the PEDCo Reports, and the Screening/Verification Program.
RSKERL/ADA  data are limited since they are from only two plants.
However, they do serve to supplement the other data in Table V-6.

e.   Wastewater  Sampling  Programs  -  Information  on  priority
pollutants  from  the  aforementioned  reports  and  surveys  was
largely qualitative, although the 308 Portfolio did contain  some
quantitative  data.   Moreover,  those  reports  did  not  always
distinguish between pollutants used by a plant and pollutants  in
the  final  effluent.  To expand the data base, EPA initiated the
Screening and Verification sampling program under which a  number
of  plants  representative  of  the  pharmaceutical manufacturing
industry  were  sampled  for  priority  pollutants  and  for  the
traditional  pollutants  (BOD5.,  COD,  and  TSS)  in  a two phase
program.  The first phase, called the screening  phase,  involved
26  plants  and  covered  a  broad cross-section of the industry.
This was followed by  a  verification  phase  which  limited  the
sampling to only five carefully selected plants.  Augmentation of
the  existing  data  base  with  the  analytical  results  of the
Screening/Verification  program  along   with   the   qualitative
information  from  the  other  studies  provided  the Agency with
sufficient information with which to characterize the  industry's
wastewaters.

The  screening program was conducted to determine the presence or
absence of priority pollutants in the wastewaters of a number  of
pharmaceutical  plants  and to provide a quantitative estimate of
those present.  The information was  then used to limit the search
to specific priority pollutants for  the verification program  and
to  identify plants likely to provide  information to characterize
accurately the  industry wastewaters.

                                 62

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Priority
Pollutant
                   TABLE V-6
 SUMMARY OF MAJOR* PRIORITY POLLUTANTS IDENTIFIED
      FROM MULTIPLE SOURCES OF INFORMATION
                                             Screening S
            RTP   PECCo  RSKERL/  308        Verification
	Study  Recorts ADA   Portfolio   Sampling Program
Acid Extractables
65  Pbenol

Ease Extractables
T5T72-Dicfalorofcenzene

Volatile Crcianica
4   Benzene
6   Carbon Tetrachloride
11  1,1,1 - Trichloroethane
23  Chloroform
29  1,1-Dichloroethylene
30  1,2-Trans-Cichlcroethylene
38  Ethylbenzene
            X
            X
            X
X
X

X
X
X

X
X
                                  X
                                  X
                                             X
                                             X
                                             X
44  Methylene Chloride          XX              X
66  Toluene                     XX              X

Petals
119 CfcroiriutP                                    XX          X
120 ccpper                             X        XX          X
122 lead                               XXX          X
123 Mercury                                     XX          X
124 Nickel                                            X          X
128 Zinc                               X        X     X          X

Cthera
121 Cyanide                            X        x     x          X

*    For  this  table  toxic  compounds  were  defined as "major"
priority pollutants  in accordance with the  following criteria  for
each data source:

FTP - The pollutant  was  reported by at least one plant  (26  plants
reporting)
EEDCo - The pollutant was  found in two or more sufccategories  (130
plants studied).
BSKERL/ADA •• The pollutant was reported by  at least one  plant   (2
plant study).
308  -  The  pollutant   was  identified fcy  25 or more plants  (464
plants surveyed).
Screening/Verification - The  pollutant was  detected  at ten   or
ffore plants  (26 plants sampled).
                                   63

-------
Major  processing  areas  and  subcategory  coverage,  range   of
wastewater  flows, and an assortment of both in-plant and end-of-
pipe  treatment  technology/techniques  were  used  as  selection
criteria  for  the screening plants. Multiple subcategory plants,
as well as plants within only one subcategory, were  deliberately
sought.   Similarly,  EPA made a special effort to include plants
with wastewater flows less than 1000 GPD and more than  2.5  MGD.
Descriptions  of  the  plants  and  of  the  sampling  points are
presented in Appendix 0 of the Proposed Development Document.

Included in the screening group  were  nine  direct  dischargers,
seven  indirect  dischargers,  three  zero  dischargers and seven
plants which utilized more than one mode of  discharge.   In  the
latter  group there were three plants that were both indirect and
zero dischargers, three plants that were  both  direct  and  zero
dischargers  and  one  plant  that  utilized  all  three modes of
discharge.   The   screening   plants   and   their   subcategory
designations are listed below:
          Plant ID No.  Subcategory
            Plant ID No.  Subcategory
            12015
            12022
            12026
            12036
            12038
            12044
            12066
            12097
            12108
            121 19
            12132
            12161
            12204
D
AC
C
A
ABCD
AD
BCD
CD
ACD
AB
AC
ACD
ABCD
12210
12231
12236
12248
12256
12257
12342
1241 1
12420
12439
12447
12462
12999
BC
AD
C
D
ABCD
ABCD
ACD
BCD
BD
CD
ABCD
A
CD
The  verification  program  was  developed  to  confirm  the  presence  of
the  priority   pollutants  that   were  identified by  the  screening
program  and  to  provide  quantitative  pollutant  data with   a   known
precision  and  accuracy.   The   analytical  results  from   these
episodes serve  as a basis for technology selection and for  use  in
the  rulemaking  effort.

Selection  of the  five plants  for  the   verification  program was
based   in  part  on general criteria presented in Section  II  of the
Proposed Development Document.   A criterion  mentioned  earlier and
which  weighed heavily in  the   final  selection process   was the
assortment  of  major priority pollutants  that were  being used  as
raw  materials for the manufacture of Pharmaceuticals.  Table V-7
lists   the  priority pollutants  which  appear in the  waste streams
of   each  of the  screening   plants.    Other  plant   specific
                                  64

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                 TABLE V-7

SUMMARY OF PRIORITY POLLUTANT OCCURRENCE

            SCREENING PLANT DATA
                         No. of Occurrences
Detected Above 500

No.*
IB
2V
3V
4V
5B
6V
7V
SB
9B
10V
11V
12B
13V
14V
15V
16V
17B***
18B
19V
20B
21A
22A
23V
24A
25B
26B
27B
28B
29V
30V
31A
32V
33V
34A
35B
36B
37B
38V
39B

Compound
acenaphthene
acrolein
acrylonitrile
benzene
benzidine
carbon tetrachloride
chlorobenzene
1 ,2,4-trichlorobenzene
hexachlorobenzene
1 ,2-dichloroethane
1,1, 1-trichloroe thane
hexachloroethane
1 , 1-dichloroe thane
1 , 1 ,2-trichloroethane
1, 1,2,2-tetrachloroe thane
chloroethane
bis(chloromethyl) ether
bis(2-chloroethyl) ether
2-chloroethylvinyl ether
2-chloronaphthalene
2,4,6-trichlorophenol
parachlorometa cresol
chloroform
2-chlorophenol
1 ,2-dichlorobenzene
1 , 3-dichlorobenzene
1,4-dichlorobenzene
3, 3'-dichlorobenzidine
1 , 1 -dichloroethy lene
1-2-trans-dichloroethylene
2, 4-dichlorophenol
1 ,2-dichloropropane
1 , 3-dichloropr opylene
2,4-dimethylphenol
2, 4-dinitrotoluene
2,6-dinitrotoluene
1 ,2-dipheny Ihydrazine
ethylbenzene
fluoranthene
Influent
(25)**
4 (16%)


15 (60%)
1 (4%)
3 (12%)
5 (20%)


5 (20%)
8 (32%)

4 (16%)
4 (16%)

2 (8%)

1 (4%)


1 (4%)

16 (64%)
1 (4%)
2 (8%)

1 (4%)

5 (20%)
1 (4%)



1 (4%)
2 (8%)
1 (4%)
1 (4%)
12 (48%)
1 (4%)
Effluent ug/L in
(20)** Effluent (20)**



3 (15%)

1 (5%)



4 (20%) 1
4 (20%)


1 (5%)



1 (5%)




9 (45%)





2 (10%)




1 (5%)
1 (5%)


2 (10%)

                                                    Max. Effluent
                                                       Level
                                                        ug/L
                                                         120

                                                          16
                                                         500
                                                          33
                                                          14
                                                          20
                                                         110
                                                         180
                                                          15
                                                          14
                                                         160
                       65

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TABLE V-7 (continued)
              No. of Occurrences
Detected

No.*
40B
41B
42B
43B
44V
45V
46V
47V
48V
49V***
50V***
51V
52B
53B
54B
55B
56B
57A
58A
59A
60A
61B
62B
63B
64A
65A
66B
67B
68B
69B
70B
71B
72B
73B
74B
75B
76B
77B
78B
79B
SOB
81B
82B

Compound
4-chlorophenyl phenyl ether
4-bromophenyl phenyl ether
bis(2-chloroisopropyl) ether
bis(2-chloroethoxy) methane
methylene chloride
methyl chloride
methyl bromide
bromoform
dichlorobromomethane
trichlorofluoromethane
dichlorodifluoromethane
chlorodibromomethane
hexachlorobutadiene
hexachlorocyclopentadiene
isophorone
naphthalene
nitrobenzene
2-nitrophenol
4-nitrophenol
2,4-dinitrophenol
4,6-dinitro-o-cresol
N-nitrosodimethylamine
N-nitrosodiphenylamine
N-nitrosodi-n-propylamine
pentachlorophenol
phenol
bis(2-ethylhexyl) phthalate
butyl benzyl phthalate
di-n-butyl phthalate
di-n-octyl phthalate
diethyl phthalate
dimethyl phthalate
benzo(a) anthracene
benzo(a) pyrene
3,4-benzofluoranthene
benzo(k) f luoranthane
chrysene
acenaphthylene
anthracene
benzo(ghi) perylene
fluorene
phenanthrene
dibenzo(a,h) anthracene
Influent
(25)**


3 (12%)

17 (68%)
1 (4%)
1 (4%)
1 (4%)






2 (8%)
1 (4%)
1 (4%)
3 (12%)
3 (12%)



1 (4%)

2 (8%)
14 (56%)
10 (40%)
2 (8%)
3 (12%)

1 (4%)







2 (8%)

1 (4%)
1 (4%)

Effluent
(20)**


2(100%)

15 (75%)


1 (5%)










1 (5%)

1 (5%)




4 (20%)
8 (40%)

4 (20%)

1 (5%)












Above; 500
ug/L"in
Effluent (20)**




2






































                                           Max. Effluent
                                              Level
                                               ug/L
                                               2600
                                                 44
                                                 15

                                                 15
                                                120
                                                 68

                                                 15

                                                 20
          66

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                                 TABLE V-7 (continued)
                                              No. of Occurrences
Detected
Compound
Influent
(2$)**
Effluent
(20)**
Above 500
ug/L'in
Effluent (20)**
No.*

 83B      indeno(l,2,3-C,D)pyrene
 84B      pyrene
 85V      tetrachloroethylene           4 (16%)    2 (10%)
 86V      toluene                     16 (64%)    5 (25%)
 87V      trichloroethylene              3  12%)    2 (10%)
 88V      vinyl chloride
 89P      aldrin
 90P      dieldrin
 91P      chlordane
 92P      4,4'-DDT
 93P      4,4'-DDE
 94P      4,4'-DDD
 95P      alpha-endosulfan
 96P      beta-endosulfan
 97P      endosulfan sulfate
 98P      endrin
 99P      endrin aldehyde
100P      heptachlor
101P      heptachlor epoxide
102P      alpha-BHC
103P      beta-BHC
104P      gamma-BHC (lindane)
105P      delta-BHC
106P      PCB-1242
107P      PCB-1254
108P      PCB-1221
109P      PCB-1232
11 OP      PCB-1248
11 IP      PCB-1260
112P      PCB-1016
113P      toxaphene
114M     antimony (total)              10 (40%)    3 (15%)
115M     arsenic (total)                5 (20%)    3 (15%)
116       asbestos (fibrous)
117M     beryllium (total)               1 (16%)
118M     cadmium (total)               8 (32%)
119M     chromium (total)             23 (92%)
120M     copper (total)                24 (96%)
121       cyanide (total)               11 (4*%)
122M     lead (total)                  13 (52%)
123M     mercury (total)              16 (6*%)
124M     nickel (total)                 1* (56%)    9 (45%)
125M     selenium (total)               7(28%)    3(15%)
                          Max. Effluent
                              Level
                              ug/L
                                18
                              1350
                                11
2
5
   (10%)
   (25%)
15 (75%)
16 (80%)
10 (50%)
 9 (45%)
12 (60%)
  90
  30

   2.0
  40
 304
  63
7700
 400
   1.58
 310
  56
                                           67

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                                  TABLE V-7  (continued)
                                                No. of Occurrences
 126M
 127M
 128M
 129B
                   Compound
                                            Detected
silver (total)
thallium (total)
zinc (total)
2,3,7,8-tetrachloro-
   dibenzo-p-dioxin (TCDD)
Influent
 (25)**

 7 (28%)
 5 (20%)
21 (84%)
Effluent
 (20)**

 3 (15%)
 4 (20%)
17 (85%)
                                                     Above 500
                                                      ug/L-in
                                                   Effluent (20)**
Max. Effluent
    Level
    ug/L

      40
      29
     403
* V - volatile organics
  A - acid extractables
  B - base/neutral extractables
  P - pesticides
  M- metals

**  Indicates number of plant streams.

*** Deleted from further consideration by 46 FR 10723 and 46 FR 2266.
                                             68

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characteristics  that  were  considered  in  the  final selection
process are summarized below on a plant-by-plant basis.

Plant No. 1241 1 .   Plant 124-11 was found  to  have  in  its  waste
streams  three  of  the  common  priority  pollutants used by the
industry:  methylene  chloride,  chloroform,  and  toluene.   The
presence  of  these  pollutants,  a  process area involving three
subcategories, utilization of  a  solvent  recovery  system,  and
pretre.atment  of  wastewater followed by aerated lagoon treatment
justified this plant for verification sampling.

Plant No. 12038.   This plant was selected  for  sampling  in  the
verification   program  because  of  its  use  of  potential  BAT
technology  including   steam   stripping,   aerobic   biological
treatment,  and  thermal  oxidation.   The  presence  of  several
priority pollutants, including nitrosamines, the existence  of  a
large  historical  data  base  relating  to nitrosamines, and the
inclusion  of  both  pesticides  and   Pharmaceuticals   in   the
manufacturing   operations   at   the  plant  were  factors  also
considered in the selection process.

Plant No. 12236.   Limitation to one subcategory,  reported  flows
of  about 0.81 MGD, use of cyanide as raw material, and treatment
of its wastewaters by the activated sludge process qualified this
plant for the verification program.  Also of  interest  were  its
use of in-plant treatment processes including cyanide destruction
and solvent recovery.

Plant  No.  12026.   A  treatment  train  consisting of activated
sludge,  aerated  lagoon,  and  polishing  pond  after   in-plant
treatment  by  solvent  recovery  were the reasons this plant was
selected for verification sampling.  It has a  reported  flow  of
0.101 MGD and belongs in Subcategory C.

Plant  No.  12097.   Plant 12097 is a multiple subcategory  (C, D)
plant with a reported flow of 0.035 MGD.  Its use of  cyanide  in
production  and a treatment system consisting of in-plant solvent
recovery, activated sludge, and physical-chemical treatment  were
considered in selecting this plant.

2.   Results of Screen i ng/Ver i f i cat ion Program

A plant-by-plant summary  of  the  analytical  results  from  the
sampling  program  is  presented  in  Appendix  G of the Proposed
Development Document.

Table V-8 lists the traditional and priority pollutants that were
identified and the frequency at  which  they  were  found   to  be
present  in the waste streams.  Although a number of the priority
pollutants appeared in the waste stream, only a few of them  were
sufficiently  repetitive  to  cause concern.  Pesticides and PCBs
were detected in one of the plant's effluent but were not due  to
pharmaceutical-related activity.

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                            TABU-  V-8

      ANALYSIS OF PRIORITY POLLUTANT CONCENTRATIONS  (ug/1)
                Screening/Verification  Data  Rase
Influent
Based on Values Equal to or
Priority Pollutant Nu
Add
21
24
31 *
34
•57
5ft
60
64
65
Rase
1
25
27
35
42
54
62
66
P
Extractables
2 ,4 ,6-tri chl orophenol
?-chlorophenol
2 ,4-di chl orophenol
2, 4-dimethyl phenol
2-n1trophenol
4-n1trophenol
4,6-d1n1tro-o-cresol
pentachl orophenol
phenol
Neutral s
acenaphthene
1 . 2-d1 chl orobenzene
1 ,4-d1 chl orobenzene
2,4-d1n1trotoluene
hi s (2-chl orol soprooyl )
ether
Isophorone
N-nl trosodl phenyl amlne
h1s(2-ethylhexyn
Greater
mber of
lants
1
1
1
1
2
2
1
2
20
2
2
1
1
2
2
1
R
than (10 uq/n
Number of
Observations Minimum Maximum
1
1
1
1
2
2
1
2
36
2
2
1
1
2
2
1
10
20
50
10
62
23
181
L5
42
12
35
12
90
63
300
11
12
10
20
50
10
62
119
1600
15
62
51,000
92
20

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67
68
70
76
80
81
butyl benzyl phthalate
di-n-butyl pbthalate
diethylL phthalate
anthracene
fluoxene
(henanfchrene
3
4
1
1
1
1
3
ffi
H
11
H
n
Volatile Orqanics
4
6
7
10
11
14
15
23
29
33
38
44
45
47
49
65
86
87
tenzen«
carbon tetrachloride
chlocofcenzene
1 , 2-dicbloroethane
1,1, 1-ftrichloroethane
1, 1 ,2-<:richloroethane
1,1,2,2-tetrachloro-
ethane
chlcroiEorm
1, 1-dioMoroetbylene
1,3-diohlcrcpropylene
etbylbenzene
ffethylune chloride
ntetbyl chloride
broaofoi:m
trichlorof luorctne thane
tetrachloroethylene
toluene
tricblOEoethylene
11
3
4
8
8
2
1
14
1
1
9
18
2
1
1
8
14
2
19
5
6
17
11
2
11
22
11
11
18
3H
4)
2
11
«
2$
2
12
18
61
14
27
14
719
20
61
14
27
14
18
20
61
14
27
14
250
19
61
14
27
14
                                             406
                                               1
                 IS  10,300    120  1586   3186
                 12     300     18    81    124
                 11 123,000   3206 36,405 55,025
                 12  14,000     62  2516    4944
                 17   1,300     22   169     383
                 19      20     20    20      1
                 20      20     20    20

                 26    1620    170   396    470
                230     230    230
                100     100    100   100
                 11  42,000     2H  3237  10,020
                 16 200,000        11,356 37,952
                 59  13,000  8,600  7,565  5,439
                 12      12    1.2     12
                970     970    970   970
                 14      36     31    28      10
                 50 227,000   310  21,075 50,223
                 11     124     68    68      80
71

-------
88   vinyl chloride
Hetale
114  antimony
115  arsenic
118  cadmium
119  chromium
120  copper
122  lead
*123 xrercury
124  nickel
125  selenium
126  silver
127  thallium
128  zinc
.Cther
121  cyanide
130  ECO{mg/l)
131  COD(uig/l)
132  1SS (ng/1)
                                                           14
14
14
8
n

-------
Effluent
Priority Pollutant Number of Number of
Plants Observations Minimum Maximum. Median
Acid
3*
58
65
Ease
42
66

68
70
60
Extractablea
2, 4-dimethylg henol
4-nitzophenol
phenol
Keutral
bis (2-chloroisaproEylJ
ether
bis (2-ethy Ifaexy 1)
phthalate
di-n-butyl &;hthalate
diethyl pbthalate
fluorene

1
1
9

1
6

2
2
1

1
1
12

1
9

2
2
1

15
15
10

181
10

10
10
10

15
15
126

181
68

15
20
10

15
15
23

181
30

13--
15
10
Standards
Mean Deviation
15
15
47

181
36

13
15
10
*
-
46

-
21

4
7
•
Volatile Organica
2
4
6
10
1.1
21
29
38
44
45
acrolein
tenzene
carbon tetrachloride
1,2-dichloroethane
1,1, 1- trie h lor oe thane
chloroform
1,1-dichloroetyhlene
ethylbenzene
fftbylene chloride
•ethyl chloride
1
1
2
5
4
6
1
3
14
2
1
1
2
9
6
7
1
3
21
4
100
120
16
22
10
14
180
14
12
100
100
120
61
500
33
150
180
22
8100
410
100
12'0;
39
62
20
90
180
17
120
310
100
120
39
158
21
79
180
18
863
283
•
•
32
169
11
55
-
4
1852
139
                                   73

-------
49   trichlorof luoroirethane
85   tetrachloroethylene
86   toluene
£7   trichloroethylene
Petals
114  antinony
115  arsenic
118  cadmium
119  chromium
120  copper
122  lead
*123 mercury
124  nickel
125  selenium
126  silver
127  thallium
128  zinc
Cther
121  cyanide
**130 BOO
**131 COD
•*132 TSS
*A11 non-remarked data considered
**Ex£ressed in mg/1
1
1
4
1
2
3
1
13
13
9
11
8
2
1
2
17
6
13
13
13
1
1
4
1
5
6
1
21
25
14
19
16
5
1
5
32
11
25
30
29
420
18
too
HI
20
10
40
10
1'»
13
0.1
19
12
40
10
13
30
10
216
0.1
420
18
315
14
51
20
40
304
106
400
1.3
300
56
40
129
2009
7700
1090
3293
1200
420
18
185
14
31
12
40
27
31
33
0.7
51
45
40
11
118
100
84
528
88
420
18
196
14
34
13
40
77
38
64
0.7
83
42
40
37
240
'827
155
911
237
-
.
89
*
15
4
.
94
24
100
0.5
81
18
•
52
378
2282
211
921
338
                                  74

-------
Wastewaters  entering  and  leaving  the  end-of-pipe  wastewater
treatment train were among those waste streams that were  sampled
in  this  program.  Concentration levels for many of the priority
pollutants in the final effluent are relatively low.  The reasons
for this are: (1) in-plant  treatment  and  process  controls   to
minimize   specific   wastewater   pollution,   (2)  dilution   of
concentrated process  wastewater  with  other  less  concentrated
wastewaters, and  (3) incidental removal of some specific chemical
pollutants by end~of-pipe treatment.

D.  MASTEWATER "FLOW  CHARACTERISTICS

In  order  to  characterize   the  waste  from   plants   in    the
pharmaceutical  industry,  a  determination was made from 308 data
of the total industry wastewater  flow  rate  and  its  component
process  subcategory  flows   for direct and indirect dischargers.
In Table V-9, actual  plant   flow  data  are  compared  to  flows
thought to be characteristic  of the various subcategories.  These
are  based on actual single-subcategory plant total flow adjusted
for the number of occurrences for each subcategory.  The averages
of these flows are  also  useful  as  base-case  flows  for  cost
analysis.

Approximately  70 percent of the direct and  indirect dischargers
(not  including   zero  dischargers)  within   the   308   Data  Base
reported  wastewater flows totaling about  80  MGD.  Of this, about
45 MGD is from 25 reported direct  dischargers.    (This estimate
does  not include the process flow from plant  12256 which  has  not
been accurately determined.)

Using the reported single-subcategory plant flows  as  a  means   of
estimating   flow  attributable to each subcategory,  the  plants  not
reporting flow are estimated  to add another  13  MGD (93  MGD  total
estimated discharge flow  for  the plants  in the  data base).   Table
V-9  summarizes   reported and estimated wastewater flows  for  the
industry as  represented by the 308 Data Base;  this information is
more comprehensively  covered in  Appendix   J   of the  Proposed
Development  Document.

E. PRECISION AND ACCURACY PROGRAM

The  Precision   and   Accuracy  (P/A)   Study   is  a   fundamental,
continuing   program   to   insure   the  reliability and validity of
analytical   laboratory   techniques.    The   P/A  program  is   not
utilized  as  a   separate data   base  in  support of  the proposed
limitations,  but is   used primarily   to   substantiate  the  data
illustrated in Table  V-10.

Precision    refers    to    the   reproducibility  among  replicate
observations.    In   an   Analytical    Quality    Control    Program,
precision   is determined  not on reference standards,  but by the
use of  actual wastewater  samples which  cover  a  wide  range  of
                                  75

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                           TABLE V-9
           ANALYSIS OF WASTEWATER FLOW CHARACTERISTICS
                        (BASIS: 308 DATA)

Direct Discharger Flow (All plants reporting data)
     (Without Inclusion of Plant 12256)

Indirect Discharge Reporting Flow (178 plants)

     Total Flow Reported

Total Single Subcategory Flow/No, plants (with data)
Subcat . A
Subcat. B
Subcat. C
Subcat. D
1 .30/3
0.67/15
8.80/34
9.80/131
« 0.435
«= 0.045
- 0.260
« 0.075
                                       45 MGD
                                         (15)

                                         35

                                         30 MGD
Indirect Discharger Estimated Flow for Non-Reporting Plants
     Subcat. A
     Subcat. B
     Subcat. C
     Subcat. D
0.435 X 5  occurrences
0.045 x 16 occurrences
0.260 x 14 occurrences
0.075 x 90 occurrences
Estimated Unreported Flow

Total Discharge Flow Estimated for Data Base
     (Without Inclusion of Plant 12256)
2,175 MGD
0.72
3.64
6.75
                                         13

                                         93 MGD
                                         (63)
                             76

-------
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-------
 concentrations   and   a   variety
 encountered  by  the analyst.
of interfering materials usually
Accuracy refers  to  a  degree of  difference  between  observed  and
actual  values.   Accuracy  should   also  be determined on actual
wastewater  samples  routinely analyzed   and,   preferably,   on  the
same series as those  used  in the precision determinations.

Through  this  process,  data  obtained  by  analysis  of multiple
samples were compared   to  demonstrate  that  (a)   they  present
clearcut evidence that  the analyst  is  indeed capable of analyzing
the  samples for   that particular parameter   (i.e.,  he has  the
standard method  under control and is capable of  generating  valid
data)  and   (b)  the  data can  be used in the evaluation of daily
performance in reference to replicate   samples,   spiked  samples,
and  in  the preparation of quality control  charts.  This type' of
quality assurance program  is applicable to and  can be  adapted  for
all types of analytical procedures.

TRW and Radian performed,  on a  split-sample basis,  a P/A study on
a series of 24-hour  composite  influent  and   effluent  samples
collected    from a  single  pharmaceutical   manufacturing  plant
(12236)  representing   Subcategory   C   (chemical    synthesis).
Extraction  of the non-volatile  organic (NVO)  sample  for the basic
recovery  study  was  performed  using  continuous,  liquid/liquid
•extractors.  Volatile Organics  (VOAs)   wer'e  analyzed   using  the
purge-and-trap   procedure  adopted for  this   study.    Standard
spiking levels were used by both laboratories   as  specified   by
EPA.   The   extract volumes were selected depending  upon expected
concentration of the  priority pollutants in the   sample  and  the
established linear response range  of  the GC/MS  instruments.   All
pollutants  detected in  the samples  are summarized in Table V-10.

The  values reported  by   the   two laboratories  for    priority
pollutants   are well   within   the detection   limits   of   GC/MS
analysis, with the  exception of the values reported  for methylene
chloride, toluene,  and  chloromethane.   The values  from  the  two
laboratories are   also moderately close to each other.   In some
cases,  methylene   chloride,  toluene,   and  chloromethane  were
present  in such   high concentrations that, although  reasonable
recovery and quantitation  could be  obtained,  the results are  not
meaningful   due  to  instrument  saturation.   The high levels of
these compounds  apparently did  interfere  with   the  analysis   of
other  priority  pollutants.    Recoveries  of 2,4-dimethylphenol,
benzidine,  and the  phthalates were  low and erratic.

The detection of some of the priority   pollutants  could  be  the
result  of   contamination   by sources  in the field or  laboratory.
It is common practice to equip  automatic composite samplers with
polyvinyl chloride  (tygon)  tubing.   Phthalates are widely used as
plasticizers to  ensure  that -the tubing remains soft  and flexible.
These  compounds have a tendency to migrate  to the surface of  the
tubing and  leach out  into  water   passing   through  the  sample
                                 78

-------
tubing.   Results  of  analyses  shown in Table V-10 indicate the
phthalates vary between laboratories.   Sample  contamination  is
possible   and,   therefore,   some  of  the  results  cannot  be
conclusively attributed to the wastewater.
                                 79

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A.
                      SECTION VI

           SELECTION OF POLLUTANT PARAMETERS

INTRODUCTION
The  priority    (toxic)   and   traditional    (conventional    and
nonconventional)   pollutants  characterized   in   Section  V   are
discussed  in  this  section  in   light  of  their  occurrence   in
pharmaceutical   industry  wastewaters  and  their  effects on  the
environment.

B.   TRADITIONAL POLLUTANTS

The  Clean  Water  Act  of  1977   (P.L.  95-217)   requires    the
Administrator to establish effluent limitations and standards  for
traditional pollutants.  Among these, the conventional parameters
of biochemical oxygen demand (BOD), total suspended solids (TSS),
pH,  and  oil  and  grease  and the nonconventional parameters of
chemical oxygen demand  (COD), total organic carbon (TOO,  color,
ammonia,  nitrogen, and phosphorus were considered.  Those chosen
as representative of specific and persistent  pollution  problems
across the industry were BOD5.,  TSS, COD and pH.

These  pollutant parameters were  identified in 100 percent of  the
plant effluents for which data were obtained.   Pollutant  levels
in   treatment   influent  and  untreated  effluent  streams   are
frequently  high,  particularly   in   Subcategories   A   and   C
(fermentation and synthesis, respectively).

Other  conventional  parameters  subject  to regulation under  the
Administrator's  discretion  are  oil  and  grease,   and   fecal
coliform.   Although  they  do  appear  as problems in some plant
process wastewater,  oil  and  grease  are  neither  sufficiently
widespread nor severe enough to justify regulation on an industry
wide  basis.   Fecal  coliform  is  not  of  significance  in  the
industrial wastewater effluents of this industry.   Similarly,  the
nonconventional parameters of color, phosphorus and various forms
of nitrogen are not judged to present a frequent  enough  problem
to  justify regulation on a national basis.  TOC is considered  to
be so closely related to BOD and COD that separate  attention   is
not necessary.

1.  Biochemical Oxygen Demand

BOD  is  the  quantity  of oxygen required for the biological and
chemical oxidation of waterborne substances under ambient or test
conditions.  Substances that may contribute to  the  BOD  include
carbonaceous organic materials  usable as a food source by aerobic
organisms;  oxidizable  nitrogen  derived from nitrites,  ammonia,
and organic nitrogen compounds  that serve as  food  for  specific
bacteria;  and  such  chemically  oxidizable materials as ferrous
iron,  sulfides,  sulfite,  and  similar  reduced-state  inorganics

                                 81

-------
that  will react with dissolved oxygen or that are metabolized by
bacteria.

The BOD  of  a  waste  adversely  affects  the  dissolved  oxygen
resources  of a body of water by reducing the oxygen available to
fish, plant life, and other aquatic species.  Total exhaustion of
the dissolved oxygen in water results in anaerobic conditions and
the production of such undesirable gases as hydrogen sulfide  and
methane.  The reduction of dissolved oxygen can be detrimental to
fish  populations,  fish  growth rate, and organisms used as fish
food.  A total lack of oxygen due to excessive BOD can result  in
the  death  of  all  aeroJDic  aquatic inhabitants in the affected
area.

Water with a high  BOD  indicates  the  presence  of  decomposing
organic  matter and associated  increased bacterial concentrations
that may degrade water quality  and minimize potential uses of the
water.  This organic material   promoting  a  high  BOD  can  also
increase algal concentrations and cause blooms.

2.  Total Suspended Solids

Suspended  solids   in  wastewater  are normally measured as  total
suspended solids.   They can  include both  organic  and  inorganic
materials.  The  inorganic materials may  include sand, silt,  clay,
and,  possibly,  toxic metal  compounds.  The organic fraction may
include  such materials as  grease,  oils,   animal  and  vegetable
waste  products, fibers, microorganisms  (algae, for example), and
many other dispersed  insoluble  organic compounds.   These   solids
may  settle  rapidly  and  form  bottom  deposits  that are  often  a
mixture  of both  organic and  inorganic  solids.

Solids may be  suspended  in water .for  a time and   then   settle   to
the  bed of   the  stream or  lake.  They  may be inert; they may  be
slowly   biodegradable materials;  or    they  may    be   rapidly
decomposable   substances.  While in  suspension,  they  increase  the
turbidity of  the water,  reduce   light  penetration,   and   thereby
impair   the   photosynthetic   activity  of   aquatic plants.   After
settling to  the  stream  or  lake  bed,  the  solids  can   form   sludge
banks   which,   if  largely  organic,  create  localized  dead  areas  in
the water body and result  in anaerobic  and  undesirable   benthic
conditions.     Aside   from   any  toxic   effect   attributable   to
substances  leached out  by  water, suspended solids may  kill  fish
and shellfish by causing abrasive injuries, by clogging gills  and
respiratory   passages,   by  screening light,  and by  promoting  and
maintaining  the development  of  noxious conditions through   oxygen
depletion.    Suspended   solids  also reduce the recreational value
of the water.

 3.  Chemical Oxygen Demand

 COD is a chemical oxidation test devised as an  alternate  method
 of estimating the total oxygen demand of a wastewater.   Since the
                                  82

-------
method  relies  on  the  oxidation-reduction  system  of chemical
analyses rather than on biological factors, it is  more  precise,
accurate,  and  rapid than the BOD5_ test.  The COD test is widely
used to estimate the total oxygen demand (ultimate rather than 5-
day BOD) required to oxidize the compounds in a  wastewater.   It
is  based  on  the  fact  that,  with  the  assistance of certain
inorganic catalysts, strong chemical oxidizing agents under  acid
conditions can oxidize most organic compounds.

The COD test measures organic matter that exerts an oxygen demand
and  that  may  affect  public health.  It is a useful analytical
tool for pollution control activities.  Most pollutants  measured
by  the  BODS^ test can be measured by the COD test.  In addition,
pollutants more resistant to biochemical oxidation  can  also  be
measured  as  COD.   COD  is  a  more inclusive measure of oxygen
demand than BOD5_ and results in higher oxygen demand values  than
BOD5.

The COD of a wastewater normally exceeds BODS^ since it is usually
constituted of those materials contributing to the BOD level plus
those   more   resistant   to   biochemical   oxidation.    Joint
consideration of  COD  and  BOD  measurements  can  indicate  the
relative biodegradability of the pollutants and the levels of the
chemical  pollutants  not  easily  bio-oxydized.  The correlation
between the COD and BOD concentrations in a specific plant  waste
resulting  from a particular operation is applicable only to that
waste.  Furthermore, the level of organic pollutants as indicated
by COD do not correlate with the  level  of  individual  priority
pollutants.

Compounds  more  resistant  to biochemical oxidation are of great
concern because of their slow, continuous oxygen  demand  on  the
receiving  water  and  also  because of their potentially harmful
effects on the health of humans and aquatic life.  Many of  these
compounds   result   from  industrial  discharges;  some  of  the
compounds have been found to have  carcinogenic,  mutagenic,  and
similar  adverse  effects.   Concern  about  these  compounds has
increased as a result of demonstrations that their long  life  in
receiving waters (the result of a low biochemical oxidation rate)
allows   them  to  contaminate  downstream  water  intakes.   The
commonly used systems of water purification are not effective  in
removing  these  types  of  materials  and  such  disinfection as
chlorination may convert them into even more hazardous materials.

C.  PRIORITY POLLUTANTS

The frequency and level of priority pollutant occurrence  in  the
wastewaters of the industry were considered in order to determine
the  manner  in  which  these pollutants might be regulated.  The
diversity of process  and  materials  employed  by  the  industry
brings  about  a  broad  presence,  with  virtually  every  toxic
pollutant  compound  listed   in   the   modified   comprehensive
Settlement  Agreement  present  in  the  effluent of at least one
                                 83

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plant.  However, none are present in the effluent in all or
a predominant part of the industry.
even
Under  the  provisions of Paragraph 8 of the Settlement Agreement
in Natural Resources Defense Council, Inc. v. Train, 8  ERC  2120
(D.D.C.  1976),  modified,  12 ERC 1833 (D.D.C. 1979) modified by
Orders dated October 26,  1982, and August 2,  1983,  guidance  is
provided   to  the  Agency  on  exclusion  of  specific  priority
pollutants, subcategories", or categories from  regulations  under
the effluent limitations  guidelines, standards of performance and
pretreatment standards. (1)(2) This paragraph is excerpted below:

     "8(a)   The  Administrator may exclude from regulation under
     the  effluent  limitations  and  guidelines,  standards   of
     performance,  and/or  pretreatment standards contemplated by
     this  Agreement  a   specific  pollutant   or   category   or
     subcategory  of  point  sources  for  any  of  the following
     reasons, based upon  information available to him:

     (i)    For  a  specific  pollutant  or  a   subcategory   or
     category,  equally   or  more stringent protection is already
     provided  by  an  effluent,  new  source   performance,   or
     pretreatment  standard  or  by  an  effluent  limitation and
     guideline promulgated pursuant to Section(s) 301, 304,  306,
     307(a), 307(b) or 307(c) of the Act;

     (ii)   For a specific  pollutant,  except  for  pretreatment
     standards, the specific pollutant is present in the effluent
     discharge  solely  as  a  result  of  its presence in intake
     waters taken from the same body of water into  which  it  is
     discharged  and,  for  pretreatment  standards, the specific
     pollutant is present in the  effluent  which  is  introduced
     into  treatment works (as defined in Section 212 of the Act)
     which are publicly owned solely as a result of its  presence
     in  the point source's intake waters, provided however, that
     such point source may be subject to an appropriate  effluent
     limitation  for  such pollutant pursuant to the requirements
     of Section 307;

     (iii)  For  a  specific  pollutant,  the  pollutant  is  not
     detectable  (with  the  use  of  analytical methods approved
     pursuant to  304(h)  of  the  Act,  or  in  instances  where
     approved  methods  do  not exist, with the use of analytical
     methods which represent state-of-the-art capability) in  the
     direct  discharges   or in the effluents which are introduced
     into publicly-owned  treatment works from sources within  the
     subcategory  or  category;  or  is detectable  in the effluent
     from only a small number of sources within  the  subcategory
     and the pollutant is uniquely related to only those sources;
     or  the  pollutant   is  present only in trace amounts and is
     neither causing nor  likely to cause  toxic  effects;  or  is
     present   in  amounts too small to be effectively reduced by
     technologies known to the Administrator;  or  the  pollutant
                                 84

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     will   be   effectively  controlled  by  the technologies upon
     which  are based other effluent limitations  and  guidelines,
     standards of  performance,  or pretreatment standards;  or

     (iv)    For   a  category  or subcategory, the amount  and the
     toxicity  of each pollutant in the discharge does not  justify
     developing national   regulations  i'n  accordance  with  the
     schedule  contained in Paragraph 7(b).

     (b)     The   Administrator may exclude from regulation under
     the  pretreatment standards contemplated  by  this  Agreement
     all   point sources  within a point source category or point
     source subcategory:

     (i)     If 95  percent  or more of all  point  sources  in  the
     point  source   category   or  subcategory  introduce  into
     treatment works (as defined in Section 212 of the Act) which
     are  publicly  owned only pollutants which are susceptible  to
     treatment by  such treatment works and which do not interfere
     with,  do  not  pass through, or are not otherwise incompatible
     with such treatment works; or

     (ii)     If  the  toxicity  and  amount  of  the incompatible
     pollutants (taken together) introduced by such point sources
     into treatment works (as defined in Section 212 of the  Act)
     that  are  publicly  owned  is  so  insignificant  as not to
     justify developing a pretreatment regulation..."

a.    Pollutants Excluded from Direct Discharger Regulations

Table.  V-7  lists   the  occurrence,  frequencies  and  levels  of
priority  pollutants  found in samples collected in the screening
survey.  The priority pollutant data provided  in  the  308  data
base was used  to help develop the group of plants which were then
screened  for   priority pollutants.  However, these data were not
used to support Paragraph  8  exclusion  of  priority  pollutants
found in the S/V study because many of the 308 priority pollutant
responses  were incomplete or of a non-quantitative nature.  This
was due in part to the fact that many plants had not performed   a
priority  pollutant  scan  of their wastewater.  The 308 priority
pollutant data were used to exclude  those  which  were  uniquely
related   to  individual  sources  or  occur  as  the  result  of
non-pharmaceutical operations.

Compounds numbered  17B, 49V, and 50V have been deleted by  46  FR
10723 on February 4, 1981 and 46 FR 2266 on January 8, 1981.  The
remaining  list  of  priority pollutants was  considered under the
individual subparagraphs of Paragraph 8.  The compounds that  can
be  excluded  under  each  provision are  tabulated  in Tables VI-1
through VI-4,  with  those which  can be excluded by more  than  one
provision being noted by an asterisk  (*).
                                  85

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                                TABLE VI-1
     PRIORITY POLLUTANTS EXCLUDED FROM DIRECT DISCHARGER REGULATIONS
                                 BASED ON
                 CONTROL BY OTHER LIMITATION TECHNOLOGIES
Paragraph 8 (a) (i) "For a specific pollutant effectively controlled by
            the technology upon which are based upon other effluent
            limitations guidelines, standards of performance,  or pretreatment
            standards ..."
 4V     benzene
23V     chloroform
11V*    1,1,1-trichloroethane
13V*    1,2-dichloroethane
38V     ethyl benzene
45V     methyl chloride
85V     tetrachloroethylene
86V     toluene
87V*    trichloroethylene
58A*    4-nitrophenol
59A*    2,4-dinitrophenol
65A     phenol
25B*    1,2-dichlorobenzene
(Air stripping and/or biodegradation)
(Air stripping)
(Air stripping)
(Air stripping)
(Air stripping and/or biodegradation)
(Air stripping)
(Air stripping)
(Air stripping and/or biodegradation)
(Air stripping)
(Biodegradation)
(Bi odegradati on)
(Biodegradation)
 (Biodegradation)
   Indicates exclusion under two or more separate provisions  of
   Paragraph 8.
                  V - Volatile organics
                  A - Acid extractables
                  B - Base/neutral  extractables
                  P - Pesticides
                  M - Metals

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                                 TABLE W-2

PRIORITY POLLUTANTS OCCLUDED FROM DIRECT DISCHARGER REGULATIONS
                                  BASED ON
                            LOW-LEVEL PRESENCE
     Paragraph 8   (a) (iii)  "For a  specific  pollutant...present  only  in  trace
                   amounts and is neither causing nor  likely  to  cause toxic
                   affects; or is present in amounts too small to be effectively
                   reduced by technologies known to the Administrator..."
       6V*   carbon tetrachloride            27B*
       7V    chlorobenzene                  28B*
       11V*   1,1,1-trichloroethane           35B*
       13V*   1,1-dichloroethane              36B*
       14V*   1,1,2-trichloroethane           39B*
       15V*   1,1,2,2-tetrachloroethane       40B*
       16V*   chloroethane                   4 IB*
       19V*   2-chloroethylvinyl ether         43B*
       30V*   1,2-trans-dichloroethylene       52B*
       32V*   1,2-dichloropropane             53B*
       33V*   1,3-dichloropropylene           54B*
       38V*   ethylbenzene                   55B*
       46V*   methyl bromide                56B*
       47V*   brornoform                     6 IB*
       48V*   dichlorobromomethane          62B*
       51V*   chlorodibromomethane          63B*
       85V*   tetrachloroethylene             66B**
       87V*   trichloroethylene               67B**
       88V*   vinyl chloride                  68B**
       21A*   2,4,6-trichlorophenol           69B**
       22A*   parachlorometa cresol          70B**
       24A*   2-chlorophenol                 71B**
       31A*   2,4-dichlorophenol»              72B*
       34A*   2,4-dimethylphenol             73B*
       37A*   1,2-diphenylhydrazine           74B*
       57A*   2-nitrophenol                  75B*
       58A    4-nitrophenol                  76B*
       59A*   2,4-dinitrophenol               77B*
       64A*   pentachlorophenol              78B*
       65A    phenol                        79B*
       IB*   acenaphthene                  SOB*
       5B*   benzidine                      8 IB*
       8B*   1,2,4-trichlorobenzene          82B*
       9B*   hexachlorobenzene              83B*
       12B*   hexachloroethane               84B*
       18B*   bis(2-chloroethyl) ether        129B*
       20B*   2-chloronaphthalene
       25B*   1,2-dichlorobenzene           114M
       26B*   1,3-dichloroberizene           115M
1,4-dichlorobenzene
3,3-dichlorobenzidine
2,4-dinitrotoluene
2,6-dinitrotoluene
fluoranthene
4-chlorophenyl phenyl ether
4-bromophenyl phenyl ether
bis(2-chloroethoxy) methane
hexachlorobutadiene
hexachlorocyclopentadiene
isophorone
naphthalene
nitrobenzene
N-nitrosodimethylamine
N-nitrosodiphenylamine
N-nitrosodi-n-propylamine
bis(2.rethylhexyl) phthalate
butyl benzyl phthalate
di-n-butyl phthalate
di-n-octyl phthalate
diethyl phthalate
dimethyl phthalate
benzo(a)anthracene
benzo(a)pyrene
3,4-benzofluoranthene
benzo(k)fluoranthane
chrysene
acenaphthylene
anthracene
benzo(ghi)perylene
fluorene
phenanthrene
dibenzo(a,h)anthracene
indeno(l ,2,3-C,D)pyrene
pyrene
2,3,7,8-tetrachloro-dibenzo-p-
dioxin.(TCDD)
antimony (Total)
arsenia (Total)
                                   87

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                           TABLE VI-2 (CONPD.)

PRIORITY POLLUTANTS EXCLUDED FROM DIRECT DISCHARGER REGULATIONS
                                 BASED ON
                           LOW-LEVEL PRESENCE
     117M*  beryllium (Total)
     118M*  cadmium (Total)
     119M   chromium (Total)
     120M   copper (Total)
     122M   lead (Total)
     123M   mercury (Total)
     124M   nickel (Total)
     125M*  selenium (Total)
     126M*  silver (Total)
     127M   thallium (Total)
    *   Indicates exclusion under two or more separate provisions of Paragraph 8.

    ** Phthalates likely resulting from sample contamination.


        V -  Volatile organics

        A -  Acid extractables

        B -  Base neutral extractables

        P -  Pesticides

        M -  Metals
                                  88

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                                 TABLE VI-3

PRIORITY POLLUTANTS EXCLUDED FROM DIRECT DISCHARGER REGULATIONS
                                  BASED ON
                         INFREQUENT OCCURRENCE


     Paragraph 8   (a) (iii) "For a specific pollutant...detectable in the effluent
                   from only a small number of sources within the subcategory
                   and the pollutant is uniquely related to only those sources..."
       2V    acrolein                       60A
       3V    acrylonitrile                   64A*
       6V*   carbon tetrachloride             IB*
              (tetrachloromethane)            5B*
       7V*   chlorobenzene                   8B*
       10V*   1,2-dichloroethane               9B*
       13V*   1,1-dichloroethane              12B*
       14V*   1,1,2-trichloroethane           18B*
       15V*   1,1,2,2-tetrachloroethane        20B*
       16V*   chloroethane                   25B*
       19V*   2-chloroethyl vinyl              26B*
              (mixed)                        27B*
       29V    1,1-dichloroethylene            28B*
       30V*   1,2-trans-dichloroethylene       35B*
       32V*   1,2-dichloropropane             36B*
       33V*   1,3-dichloropropylene           39B*
              (!93-dichloropropene)           4 OB*
       38V*   ethylbenzene                   4 IB*
       45V    methyl chloride                42B
              (chloromethane)                43B*
       46V*   methyl bromide                52B*
              (bromomethane)                53B*
       47V*   bromoform                     54B*
              (tribromomethane)              55B*
       48V*   dichlorobromomethane          56B*
       51V*   chlorodibromomethane          61B*
       85V*   tetrachloroethylene             62B*
       87V*   trichloroethylene               63B*
       88V*   vinyl chloride                   72B*
              (chloroethylene)                73B*
       21A*   2,4,6-trichlorophenol           74B*
       22A*   parachlorometa cresol          75B*
       24A*   2-chlorophenol                 76B*
       31A*   2,4-dichlorophenol              77B*
       34A*   2,4-dimethylphenol              78B*
       37A*   1,2-diphenylhydrazine           79B*
       58A*   4-nitrophenol                   SOB*
       59A*   2,4-dinitrophenol               81B*
4,6-dinitro-o-cresol
pentachlorophenol
acenaphthene
benzidine
1,2,4-trichlorobenzene
hexachlorobenzene
hexachloroethane
bis(2-chloroethyl) ether
2-chloronaphthalene
1,2-dichlorobenzene
1,3-dichlorobenzene
1,4-dichlorobenzene
3,3-dichlorobenzidine
2,4-dinitrotoluene
2,6-dinitrotoluene
fluoranthene
4-chlorophenyl phenyl ether
4-bromophenyl phenyl ether
bis(2-chloroisopropyl) ether
bis(2-chloroethoxy) methane
hexachlorobutadiene
hexachlorocyclopentadiene
isophorone
naphthalene
nitrobenzene
N-nitrosodi methylamine
N-nitrosodiphenylamine
N-nitrosodi-n-propylamine
benzo(a)anthracene
benzo(a)pyrene
3,4-benzofluoranthene
benzo(k)fluoranthene
chrysene
acenaphthylene
anthracene
anthracene
fluorene
phenanthrene
                                   89

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                           TABLE VI-3 (CONPD.)

PRIORITY POLLUTANTS EXCLUDED FROM DIRECT DISCHARGER REGULATIONS
                                BASED ON
                        INFREQUENT OCCURRENCE
 82B*
 83B*
 84B*
129B*

 89P**
 90P**
 91P**
 92P**
 93P**
 94P**
 95P**
 96P**
 97P**
 98P**
 99P**
100P**
101P**
102P**
103P**
104P**
105P**
106P**
107P**
108P**
109P**
HOP**
111P**
112P**
113P**
117M*
118M*
125M*
126M*
             dibenzo(a,h) anthracene
             indeno(l,2,3-C,D)pyrene
             pyrene
             2,3,7,8-tetrachloro-dibenzo-p-
             dioxin(TCDD)
             aldrin
             dieldrin
             chlordane
             alpha-endosulfan
             beta-endosulfan
             endosulfan sulfate
             endrin
             endrin aldehyde
             heptachlor
             heptachlor epoxide
             alpha-BHC
             beta-bhc
             gamma-BHC (lindane)
             delta-BHC
             PCB-1242
             PCB-1254
             PCB-1221
             PCB-1232
             PCB-1248
             PCB-1260
             PCB-1016
             toxaphene
             beryllium (Total)
             cadmium (Total)
             selenium (Total)
             silver (Total)
    *   Indicates exclusion under two or more separate provisions of Paragraph 8.

    ** Infrequent presence due to operations on site other than pharmaceutical.


                                 V -  Volatile organics
                                 A -  Acid extractables
                                 B -  Base neutral extractables
                                 P -  Pesticides
                                 M -  Metals
                                 90

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                           TABLE VI-4

PRIORITY POLLUTANTS EXCLUDED FROM DIRECT DISCHARGER REGULATIONS
                            BASED ON
    PRESENCE IN AMOUNTS TOO SMALL TO BE EFFECTIVELY REDUCED
           BY TECHNOLOGIES KNOWN TO  THE ADMINISTRATOR
             66B

             68B

             70B

            114M

            115M

            118M

            119M

            120M

            122M

            123M

            124M

            125M

            126M

            127M

            128M
Bis(2-ethylhexyl) phthalate

Di-n-butylphthalate

Diethylphthalate

Antimony

Arsenic

Cadmium

Chromium

Copper

Lead

Mercury

Nickel

Selenium

Silver

Thallium

Zinc
                  B = Base neutral extractable

                  M = Metal
                             91

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Table  VI-1 lists compounds whose incidental removal  is likely to
be  brought  about  by  technologies  instituted  to  meet  other
limitations and indicates the incidental mechanism(s) responsible
for   removal.    A   significant   example   is   phenol   whose
biodegradability makes it likely that substantial removal will be
accomplished by  activated  sludge,  aerated  lagoons,  or  other
biological  treatment  systems  targeted  for  BOD  removal.  Air
strippable volatiles  are  also  likely  to  be  removed  through
aeration and exposure to the atmosphere.

Table  VI-2  lists  pollutants  present at levels insufficient to
justify regulation.  Some are  present  at  no  more  than  trace
amounts  (at  or below the detection limits) and others at levels
below  or  essentially  the  same  as  removal  capabilities   of
applicable   technologies.    Those   compounds  with  sufficient
volatility and low solubility to be  effectively  steam  stripped
can  be  removed  to no better than about 50 micrograms per liter
(pg/1). (72) Earlier consideration by  the  Agency  (98)  of  the
treatability  of  a  number  of  the  more  significant  priority
pollutants indicates the following typical treatability criteria,
expressed on a 5-day maximum basis:
            8B 1,2,4-Trichlorobenzene
           11V 1,1,1-Trichloroethane
           13V 1,1-Dichloroethane
           23V Chloroform
           25B 1,2-Dichlorobenzene
           26B 1,3-Dichlorobenzene
           27B 1,4-Dichlorobenzene
           44V Methylene Chloride
           55B Naphthalene
           86V Toluene
            4V Benzene
           69B Di-n-Octyl Phthalate
 50-100
500-600
500-600
500-600
400-500
400-500
400-500
    500
400-500
    400
    400
    100
Metal treatability levels  are  indicated  in  Table  VI-5.   The
priority  pollutants  in  Table  VI-2  were  excluded  based on a
comparison of the aforementioned  treatability  levels  with  the
screening  and  verification  effluent  data in Appendix G of the
Proposed Development Document.

Also included in Table VI-2 are  a  number  of  phthalates  whose
presence is likely the result of sample contamination by sampling
equipment.

Table   VI-3   considers  the  frequency  of  occurrence  in  the
Screening/Verification plant data.  Those occurring infrequently,
even though at significant levels, are excluded where a review of
process wastewater from all of the Screening/Verification  plants
indicates that such occurrence is mainly related to those limited
sources.   Some  priority  pollutants  analyzed  in  the effluent
wastewater of  one  or  more  Screening/Verification  plants  are
                                  92

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                          TABLE VI-5

        ESTIMATED ACHIEVABLE LONG-TERM AVERAGE EFFLUENT
       CONCENTRATIONS FOR THE PRIORITY POLLUTANT METALS

                  Final Concentration (»q/l)*
Metal
Antimony
Arsenic
Beryllium
Cadmium
Copper
Chromium III
Lead
Mercury
Nickel
Silver
Selenium
Thallium
Zinc
Lime
Settling
800-1500
500-1000
100-500
100-500
500-1000
100-500
300-1600
-
200-1500
400-800
200-1000
200-1 000
500-1500
Lime
Filter
400-800
500-1000
1 0-1 00
50-100
400-700
50-500
50-600
—
1 00-500
100-400
100-500
1 00-500
400-1200
Sulfide
Filter
-
50-100
-
10-100
50-500
•~
50-400
10-50
50-500
50-200
-
—
20-1200
References
116
118,
116
117,
124,
117,
121,
113,
119,
126
118,
122,
120,
118,
120,
116
116
114,

120,

118,
125
118,
123,
115,
120,
120,
124
121,
123,
121,


118,

121

123,
119,
124, 125
118,
121,
121,
128
124
126


123,
                                                    124
*Estimated achievable levels reported in the Inorganic Chemicals
 Manufacturing Development Document (Ref.  127) based on additional
 references cited.
                              93

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clearly   not  the  result  of  pharmaceutical  operations.   For
example, one plant  is  known  to  also  produce  pesticides  and
consequently exhibits pesticides in the mixed wastewater.

Table  VI-4  lists  those pollutants which are present in amounts
too small to be effectively reduced by the technologies known  to
the  Administrator.  At proposal, methylene chloride was included
in this list.  With the exception of  methylene  chloride,  there
has been no change in our rationale for not establishing effluent
limitations  guidelines  and standards for the TVOs.,  In the case
of methylene chloride, at proposal  EPA  stated  that  discharges
were  controlled  by  effluent  limitations  reflecting  the best
practicable  control  technology  currently   available.    After
proposal,  EPA  received no comments on the proposed exclusion of
this toxic pollutant.  However, a reexamination of  the  existing
information  on  the  use  and discharge of methylene chloride by
direct discharging pharmaceutical plants indicates that, in fact,
treatable levels of methylene chloride may remain even after  the
implementation of BPT (i.e., biological treatment).

Available  data  show  that  in cases where the concentrations of
methylene chloride discharged to biological treatment systems are
greater  than  5  mg/1,   treatable  concentrations  of  methylene
chloride  remain  in the effluent.  Methylene chloride is used in
about 15 percent of all  fermentation,  chemical  synthesis,  and
extraction  processes  and  to  a  lesser  extent  in formulation
operations.  EPA's data show that 15, of the 51 direct discharging
pharmaceutical   plants   use   methylene   chloride   in   their
manufacturing processes.  For these reasons, EPA reconsidered its
original Paragraph 8 determination.

The  Agency  considered  establishing more stringent BAT effluent
limitations guidelines for methylene chloride based  on  in-plant
steam  stripping  technology in addition to biological treatment.
This treatment technology would insure  that  only  low  effluent
concentrations   of   methylene  chloride  would  be  discharged.
However, EPA found that the costs  of , installing  and  operating
steam   strippers   to   control   methylene   chloride  are  not
insignificant.  The Agency estimates that nine direct discharging
plants would incur average capital and average total annual costs
of  $0.736   million   and   $0.712   million   (1982   dollars),
respectively,  per plant.  EPA estimates that the installation of
steam stripping technology would reduce current discharge  levels
of  methylene chloride by 60,700 pounds per year at these plants.
This compares  to  the  651,000  pounds  per  year  of  methylene
chloride  that  are now removed by biological treatment, the best
practicable  control  technology  currently  available  for  this
industry.  EPA also determined that steam stripping technology is
extremely energy intensive and would increase energy use at these
nine  direct  dischargers  by the equivalent of 94,300 barrels of
oil per year.  The Agency projects  that  the  average  methylene
chloride  removal  cost  resulting  from the application of steam
                                  94

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stripping technology would be $103 per pound, when the full value
of the recovered solvent is assumed.

After considering the relative  toxicity  of  this  pollutant  in
light  of these costs, and all the other factors, EPA decided not
to issue categorical regulations  limiting  methylene   chloride
discharges   from   the   pharmaceutical   industry  based on the
addition of treatment  technology  beyond  biological • treatment.
The Agency has also decided not to establish limitations based on
biological  treatment  because  they  would  not effect a further
removal  of  methylene  chloride.   Another  factor,  while   not
directly   a   basis   for   these   decisions,   confirmed   the
reasonableness of the weight EPA accorded  to   cost  and  energy
factors.   The  Agency  determined  that  much  of  the methylene
chloride which would be removed by steam stripping will otherwise
volatilize during biological treatment.  Our data  indicate  that
the  volatilized  methylene  chloride will not be at levels which
create a health risk.

Data on  the  capabilities  of  steam  stripping  and  biological
treatment  technologies  to  reduce  the  discharge  of methylene
chloride and on  the  cost  of  installing  and  operating  steam
strippers  to  control  toxic  volatile  organics is presented in
Section VII and Appendix A.  This  information  may  be  used  by
permit  writers  in  developing  permit Limitations for methylene
chloride on a case-by-case basis where necessary.

The one priority pollutant  detected  at  sufficient  levels  and
frequency  to  warrant  control  by  all  direct  dischargers  is
cyanide.

b.   Pollutants  Excluded  from  Regulation  under   Pretreatment
Standards

Paragraph  8(b)  (ii)  of the Settlement Agreement allows for the
exclusion of those pollutants whose toxicity and  amounts  (taken
together)  are  so  insignificant as not justify regulation under
pretreatment standards.  These pollutants which were found in the
wastewater of 11 indirect discharger screening plants are  listed
in  Table VI-6 and include toxic metals, phenols, methyl chloride
and various phthalates.  (The  presence  of  the  last  group  of
pollutants  cannot be attributed with certainty to pharmaceutical
manufacturing   operations.)    These   pollutants   were   found
infrequently  and  at  low concentrations and, therefore, are not
required to be controlled by  pretreatment  standards.   Eighteen
other pollutants (cyanide and 17 toxic solvents) which are listed
in  Table  VI-7  were  considered  for  control  by  pretreatment
standards.  The remaining toxic pollutants were not  detected  in
the wastewater of indirect discharging pharmaceutical plants.

After  examining  all  of  the  available data, EPA 'has concluded
that, with the  exception  of  cyanide,  methylene  chloride  and
chloroform,  these  pollutants should be excluded from regulation

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                                    TABLE VI-6

           POLLUTANTS EXCLUDED FROM PRETREATMENT STANDARDS
No.    	Compound	

 1W   1,1,2-trichloroethane
 15V   1,1,2,2-tetrachloroethane
 16V   chloroethane
 19V   2-chloroethylvinyl ether
 32V   1,2-dichloropropane
 33V   1,3-dichloropropylene
 48V   dichlorobromomethane
 51V   chlorodibromomethane
 88V   vinyl chloride
  IB   acenaphthene
  5B   benzidine
 8B   1,2,4-trichlorobenzene
 9B   hexachlorobenzene
 12B   hexachloroethane
 18B   bis(2-chloroethyl) ether
 20B   2-chloronaphthalene
 25B   1,2-dichlorobenzene
 26B   1,3-dichlorobenzene
 27B   1,4-dichlorobenzene
 28B   3,3'-dichlorobenzidine
 35B   2,4-dinitrotoluene
 36B   2,6-dinitrotoluene
 37B   1,2-diphenylhydrazine
 39B   fluoranthene
 40B   4-chlorophenyl phenyl ether
 41B   4-bromophenyl phenyl ether
 42B   bis(2-chloroisopropyl) ether
 43B   bis(2-chloroethoxy) methane
 52B   hexachlorobutadiene
 53B   hexachlorocyclopentadiene
 54B   isophorone
 55B   naphthalene
 56B   nitrobenzene
 61B   N-nitrosodimethylamine
 62B   N-nitrosodiphenylamine
 63B   N-nitrosodi-n-propylamine
 66B   bis(2-ethylhexyl) phthalate
 67B   butyl benzyl phthalate
 68B   di-n-butyl phthalate
No. of Occurrences
in Indirect
Wastewaters
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
5*
0
0
Max. Indirect
Wastewater
Concentration








•







12

















12

2700*


                                                                        Basis For
                                                                        Exclusion
                                                                     Infrequent
                                                                        ii
                                                                        it
                                                                        ii
                                                                        ti
                                                                        it
                                                                        ti
                                                                        11 & low level
                                                                        11 & low level
                                                                        it
                                                                        it
                                                                        it
                                                                        ii
*  Phthalate occurrence likely the result  of sample contamination by sample tubing.
                                      96

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                               TABLE VI-6 (Continued)
No.

 69B
 70B
 71B
 73B
 74B
 75B
 76B
 77B
 78B
 79B
 SOB
 81B
 82B
 83B
 84B
129B

 89P
 90P
 91P
 92P
 93P
              Compound
 95P
 96P
 97P
 98P
 99P
100P
101P
102P
103P
104P
105P
106P
107P
108P
109P
HOP
HIP
112P
113P
114M
115M
117M
118M
119M
       di-n-octyl phthalate
       diethyl phthalate
       dimethyl phthalate
       benzo(a) pyrene
       3,4-benzofluoranthene
       benzo(k) f luoranthane
       chrysene
       acenaphthylene
       anthracene
       benzo(ghi) perylene
       fluorene
       phenanthrene
       dibenzo(a,h) anthracene
       indeno(l,2,3-C,D) pyrene
       pyrene
       2,3,7,8-tetrachloro-
         dibenzo-p-dioxin (TCDD)
       aldrin
       dieldrin
       chlordane
       4,4'-DDT
alpha-endosulfan
beta-endosulfan
endosulfan sulfate
endrin
endrin aldehyde
heptachlor
heptachlor epoxide
alpha-BHC
beta-BHC
gamma-BHC (lindane)
delta-BHC
PCB-1242
PCB-1254
PCB-1.221
PCB-1232
PCB-1248
PCB-1260
PCB-1.016
toxaphene
antimony (total)
arsenic (total)
beryllium (total
cadmium (total)
chromium (total)
No. of Occurrences
    in Indirect
   Waste waters

        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0

        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        0
        7
        3
        2
        3
       11
                                              Max. Indirect
                                               Wastewater
                                              Concentration
              Basis For
              Exclusion
                                                             Infrequent
                                                                it
                                                                n
                                                                n
                                                                n
210

  2
 32
650
                                                                      treatable level
                                                                    n
                                                                    it
n
n
n
it
                                                                                ii
                                                                                ii
                                                                                n
                                     97

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                               TABLE VI-6 (Continued)
No.

120M
122M
123M
12m
125M
126M
127M
128M
116
       Compound
copper (total)
lead (total)
mercury (total)
nickel (total)
selenium (total)
silver (total)
thallium (total)
zinc (total)
No. of Occurrences
    in Indirect
   Wastewaters

       11
        8
        7
        8
        3
        1
        2
       10
 Max. Indirect
 Wastewater
Concentration

     150
     286
      50
     630
      30
      21
      43
     522
    Basis For
    Exclusion
  treatable level
it
it
it
ti
n
it
it
n
it
                                     98

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                      TABLE VI-7
POLLUTANTS CONSIDERED FOR PRETREATMENT STANDARDS
                                              Max. Wastewater
                           No. of Occurrences   Concentration Level
                                                   (ug/L)
                                                     590
121
cyanide ^
Volatile Organics:
2V
3V
4V
6V
7V
10V
11V
13V
23V
29V
30V
38V
44V
47V
85V
86V
87V
acrolein 2
acrylonitrile 1
benzene 6
carbon tetrachloride 1
chlorobenzene 2
1,2-dichloroethane 2
1,1,1-trichloroethane *
1 , 1 -dichloroe thane 3
chloroform 6
l,l»dichloroethylene 2
1 ,2-trans-dichloroethylene 1
ethylbenzene 3
methylene chloride 9
bromoform 1
tetrachloroethylene 1
toluene ^
trichloroethylene 1
                                                      100
                                                      100
                                                      580
                                                      300
                                                       11
                                                      290
                                                  360,000
                                                       27
                                                    1,350
                                                       10
                                                      550
                                                       21
                                                  890,000
                                                       12
                                                        2
                                                     1,050
                                                        7
                         99

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by the provisions of Paragraph 8  of  the  Settlement  Agreement.
Thirteen  of  these  pollutants  have been excluded because their
amount and toxicity, taken together, are so insignificant as  not
to   justify   developing   uniformly   applicable   pretreatment
regulations.  Of  the  remaining,  there  are  two  (benzene  and
toluene)  which,  while  not  as  insignificant,  nonetheless are
unlikely to pass through POTWs.

In the case of benzene and toluene, the data indicate that direct
discharger median percent reductions exceed POTW  median  percent
reductions  by  less  than  5  percent  (100  percent  for direct
dischargers versus 99 percent for  benzene  and  97  percent  for
toluene  at  POTWs).  In light of the fact that EPA had less data
in the POTW studies on benzene and toluene than it had  for  some
other  pollutants  and  in  light of the variability in analyzing
samples for organic priority  pollutants  at  the  concentrations
typically  found  in  end-of-pipe biological systems at POTWs and
pharmaceutical plants, EPA believes that differences of 5 percent
or less between the direct discharger and POTW data  for  benzene
and toluene are unlikely to reflect real differences in treatment
efficiency.   Therefore,  EPA  has  determined  that  benzene and
toluene do not pass through POTWs.

However, a potential interference problem could exist  for  these
two toxic volatile organics because of a potential fire/explosion
hazard.   Benzene  and  toluene  water  mixtures  have  low flash
points.  Relatively small concentrations  of  these  solvents  in
water  mixtures (about 180 ing/1) can cause spontaneous combustion
in  the  vapor  space  above  the  water  mixture  under  certain
conditions.     EPA's    latest    information   indicates   that
fire/explosions, while not impossible, are unlikely.  Benzene and
toluene levels above the minimum concentrations required to cause
combustion have not been reported in discharges  from  plants  in
the pharmaceutical industry.  Because pass through does not occur
and  interference is unlikely> there is no basis for establishing
nationally  applicable  categorical  pretreatment  standards  for
benzene  or  toluene.   However,  under  the general pretreatment
regulation, 40 CFR  8403.5,  an  individual  POTW  may  establish
pretreatment  standards  if  benzene  and toluene discharges from
pharmaceutical users result in interference.  Section VII of this
document contains suggested pretreatment  standards  for  benzene
and toluene, based on steam stripping, for consideration by POTWs
establishing standards under 8403.5.

At   direct   discharging  pharmaceutical  manufacturing  plants,
chloroform is reduced to levels that are below  its  treatability
through   volatilization   in   biological   treatment   systems.
Therefore, we have excluded chloroform from BAT regulations under
the  provisions  of  paragraph  8(a)(iii)   of   the   Settlement
Agreement.   As  for  indirect  dischargers, the Agency has found
that  POTWs  to  which  high  concentrations  of  chloroform  are
discharged  achieve  high  chloroform  removal  (greater  than 95
percent).  Therefore,  POTWs  receiving  high  concentrations  of
                                 100

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chloroform  as a result of pharmaceutical discharges are unlikely
to experience pass through.   For  the  above  reasons,  EPA  has
decided  not  to  establish  pretreatment  standards  controlling
chloroform from indirect discharging pharmaceutical plants.

Through this process, the Agency determined that  only  methylene
chloride  was a candidate for national PSES and PSNS regulations.
To address the issue  of  pass  through,  EPA  studied  50  well-
operated  POTWs  that  use  biological treatment to determine the
extent  to  which  priority   pollutants,   including   methylene
chloride,  are  reduced  by  such  POTWs.(136)  The  Agency  also
conducted a sampling episode  in  response  to  comments  on  the
proposed regulation in order to determine whether pass through of
toxic  volatile  organics  is occurring at POTWs as the result of
discharges from  pharmaceutical  plants.   During  this  sampling
episode, the influent and effluent of a well operated POTW having
secondary  treatment  in-place  as  well  as  the effluent from a
pharmaceutical plant were sampled  to  determine  the  levels  of
toxic  volatile  organics  present.   The results of the sampling
episode indicate that there is pass through of methylene chloride
at the sampled POTW and that this pass through is principally the
result of discharges of methylene chloride from a  pharmaceutical
manufacturing  facility.   A  more  complete  discussion  of  the
sampling episode and the results may be found in the contractor's
report  entitled  "Pretreatment  Standards  Evaluation  for   the
Pharmaceutical  Manufacturing Category - Data Evaluation Report",
August, 1983.(137)

EPA found, however, that the installation and operation of  steam
strippers  to  reduce  methylene  chloride discharges to POTWs by
pharmaceutical  plants  would  result  in  costs  that  are   not
insignificant.  EPA estimates that 25 indirect discharging plants
would  incur capital and total annual costs of $0.748 million and
$0.768 million (1982  dollars),  respectively,  per  plant.   The
Agency  projects  that  one  indirect  discharging pharmaceutical
plant  would  close  if  required  to  install  steam   stripping
technology.  Steam strippers are also equally energy intensive at
indirect  discharging  plants  as  at  direct  dischargers.   EPA
estimates that the operation of steam strippers at the 25  plants
would  increase energy usage by the equivalent of 315,000 barrels
of oil per year.  For these reasons  and  because  EPA  concluded
that  regulation  of  methylene chloride at direct dischargers is
inappropriate,  the  Agency  has   decided   not   to   establish
categorical PSES and PSNS for methylene chloride.

Data  on the capabilities of steam stripping technology to reduce
the discharge of methylene chloride and on the cost of installing
and operating steam strippers to control toxic volatile  organics
is presented in Section VII and Appendix A.  This information may
be  used  by  municipalities in developing pretreatment standards
for methylene chloride on a case-by-case basis where necessary.
                                  101

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                           SECTION VII

                CONTROL AND TREATMENT TECHNOLOGY
A.  INTRODUCTION

This  section  addresses  the  technologies  currently  used   or
available  to remove or reduce wastewater pollutants generated by
the pharmaceutical manufacturing industry.   Although  wastewater
flow  and raw waste load vary from plant to plant, pharmaceutical
wastewaters are treatable by the  technologies  discussed  below.
Many  possible  combinations  of  in-plant  source  controls  and
technologies and end-of-pipe treatment  systems  are  capable  of
reducing  pollutant  discharges.   However, each individual plant
must make the final decision concerning the specific  combination
of  pollution  control  measures  best  suited  to its particular
situation.

In identifying appropriate control  and  treatment  technologies,
the  Agency  assumed  that  each  manufacturing plant had already
installed or would install the equipment necessary to comply with
the 1976 BPT limitations.  The treatment  technologies  currently
in-place at plants in the pharmaceutical industry, as reported in
308   responses,  are  listed  in  Appendix  L  of  the  Proposed
Development Document.  Thus, the technologies described below are
those which can further reduce the discharge of  pollutants  into
navigable  waters  or  POTWs.   They  are  divided into two broad
classes: in-plant and end-of-pipe technologies.

Since the ultimate receiving point of a plant's wastewater (e.g.,
POTW vs. river)  can  be  critical  in  determining  the  overall
treatment  effort  required, information on ultimate discharge is
also presented in this section.

B.  IN-PLANT SOURCE CONTROL

The intent of in-plant source control is to reduce  or  eliminate
the  hydraulic  and/or  pollutant  loads  generated  by  specific
sources   within   the   overall   manufacturing   process.    By
implementing   controls   at   the  source,  the  impact  on  and
requirements of subsequent downstream treatment  systems  can  be
minimized.

Many   of  the  newer  pharmaceutical  manufacturing  plants  are
designed with the reduction of water  use  and  subsequent  mini-
mization  of  contamination  as  part of the overall planning and
plant design criteria.   Improvements  also  have  been  made  in
existing plants  to provide better control of their manufacturing
                               103

-------
processes  and  other  activities and the resultant environmental
effects.  Some examples of in-plant  source  controls  that  have
been effective in reducing pollution loads are as follows:

(1)  Production processes have  been  modified  or  combined  and
     reaction  mixtures  have  been  concentrated to reduce waste
     loads as well as to increase yields.   Processes  have  also
     been  reviewed  and  revised  to  reduce the number of toxic
     substances used.

(2)  Efforts have been made to concentrate and  segregate  wastes
     at  their  source  to  minimize  or  eliminate  wastes where
     possible.   New  process  equipment  has  been  designed  to
     produce effluents requiring no further treatment.

(3)  Several techniques have been employed to reduce  the  volume
     of  fermentation  wastes discharged to end-of-pipe treatment
     systems.  One approach involves concentrating  "spent  beer"
     wastes  by  evaporation and then dewatering and drying waste
     mycelia.  The resulting dry product in  some  instances  has
     sufficient  economic  value  as an animal feed supplement to
     offset part of the drying cost.

(4)  Several  plants  have  installed  automatic   TOC-monitoring
     instrumentation  or  both  pH  and  TOC monitoring to permit
     early  detection  of  process  upsets  that  may  result  in
     excessive discharges to sewers.

(5)  The recovery of waste solvents is a  common  practice  among
     plants  using  solvents  in  their  manufacturing processes.
     However, to reduce  further  the  amount  of  waste  solvent
     discharge,  plants  have  instituted  such  measures  as (a)
     incineration of  solvents  that  cannot  be  recovered  eco-
     nomically,   (b)  incineration  of  "bottoms"  from  solvent
     recovery units, and (c)  design and construction  of  solvent
     recovery   columns   which  operate  beyond  the  economical
     recovery point.

(6)  The use of barometric condensers can result  in  significant
     water  contamination,   depending  upon  the  nature  of  the
     materials entering the discharge water stream.   In addition,
     barometric condensers use very large  quantities  of  water,
     which  results  in substantial increases in the total amount
     of process-wastewater.  (For example,  plant  12256  utilizes
     more  than  20  MGD  of  once-through  barometric  condenser
     water.)  On the other hand, several plants are using surface
     condensers   which   do   not   involve    direct    contact
     contamination.

(7)  Several plants are using a recirculation system as  a  means
     of  greatly  reducing the amount of contaminated water being
     discharged from water-sealed vacuum pumps.
                              104

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(8)  Reduction of once-through cooling water by recycling through
     cooling towers is used in numerous  plants  and  results  in
     decreased total volume of discharge.

(9)  Separation of manufacturing  area  stormwater  is  practiced
     throughout  the industry and often facilitates the isolation
     and treatment of contaminated runoff.

(10) Spill prevention is recognized in the industry as a critical
     aspect  of  pollution  control.   In  addition  to   careful
     management  of  materials and methods, such preventive steps
     as impoundment basins are utilized in many cases.

(11) Wash waters can be reduced or eliminated in many  situations
     by  use  of  dry  cleanup  methods.  Containment control and
     removal of either liquid or solid  dry  process  wastes  can
     often  be  accomplished  using  little  or  no  water.  This
     particular  approach  can  possibly   completely   eliminate
     wastewater    discharge,   especially   in   subcategory   D
     (Formulation) plants, where  washwater  is  often  the  only
     wastewater source.
C.
IN-PLANT TREATMENT
Besides implementing source controls to reduce or  eliminate  the
waste  loads  generated  within the manufacturing process, plants
may also employ in-plant treatment directed at  removing  certain
pollutants  before  they  are  combined  with the plant's overall
wastewaters and are thus diluted.


This concept of in-plant treatment of a segregated stream  is  of
major  importance.  First, treatment technologies can be directed
specifically  toward  a  particular   pollutant.    Also,   since
wastewater  treatment  and  pollutant  removal costs are strongly
influenced by the volume  of  water  to  be  treated,  the  costs
involved  in  treating  a segregated stream are considerably less
than they  would  be  in  treating  combined  wastewater.   Also,
chemicals  other  than  those  being  treated  are less likely to
interfere with  the  treatment  technology  if  treatment  occurs
before commingling.

In-plant  treatment  processes  can  be visualized as end-of-pipe
treatment for a particular production process or stage within the
plant itself, designed to treat specific waste streams.  Although
in-plant technologies can remove a variety of  pollutants,  their
principal applications are for the treatment of toxic or priority
pollutants.   In the pharmaceutical manufacturing industry, three
classes of priority pollutants are of particular importance.   As
indicated  in  Section  V,  the  major  priority  pollutants  are
solvents, metals, and cyanide.  Thus, the  discussions  presented
below  on  in-plant  technologies  concern the treatment of these
three classes of pollutants.
                              105

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The 308  data  base  was  the  principal  source  of  information
relating  to  the use of in-plant treatment in the pharmaceutical
industry.  Most of this information came  from  the  Supplemental
308  Portfolio  responses.   In  addition, while not specifically
requested in the original 308 Portfolio, some in-plant  treatment
information  was obtained from the original 308 Portfolio plants.
It was gathered via three mechanisms:  a)  some  plants  provided
"additional"  data  or comments relative to in-plant treatment on
the questionnaire; b) a small amount of information was  gathered
by  direct  contact  with  plant personnel; and c) the wastewater
sampling programs discussed in Section II identified tne use of a
few in-plant technologies.  Some information  on  in-plant  steam
stripping was also obtained following proposal (a) as a result of
the  Agency's  efforts to locate an appropriate plant at which to
evaluate the performance of steam stripping technology and (b) as
a  result  of  responses  obtained  from  a  post  proposal   308
questionnaire concerning the discharge of toxic volatile organics
by  indirect discharging pharmaceutical plants.  The responses to
this 308 questionnaire will be discussed  in  the  part  of  this
section that deals with steam stripping.

Table VI1-1 presents a summary of in-plant treatment technologies
identified  from  the various data bases along with the number of
plants that employ each process.

1•   Cyanide Destruction Technologies

Cyanide destruction is employed in the  pharmaceutical  industry,
as  noted  by the 308 responses by limited direct inquiry, and by
information from the S/V program.

Two treatment processes  have  been  found  to  be  effective  in
treating  cyanide-bearing  waste  streams  in  the pharmaceutical
industry; chemical oxidation and high  pressure  and  temperature
hydrolysis.   Chemical  oxidation  is  a reaction in which one or
more electrons are transferred from the chemical  being  oxidized
to  the chemical initiating the transfer (oxidizing agent).  As a
result of the valance change, the  oxidized  substance  can  then
react   to  form  a  more  desirable  compound.   The  hydrolysis
treatment  requires  the  application  of  high  temperature  and
pressure  to  break  down  chemical bonds; the end result is that
more tolerable substances are formed (e.g., C02 and N02).   Under
some  circumstances, cyanide ions may combine with metals to form
inert complexes which may interfere  with  removal  of  both  the
cyanide and  the  metal.  Of  the  comonmly  encountered  metals,
                             106

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                              TABLE VII-1



                SUMMARY OF IN-PLANT TREATMENT PROCESSES




In-Plant Technology                               Number of Plants



Cyanide Destruction                                     9




Chromium Reduction                                      1




Metals Precipitation                                    4




Solvent Recovery                                       30




Steam Stripping                           .              3



Other Technologies                                     21




     Evaporation                                       10
                                   107

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chromium,  manganese, and iron form inert complexes, while nickel
and mercury form labile complexes;

                           Cyanide Complexes
          Inert

          Cr (CN)6-«
          Mn
          Fe
                                              Labile

                                              Ni (CN)4~2
                                              Hg (CN)4-2
Although they are classified as inert, cyanide will  be  released
from  the  inert  complexes  over  an  extended  period  of time.
However, this time period may exceed the residence  time  in  the
cyanide  destruction  unit and cyanide from these complexes would
not  be  destroyed.   The  labile  complexes  will   present   no
interference with cyanide destruction.

An  evaluation  of  cyanide limitations practically achievable by
chemical oxidation and hydrolysis technologies must consider  the
following:

     (1)  Theoretical reaction equilibrium limits.

     (2)  Conditions under which cyanate reversion can occur.

     (3)  Competitive reactions resulting  in  increased  oxidant
          consumption.

     (4)  Chemical interferences such as iron complexing and  the
          processing alternatives necessary to avoid them.

     (5)  Physical  interferences  which  might  hamper  reactant
          availability and design methods to overcome them.
a.
Chlorination
Destruction of cyanide by  oxidation  either  with  chlorine  gas
under  alkaline  conditions or with sodium hypochlorite is a very
common  method  of  treating  industrial  wastewaters  containing
cyanide.   Although  more  costly,  sodium  hypochlorite  is less
hazardous and is simpler to handle.  Oxidation by chlorine'  under
alkaline  conditions  can  be described by the following two-step
chemical reaction:
C12 + NaCN + 2 NaOH » NaOCN + 2 NaCl + H2O

3C12 + 6NaOH + 2NaOCN = 2 NaHC03 + N2 + 6 NaCl
                                                      2 H20
Cyanide is oxidized to cyanate completely and rapidly at a pH  of
about  9.5  to 10.0.  Usually 30 minutes are required to insure a
complete reaction.   The  oxidation  of  cyanide  to  cyanate  is
                               108

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accompanied   by   a   marked   reduction
thousandfold reduction in toxicity.
in  volatility  and  a
However,  since  cyanate  may  revert  to  cyanide   under   some
conditions, additional chlorine is provided to oxidize cyanate to
carbon dioxide and bicarbonate.  At pH levels around 9.5 to 10.0,
several  hours  are  required  for  the complete oxidation of the
cyanate, but only one hour is necessary at a pH between  8.0  and
8.5.   Also,  excess  chlorine  must  be  provided  to break down
cyanogen chloride, a highly toxic  intermediate  compound  formed
during the oxidation of cyanate.

Although  stoichiometric  oxidation  of  one  part  of cyanide to
cyanate requires only 2.73 parts of chlorine, in practice 3 to  4
parts  of  chlorine  are  used.  Complete  oxidation  of one part
cyanide to carbon dioxide and nitrogen gas theoretically requires
6.82 parts of chlorine, but nearly 8 parts are normally necessary
in practice.  The chlorine required in practice  is  higher  than
the theoretical amount because other substances in the wastewater
compete for the chlorine.

Soluble  iron interferes seriously with the alkaline chlorination
of cyanide wastes.  Iron and cyanide form a stable complex  which
is impervious to chlorine oxidation.  Similar difficulties result
from formation of nickel cyanides.  However, it has been reported
that  ferrocyanides  are  treatable by alkaline chlorination at a
temperature of 71<>C (160°F) and at a pH of about 12.0. (109)

Ammonia also interferes with the chlorine oxidation process since
the chlorine demand is increased by the formation of chloramines.
When cyanide is only being oxidized to cyanate, it is usually not
economical to remove  the  ammonia  by  breakpoint  chlorination,
which  requires  almost 10 parts of chlorine per part of ammonia.
Complete cyanate formation can be  accomplished  by  allowing  an
extra   15  minutes  contact  time.   An  example  of  a  cyanide
destruction system using chlorination is shown in Figure VII-1.

Because of some of the advantages of  the  chlorination  process,
this  technology  has  received  widespread  application  in  the
chemical industry as a whole.  It is a relatively low cost system
and does not require complicated equipment.  It  also  fits  well
into  the  flow  scheme  of a wastewater treatment facility.  The
process will operate effectively at  ambient  conditions  and  is
well  suited  for  automatic  operation,  thus  minimizing  labor
requirements.   This  technique   is   used   by   pharmaceutical
manufacturers who use cyanide in chemical synthesis.

The  chlorination  process,  however,  does  have limitations and
disadvantages. For example, toxic, volatile intermediate-reaction
products can  be  formed.   Thus,  it  is  essential  to  control
properly the pH to ensure that all reactions are carried to their
end  point.   Also, for waste streams containing other oxidizable
matter, the chlorine may be consumed in oxidizing these materials
                              109

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and this  may  interfere  with  the  treatment  of  the  cyanide.
Finally,  for those systems using gaseous chlorine, a potentially
hazardous situation exists when it is stored and handled.

The oxidation of cyanide-bearing wastewaters  by  using  chlorine
under basic conditions is a classic technology.  However, its use
by  the  pharmaceutical  industry is limited to a few plants.  In
the Agency's study of the electroplating  industry,  EPA  learned
that  cyanide  levels  around  40 vq/l are achievable by in-plant
chlorination  processes,  if  reaction  interferences   are   not
present.  (109)  In  addition, the Final Development Document for
the Inorganic Chemicals Industry (71)  indicates  that  the  free
cyanide  level  after  chemical  oxidation treatment is generally
below 100 ug/1.  The extent to which the various materials  found
in   pharmaceutical   wastewater   may  interfere  with  chlorine
oxidation is not known.  The presence of  interfering  substances
in  pharmaceutical manufacturing wastewater may, in fact, prevent
the attainment of these levels using  the  alkaline  chlorination
method.

Chemical  oxidation  of  cyanide  is currently the most prevalent
technique used  by  pharmaceutical  plants  to  destroy  cyanide.
However,  the  available  data from plants using this method does
not permit an adequate  evaluation  of  the  cyanide  destruction
capability   of  this  technique  as  applied  to  pharmaceutical
wastewater and, therefore, no data describing this the method has
been used in the development of final cyanide regulations for the
pharmaceutical manufacturing point source category.
b.
Ozonation
Ozone is a good oxidizing agent and can be used to treat  process
wastewaters  that  contain cyanide.  In fact, ozone oxidizes many
cyanide complexes  (for instance, iron and nickel complexes)  that
are  not broken down by chlorine.  Ozonation is primarily used to
oxidize cyanide to cyanate.

With traces of copper and  manganese  as  catalysts,  cyanide  is
reduced   to   very   low   levels,   independent   of   starting
concentrations and the form of the  complex.   The  oxidation  of
cyanide by ozone to cyanate occurs in about  15 minutes at a pH of
9.0  to  10.0,  but  the  reaction is almost instantaneous in the
presence of traces of copper.  The pH of  the  cyanide  waste  is
often  raised  to  12.0  in  order that complete oxidation occurs
before the pH drops to 8.0, at  which  point  cyanide  begins  to
evolve in the form of HCN.

Oxidation  of  cyanate  to  the  final end products, nitrogen and
bicarbonate, is a much slower and more difficult  process  unless
catalysts  are  present.  Therefore,  since  ozonation  will  not
readily effect further oxidation of cyanate, it is often  coupled
with   such  independent  processes  as  dialysis  or  biological
oxidation.
                               Ill

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The ozonation treatment process  is  being  used  on   an   increasing
basis.    Its  initial  applications  in   treating metal  finishing
wastewater have shown  it   to  be   quite  effective for  cyanide
removal.  Like chlorination, the ozonation process  is well  suited
to  automatic  control  and will   operate effectively  at  ambient
conditions.  Also, the reaction  product  (oxygen) is beneficial  to
the treated wastewater.  Since the  ozone  is  generated  on-site,
procurement, storage, and handling  problems are eliminated.

The ozonation process does  have  drawbacks.  It has  higher  capital
and  operating  costs  than chlorination and  similar  toxicity
problems; also, as with chlorination,  increased ozone   demand   is
possible  if  other  oxidizable  matter   is  present in  the waste
stream.   Finally, in most cases, the  cyanide is  not  effectively
oxidized  beyond the cyanate level.

c.   Alkaline Hydrolysis

Removal of cyanide from process  wastewaters can  be accomplished
without   the use of strong  oxidizing  chemicals.  For the alkaline
hydrolysis system, the principal treatment action is  based  upon
the application of heat and pressure.  In this process,  a  caustic
solution  is added to the cyanide-bearing  wastewaters to  raise the
pH  to between 9.0 and 12.0.  Next, the wastewater  is transferred
to a continuous flow  reactor  where   it  is  subjected  to  tem-
peratures  of about 165°C to 185°C  (329°F to 365°F) and  pressures
from approximately 90 to 110 psi.   The breakdown  of  cyanide   in
the  reactor  is  generally accomplished  with a residence  time  of
about 1.5 hours.  An example of  an  alkaline hydrolysis system for
treating  cyanide-bearing wastewaters  is shown in Figure  VI1-2.

The absence  of  specific   chemical   reactants  in  this process
eliminates  procurement, storage, and handling problems.  As with
other cyanide processes, alkaline hydrolysis is  well  suited   to
automatic control.

In   the   pharmaceutical    industry,   wastewaters  having  high
concentrations of cyanide   are  more  likely  to  be  treated   by
alkaline hydrolysis, for economic reasons.

As  in the case of chlorination, data are available regarding the
pharmaceutical industry's use of alkaline hydrolysare for cyanide
treatment.  The data available from these plants  indicated  that
the  cyanide  levels  reached  by   this technology  are similar  to
those  achieved   by   the   chlorination   process.     Long-term
performance  data  has  been submitted   by two plants  (12236 and
12235)  which  use  this  method  to  destroy  cyanide   in  their
wastewater.   The available  data  indicate  that an average effluent
level  of  5.25  mg/1 is achievable for cyanide.  This level is a
direct measure of what is achievable as a result of the  alkaline
hydrolysis technique.
                               112

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2.   Metals Removal Technologies
This discussion of metals removal technologies is presented  even
though   the  Agency  is  not  promulgating  effluent  guidelines
limitations for metals.  It is intended to aid permit writers and
others  who  may,  at  some  point,  have  an  interest  in   the
performance of these technologies.

Proven metals treatment technologies are based upon precipitation
and  filtration.   Based  on the solubility products (Ksp) quoted
for insoluble metal salts (113), the concentration of metal  ions
in a saturated solution can be calculated and are listed below:
          Compound
Metal Ion
Concentration (yq/1)
          CuS
          NiS
          ZnS
          HgS
          Cu(OH)2
          Ni(OH)-,
          Zn(OH)2
          Cr(OH)3
1
3
3
1
1
6
6
2
.6
.5
.5
.5
.8
.7
X
X
X
X
X
X
X
X
1
1
1
1
1
1
1
1
Q-36
Q-2S
0-25
0-52
Q-19
0-15
0-14
Q-31
1
8
2
3
  x 10~10
  x 10-*
  X 10-5
  x 10~l«
  25
 400
1  x 10-3
6 x 10-i
These  concentrations  represent theoretically achievable levels.
Comparison of theoretically achievable treatment levels of  metal
priority  pollutants to levels specified in final regulations for
other categories  (i.e.,  metal  finishing)  shows  that  sulfide
precipitation  is theoretically capable of removing the metals to
levels several orders of magnitude lower than the levels that are
practically achieved.  Theoretical metal concentrations resulting
from hydroxide precipitation  are  also  lower  then  the  levels
generally achievable by hydroxide precipitation as practiced.

Thus,  in  most  cases,  the  solubility  level  will  not be the
controlling factor in  establishing  minimum  levels.   Practical
limits  of  removal  are dictated by other circumstances, many of
which  are  peculiar  to  particular  treatment  processes.   The
efficiency  of  physical  removal  of precipitated solids by such
means as filtration or clarification is limited by such  particle
characteristics   as  particle  size  and  stability,  which  are
functions of pH and  of  other  chemicals  present.   Many  metal
cations  are  subject to chemical complexing that transforms them
into an unprecipitable species, causing interference  with  their
removal.

Treatment   system   performance   under   industrial   operating
conditions  is  shown  in  Table  VI-5.   The  levels  shown  are
estimates  of  practical  attainable  long-term  average effluent
concentrations for priority pollutant metals.  Of the six  metals
of  special  interest  in this study, copper, chromium, lead, and
                              114

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nickel are generally amenable to reductions to approximately  500
»g/l  at the point of metals treatment.  Although zinc reductions
to about 500  vg/1  are  reported,  1,200  ^g/1  may  be  a  more
realistic limit for the zinc content of wastewater since a higher
final  concentration  is  also  reported  for all three treatment
methods.   Mercury  concentrations,  though  not   treatable   by
alkaline  precipitation,  may  be reduced to around 50 ug/1 after
sulfide precipitation and filtration.
a.
Chemical Reduction
Chromium and some other metals must be reduced  from  their  high
valence   states  before  they  can  be  precipitated.   This  is
accomplished by chemical reduction, a reaction in  which  one  or
more  electrons  are transferred from the chemical initiating the
transfer (reducing agent) to the chemical being reduced.

An  application  of  chemical  reduction  in  the  treatment   of
industrial  wastewater is in the reduction of hexavalent chromium
to trivalent chromium.  Chromium is a common metal contaminant in
pharmaceutical industry wastewaters; its  chemical  reduction  is
employed as an in-plant treatment by the industry.  The reduction
enables  the  trivalent  chromium in conjunction with other metal
salts to be separated from  solution  by  precipitation.   Sulfur
dioxide,  sodium  bisulfite,  sodium  metabisulfite,  and ferrous
sulfate are strong reducing agents in aqueous solution  and  are,
therefore,  useful  in  industrial waste treatment facilities for
the reduction of hexavalent chromium to trivalent chromium.

The chemical reduction of chromium wastes by sulfur dioxide is  a
well-known  and  widely accepted treatment technology in numerous
plants employing chromium or other high  valence  ions  in  their
manufacturing  operations.   An application of this technology to
treat process wastewaters containing chromates  is  described  in
Figure  VII-3.   The  reactions  involved  may  be illustrated as
follows:
       3S05
         3H20
= 3H,S03
       3H2S03 + 2H2Cr04    = Cr2(S04)3 + 5H20

This reaction is favored by a low pH;, a value of 2.0 to  3.0   is
normally  required  for  complete  reduction.  At pH levels above
5.0, the reduction  rate  is  slow.   Such  oxidizing  agents   as
dissolved  oxygen  and  ferric  iron interfere with the reduction
process by consuming the reducing agent.  The sulfate precipitate
can be removed by filtration or clarification.

Chemical reduction has been  used  quite  successfully  to  treat
large  concentrations  of  hexavalent  chromium  {e.g., from metal
finishing operations).  This method is well suited  to  automatic
control and may be used under ambient conditions.
                               115

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Chemical  reduction,  however,  is  not without some limitations.
Careful pH control  is  required  for  effective  reduction.   In
addition,  when waste streams contain other reducible matter, the
reducing agent may be  consumed,  depleting  that  available  for
treatment  of  the  metals.  Also, for those systems using sulfur
dioxide, a potentially hazardous  situation  exists  when  it  is
stored and handled.  Data  indicate that chromium levels below 500
Mg/1  can  be achieved from in-plant chromium reduction processes
in  combination  with   hydroxide   precipitation   followed   by
clarification.(109)

b.   Alkaline Precipitation

The solubility of metal hydroxides, in most cases, is a  function
of  pH;  therefore,  the success of metal hydroxide precipitation
treatment is heavily dependent on the pH level of  the  solution.
In  order to achieve optimum formation of solid metal hydroxides,
the pH of the wastewater must be adjusted to the  range  (usually
moderately  alkaline) found to be most effective for the metal(s)
involved.  This is accomplished by measured addition of  lime  to
the wastewater with concurrent pH monitoring.

Following  the  attainment  of  optimum  pH conditions, the solid
metal hydroxides are coagulated (using coagulating agents)  in  a
clarifier  and  deposited  as sludge.  Proper clarifier design and
good coagulation are important prerequisites for efficient metals
removal by alkaline precipitation.

If substantial sulfur compounds are present  in  the  wastewater,
caustic  soda  (sodium  hydroxide) may be used instead of lime to
prevent calcium sulfate formation  which  would  increase  sludge
volume.    Treatment   chemicals   for   adjusting  pH  prior  to
clarification may be added to a rapid mix tank, to a mix box,  or
directly to the clarifier, especially in batch clarification.  If
such  metals as cadmium and nickel are in the wastewater, a pH in
excess of 10.0 is required for effective precipitation.  This pH,
however, is unacceptable for  discharged  wastewater;  therefore,
the pH must be reduced by  adding acid.  The acid is usually added
as  the  treated  wastewater flows through a small neutralization
tank prior to discharge.   An example of a metals removals  system
using alkaline precipitation is shown in Figure VII-4.

There   are   several   advantages   to   the   use  of  alkaline
precipitation.  In the first place, it  is  a  well  demonstrated
wastewater  treatment technology.  It is well suited to automatic
control and will operate at ambient conditions.   Also,  in  many
instances, preceding treatment steps adjust the waste  (especially
pH) to aid the alkaline precipitation process.  The end result is
that   the   costs   associated   with  this  technology  may  be
substantially lower than those  for  other  processes.   However,
this  method  is  subject  to  interference when mixed wastes are
treated.  In addition, this process can generate relatively  high
quantities of sludge that  also require disposal.
                               117

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Alkaline  precipitation  is  a  classic  technology being used by
plants in a number of industry categories, although  its  use  by
the  pharmaceutical  industry has been limited.  The EPA study to
develop BPT regulations for  the  electroplating  industry   (109)
indicated  that  the alkaline precipitation process is capable of
achieving the following long-term effluent levels: 300  ug/1  for
chromium  and  zinc,  200 ug/1 for copper, 100 ug/1 for lead, and
500 ug/1 for nickel.

c.    Sulfidle Precipitation

In  this  process,  heavy  metals  are  removed  as   a   sulfide
precipitate.   Sulfide  is  supplied  by  adding  a very slightly
soluble metal sulfide that has a solubility somewhat greater than
that of the sulfide  of  the  metal  to  be  removed.   Normally,
ferrous  sulfide  is  used.   It is fed into a precipitator where
excess sulfide is retained in a sludge blanket that acts both  as
a  reservoir  of  available  sulfide  and  as a medium to capture
colloidal particles.

The process is applicable for treatment of all heavy metals.  The
process equipment required  includes  a  pH  adjustment  tank,  a
precipitator,  a  filter,  and pumps to transport the wastewater.
The filter is optional and may be a standard, dual-media pressure
filter.

A  variation  of  the  process  utilizes  sulfide  for   reducing
hexavalent  chromium.  Ferrous sulfide at a pH of 8.0 to 9.0 acts
as  an  agent  to  reduce  the  hexavalent  chromium   and   then
precipitates  it as a hydroxide in one step.  Hexavalent chromium
wastes do riot have to be isolated and pretreated by reduction  to
the trivalent form.

With  respect  to the generated sludge, sulfide sludges have been
found to be less subject  to  leaching  than  hydroxide  sludges.
However, sulfide precipitation produces sludge in greater volumes
(requiring  more  available  storage  space) and requires greater
expenditures for  chemicals  than  does  alkaline  precipitation.
Pollutant  levels  after treatment with sulfide precipitation are
very   similar   to   the   pollutant   levels   after   alkaline
precipitation.

3.    Solvent Recovery and Removal

Solvents are used extensively in the pharmaceutical manufacturing
industry.    Because   such   materials   are   expensive,   most
manufacturers  try  to  recover  them in order to purify them for
reuse whenever possible.  Solvent recovery  operations  typically
employ such techniques as decantation, evaporation, distillation,
and  extraction.   The  feasibility  and  extent  of recovery and
purification are governed largely by the quantities involved  and
by  the  complexity  of  solvent  mixtures  to  be separated.  If
recovery is not economically practicable, the used  solvents  may
                               119

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have  to   be  disposed   of  by  means  of  incineration,  landfilling,
deep-well  injection,  or  contract  disposal.

Even when  an effort  is made to recover  solvents,  some  wastewater
contamination   can   be   expected.  Removal  of  small quantities  of
organic  solvents  from   the   segregated    wastewater    can  '  be
accomplished  by  such   techniques   as   steam  stripping or  carbon
adsorption.   Further   removal   of   solvents    from    combined
end-of-pipe  wastewater   may  result from biological  treatment  or
from surface evaporation in the treatment system.

4.   Steam Stripping
a.
Introduction
Steam stripping  is the  transfer of  the volatile  constituents of  a
wastewater to the vapor phase which occurs when  steam   is  passed
through a preheated wastewater.  Extremely volatile compounds  can
be  steam  stripped  from wastewater  in flash tanks which provide
essentially one  stage of liquid-vapor  contact.   More  difficult
separations   are   conducted  in   columns  filled  with  packing
materials which  provide  large  surface  areas   for  liquid-vapor
contact.   Conventional  fractionating  columns,  which contain  a
series of liquid-vapor  contact stages,  are  used  for  the  most
difficult  separations.   Flash  tanks,  packed  towers, and plate
columns are used extensively in the chemical  process   industries
and   their   designs   are  discussed  in  chemical  engineering
textbooks.  (138)  (139)  (140)  Hwang   and   Fahrenthold   have
considered  the  thermoclynamic aspects of steam  stripping organic
priority pollutants from wastewater.  (72) The authors predict  the
effluent  concentrations  theoretically   achievable   by   steam
stripping  and   the  actual number of liquid-vapor contact stages
required.

Steam  stripping is  an  available  technology  for  removal  of
methylene  chloride,  toluene,  chloroform, and  benzene.  Section
VIII presents suggested limits for these four pollutants based on
the performance  of wastewater steam strippers at a pharmaceutical
plant.  Steam stripper operations at plant  12003  are  discussed
following the general discussion of steam stripping.

b.   General

In a steam stripper, the components of a wastewater are separated
by partial vaporization.  When contacted with steam, the volatile
organic compounds in a  wastewater  are  driven  into  the  vapor
phase.   The extent of the separation is governed by the physical
properties of the organic compounds, the temperature and pressure
at which the stripper is operated, and the arrangement  and  type
of equipment used.

A column used to steam strip solvents from wastewater is shown on
Figure  VI1-5.   Solvent  contaminated  process  wastewaters  and
                              120

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                                                       COOLING
                                                       WATER
                                                                     VENT TO
                                                                     EMISSIONS
                                                                     CONTROL
                                                                         OPTIONAL
                                                                       I CONDENSATE
                                                                       | DRUM
   STRIPPED
   WASTEWATER
                                                                                     RECOVERED
                                                                                     SOLVENT
                                                   PACKED
                                                   OR
                                                   TRAY
                                                   COLUMN
                                                                                  ^  RECYCLE
                                                                             	P> TO GRAVITY
                                                                                     PHASE
                                                                                     SEPARATION
                                                                                     TANK
                                                                                    \ STEAM
                                                                                     RECOVERED
                                                                                     SOLVENT
FIGURE VII-6. TYPICAL EQUIPMENT FOR STEAM STRIPPING SOLVENTS FROM WASTEWATER.
                                             121

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condensed overhead  vapors  from  the  stripper  are  allowed  to
accumulate   in  a  gravity  phase  separation  tank.   When  the
equilibrium solubility of the solvents in water is  reached,  the
difference  between  the  specific gravities of the water and the
solvents results  in  the  formation  of  two  immiscible  liquid
layers.   One  layer  contains the immiscible solvents; the other
layer is an aqueous solution which is  saturated  with  solvents.
The  solvent  layer is pumped to storage.  The composition of the
recovered solvent and economic factors will determine whether the
solvent  is  reused  within  the  plant,  disposed  of,  used  as
incinerator  fuel,  sold  to other industrial users, or sold to a
solvent  reclamation  facility.   Solvents  recovered  by   steam
stripping  are  normally  not  reused  directly in pharmaceutical
synthesis because of FDA purity requirements.

The aqueous layer from  the  gravity  phase  separation  tank  is
pumped  through  a  preheater  where the temperature is raised by
heat exchange with the stripper effluent.  If the  feed  contains
high   concentrations  of  suspended  solids,  a  filter  can  be
installed prior to  the  preheater  to  prevent  fouling  in  the
preheater and the column.

After  preheating,  the  solvent saturated water is introduced at
the top or near the middle of the column  and  flows  by  gravity
through  the  stripper.  The hot effluent, which is discharged at
the bottom of the stripper, is used as a  heating  medium  in  the
feed  preheater.   Steam  is injected through a sparger and rises
countercurrent to the flow of the water.

The solvent laden overhead vapors are condensed and  the  organic
and  aqueous  layers  are  allowed  to  separate  by gravity in a
condensate drum.  The solvent can be recovered by  decanting  the
immiscible  liquid  layers,  or by recycling the condensed vapors
directly to the gravity phase separation tank.  This practice  is
particularly  advantageous  in  cases  where the wastewater to be
steam stripped contains low concentrations of the solvent  to  be
recovered.   As  the condensate mixes with the wastewater already
in the tank, the solvent concentration  increases  to  the  point
where a two phase mixture is formed.  The aqueous phase, which is
fed  to  the  column,  will  be saturated with solvent.  The most
economical operation of a wastewater steam stripper  occurs  when
the feed is saturated with the solvent to be recovered.

In certain situations, reflux may be required to produce overhead
vapors  which,  when  condensed,  will  separate  into immiscible
liquid  layers.   Initially,  the  condensate   is   allowed   to
accumulate  in a condensate drum.  When the solvent concentration
exceeds the water solubility limit, two liquid layers form.   The
solvent  rich  layer  is  pumped  to  storage.   A portion of the
solvent  saturated  aqueous  layer  is  returned  to  the  column
(refluxed)  and  the  remainder  is recycled to the gravity phase
separation tank.  The reflux is introduced at  a  position  above
the point where the feed enters the column.
                              122

-------
At  plants where steam pressure fluctuations can occur, automatic
feedback controllers are commonly used to  maintain  the  desired
solvent  concentrations  in  the  stripper  bottoms  and overhead
vapors.  A detailed discussion of the use of  automatic  feedback
controllers  for  this  purpose is included in the 4th Edition of
the Chemical Engineers Handbook. (141)

Information gathered by the Agency indicates that steam stripping
is used to remove organic  solvents  and  other  pollutants  from
wastewater discharges from at least six pharmaceutical plants and
that steam stripping is also used to treat similar wastewaters in
other  industries.  Data on the removal of toxic volatile organic
pollutants in steam strippers  at  plants  where  pesticides  and
organic  chemicals are manufactured are presented in the Proposed
Development Document  for  Effluent  Limitations  Guidelines  and
Standards  for  the  Pesticides Point Source Category.(142) Steam
stripping operations at an  indirect  discharging  pharmaceutical
manufacturer are discussed below.

c.   Steam Stripper Operations at Plant 12003

Plant  12003  has  the  capability  to  operate  at  least  eight
different  steam strippers.  The strippers are located throughout
the plant within  production  buildings  or  at  central  solvent
recovery  operations in other buildings.  Steam stripping enables
the plant to meet a POTW requirement that  the  concentration  of
explosive  vapors  in the plant sewer pipes not exceed 40 percent
of the lower explosion limit (LED.  The LEL is monitored in each
production area with a flame-thermocouple  sensor.   Gas  samples
are automatically taken and analyzed by gas chromatography  if the
solvent  vapor  concentration exceeds 30 percent of the LEL.  The
stripped wastewaters are combined with sanitary and other process
wastewaters in  a  pretreatment  system  which  consists  of  oil
skimming, pH adjustment, and flow equalization.

The    recovered   solvents  from  the  stripping  operations  are
currently  stored  for  disposal  by  contract  hauling.    Plant
personnel  informed  EPA that they were considering using some of
the recovered  solvents  as  fuel  for  an  incinerator.    Agency
representatives visited plant 12003 during the week of May  23-27,
1983,  and sampled the influent and effluent from a packed  column
stripper and a steam distillation flash tank.

d.   Packed Column Steam Stripper

Five days of operating data from a packed column  steam  stripper
used   to remove methylene  chloride from wastewater at  plant 12002
are shown in Table VI1-2.   In  addition  to  methylene chloride,
analysis  by  plant  personnel  confirmed  that methanol, diethyl
ether, and pyridine were present in the wastewater.  Usually, the
stripper operates approximately  12 hours a day, five days a week.
During periods of low production, the stripper  is shut down  and
                               123

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wastewaters are allowed to accumulate.  When the stripper resumes
operation, it operates continuously for several days in a row.

The  major portion of the feed to the stripper is wastewater from
a batch chemical synthesis operation.  The feed is pumped to  the
underground settling tank shown on Figure VII-6.  In the settling
tank  the  wastewater  separates  into  two  layers  - immiscible
methylene  chloride  and  an  aqueous  solution  saturated   with
methylene  chloride and small amounts of methanol, diethyl ether,
pyridine, and other solvents listed in  the  footnotes  of  Table
VI1-2.   The  immiscible  methylene  chloride  is  pumped off the
bottom of the settling tank to a spent solvent holding tank.  The
aqueous solution is pumped to the stripper feed tank.   The  feed
rate  to  the  column is controlled by an automatic flow valve on
the discharge side of the feed purnp.

The wastewater  is  pumped  through  an  influent  filter  and  a
preheater before it enters the top of the column through a liquid
distributer - a special pipe outlet which serves to wet the tower
packing  uniformly.   The  ten-inch  diameter column contains one
19-foot section packed with  one-inch  diameter  stainless  steel
pall rings.  Steam is injected through a sparger in the bottom of
the   stripper.   The  overhead  vapors  from  the  stripper  are
condensed and recycled to the underground settling tank.

The results of the five days of verification sampling  are  shown
in  Table VII-2.  The average influent concentration of methylene
chloride was 8,800 mg/1.  The column influent also contains  high
concentrations of inorganic salts.  According to plant personnel,
the  influent  and  effluent  filters  shown on Figure VII-6 were
installed to prevent fouling in the feed preheater.  The  average
effluent  concentration  of  methylene chloride was 6.9 mg/1 when
the column was operated close to  the  design  specifications  of
98°C  overhead  vapor  temperature.   This corresponds to greater
than 99 percent removal  of  methylene  chloride  in  the  packed
column  stripper.   The  packed  column was operating under upset
conditions, as indicated by a drop  in  the  temperature  of  the
overhead  vapors  below  85°C,  during  10  of  the  40  overhead
temperature readings taken during sampling.
e.
Steam Flash Tank
Five days of operating data from a steam flash tank used to strip
toluene from wastewater at plant '12003 are shown in Table  VI1-3.
In  addition  to  toluene,  analysis by plant personnel confirmed
that  methanol,  ethanol,  acetone,  isopropanol,  methyl   ethyl
ketone,  and  diethyl  ether were present in the wastewater.  The
flash tank normally operates 7 hours a day, 5 days a week.
                               129

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Wastewaters from batch pharmaceutical processes,  a  vacuum  pump
system,  and  steam  ejectors are accumulated in two 5,000 gallon
settling tanks as shown  on  Figure  VI1-7.   A  connecting  line
maintains the liquid height at the same level in both tanks.  The
accumulated   wastewater  separates  into  two  liquid  layers  -
immiscible toluene and an aqueous solution of toluene  and  small
amounts  of methanol, ethanol, acetone, isopropanol, methyl ethyl
ketone, diethyl ether, and other solvents listed in the footnotes
of Table VII-3.  The immiscible toluene flows  by  gravity  to  a
spent  solvent  holding  tank.   The  aqueous  solution is pumped
through two preheaters and enters the top of the 500 gallon flash
tank through a  spray  nozzle.   Toluene  is  stripped  from  the
wastewater  by  steam  which is injected through a sparger in the
bottom of the flash tank.   The  overhead  vapors  are  partially
condensed  arid  introduced  to  a  condensate  drum.   The liquid
condensate is recycled to the settling tanks.  Uncondensed vapors
from the condensate drum enter a scrubber where they are absorbed
in previously uncontaminated cooling water.  The  scrubber  water
is  recycled  to  the  settling tanks and the scrubbed vapors are
vented to an emissions control system.

As shown in Table VII-3, the  concentration  of  toluene  in  the
influent  to the flash tank ranged from 320.5 mg/1 to 4,300 mg/1.
It is suspected that the high  influent  concentration  of  4,300
mg/1  on  May 27 was caused by a low liquid level in the settling
tanks.  This probably resulted in a  portion  of  the  immiscible
toluene  being fed to the column along with the miscible solution
of toluene and water.   The  effluent  concentration  of  toluene
ranged   from  0.39  mg/1  to  229.0  mg/1.   The  high  effluent
concentration of 229.0 mg/1 occurred  on  May 26  when  the  tank
operated under upset conditions.   The temperature of the overhead
vapors  during the upset period was 91°C;  the average temperature
of the overhead vapors during the rest of the week was 99°C.   The
average influent and effluent concentrations  for  the  five  day
period  were  516  mg/1 and 4.5 mg/1, respectively,  excluding the
upset periods.  This  corresponds  to  greater  than  99  percent
removal of toluene in the flash tank.

f.   Data Applicability

The vapor-liquid equilibrium relationship of an organic  compound
in  a wastewater forms the basis for determining its removability
by  steam  stripping.   The   magnitude   of   the   vapor-liquid
equilibrium  constant  serves  as  a  measure  of the theoretical
removal effectiveness.
                               133

-------
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                                  134

-------
The vapor-liquid equilibrium constant, or K-value, is defined  as
the ratio of the equilibrium mole fraction of an organic compound
in  the  vapor  phase,y^, to its equilibrium mole fraction in the
wastewater phase, x-j

     , _ *1  •
     Ki= X1

The vapor-liquid equilibrium constant can be calculated from:
where Yl  is the activity coefficient of the organic compound i in
the wastewater, p.   is the vapor pressure of the  pure  substance
at  the  steam stripper operating temperature, and P is the total
pressure.  This expression, which holds for low pressures,  is  a
simplified  form  of  the  rigorous  thermodynamic equation.  The
vapor-liquid  equilibrium  constants  calculated  by  Hwang   and
Fahrenthold  for aqueous solutions of toluene, benzene, methylene
chloride, and chloroform are listed below.(72)
Compound

Toluene
Benzene
Methylene Chloride
Chloroform
Average K-Value at 100°C & .1 Atm

             1 ,156
             1 ,215
               941.4
               635.5
The suggested limits in Section VIII for benzene are based on the
performance of the steam  distillation  flash  tank  in  removing
toluene  from  pharmaceutical  process wastewater at plant 12003.
The suggested limits for chloroform are based on the  performance
of  the  packed  column  steam  stripper  in  removing  methylene
chloride from pharmaceutical process wastewater at  plant  12003.
In  both  cases,  the use of identical limits is justified by the
above   similarities   between   the   vapor-liquid   equilibrium
constants.

g.   Other Data Gathering

In order to determine the extent  to  which  the  wastewaters  of
indirect  discharging  pharmaceutical plants were contaminated by
toxic volatile organics, the Agency sent  308  questionnaires  to
nine  indirect  discharging plants which had indicated the use of
toxic volatile organics.  The Agency also sent questionnaires  to
six  other plants that had commented on the proposed pretreatment
standard for total toxic volatile  organics  (see  47  FR  53585,
Nov. 26,  1982).(141) The Agency sought information on wastewater
contamination by toxic volatile organics in order to develop  its
plant-by-plant  cost estimates for steam stripping technology.  A
copy of the questionnaire that  was  sent  to  the  participating
pharmaceutical  plants  may  be  found  in  the  record  of  this
rulemaking.
                                135

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Responses to the questionnaire were received from
company  response  for  another  plant not sent a
Five plants reported  contamination  of  part  of
wastestream   by   one   or   more  toxic  volati
concentrations greater than 10 mg/1.  The  median
process wastewater contaminated by toxic volatile
percent  at  the  five  plants.   This  percentag
development of plant-by-plant  steam  stripping
discussed in Appendix A.

5.   Carbon Adsorption
 16 plants  (one
 questionnaire) .
  their  process
le  organics  at
  percentage  of
 organics was 26
e  was  used  in
costs  which  is
Adsorption is defined as the adhesion of dissolved  molecules  to
the  surface  of  solid  bodies  with  which they are in contact.
Granular activated carbon particles have two properties that make
them effective and economical adsorbents.   First,  they  have  a
high  surface  area per unit volume which results in faster, more
complete adsorption.  Second, they have  a  high  hardness  value
which lends itself to reactivation and repeated use.

The  adsorption  process  typically  is  preceded  by preliminary
filtration or clarification  to  remove  insolubles.   Next,  the
wastewaters  are  placed in contact with carbon so adsorption can
take place.   Normally,  two  or  more  beds  are  used  so  that
adsorption  can  continue  while  a  depleted bed is reactivated.
Reactivation is accomplished by heating the carbon between  870°C
to  980°C  (1600°F to 1800°F) to volatize and oxidize the adsorbed
contaminants.  Oxygen in the furnace is  normally  controlled  at
less  than  1  percent  to  avoid  loss  of carbon by combustion.
Contaminants may be burned in an afterburner.

Carbon adsorption  is  primarily  designed  to  remove  dissolved
organic  material from wastewater, although it can to some extent
remove chromium,  mercury  and  cyanide.   A  discussion  of  the
technical and economic feasibility of activated carbon adsorption
technology  may  be found in "Treatability of Priority Pollutants
in  Wastewater  by  Activated  Carbon,"  S.  T.  Hwang   and   P.
Fahrenthold, U.S. EPA, 1979.

The  potential  use  for  this  technology  by the pharmaceutical
industry  is  limited.   Concentrations  of  most  of  the  toxic
pollutants (metals, volatile organics and cyanide) characteristic
of   pharmaceutical   wastewater   are   generally  reduced  more
effectively and  with  less  cost  by  the  previously  discussed
technologies  or  through  biological treatment than by activated
carbon adsorption.  Phenols, the other group of pollutants  found
in   pharmaceutical   wastewaters  are  biodegradeible  and  their
concentrations can be reduced by improved  biological  treatment.
Carbon  adsorption is particularly applicable in situations where
organic material in low concentrations not amenable to  treatment
by other technologies must be removed from wastewater.
                               136

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The  equipment  necessary  for  an  activated  carbon  adsorption
treatment system consists of a preliminary  clarification  and/or
filtration  unit  to  remove the bulk of the solids, two or three
columns packed with activated carbon, and pumps and piping.  When
on-site regeneration is employed,  a  furnace,  quench  tanks,  a
spent  carbon  tank,  and a reactivated carbon tank are generally
required.  Contract regeneration  at  a  central  location  is  a
frequent commercial practice.
An  example  of
Figure VII-8.
            an  activated carbon adsorption unit is shown in
Carbon adsorption systems are compact, will tolerate variation in
influent concentrations and  flow  rates  and  can  be  thermally
desorbed  to  recover the carbon for reuse.  Economic application
of carbon adsorption is limited to the removal of  low  pollutant
concentrations.     Competititive    adsorption   of   non-target
constituents, as well as blinding by suspended solids, can  cause
interference.

D.  END-OF-PIPE TREATMENT

In-plant   treatment   processes   are  used  to  treat  specific
pollutants  in  segregated  waste  streams;   end-of-pipe   (EOP)
technologies usually are designed to treat a number of pollutants
in  a  plant's  overall  wastewater  discharge.  The types and/or
stages  of  EOP  treatment  are  primary  treatment,   biological
treatment,  and  tertiary  treatment.  Depending on the nature of
the pollutants to be removed and the degree of removal  required,
combinations of the available technologies are used.

As in the case of in-plant treatment, the 308 Portfolio data base
was  the  principal source of information for identifying the use
of  EOP  treatment  by   the   pharmaceutical   industry.    This
information  was  requested in both 308 Portfolio mailings.  As a
cross-check for accuracy  and  completeness,  the  308  Portfolio
responses were compared with information available from the other
data bases.

Table VII-4 presents a summary of the EOP technologies identified
by  the  various data bases, along with the number of plants that
employ each process.
1
Primary Treatment
Primary treatment, a form of physical/chemical treatment,  refers
to  those  processes  that  are nonbiological in nature.  Primary
treatment involves (a) the screening of the  influent  stream  to
remove   large  solids  and  (b)  gravity  separation  to  remove
settleable solids and floating materials.  Commonly used  primary
treatment  technologies in the pharmaceutical industry are coarse
solids   removal,   primary   sedimentation,   primary   chemical
flocculation/clarification, and dissolved air flotation.
                               137

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                                                     SURFACE
                                                     WASH
                                                       CARBON
                                                       BED SURFACE
CARBON
INLET &
OUTLET
                                                 ^,-SAND

                                                   GRAVEL

                                                   FILTER BLOCK



                                                   WATER OUTLET
                         FIGURE VH-8

              ACTIVATED CARBON ADSORPTION UNIT
                             138

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                              TABLE VII-4

               SUMMARY OF END-OF-PIPE TREATMENT PROCESSES
                            (Data Base: 308)
End-of-Pipe Technology

Equalization

Neutralization

Primary Treatment

     Coarse Settleable Solids Removal
     Primary Sedimentation
     Primary Chemical Flocculation/Clarification
     Dissolved Air Flotation

Biological Treatment

     Activated Sludge
          Pure Oxygen
          Powdered Activated Carbon
     Trickling Filter
     Aerated Lagoon
     Waste Stabilization Pond
     Rotating Biological Contactor
     Other Biological Treatment

Physical/Chemical Treatment

     Thermal Oxidation
     Evaporation

Additional Treatment
Number of Plants

       62

       80

       61

       41
       37
       12
        3

       76

       52
        1
        2
        9
       23
        9
        1
        2

       17

        3
        6
      Polishing  Ponds
      Filtration
       '   Multimedia
           Activated Carbon
           Sand
      Other Polishing
           Secondary Chemical Flocculation/Clarification
           Secondary Neutralization
           Chlorination
       40

       10
       17
        7
        4
        5
       17
        5
        5
       11
 Note:  Subtotals may not add to totals  because:  1)  some plants employ
       more than one treatment process? 2) minor treatment processes
       were not listed separately;  3) details for some treatment
       processes were not available.
                                     139

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 2.  Biological  and  Tertiary Treatments

 Biological   treatment   is   the  principal   method  by  which many
 pharmaceutical  manufacturing plants  are now meeting existing  BPT
 regulations.    Although it  is discussed as a single EOF treatment
 alternative,  biological treatment  actually encompasses a  variety
 of  specific  technologies   such  as  aerated lagoons,   activated
 sludge,  trickling filters,  and  rotating  biological  contactors.
 Since  there  are numerous publications  available  that describe all
 aspects  of   the operations  (advantages,  limitations,  and  other
 pertinent  facts),   discussions, of  these   specific   treatment
 processes  will be presented  in  only  moderate  detail  in this
 document.  Although each has its own unique characteristics,  they
 are all  based on one   fundamental  principle:   the  reliance  on
 aerobic   and/or anaerobic  biological microorganisms for  the
 removal  of oxygen-demanding compounds.

 An aerated lagoon is one example of  a   treatment facility  which
 utilizes aerobic   biological  processes.    It   is   essentially a
 stabilization  basin  to which  air  is  added   either   through
 diffusion  or  mechanical agitation.   The  air provides  the oxygen
 required for  aerobic biodegradation  of   the  organic  waste.    If
 properly designed,  the air  addition will provide  sufficient
 mixing to maintain  the  biological  solids in  suspension so   that
 they   can  be  removed   in  a secondary  sedimentation tank.   After
 settling, sludge may be recycled to  the head of the  lagoon  to
 ensure the presence of  a properly  acclimated seed.   When operated
 in  this manner, the aerated lagoon  is  analogous to the activated
 sludge process.  The viable biological  solids level  in  an  aerated
 lagoon is low when  compared to that  of  an  activated sludge  unit.
 The  aerated  lagoon relies primarily on  detention time  for the
 breakdown and removal of organic matter; aeration periods  of  3  to
 8 days or more  are  common.

 The activated  sludge   process   is   also  an aerobic  biological
 process.    The basic   process  components  include an  aerated
 biological reactor,  a clarifier  for  separation of biomass, and   a
 piping   arrangement  to  return separated biomass  to  the  biological
 reactor.  The aeration  requirements  are similar  to   those* of  an
 aerated  lagoon  in that  aeration  provides the necessary  oxygen for
 aerobic  biodegradation  and mixing  to maintain  the  biological
 solids in suspension.   The  available activated   sludge   processes
 that   are    used    in   the treatment of   wastewaters  include
 conventional, step-aeration, tapered-aeration, modified-aeration,
 contact-stabilization,  complete-mix  and extended-aeration.

A trickling filter  is a  fixed-growth biological  system  where   a
thin-film biological slime  develops  and coats the surfaces of  the
supporting medium as wastewater makes contact.   The  film consists
primarily  of   bacteria,  protozoa,  and  fungi  that feed on  the
waste.   Organic matter and  dissolved oxygen  are  extracted  and  the
metabolic end products are  released.     Although  very   thin,   the
biological  slime   layer  is  anaerobic  at  the bottom so hydrogen
                               140

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sulfide,  methane,  and  organic  acids  are  generated.    These
materials  cause  the slime to periodically separate  (slough off)
from the supporting medium and be carried through the system with
the hydraulic flow.  The sloughed biomass must be  removed  in  a
clarifier.

Trickling  filters are classified by hydraulic or organic loading
as "low rate" or "high rate." Low-rate filters generally  have  a
hydraulic  loading  rate  of  1 to 4 million gal./acre/day  (or an
organic loading rate of 300 to 1,000 Ib.   BOD5_/acre-ft./day),  a
depth  of  6 to 10 feet, and no recirculation.  High-rate filters
have a hydraulic loading rate of 10 to 40 million  gal./acre/day,
an  organic loading rate of 1,000 to 5,000 Ib. BOD5_/acre-f t./day,
a depth of 3 to 10 feet, and a recirculation rate of 0.5 to  4.0.
High-rate  filters  can  be  single  or  two  stage.   The medium
material used in trickling filters must be  strong  and  durable.
The most suitable medium in both the low and high-rate filters is
crushed stone or gravel graded to a uniform size.

The  rotating  biological  contactor  (RBC) process consists of a
series of disks constructed  of  corrugated  plastic  plates  and
mounted  on a horizontal shaft.  These disks are placed in a tank
with contour bottom and immersed to approximately 40  percent  of
the  diameter.  The disks rotate as wastewater passes through the
tank and a  fixed-film  biological  growth  similar  to  that  on
trickling  filter  media  adheres  to  the  surface.  Alternating
exposure to the wastewater and the oxygen in the air  results  in
biological  oxidation  of  the  organics  in the wastes.  Biomass
sloughs off (as in the trickling filter) and is  carried  out  in
the effluent for gravity separation.  Direct recirculation is not
generally practiced with the rotating biological disks.

There  are other biological treatment techniques not specifically
mentioned  in  this  section  which  utilize  either  aerobic  or
anaerobic biodegradation or both.  These are stabilization ponds,
anaerobic   lagoons  and  facultative  lagoons.   In  facultative
lagoons,  the  bacterial  reactions  include  both  aerobic   and
anaerobic decomposition.

Besides  the  direct  utilization  of  these treatment processes,
biological treatment also encompasses two  other  approaches;  in
this  report,  they are referred to as biological enhancement and
biological  augmentation.   Generally,    these   variations   are
accomplished  by  (a)  modifications  made  in  the  conventional
biological  treatment  itself  or  (b)    conventional   processes
combined  into  a  multi-stage  system.    Examples  of biological
enhancement are  pure  oxygen  activated  sludge  and  biological
treatment    with    powdered   activated   carbon.     Biological
augmentation  could   be   trickling   filter/activated   sludge,
activated   sludge/   rotating   biological   contactor,  aerated
lagoon/polishing  pond,  or  any  combination  of  two  or   more
conventional biological treatment processes.
                               141

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The  differences  in performance due to differences in the number
of biological treatment stages employed rest on the applicability
of plug-flow/back-mix effects.  A true plug-flow system, such  as
a narrow channel lagoon, approaches equivalence to an infinity of
stages if the food/microorganism (F/M) ratio is maintained.  This
tends  to  beneficially maximize the availability of nutrients, a
function of the concentration  of  biodegradable  pollutants.   A
fully back-mixed system (as an activated sludge unit tends to be)
operates  throughout  at  its  exit  concentration.  It is thus a
distinct, finite stage incremental with any stage  before  it  or
after it.

In practice, these distinctions are not clearcut.  Since there is
some  back-mixing  even  in  a  channelled lagoon, separations of
units or even of cells within one unit may be beneficial.   Also,
in  most mixed systems, the concentration gradient established is
sufficient  for  some  increase   in   the   effective   nutrient
concentration   and,   consequently,  the  optimum  microorganism
concentration.

In many systems, design factors  other  than  the  concentration-
induced  driving  force may overshadow the concentration gradient
and prevent simple performance correlation.

Comprehensive  consideration  of  the  criteria  affecting   bio-
reaction performance suggests the following to be significant:
     (1)

     (2)



     (3)


     (4)


     (5)


     (6)



     (7)
Influent concentration of pollutants.

Resistive characteristics of the BOD pollutants and the
resultant  K  value  (i.e.,  how  easily  the  BOD   is
biodegraded).                  «

Presence of  potential  interfering  pollutants  (e.g.,
constituents toxic to the microorganisms).

Bio-reaction characteristics and concentration  of  the
microorganisms present.
Dissolved oxygen content and distribution at
the point of adequate 02 availability.
least  to
Sludge  recycle  as   it   may   affect   microorganism
availability  and  character  as represented by the F/M
ratio.

Contact efficiency of pollutants and microorganisms, as
may be induced by agitation, flow pattern, and MLVSS.
                               142

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     (8)  Availability  and  balance  of   nutrients,   including
          nitrogen and phosphate.

     (9)  Required target effluent.

     (10) Temperature (e.g., seasonal effects).

The proper design of biological systems in addition to developing
optimum operating criteria, must also take into account how  much
of  the  system's  potential  capacity  will  be  used so that an
optimum  modification  approach  will  be  available.   The  most
economical  approach  may  be  simple  adjustments  of  operating
variables to exploit existing capacity  fully.   The  adjustments
may  require  such  minor  changes as increasing agitation, power
input, or sludge recycle rate or,  at the extreme, may require the
addition of an independently functioning system.  In many  cases,
the  optimum  upgrade  may be a combination of existing component
units integrated with balanced new  units.   This  is  likely  to
result  in  a  system  complex  dictated  in  part by performance
requirements and in part by equipment already in place.
Some examples of typical augmented biological configurations
shown in Figure VII-9.
are
Tertiary  treatment  usually  means  any  treatment  following  a
biological treatment  system.   The  treatment  technologies  are
quite  varied  and  are  normally applied for the removal of such
pollutants as a  specific  priority  pollutant  class,  nitrogen,
color,  and so forth.  Some tertiary treatment processes are also
applicable  to  in-plant  or  primary  treatment  schemes.    The
location  in the overall treatment concept determines whether the
operation is termed a tertiary treatment process.

Biological treatment systems are mainly . intended  to  reduce  the
level  of  the traditional pollutants BOD and COD.  Some priority
pollutants may be removed incidentally, even though not  targeted
by the treatments.

Biological   treatment   removal  efficiency  is  a  function  of
treatment   intensity,   detention   time,   and   such    system
characteristics    as    bioreaction   rate   constant,   biomass
concentration, and biomass contact efficiency.  The configuration
of the system is important since it affects  these  factors,  but
the  effectiveness is not necessarily benefitted by splitting the
bioreaction  into  a   number   of   steps.    In   a   plug-flow
(non-backmixed)  system,  there is a continuation of reaction and
little inherent  effect  of  staging  as  in  certain  separation
techniques and driving force systems.  There may be reaction rate
advantages  in  a  back-mixed  system  which  might  accrue  from
staging, but these  must  be  evaluated  for  a  specific  system
considering  microorganism  availability,  contact efficiency and
other factors.
                              143

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Economic concerns often dictate  a  design  which  uses   (a)  one
biotechnique  in preference to others (b) more than one technique
as the reaction progresses (e.g., activated sludge and  trickling
filter)  or  {b)  various  arrangement  configurations.   However,
these design choices are highly  site  and  waste  specific,  and
generalizations  should  be  avoided in the comparison of systems
and in the choice a particular treatment configuration.

One of the Agency's data-gathering programs  requested  long-term
traditional pollutant data from the industry.  The long-term data
consisted  of raw daily or weekly influent and effluent data that
covered a period of about one year  and  were  obtained   from  22
plants  employing  some type of biological treatment.  Additional
long-term data was submitted after proposal  by  new  plants  and
also  by  plants  that  had submitted data prior to the proposal.
For purposes of predicting what the industry can achieve  in  the
way  of  traditional pollutant control by biological enhancement,
the long-term data represent the best available data.   Summaries
of  the  long-term  data  are  presented  in Table V-l.   The data
submitted by plants before and after proposal are  summarized  in
Table IV-1.  Many of these plants have achieved performance which
is better than that required by the BPT regulations for BOD^, COD
and  TSS.   These  data  were  used  to  develop  final   BPT  TSS
limitations and proposed NSPS limitations for the  pharmaceutical
industry.

3.   Solids Removal

Removal of. solids from wastewater can occur at several points  in
the  treatment  sequence.  Grit removal by screening, filtration,
or sedimentation is often necessary  as  a  preliminary   step  in
primary  treatment.   After secondary biological treatment, it is
generally necessary to complete the removal of sludge  and  other
solids  by  means  of  clarification,  filtration,  or  a special
operation such as flotation.   Further solids  removal  occurs  in
tertiary treatment stages.
a.
Clarification
Clarification is a method  of  removing  suspended  or  colloidal
solids  by  means  of  gravity sedimentation.  Since the settling
rate of suspended  solids  is  dependent  on  particle  size  and
density (the smaller the particle size and the closer the density
to  that  of  water, the slower the settling rate), flocculant or
coagulant aids  sometimes  must  be  added  to  promote  bridging
between  particles  and  to  render them more settleable.  A slow
settling rate  and  the  stability  of  colloidal  mixtures  make
chemical   clestabilization   and   agglomeration   of   colloidal
suspensions necessary.

Clarifiers are usually large  containment  vessels  that  have  a
continuous water throughput.  A conventional clarification system
utilizes  a  rapid  mix  tank  to mix chemicals with the entering
                              145

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water; the  wastewater  is  then  subjected  to  slow  agitation.
Provision  for  the removal of settled solids  is also a necessary
part of the system.

Typical clarifiers are shown in Figure VII-10.

b.   Filtration

Filtration is a basic solids  removal  technology  in  water  and
wastewater  treatment.  Silica sand, anthracite coal, garnet, and
similar granular inert materials are among the most common  media
used, with gravel serving as a support material.  These media may
be  used  separately  or  in  various  combinations.   Multimedia
filters  may  be  arranged  in  relatively  distinct  layers   by
balancing  the  forces  of  gravity,  flow,  and  buoyancy of the
individual  particles.   This  is   accomplished   by   selecting
appropriate  filter  flow  rates,  media  grain  size,  and media
densities.

The most common filtration system  is  the  conventional  gravity
filter.   It normally consists of a deep bed of granular media in
an open-top tank.  The direction of flow through  the  filter  is
downward and the flow rate is dependent solely on the hydrostatic
pressure  of  the  water  above  the filter bed.  Another type of
filter is the pressure filter.  In this case, the basic  approach
is  the same as a gravity filter, except the tank is enclosed and
pressurized.

As wastewater is processed through the  filter  bed,  the  solids
collect   in   the   spaces   between   the   filter   particles.
Periodically,  the  filter  media  must  be  cleaned.   This   is
accomplished  by  backwashing  the  filter  (reversing  the  flow
through the filter  bed).   The  flow  rate  for  backwashing  is
adjusted  in  such  a way that the bed is expanded by lifting the
media particles.  This expansion and subsequent motion provides a
scouring action which effectively dislodges the entrapped  solids
from the media grain surfaces.  The backwash water fills the tank
up  to  the level of a trough below the top lip of the tank wall.
The backwash is collected in the trough, fed to a  storage  tank,
and  recycled into the waste treatment stream.  The backwash flow
is continued until the filter is clean.

An example of a filtration unit is shown in Figure VII-11.

c.   Flotation

Flotation is an optional  method  of  clarification  utilized  to
treat  some  industrial  waste in which the suspended solids have
densities less than that of water.  Air-assisted flotation may be
applied to some systems with solids slightly heavier than  water.
As  with  conventional  clarifiers,  flocculants  are  frequently
employed to enhance the efficiency of flotation.
                              146

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FLOAT-
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VALVE
                              ;v-  i//i":
                                  FIGURE vn-n

                               FILTRATION UNIT
                              148

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E.  ULTIMATE DISPOSAL

In any evaluation of control and treatment technologies,  one  of
the  most  important  considerations  is  the  ultimate  disposal
methods used by the  industry.   Whether  a  plant  is  a  direct
discharger to surface waters, an indirect discharger to POTWs, or
a  zero  discharger  can be a critical factor in determining what
technologies are  most  appropriate  for  controlling  its  waste
discharge.   Table  VI1-5  summarizes  the  methods  used  by the
pharmaceutical manufacturing industry for the  ultimate  disposal
of  its  process  wastewaters.   This  table  was prepared from a
listing of each plant's individual disposal methods (see Appendix
C).

Approximately 12 percent of the  466  manufacturing  plants  have
direct  discharges.   Seven  of  these  plants also have indirect
discharges, while another nine use  zero  discharge  methods  for
some  of  their  smaller  waste  streams.   The  majority  of the
industry are indirect  dischargers.   About  59  percent  of  the
plants  in  the  Agency's  latest  data  base discharge to POTWs.
Seven of these plants also have direct  discharges  (non-process)
and  another  25  use zero discharge techniques for some of their
smaller waste streams.  Almost 29 percent  of  the  manufacturing
plants use only such zero discharge methods as contract disposal,
evaporation,  ocean  dumping,  or  complete  recycling  or do not
generate process wastewaters  requiring  disposal.   Seventy-five
percent  of  the zero dischargers were classified as such because
they generated no process wastewaters requiring disposal.
                               149

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                              TABLE VII-5

                     SUMMARY OF WASTEWATER DISCHARGES
Methods of Discharge
Number of Plants
in the Industry
          Number of Plants
          by Subcategories
     Direct Only                   42
     Direct with Minor  Zero          9
     Discharge
Total Direct Dischargers            51
     Indirect Only                 256
     Indirect with Minor Zero       21
     Discharge
Total Indirect Dischargers         277
Combined Direct/Indirect             4
Dischargers

SUBTOTAL                           332

Zero Dischargers                  134

TOTAL                              466
                       6
                       2

                       8
                      19
                       7

                      26
                       1
                      35
                      37
              B

              4
              4

              8
             54
              8

             63
              1
         16
          6

         22
         70
         15

         85
          2
  D

 27
  4

 31
207
 17

224
  3
             72   109   258
                                  27   114
             81   136   372
NOTE:     Subcategory counts will not equal industry totals because of
          multiple subcategory plants.
     FATE OF WASTEWATERS AT ZERO DISCHARGE PLANTS (TOTAL INDUSTRY)


Discharge Method
    Zero
Dischargers
Direct
w/Zero
Indirect
 w/Zero
No Process Wastewater
Contract Disposal
Deep Well Injection
Evaporation
Land Application
Ocean Dumping
Recycle/Reuse
Septic System
Subsurface Discharge
No Data

Total
     98
      7
      0
      7
      6
      2
      2
      6
      4
     _2

    134
  0
  3
  1
  1
  3
  1
  0
  0
  0
   0
   7
   2
   3
   5
   2
   1
   2
   3
            25
                                    150

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                          SECTION VIII

      ANALYSIS OF LONG TERM DATA FOR POLLUTANTS OF CONCERN


This section describes the analysis  of  long-term  cyanide  data
submitted  to  EPA  by pharmaceutical plants utilizing biological
treatment  systems  and  in-plant  cyanide   destruction.    Also
described  in  this  section are the analyses of data obtained by
the Agency as a result of its steam stripper sampling efforts and
the  analyses  of  the  data  used  to  develop  final  BPT   TSS
limitations  and  final  BPT alternative concentration-based BOD5_
and COD limitations.  The first  part  of  this  section  details
which  plant  data  were  used to develop the final and suggested
limitations and discusses reasons for the deletion of some of the
submitted data.  Data verification procedures  are  described  as
well  as  the  contents of the data base on which limitations are
based.  The second part of this section describes the statistical
methodology used  to  determine  appropriate  daily  maximum  and
maximum 30-day average variability factors.

A.  DESCRIPTION AND TECHNICAL ANALYSIS OF DATA

The Agency used data from one facility  (12236)  to  develop  the
proposed  cyanide  limitations  and  standards  based on  in-plant
cyanide  destruction  and  biological  treatment  (47  FR 53584;
November 26,   1982).   Included in the proposed regulations was  a
              additional  data  on  the  performance  of  cyanide
              systems  in  use  by  pharmaceutical  manufacturing
             After proposal, the  Agency  received  data  on  the
             of  cyanide  destruction  systems  from three plants
(12135, 12235 and 12236).  The discussion in this section focuses
on how these data were used to derive final  cyanide  limitations
and standards.
request  for
destruction
facilities.
performance
 In  the  preamble   to   the proposed  regulation,  the  Agency  stated
 that, based on available  information  from   other   industries,   a
 pretreatment  standard  of   1.2  mg/1   for   total   toxic  volatile
 organics  (TTVO) might be  appropriate if adequate supporting  data
 could   be    obtained   from   the   pharmaceutical  industry.    The
 technology basis for this suggested  standard was  in-plant   steam
 stripping.    In  response to comments  on this suggested standard,
 the Agency gathered data  on  the performance of a  steam  stripper
 and  flash  tank   at  plant   12003 by  sampling steam stripper and
 flash tank influent and effluent streams.   Although  the Agency is
 not  proposing  or promulgating   regulations  based   on   steam
 stripping   technology,   analysis  of   the   data  obtained   since
 proposal will be presented  in this section  along  with suggested
 limitations for certain toxic volatile organics.

 in November of  1982, the  Agency proposed a  BPT TSS limitation for
 all   subcategories of  plants  based  on   a  long-term   average
 concentration of   75   mg/1.  This   limitation was  derived  by
                              151

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averaging  the  effluent  TSS  concentrations  of all plants with
biological treatment in-place and was  intended  to  replace  the
existing  BPT  TSS  limitations on subcategory B, D, and E plants
and to establish BPT TSS limitations for subcategories  A  and  C
for  which  BPT  TSS  limitations  had  not been established.  In
response to a comment on these proposed limitations,  the  Agency
has  evaluated  the  latest data on the performance of biological
treatment systems with regard to TSS and concluded that  the  BPT
TSS limitation should be related to the BPT BOD5_ limitation.  The
Agency   also   proposed   alternative   BPT  concentration-based
limitations for  BOD5_  and  COD  for  all  subcategories.   These
limitations  were  proposed in order that plants with low average
raw waste BOD5_ and COD concentrations would not  have  to  comply
with  more  stringent  BPT  limitations  on BOD5_ and COD than the
proposed BCT BOD5_ and BAT  COD  limitations.   No  comments  were
received   on   these  proposed  alternative  concentration-based
limitations.  Although BCT BOD5_ and BAT COD limitations  are  not
being  finalized in this rulemaking, the Agency is finalizing BPT
alternative  concentration-based   BOD5_   and   COD   for   three
subcategories   based   on   its  analysis  of  conventional  and
nonconventional  pollutant  data   from   facilities   in   these
subcategories.

The  data analyses performed and the results of these analyses in
each of the above areas are discussed below:
1
Cyanide Destruction Data Analysis
The Agency proposed cyanide limitations based on  data  submitted
by  plant  12236.   These  data  were gathered during the 1978-79
period and  consisted  of  a  series  of  daily  measurements  of
end-of-pipe  cyanide  concentrations.   The  wastewater  from the
cyanide destruction system at the plant was combined  with  other
waste  streams,  some  of which contained small concentrations of
cyanide as low as 1.0 mg/1.   These  combined  streams  were  then
subjected   to   biological   treatment  and  the  effluent  from
biological  treatment  systems   was   monitored   for   cyanide.
Consequently,  the  concentrations  used  to develop the proposed
limits were not a  direct  measure  of  the  performance  of  the
cyanide  destruction system at this plant.  Also, in its comments
on the proposed regulation,  this plant indicated that these  data
were  gathered during a period when the processes which generated
cyanide wastes were  operating  at  less  than  normal  capacity.
Plant  12236  submitted  new  cyanide  data  on the effluent from
cyanide destruction corresponding to the period of  time  of  its
earlier  submission.   This plant also submitted cyanide effluent
data, both in-plant and end-of-pipe, from a later time period  in
which  the  cyanide  waste generating processes were operating at
normal capacity.  The Agency also received similar  data  on  the
performance  of  cyanide  destruction  technology  from two other
plants (12235 and  12135.).   Plants  12235  and  12236  used  the
alkaline  hydrolysis  technique,  while  plant 12135 employed the
alkaline chlorination technique for cyanide destruction.
                              152

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After an evaluation of each data set, the Agency decided  to  use
the  recently  submitted  data  from  plants  12235  and 12236 to
develop long-term average cyanide concentrations and  variability
factors.    These   data   sets   were   chosen  based  on  three
considerations: (1) the cyanide destruction units  were  operated
to  the  limit  of their capacity during the period that the data
were obtained, (2) the data were obtained during periods  at  the
plant  when  the  processes which generate cyanide bearing wastes
were operating at normal capacity  and  (3)  the  submitted  data
directly  measured the performance of cyanide destruction.  After
analysis of the data from plant 12135, the Agency concluded  that
the  system  at  the  plant  was  not  being operated in order to
achieve  the  effluent  concentrations  of   cyanide   that   are
consistent  with  the  design  specifications  of  the unit.  The
pre-proposal data submitted by plant 12236 was not  used  because
it  was obtained during periods when the cyanide waste generating
processes were operating at less than normal capacity.

After deciding on which data sets to use in developing the  final
cyanide  limitations  and  standards, the Agency performed a data
screening analysis on individual  data  points  from  these  data
sets.   This  analysis was identical to that performed during the
development  of  the  proposed  regulations.   (See  "Statistical
Support  for  Pharmaceutical  Rulemaking  -  September, 1983" for
details of this analysis.)  The result of this analysis was  that
four  data  points  from each submission were targeted as suspect
results.  These points were deleted  from  the  data  sets  after
contact  with  plant  personnel indicated that these observations
were not consistent with the proper  operation  of  these  units.
For   the   cyanide  destruction  unit  data,  long-term  average
concentrations, the number of  observations  and  the  calculated
variability factors for each set of observations are presented in
Table VIII-1.  The calculation of the variability factors will be
discussed  later  in  this section.  The long-term average of the
cyanide destruction unit  effluent  concentrations  derived  from
each data set  (12235 and 12236) were weight-averaged according to
the  number of observations available in each data set to yield a
long-term average performance value.  Weight-averaged variability
factors were also calculated in the same way.  These results also
appear  in Table VIII-1.

The maximum 30-day average and daily maximum cyanide  limitations
and  standards  which  are derived from the multiplication of the
long-term   weighted   average   performance   values   and   the
weight-averaged variability factors are found in Table VIII-2.

These limitations and standards are appropriate if monitoring for
purposes  of  demonstrating  compliance  with the limitations and
standards is conducted on the effluent from the  cyanide  control
technology  unit.   If  monitoring by direct dischargers  who use
biological systems to treat the effluent from cyanide destruction
systems along with the remainder of the plant process  wastewater
is  conducted after biological treatment, then a different set of
                              153

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                               TABLE  VIII-1

           LONG TERM AVERAGE CYANIDE  CONCENTRATIONS  (LTAs)  AND
                        VARIABILITY FACTORS  (VFs)
                      FROM CYANIDE DESTRUCTION UNITS
Plant
              LTA
              ling/1)
12235         3.28

12236         6.52

Weighted LTA  =  5.25

Weighted 30-Day Maximum Average V.F.

Weighted Daily Maximum VF  =  6.39
No. of
Observations
189
293
30-Day
Max.
2.06
1.62
Daily
Max. V.F.
7.31
5.79
                                      =  1.79
                                 154

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                               TABLE VIII-2

           30-DAY MAXIMUM AVERAGE AND DAILY MAXIMUM LIMITATIONS
                        AND STANDARDS FOR  CYANIDE*
Regulation
BPT, BAT, PSES
PSNS and NSPS
30-Day Maximum
Average concentrations (mg/1)

          9.4
Daily Maximum
Concentration (mg/1)

       33.5
* These concentration limitations and standards apply to the effluent
  from cyanide destruction system and only if all  cyanide bearing wastes
  are being treated by the cyanide destruction unit.
                                    155

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numerical limitations apply.  These  alternate  limitations  were
developed  by accounting for that removal of cyanide which occurs
as the result of biological treatment.  The Agency  attempted  to
estimate  the removal of cyanide achieved by biological treatment
from the post-proposal data submitted by plant  12236.   However,
although  daily in-plant and end-of-pipe effluent data pairs were
submitted covering about nine months,  no  cyanide  concentration
data  on the influent to biological treatment was available.  The
fact   that   process   streams   containing    relatively    low
concentrations of cyanide were not treated by cyanide destruction
but  were  mixed  with the treated cyanide waste stream and other
non-cyanide bearing waste streams prior to  biological  treatment
prevented  the  Agency from determining the removal of cyanide by
the biological system.

Some data were available from the S/V program on the  removal  of
cyanide  by  biological  treatment  systems.  The average percent
removal of cyanide achieved by the biological  treatment  systems
of  plants in the S/V program was 70 percent.  The Agency is also
aware that the median cyanide removal percentage calculated  from
the  data gathered during the Agency's 50 plant POTW study was 59
percent.(136) EPA based  its  estimate  of  the  cyanide  removal
capability of biological treatment systems on the POTW data.  The
Agency  believes  that  the pharmaceutical plants with biological
treatment will achieve at least this level of removal because the
biological treatment systems of  direct  dischargers  on  average
have  longer  detention times and more aeration than do the POTWs
in EPA's  study.   Based  on  this  information,  EPA  determined
alternate limitations which are appropriate when monitoring after
biological treatment.

A  number of factors have been considered in developing alternate
cyanide limitations and standards.  These include the variability
in the effluent cyanide concentrations from a biological  system,
the  removal  of cyanide achieved by biological treatment and the
effect of  dilution  by  other  process  streams  not  containing
cyanide.    A   limitation  based  on  cyanide  destruction  plus
biological treatment that is appropriate for  direct  dischargers
who  monitor  for  cyanide  at  the  final  discharge  point  (or
end-of-pipe) was developed by  first  multiplying  the  long-term
average cyanide destruction effluent concentration (5.25 mg/1) by
the median biological treatment removal factor (0.41 which equals
1.00-0.59).     The    resulting    long-term   average   cyanide
concentration (2.15 mg/1) was then multiplied  by  a  variability
factor   calculated   from  end-of-pipe  cyanide  data  to  yield
equivalent   maximum   30-day   average   and    daily    maximum
concentrations which account for the cyanide reduction attainable
by  cyanide destruction in combination with biological treatment.
(These variability factors have been developed  from  end-of-pipe
cyanide  destruction  data submitted by plant 12236 and are found
in Table VIII-3.)  These allowable concentration limits were then
multiplied by a dilution factor R which equals the ratio  of  the
cyanide  contaminated  wastewater to the total process wastewater
                             156

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                               TABLE VII1-3

           30-DAY MAXIMUM AVERAGE AND DAILY MAXIMUM VARIABILITY
          FACTORS DERIVED FROM END-OF-PIPE DATA FROM PLANT 12236
Long Term
Average CN Cone.
    (rag/1)

   0.33
No. of
Observations
   293
30-Day Max.
Ave. V.F.
                                                  1.53
Daily Maximum
     V.F.
                                             2.73
                              157

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discharge flow to yield the alternate maximum 30-day average  and
daily  maximum  end-of-pipe limitations and standards.  The above
calculations are presented below:

     1.    Equivalent Long-Term Average Cyanide Concentration

          (5.25 mg/lXl .00-0.59) =2.15 mg/1

     2.    Equivalent Limitations and Standards

          Max. 30-Day Ave. = (2.15) (1.53) R = 3.3 R mg/1
          Daily Maximum = (2.15)(2.73)R = 5.9 R mg/1

The  ratios  of  equivalent  limitations  and  standards  to  the
end-of-cyanide   destruction   limitations   and   standards  are
(3.3)(R)/(9.4) or (0.35HR) and (5.9)(R)/(33.4) or (0.18)(R)  for
the  maximum  30-day  average  and  daily maximum limitations and
standards,  respectively.   These  ratios  are  included  in  the
explanation following each direct discharger regulation (BPT, BAT
and  NSPS)  and  are  to  be  used to convert from end-of-cyanide
destruction limitations and standards to alternate final effluent
or end-of-pipe limitations  and  standards  (see  48  FR  49808).
Indirect   dischargers   who   conduct   end-of-pipe   compliance
monitoring  must  comply  with  the  end-of-cyanide   destruction
limitations  multiplied  by  the  dilution factor R.  The cyanide
limitations and standards which are applicable at  the  alternate
monitoring  points for direct and  indirect dischargers are listed
in Table VIII-4.  The following rules apply to direct dischargers
concerning the alternate limitations and standards:

(1)  If all cyanide-containing waste streams are  diverted  to  a
cyanide  destruction  unit  and  the  effluent  from  the cyanide
destruction unit is discharged to a biological treatment  system,
self-monitoring  may be conducted at the final effluent discharge
point in which case the  alternate  maximum  30-day  average  and
daily maximum limitations cited above apply.

(2)  If all cyanide-containing waste streams are not treated in a
cyanide destruction unit or if  the  effluent  from  the  cyanide
destruction  unit  is  not  discharged  to a biological treatment
system,  self monitoring must be conducted at the  final  effluent
discharge point and the alternate  limitations apply.

2.   Analysis p_f Steam Stripper Data

The Agency analyzed forty effluent samples from a  packed  column
steam  stripper  and  ten  effluent  samples  from  a  flash tank
stripper located at plant 12003.  The packed column stripper  was
used  to steam strip methylene chloride, while the flash tank was
used to steam strip toluene.  The average influent concentrations
treated by these strippers were  8,800  mg/1  and  516  mg/1  for
methylene chloride and toluene, respectively.   It should be noted
that  these  influent  concentrations  are  not equivalent to the
                              158

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Regulation


BPT, BAT
and NSPS

BPT, BAT
and NSPS

PSES and PSNS

PSES and PSNS
                               TABLE VIII-4

               ALTERNATE CYANIDE LIMITATIONS AND STANDARDS
Monitoring
   Point
   B

   A

   B
30-Day Maximum
Average (mg/1)
    9.4


    3.3 R

    9.4

    9.4 R
     A = End-of-cyanide destruction unit
     B = Final effluent point
Daily Maximum
:Tnig/T)
   33.5


    5.9 R

   33.5

   33.5 R
                                159

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actual concentrations of streams being stripped because  part  of
the  feed  stream consists of recycled condensed overhead streams
which  are  saturated  with  methylene  chloride   and   toluene.
Nonetheless,  the  average removal efficiencies of both strippers
were better than 99 percent.

Along with the effluent concentration data from  both  strippers,
the  Agency also collected other operational data to determine if
the effluent concentration observations were made when  the  unit
was  being  operated  in  accordance  with design specifications.
These data are summarized in Tables VI1-2 and  VI1-3.   When  the
effluent  methylene  chloride concentration data were reviewed in
the context of operational data collected,  EPA  determined  that
when  the  overhead  temperature  on  the stripper unit was below
85°C, high effluent bottom concentrations of  methylene  chloride
were   observed.   Consequently,  10  of  the  40  concentrations
reported in Tables VI1-2 and VI1-3 were not used  to  develop  an
average  performance  value  for the steam stripping of methylene
chloride.  The  average  performance  value  determined  for  the
remaining  30  observations  is  6.94  mg/1,  which is within the
design range of the stripper.  The variability factors associated
with this average performance are found in Table VII1-5.

The Agency also collected steam stripping data from a flash  tank
used   to  steam  strip  toluene.'   All  the  data  obtained  (10
observations of effluent toluene  concentrations)  were  compared
with  the  available data on the unit operation for the same time
period.  The Agency determined  that  one  observation  was  made
while the unit was operating under upset conditions (the overhead
temperature at the time the observation was made was considerably
below the average overhead temperature at the time that the other
observations  were  made).   The average performance value of the
flash tank steam stripper with regard to the steam  stripping  of
toluene  was  4.48 mg/1.  The variability factors associated with
the nine observed data  points  used  to  generate  this  average
performance value are found in Table VII1-5.

In  the  preamble to the final regulation, the Agency states that
four TVOs (methylene chloride, benzene, chloroform  and  toluene)
were  listed  as  possible  candidates  for  regulation  and that
suggested limitations for controlling the discharge of these TVOs
would be presented in this document.   Although  the  Agency  has
only  presented  data   (see  Section  VII)  which  describes  the
effluent levels that can be achieved by the application of  steam
stripping    technology    to    wastewaters    containing   high
concentrations of methylene  chloride  and  toluene,  the  Agency
believes  that  these  data  can  be used to recommend limits for
benzene and chloroform as well.

As noted  in  Section  VII,  benzene  and  toluene  have  similar
vapor-liquid  equilibrium  constants as do methylene chloride and
chloroform.  Since vapor-liquid equilibrium  constants  determine
the  extent to which waste streams containing volatile components
                              160

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                               TABLE VII1-5
              Average Concentrations and Variability  Factors
                    Derived From Steam Stripping Data
Pol 1utant

Methylene
 Chloride

To!uene
Average of
Observations
(mg/1)
    6.94

    4.48
No. of
Observations
     30

      9
                                                Variability  Factors
30-Day Max.     Daily
Average         Maximum
    1.37

    1.81
5.07

9.70
                               161

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can be steam stripped, the Agency believes that  the  application
of   a   flash   tank  steam  stripper  to  streams  having  high
concentrations of benzene should result in effluent levels  equal
to  those  presented  for toluene in Section VII.  Similarly, the
Agency believes that the application of  a  packed  column  steam
stripper  to streams containing high concentrations of chloroform
should produce  effluent  levels  equal  to  those  obtained  for
methylene  chloride  in  Section  VII.   Therefore,  two  sets of
suggested TVO limits are  presented  in  Table  VII1-6;  one  for
benzene   and   toluene   and  one  for  methylene  chloride  and
chloroform.

3.   Conventional Pollutant Data Analysis

a.   BPT TSS Limitations

As explained previously, in November of 1982, the Agency proposed
a BPT TSS limitation for all subcategories of plants based  on  a
long-term  average concentration of 75 mg/1.  This limitation was
intended to replace the overly stringent BPT TSS  limitations  on
subcategory   B,  D  and  E  plants  and  to  establish  BPT  TSS
limitations for subcategory A and C plants.  The original  overly
stringent  BPT TSS limitations were based on data from two plants
whose operations were not characteristic of the entire  range  of
operations employed at plants in the B, D, and E subcategories.

One  commenter  on the proposed rules stated that a single number
concentration limit for TSS is not appropriate for high raw waste
load plants, but may  be  appropriate  for  low  raw  waste  load
plants.

The  existing  BPT regulations, promulgated in 1976, are based on
the application of biological treatment.  They require that  each
pharamaceutical  plant,  regardless  of subcategory, achieve a 90
percent reduction in  BOD5_.   Biological  treatment  systems  are
designed  to  remove BOD by converting soluble BOD into insoluble
matter, TSS.  The TSS  generated  in  the  biological  system  is
removed  using  sedimentation  technology.   The  amount  of  TSS
removed is a function of the design of the clarifier or  settling
pond.   The  level  of  TSS  entering the sedimentation system is
directly related to the amount of soluble BOD  removed.   Because
each plant has a different BOD raw waste concentration, each must
remove  a  different  amount  of  soluble  BOD to comply with the
percent reduction limitations.  This leads to the generation of a
different amount of TSS at each plant that must be removed in the
clarifier or settling pond.  A single number concentration  limit
for  TSS  is  not  compatible  with the BPT percent reduction BOD
limitations, which, in practice, vary from plant to plant over  a
range  of 15 mg/1 to almost 400 mg/1.  A single number limitation
would require some plants to install more advanced treatment than
that technology identified as BPT.  It would also mean  that  low
raw  waste  load  plants would be able to operate their treatment
systems inefficiently and still comply with the  proposed  single
                              162

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                                TABLE VII1-6
                         Suggested  TVO Limitations
Pollutant
Methylene Chloride
Chloroform
Toluene
Benzene
30-Day Maximum
Average Limit (mg/1)
       9.5
       9.5
       8.1
       8.1
Daily Maximum
Limit (mg/1)
    35.2  *
    35.2
    43.5
    43.5
                              163

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number  limitation.   Consequently,  relating  the  effluent  TSS
concentration  to  either   the   influent   or   effluent   BOD5.
concentration  generated  at  each  plant  appears to be the most
equitable and reasonable  way  of  establishing  TSS  limitations
based on biological treatment.

Consistent   with  the  previous  discussion,  the  Agency  first
attempted to develop  a  mathematical  relationship  between  the
average effluent TSS and average influent BOD5. concentrations for
plant  subcategory  groups  (A,  C and AC) and (B, D and BD) from
dcfta submitted by plants with biological treatment in-place  (see
Table VIII-7).  Plants which had some form of effluent filtration
in-place  were  specifically  excluded from this analysis because
effluent filtration  was  not  identified  as  part  of  the  BPT
technology  train.   The  Agency chose these plant groups because
the subcategorization analysis (see Section  IV)  indicated  that
the  influent  and  effluent  characteristics  of plants in these
groups  are  similar.   It  was   hypothesized   that   different
relationships  between  influent  BOD5.  and  effluent  TSS  would
probably be obtained for these two groups of plants.   Using  the
data  at  hand,  various linear and non-linear relationships were
considered and estimated for each group of  plants.   Statistical
relationships  could  not be established for each group of plants
(that is, statistical tests did  not  support  the  existence  of
proposed  relationships  in  both  plant groups with a sufficient
degree  of  confidence).   More  importantly,  the   Agency   was
concerned  with  establishing  such  relationships based on small
numbers of pairs of average influent BOD and effluent TSS values,
some of which were based on daily monitoring data,  while  others
were   simply   reported   averages   without   supporting  data.
Therefore, the Agency did  not  rely  on  estimated  mathematical
relationships   between   effluent  TSS  and  influent  BOD5.  for
individual plant subcategories.

Since the effluent BOD5. and TSS concentrations from a  biological
treatment system are related, the Agency calculated the ratios of
average  effluent  TSS  to  average  effluent BOD5..  These ratios
appear  in  Table  VIII-7.   The  mean  and  median  ratios  were
calculated  for  four  subcategory plant groups;  (1) A, C and AC,
(2) B, D and BD,  (3) A, C and AC and B, D and  BD,  and   (4)  all
plants  regardless  of subcategory.  These mean and median ratios
are found in Table VIII-8.  An inspection of  the  data   in  this
table  shows  a  slight  variation in the mean ratios of the four
subcategory plant groups while the median ratio is  1.7  for  all
groups.   In establishing a relationship between the BPT effluent
BOD5. concentration and the BPT effluent  TSS  concentration,  the
Agency  was faced with the choice of using the mean ratios or the
median ratio.  The Agency  chose  the  latter  approach  for  two
reasons.   First,  the  median ratio is consistent with ratios of
the  BPT  maximum  30-day  average  TSS  and   BOD5.   limitations
established for related industrial categories based on biological
treatment  (see  Table  VIII-9).  Secondly,  the use of the median
value is indicated because there   is  considerable  disparity  as
                              164

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                          Table VIII-7

    Ratios of Effluent TSS (mg/1) To Effluent BOD (mg/1)
for Biological Treatment Plants Without Effluent Filtration
PLANT CODE
12038
12119
20165
12022
12026
12036
12132
12187
1 2236
12462
33333
20257
55555
11111
12015
1 2089
12098
12085
12117
12239
12248
12283
12287
12298
12307
12459
12463
1 2471
20037
20201
20319
Sub-
category
A,B,C,D
A,D
B,C
A,C
C
A
A,C
C
C
A
C
C
C
C
D
B,D
D
D
B
D
D
D
D
D
D
D
B,D
B
D
D
D
Inf.
BOD mg/1
662.
ND
123
2141.6
3670
1570.8
2898.4
ND
1361.6
1765.4
3115.2
484
2949
948.8
232.6
ND
ND
ND
34.5
1573
294.4
ND
ND
ND
ND
69.5
102.2
50
ND
ND
ND
Eff.
BOD mg/1
28.3
7.3
25
110.2
108.1
33.1
66.6
707.3
156
117.5
121
143
79
164.5
9.70
13
409.9
32.2
1.94
284
26
35
56
15
11.4
3.8
5.7
14
20
6
15
Eff.
TSS mg/1
17.2
70.2
16
84.9
283.7
78.2
452.9
60.5 '
108
582.3
212
74
62
385.0
10.8
13
392.1
29.6
16
174
60.4
50
13
26
32.30
16.7
9.6
59
47
14
8.5
Ratio
Eff. TSS
Eff. BOD
0.6
9.6
0.6
0.8
2.6
2.4
6.8
0.1
0.7
5.0
1.8
0.5
0.8
1.7
1.1
1.0
1.0
0.9
8.3
0.6
2.3
1.4
0.2
1.7
2.9
4.4
1.7
4.2
2.4
2.3
0.6
                       165

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                               TABLE  VIII-8
              Summary of Median and Mean Ratios  of Effluent
              TSS to Effluent BODs for  Various Plant Groups
Group          Subcategories             N.
  1              A, C, A/C               11
  2              B, D, B/D               17
  3           '   B, D, B/D, A, C, A/C    28
  4              All Combinations        31

      N = Numbers of Observations
Mean
2.1
2.2
2.1
2.3
Median
  1.7
  1.7
  1.7
  1.7
                                 166

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                               TABLE VIII-9
                    Comparison of Ratios of BPT 30-Day
         Maximum Average Limitations for TSS(mg/l)  and  BOD(mg/l)
  Established for Related Industrial Categories Based on  Biological Treatment
Industry

Organic Chemicals
Plastics and Synthetic
 Fibers*
Leather Tanning
Pulp and Paper*
TSS(mg/l)
   45
  111
  110
BODR(mg/l)
   37
   76
   70
Ratio
 1.2
 1.5
 1.6
*Subcategory Average
                               167

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well as uncertainty with   regard   to   the   number   of   individual
observations  used  to  compute   the  data  averages  found  in Table
VIII-7.  Some of  the data  averages are based   on  long-term   data
submissions  and  data  submitted  after the November 1982  proposal
(i.e. these  averages   were   calculated from   known  numbers  of
observations).    On  the   other   hand,  the number of observations
used  to  compute the  averages   found in the  308   Portfolio
submissions   is   not  known.    Therefore,  a weight averaging
procedure utilizing the number of data points  used  to  develop the
averages was not  possible.  Since the use  of a weight averaging
procedure  to  determine   the  mean  ratio was  not possible and
because an  unweighted  average   provides   equal  weighting,   the
Agency  chose  the  median ratio  (1.7)   to   establish   BPT   TSS
limitations for all subcategories.

Therefore, the Agency has  determined  that  the  final effluent   TSS
limitations  which  are applicable to all  subcategories of plants
regulated in the  1976 regulations,  will state  that   the   BPT   TSS
limitation  applicable  to a  given   plant will be equal to the
average effluent  BODji concentration  achieved   after  90  percent
reduction from the raw  waste  level multiplied  by a  factor of  1.7.
This  product  is then multiplied by the maximum  30-day average
variability factor which is   3.0   to   yield the  30-day  maximum
average  limitation.    The  variability factor remains unchanged
from the 1976 regulation.
b.
Alternative BPT BODS and COD Limitations
The Agency has reviewed the available data on the performance  of
biological  treatment  systems with regard to the pollutants BOD5_
and COD in connection  with  the  1976  BPT  limitations  on  the
discharge  of  these  pollutants.  The Agency has determined that
the biological  treatment  operations  of  subcategory  B  and  D
facilities  are  characterized by significant lower raw waste and
effluent BODJ5 and COD concentrations than those of subcategory  A
and  C facilities (see Section IV).  Consequently, an application
of the 90 percent BODJ5 and 74 percent COD reduction  requirements
would  mean  that  some  subcategory B and D plants would have to
achieve significantly lower effluent concentrations of  BOD^  and
COD  than  are required of most subcategory A and C plants as the
result of  the  application  of  the  same  requirements.   After
reviewing the technology basis of the 1976 regulation, the Agency
has   determined  that  alternative  minimum  concentration-based
limitations on the discharge of BODjj^ and COD are  appropriate  to
be  consistent  with the technology basis of the 1976 regulation.
These alternative limitations will have the practical  effect  of
ensuring that subcategory B and D plants with low raw waste loads
of  BOD_5_  and  COD  will  not  have  to  achieve inordinately low
effluent concentrations of BOD_5_ and COD as a result of BPT.

The alternative maximum 30-day average  BPT  BODj[  limitation  is
obtained  by  multiplying  the  long-term  average  effluent BOD5_
concentration characteristic of low raw waste subcategory B and D
                            168

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facilities employing biological treatment (15 mg/1)  by  the  BPT
BOD5.  variability  factor  (3.0).   The  15 mg/1 average effluent
concentration  is  also  approximately  equivalent  to  the  BODS^
performance  criterion  for  POTWs with secondary treatment.  The
alternative maximum 30-day average BPT GOD limitation is obtained
by multiplying the long-term average effluent  COD  concentration
characteristic  of  low  raw waste subcategory B and D facilities
(TOO mg/1) by the BPT COD variability factor  of  2.2.   The  TOO
mg/1  average  effluent  concentration  approximates  the highest
average effluent concentration reported by a subcategory B  or  D
facility  in  compliance  with  both of the BPT percent reduction
limitations (95.8 mg/1).

While the Agency has not collected post-BPT  data  from  research
only  (Subcategory  E)  plants, the information from the 1976 BPT
rulemaking   indicates   that   the   BOD5.   and   COD   influent
characteristics  of  subcategory E only type facilities are quite
similar to those of subcategory B and D  facilities.   Therefore,
the  alternative BPT BOD5_ and COD concentration-based limitations
will apply to subcategory E facilities as well as to  subcategory
B and D facilities.

B.   EFFLUENT VARIABILITY ANALYSIS

1.   Introduction

The quantity of pollutants discharged from  wastewater  treatment
systems  varies  daily.   EPA  accounts  for  this variability in
deriving standards limiting the amount of a pollutant that may be
discharged.  The statistical procedures used by  EPA  to  analyze
the  variability  of  conventional and toxic pollutant discharges
from the pharmaceutical industry are described below.

2.   Daily Variability Factors

The daily variability factor is  defined  as  the  ratio  of  the
estimated  99th percentile of the distribution of daily pollutant
values to the estimated mean value of the  distribution.   For  a
specific  pollutant discharged from a facility, EPA estimated the
mean and 99th percentile from all  daily  effluent  values  which
were  not  deleted on the basis of being erroneous or descriptive
of aberrant performance.

In developing daily variability factors,  the  Agency  considered
both  parametric   (e.g.,  normal,  lognormal)  and  nonparametric
estimation procedures.  In the course of  examining  the  various
parametric  approaches  and  the data, it became apparent that no
individual parametric distributional assumption  would  apply  to
all  plant/pollutant  data  sets.   For  that  reason, the Agency
relied on a nonparametric procedure when enough daily  data  were
available  to  apply the procedure and on a 2-parameter lognormal
distribution when the  amount  of  data  was  not  sufficient  to
utilize the nonparametric procedure.  Nonparametric procedures do
                              169

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not require satisfying assumptions on the form of the probability
distribution  of the underlying data.  The specific nonparametric
procedure has been used previously by  the  Agency  to  determine
daily   variability  factors  for  other  industries  (e.g.,  BPT
pesticide industry regulations).  The lognormal distribution  has
also  been  used  with effluent discharge data, because such data
are generally skewed to a few large values and are bounded in the
lower concentration range by zero.  This dual approach provides a
consistent methodology which minimizes the number of  statistical
assumptions required to analyze the data, while utilizing as much
plant   data  as  possible  for  the  treatment  technologies  of
interest.

The nonparametric procedure estimates the 99th pe re-entile from  a
set  of  daily discharge measurements by determining the smallest
ordered discharge value in that set of values  which  is  greater
than  or equal to the population 99th percentile with probability
at least 0.5.  That is, for a specified value of n, determine the
smallest ordered value X(j.) such that:
P[X(j) > 99th percentile]-  1 - J
                                               .       .
                                          (.99)1 (.Ol)""1  > .5
The smallest ordered discharge value, satisfying this  criterion,
was determined by nonparametric methods  (see, e.g., J.D. Gibbons,
Nonparametric Statistical Inference, McGraw-Hill,  1971 (86)).  An
estimate  chosen  in this manner is sometimes referred to as a 50
percent reliable estimate, or 50 percent tolerance level, for the
99th percentile and is interpreted as the value  below  which  99
percent of the values of a future sample of size n will fall with
probability  0.5.  Nonparametric tolerance estimates have a lower
bound on the number of observations required to construct such an
estimate.  For a nonparametric tolerance  estimate  of  the  99th
percentile, a minimum sample size of 69 observations is needed in
order  to satisfy the specified probability criterion of at least
0.5.  Therefore, the nonparametric procedure was applied only for
plant/pollutant data sets with  69  or  more  observations.   The
arithmetic average of a facility's daily effluent values was used
for  the  denominator  of  the  nonparametric  daily  variability
factor.
                              170

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For  plant/pollutant  data  sets  with   less   than   69   daily
observations,  a  2-parameter  lognormal distribution was used to
estimate the 99th percentile and long-term average of  the  daily
variability  factor.   The  2-parameter lognormal distribution is
the probability distribution whose natural logarithm has a normal
distribution, and is characterized by parameters » and * relative
to its logarithmic distribution.  If Y^ = In Xi7_i =1,  ..,,  n,
then  the  estimates  of the parameters are fl = Y (sample mean of
the natural logarithms), and
The daily variability factor is then calculated as

                        A      *.„*

                   VF
                         A
                        E(X)
Where 1 - 2.326, the standard -normal 99th per cent ile and
                            n
                                         21
is used to determine a  minimum  variance  unbiased  estimate  of
E(X).

3.   Thirty-day Average Variability Factor

A 30-day average variability factor VF30) is defined as the ratio
of the estimated 99th percentile of the  distribution  of  30-day
averages  of  daily  pollutant  values to the estimated long-term
mean value.  A 30-day average is the arithmetic jnean of  30-daily
measurements;  the  sets of measurements used in determining each
monthly average are assumed to be distinct.  The  long-term  mean
is  the  long-term  arithmetic mean of 30-day averages and is the
same as the long-term mean estimated  from  the  daily  pollutant
values.

The  30-day  average  variability  factors  were developed on the
basis of a statistical result known as the Central Limit  Theorem
(CLT).  The theorem states that, under general and nonrestrictive
assumptions  the  distribution  of  a  sum  of a number of random
variables, say n, is approximated  by  the  normal  distribution.
The  approximation  improves  as  the  number of terms in the sum
increases.  The CLT  is  quite  general  in  that  no  particular
distributional  form  is  assumed  for  the  distribution  of the
individual values.  Thus, this approach  is  also  nonparametric.
In  most  applications  (as  in  determining  30-day  variability
                                171

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factors), the theorem  is used to approximate the distribution  of
the  average  of n observations of a random variable.  The result
is important because it makes it possible to compute  approximate
probability  statements  about  the  average   in  a wide range of
cases.  For instance,  it is possible to  compute  a  value  below
which  a  specified  percentage  (e.g.,  95 or 99 percent) of the
averages on n observations are likely to  fall.   Most  textbooks
state   that  25  or   30  observations  are  sufficient  for  the
approximation to be valid although in many cases  10  or  15  are
adequate.   In  applying  the  CLT to the determination of 30-day
limitations, EPA approximates the distribution of the average  of
30   observations   drawn   from   the   distribution   of  daily
measurements.

Various forms of  this  theorem  exist  and  are  applicable  for
different  situations.   A  key  assumption  in the most familiar
version of the Central  Limit  Theorem  is  that  the  individual
measurements  are  independent.   That  is,  it  is  assumed that
measurements made on successive days, or any fixed number of days
apart,  are  statistically  independent  or  not  related.   This
assumption  of  independence  is  rarely satisfied in an absolute
sense in effluent data.  In many cases, however,  the  assumption
is  satisfied  to a degree sufficient to yield a suitable result.
Because many of the  facilities  used  to  determine  variability
factors  were  known   to have substantial detention periods, such
effluent data  can  be  expected  to  exhibit  some  evidence  of
dependency  in  the  daily  data.   The Central Limit Theorem can
still  be used to develop 30-day average variability  factors  in
the case of dependent  data but some of the necessary calculations
must  be  modified to  account for the dependency and more samples
(i.e., larger n) may be required  for  the  approximation  to  be
adequate.    In  the   case  of  positive  dependence  (the  usual
situation with effluent data), the modification will result in  a
larger  estimate  of   the variance of the mean of 30 observations
than would be obtained if independence is assumed.  This in  turn
results  in a larger 30-day average variability factor than would
be obtained if independence is assumed.

The technical details  of adjusting the variance for the  case  of
data  dependency  are  presented  below.   As  stated  above, the
Central Limit Theorem will still hold for dependent  observations
with  the  modification  that  the  variance  must be adjusted to
reflect the dependence among individual daily measurements.   The
covariance  between daily measurements is one way to express this
dependence; the  most  straightforward  approach  to  effect  the
necessary  modification  is  to  estimate  the  variance directly
including all the appropriate  covariance  terms.   The  variance
estimate  is based on  the following: Let Xt, X2, ..., Xn denote n
random variables each with mean n and variance *2.  In  the  case
of  the  effluent  data, the Xi_, i = 1, ..., n, represent n daily
measurements on a particular pollutant and are  assumed  to  have
the  same mean and variance.  The covariance between Xi_ and Xj_ is
(pk)(«y)2 where k « (i - j|, i *  j  and  pk  -is  the  correlation
                             172

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between  measurements   k   units  apart.   Correlation  is another
measure of dependence  and is related to  covariance.   Regardless
of  the  distribution   of  the  Xi^   the mean and variance of the
average
are:
                     mean

                     var
 and
     n-1
In + 2 Y (n - k) pk]
     k=l
In the case that Xi^  and  Xj_ are independent,  the  correlation  and
covariance   between  them  are  zero.    Therefore,  var   (Xn)  =
^ [n + 0]  « ^   which   is   the  well   known  expression  for  the
n*         n
variance of a mean of  n  independent observations.
Given  a  set of N measurements on the variable X, denoted by X,,
X2,  ..., XN, the mean  and  variance of the average of n  dependent
observations of X, denoted by Xn,  are estimated by
                             A
and
                               S* [n t 2 T (n - k)rk]
                                       k«l
respectively, where
                        o          A _
                       s2 - T (Xj > ? )2
                           i-1  N-1
and

rk  *  estimate  of  pk,  the  correlation between measurements that
are k units apart  (k < n)
                       N-k
                          (Xj - u  )(Xj+k - fr )/(N-k)*

                                  • ? )2/(N - 1)

                              173

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 In order  to   estimate  the  variance  of  Xn,   there  must  be  a
 sufficient    number  of  measurements  to  estimate  the  n  -  1
 correlations.   In the case of  an  average  of  30  observations,
 there   are    29   (lag)  correlations  that  must  be  estimated.
 Thirty-day variability factors  (incorporating  dependence)  were
 estimated for a  plant/pollutant  data  set only if two or more
 pairs were   available  to  estimate  each  of  the  necessary  29
 correlations.   If sufficient data were not available to estimate
 these correlations, then the Central Limit Theorem  was  utilized
 assuming  independence.   Thus,  the 30-day variability factor was
 calculated as      *     £-  .1/2    / where V(x30) was estimated1
              VF30 » u +
                         £-  .1/2
                        V(Xjiy)
as described above, with 2 -
percentile.
                              2.326,   the  standard  normal  99th
*See Wilks, S.S., Mathematical Statistics, Wiley & Sons, 1963, p.
552
                                174

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                           SECTION IX

      EFFLUENT REDUCTION ATTAINABLE THROUGH THE APPLICATION
 OF THE BEST PRACTICABLE CONTROL TECHNOLOGY CURRENTLY AVAILABLE
                 EFFLUENT LIMITATIONS GUIDELINES
A.
GENERAL
The best practicable control technology currently available  (BPT)
generally  is  based  upon  the  average  of  the  best  existing
performance,  in  terms of treated effluent discharged, by plants
of various sizes, ages, and unit processes within an industry  or
subcategory.  Where existing performance is uniformly  inadequate,
BPT  may be transferred from a different subcategory or category.
Limitations based on transfer of technology must be supported  by
a  conclusion  that the technology is, indeed, transferable  and a
reasonable prediction that it will be capable  of  achieving  the
prescribed  effluent  limits  (see Tanners' Council of America v.
Train,  540  F.2d  1188  (4th  Cir.  1976)).   BPT   focuses   on
end-of-pipe  treatment  technology rather than process changes or
internal controls except  where  such  changes  or  controls  are
common industry practice.

BPT  considers the total cost of the application of technology in
relation to the effluent reduction benefits to be  achieved  from
the  technologies.  The cost/benefit inquiry for BPT is a limited
balancing, which does not require the Agency to quantify benefits
in monetary terms (see, e.g., American Iron and  Steel  Institute
v.  EPA,  526  F.2d 1027 (3rd Cir. 1975)).  In balancing costs in
relation to effluent reduction benefits, EPA considers the volume
and nature of existing  discharges,  the  volume  and  nature  of
discharges  after  application  of BPT, the general environmental
effects of the pollutants, and the costs and economic  impacts  of
the  required  pollution control level.  The Act does not require
or permit consideration of water quality problems attributable to
particular  point  sources  or  industries,  or   water   quality
improvements in particular water bodies (see Weyerhaeuser Company
v. Costle, 5907 F.2d 1101 (D.C. Cir. 1978)).

B.   REGULATED POLLUTANTS

1.   Prior Regulations

EPA  promulgated  interim   final   BPT   regulations   for   the
pharmaceutical    manufacturing    point   source   category   on
November 17, 1976 (41 FR 50676; 40 CFR Part 439,  Subparts   A-E).
Pollutants   regulated   included  BOD5_,  COD,  and  pH  for  all
subcategories and TSS for subcategories B, D, and E.
                           175

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 2.    Current  Regulations

 In  addition   to   the  pollutants  regulated  under  the  previous
 rulemaking,    regulated   pollutants   now   include   TSS   for
 subcategories A  and C and cyanide for subcategories A,  B,   C  and
 D.    EPA  is also modifying TSS limitations in subcategories B,  D,
 and E by  establishing alternative minimum effluent BOD5_  and  COD
 concentrations in subcategories B,  D and E.

 C.    IDENTIFICATION OF THE BEST  PRACTICABLE  CONTROL  TECHNOLOGY
      CURRENTLY AVAILABLE

 The  best practicable control technology currently available  for
 the control of BOD5_,  COD,   pH   and  TSS  for  the  pharmaceutical
 manufacturing point source category in BPT regulations issued  in
 1976  (41  FR 50676)  is biological treatment.   Biological treatment
 is  also   the technology  basis  for   TSS   limitations    being
 promulgated for  subcategories  A and C.

 Best  practicable control technology for the control of  cyanide  is
 cyanide destruction and biological  treatment.
D.
BPT EFFLUENT LIMITATIONS
Final BPT TSS  limitations which  apply  to   all   subcategories   and
BPT  cyanide limitations which apply to subcategories A, B, C  and
are summarized below:
Parameter
TSS  (mg/1)
Total Cyanide  (mg/1)
     Alternate A
     Alternate B
                        Maximum          Daily
                     30-Day Average     Maximum

                     1.7 times BPT
                     BOD5_ Concentration
                     Limitation
                       9.4              33.5
                       9.4(.35)R        33.5(.18)R
Alternate A: Measure at effluent from cyanide  destruction  unit.
     Applies only when all cyanide-bearing wastes are diverted to
     a  cyanide  destruction unit and subsequently are discharged
     to a biological treatment system.
Alternate B: Measure at final effluent discharge point.

"R" equals the dilution ratio of the cyanide  contaminated
streams to the total process wastewater discharge flow.
                                                       waste
The  existing  BPT  limitations  for  BOD5,  COD  and  pH  remain
unchanged.    However,   alternative   30-day   average   maximum
concentrations  were  established  for  BOD5_  and  COD  for three
subcategories (B, D and E).   The  alternative  limitations  were
                            3.76

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considered  appropriate  following  a  technical  analysis of the
latest available data.  A plant shall not be required to attain a
maximum 30-day average  effluent  limitation  of  less  than  the
Equivalent of 45 mg/1 for BOD5_ and 220 mg/1 for COD.

E.   RATIONALE FOR THE SELECTION OF THE TECHNOLOGY BASIS OF BPT

Biological treatment was selected as the technology basis for BPT
regulations issued  in  1976  (41  FR  50676).   TSS  regulations
established  in  the  current rulemaking merely reflect discharge
levels associated with biological treatment required  to  achieve
BOD5_ limitations and, therefore, require no new technology.

Cyanide  destruction  was  selected  as  the technology basis for
cyanide limitations as it is a technology currently in use in the
pharmaceutical industry as well as  other  industries.   Its  use
results   in   significant   reductions   in  cyanide  levels  in
pharmaceutical industry effluents.

F.   METHODOLOGY  USED  FOR  THE  DEVELOPMENT  OF  BPT   EFFLUENT
     LIMITATIONS

1.   TSS Limitation

In November of 1982, the Agency proposed a BPT TSS limitation for
all  subcategories  of  plants  based  on  a  long-term   average
concentration  of  75  mg/1.   This  limitation  was  intended to
replace the overly stringent BPT TSS limitations for  subcategory
B, D, and E plants and to establish BPT TSS limitations for A and
C  subcategory  plants.   The  original  BPT  TSS limitations for
subcategories B, D and E were based on data from two plants whose
operations  were  not  characteristic  of  the  entire  range  of
operations  employed  at plants in the B, D, and E subcategories.
The Agency received comments on the proposed  regulation  stating
that   a  single  number  concentration  limit  for  TSS  is  not
appropriate for the pharmaceutical industry.

The existing BPT regulations, which are based on the  application
of  biological treatment,  require that each pharmaceutical plant,
regardless of subcategory, achieve  a  90  percent  reduction  in
BOD5_.   A  single  number  concentration  limit  for  TSS  is not
consistent  with  the  existing  BPT   percent   reduction   BOD5_
limitations,  which  when  converted  to  long-term  average BOD5_
effluent concentrations, vary from plant to  plant  over  a  wide
range  (e.g.,  from  about 15 mg/1 to almost 400 mg/1).  A single
number TSS limitation would require some plants to  install  more
advanced  treatment  than  that technology identified as BPT.  It
would also mean that low raw waste load plants would be  able  to
operate  their  treatment  systems inefficiently and still comply
with the proposed single number limitation.  After analyzing  all
available data, the Agency found that effluent TSS concentrations
from  biological  treatment  systems  usually  are  greater  than
corresponding effluent BOD5_ concentrations.  EPA found  that  the
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median  ratio  of  effluent  TSS  concentrations to effluent BOD5_
concentrations after biological treatment is  1.7  for  both  the
subcategory  A  and  C  and the subcategory B and D plant groups.
Consequently, the Agency is finalizing BPT  TSS  limitations  for
all five subcategories which are equal to a multiple of 1.7 times
the   existing   BPT   BOD£  limitations.   Supporting  data  and
calculation of the BOD5/TSS ratio is presented in Section VIII.

2.   Cyanide Limitations

EPA estimates that about 7 to 10 percent  of  all  pharmaceutical
plants  use and generate waterborne cyanide waste on a regular or
intermittent basis.  Cyanide destruction units  are  in-place  in
several  plants.   EPA requested that the pharmaceutical industry
provide long-term data describing the performance of these units.
Three plants provided data on the performance of cyanide  control
technology.

These  new data measured both the performance of in-plant cyanide
destruction systems directly and in combination  with  biological
treatment.   EPA  is  finalizing BPT and BAT effluent limitations
guidelines, NSPS, PSES, and PSNS for cyanide based on  data  from
these  plants.  The regulations include provisions for monitoring
either in-plant after cyanide destruction  or  end-of-pipe.   The
data and calculation of cyanide limits are presented in detail in
Section VIII.
3.   Alternative   BPT,
     Limitations
BODS   and   COD
Concentration-Based
The  Agency  is also promulgating alternative concentration-based
BOD5. and COD BPT limitations for all subcategories.  Revisions to
BPT were originally proposed in November  1982 because without the
proposed modification in  BPT  BODS^  and  COD  limitations,  some
plants would have had concentration-based BCT and BAT limitations
that  were  less  stringent  than the percent reduction-based BPT
limitations.  This condition would have  been  inconsistent  with
the  requirements  of  the  Clean  Water  Act.   No comments were
received on these alternative limitations.

Although EPA is not yet promulgating final  BCT  limitations  for
BOD5_  or  BAT  limitations  for  COD,  a  review of the available
influent and  effluent  BOD5.  and  COD  data  indicate  that  the
alternative  BODI5 and COD limitations are appropriate in any case
for subcategories B, D, and  E.   These  alternative  limitations
establish  minimum  concentration  levels  consistent  with EPA's
assessment of a  realistic  estimate  of  the  lowest  attainable
long-term  average  BOD5_ and COD concentrations representative of
the  capability  of  the  best  practicable  control   technology
currently   available   in   treating   pharmaceutical   industry
wastewaters.   In  the  low  raw  waste   load   B,   D,   and   E
subcategories,   percent   removal  limitations  would,  in  some
instances,  be   below   that   capability.    Such   alternative
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limitations  are  not  necessary  for  subcategory  A or C plants
because  available  data  indicate  that  raw  waste  loads   are
sufficiently  high  at chemical synthesis and fermentation plants
that percent removal limitations  will  not  be  as  low  as  the
alternative  limitations  established for subcategories B, D, and
E.  The calculation of alternate  concentration-based  limits  is
presented  in  Section  VIII  along  with  a  discussion  of  the
rationale for adopting them.

G.   COST OF APPLICATION AND EFFLUENT REDUCTION BENEFITS

BPT regulations for cyanide  and  TSS  are  expected  to  require
expenditures at eight plants (cyanide destruction at four plants,
TSS  control  at  five plants,  with one of these plants requiring
both).  Total investment and annual costs  are  estimated  to  be
$1.05  million  and  $0.41  million, respectively (1982 dollars).
EPA estimates that these regulations will result in  the  removal
of  127,000  pounds  per  year  of  cyanide  from the effluent of
pharmaceutical plants.

H.   NONWATER QUALITY ENVIRONMENTAL IMPACTS

Sections 304(b) and 306 of the Act require EPA  to  consider  the
non-water   quality   environmental   impacts  (including  energy
requirements) of certain regulations.  In conformance with  these
provisions,
pollution,
summarized below.
       EPA considered the effect of these regulations on air
       solid  waste  generation,  and  energy consumption as
1 .
Solid Waste
EPA estimates that the total solid waste generated to attain  the
new  BPT TSS limitations will be approximately 138,000 additional
pounds per year of wastewater treatment sludge.  This is equal to
an incremental increase of about 0.3 percent over that  currently
generated  by  the  pharmaceutical  industry to meet existing BPT
BOD5_ limitations.  The solid wastes generated through  wastewater
treatment  at  pharmaceutical  plants  have  not  been  listed as
hazardous in regulations promulgated by the Agency under Subtitle
C of the Resource Conservation and Recovery Act (RCRA) (see 45 FR
33066; May 19, 1980).  Accordingly, it  does  not  appear  likely
that  the  wastewater  sludges generated by pharmaceutical plants
under the  new  BPT  TSS  limitations  will  be  subject  to  the
comprehensive  RCRA program establishing requirements for persons
handling,  transporting,  treating,  storing,  and  disposing  of
hazardous  wastes.   The  Agency's estimates of the costs of this
regulation include the cost  of  handling   these  sludges  as  a
non-hazardous waste.

No  sludge  will  be  generated as a result of complying with BPT
effluent limitations for cyanide.
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2.
Air Pollution
EPA  does  not  believe  that  cyanide  removal  will  cause  the
generation  of  air pollutants; additionally, the Agency does not
anticipate that compliance with the  modified  and  new  BPT  TSS
limitations  will  result  in  the  generation  of additional air
pollution from pharmaceutical plants.

3.    Energy Requirements

EPA estimates that the achievement of the cyanide and the new and
modified  TSS  BPT  effluent  limitations  will  increase  energy
consumption by approximately 0.01 percent of present facility use
for all plants.
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                            SECTION X

         BEST CONVENTIONAL POLLUTANT CONTROL TECHNOLOGY
                       CURRENTLY AVAILABLE
A.
GENERAL
The  1977  Amendments  added  Section  301(b)(2)(E)  to  the  Act
establishing  "best  conventional  pollutant  control technology"
(BCT) for discharges of  conventional  pollutants  from  existing
industrial  point  sources.   Conventional  pollutants  are those
defined  in  Section  304(a)(4)  [biological   oxygen   demanding
pollutants  (BOD5J, total suspended solids (TSS), fecal coliform,
and  pH],  and  any  additional   pollutants   defined   by   the
Administrator  as  "conventional"  [oil  and grease, 44 FR 44501,
July 30, 1979].

BCT is not an additional limitation  but  replaces  BAT  for  the
control of conventional pollutants.  In addition to other factors
specified  in  Section  304(b)(4)(B),  the  Act requires that BCT
limitations   be   assessed   in   light   of    a    two    part
"cost-reasonableness"  test (see American Paper Institute v. EPA,
660 F.2d 954 (4th Cir. 1981)).  The first test compares the  cost
for  private  industry to reduce its conventional pollutants with
the costs to publicly owned treatment works for similar levels of
.reduction in their discharge of  these  pollutants.   The  second
test  examines  the  cost-effectiveness  of additional industrial
treatment  beyond  BPT.   EPA  must  find  that  limitations  are
"reasonable"  under  both  tests before establishing them as BCT.
In no case may BCT be less stringent than BPT.

EPA published its methodology for carrying out the  BCT  analysis
on  August 29,  1979 (44 FR 50732).  EPA was later ordered by the
Court of Appeals for the  Fourth  Circuit  to  correct  data  and
methodological  errors  in its BCT cost test and to develop a new
BCT methodology (see American Paper Institute v.  EPA,  660  F.2d
954  (4th Cir. 1981)).  A revised BCT methodology was proposed on
October 29, 1982 (see 47 FR 49176).  A final BCT methodology  has
not been promulgated.

Modified  BPT,  and  BAT  limitations,  NSPS, PSES, and PSNS were
proposed for the pharmaceutical industry  on  November 26,  1982.
At  that  time,  BCT effluent limitations were also proposed based
on the proposed BCT methodology contained in 47 FR 49176.
As the final BCT methodology has not yet been
document does not address BCT limitations.
                                          promulgated,  this
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                           SECTION XI

  EFFLUENT REDUCTION ATTAINABLE THROUGH THE APPLICATION OF THE
        BEST AVAILABLE TECHNOLOGY ECONOMICALLY ACHIEVABLE
                 EFFLUENT LIMITATIONS GUIDELINES
A.   GENERAL

As a result of the Clean Water Act of 1977,  the  achievement  of
BAT  has  become  the  principal  national  means  of controlling
wastewater  discharges  of   toxic   pollutants.    The   factors
considered   in   establishing   the  best  available  technology
economically achievable (BAT) level of control  include the  costs
of  applying the control technology, the age of process equipment
and  facilities,  the  process  employed,  process  changes,  the
engineering   aspects   of  applying  various   types  of  control
techniques, and non-water  quality  environmental  considerations
such  as  energy  consumption,  solid  waste  generation, and air
pollution (Section 304(b)(2)(B)).  In general,  the BAT technology
level represents, at a minimum, the best economically  achievable
performance  of plants of shared characteristics.  Where existing
performance  is  uniformly  inadequate,  BAT  technology  may  be
transferred  from a different subcategory or industrial category.
BAT may include process changes or internal controls,  even  when
not common industry practice.

The  statutory  assessment of BAT "considers" costs, but does not
require a balancing of costs against effluent reduction  benefits
(see  Weyerhaeuser  v.  Costle,  11  ERC  2149  (D.C. Cir. 1978)).
However, in assessing BAT, EPA has given  substantial  weight  to
the  reasonableness  of  costs.   The  Agency   has considered the
volume and the nature of discharges, the  volume  and  nature  of
discharges   expected  after  application  of   BAT,  the  general
environmental effects  of  the  pollutants,  and  the  costs  and
economic  impacts  of  the  required  pollution control  levels.
Despite  this  expanded  consideration  of  costs,  the   primary
determinant   of  BAT  is  effluent  reduction  capability  using
economically achievable technology.

The Agency has decided to regulate the  toxic   pollutant  cyanide
under  BAT.  Regulations for cyanide have been  made equal to BPT.
The available data on cyanide control was evaluated in   terms  of
the cyanide generating processes and the performance of  available
treatment    technology    employed    by    direct   discharging
pharmaceutical plants.  EPA was  unable  to   identify  levels  of
cyanide  control  that  are  more  stringent than that which will
occur after application  of  cyanide  destruction  technology  in
combination with biological treatment.  The identification  of the
technology basis for  cyanide control, rationale for its  selection
and  effluent   reduction benefits are presented in more  detail in
Section  IX.
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The Agency at this time is not promulgating BAT  limitations  for
the nonconventional pollutant COD.  Additional information on the
identity  of  the  pollutants  that  contribute  to  COD  and  on
applicable COD removal technologies is required  before  EPA  can
evaluate   COD   control   options.   Therefore,  the  Agency  is
postponing a final decision on appropriate  BAT  limitations  for
the nonconventional pollutant COD until a later date.  The Agency
is  continuing  its  investigation  of  appropriate  COD  removal
technologies and their costs.


B.   BAT EFFLUENT LIMITATIONS

Final BAT limitations which apply to subcategories A, B, C and  D
are summarized below:
Parameter

Total Cyanide
     Alternate A
     Alternate B

COD
   Maximum          Daily
30-Day Average     Maximum
  9.4              33.5
  9.4(.35)R        33.5(

      (Reserved)
18)R
Alternate  A:  Measure at effluent from cyanide destruction unit.
     Applies only when all cyanide-bearing wastes are diverted to
     a cyanide destruction unit and subsequently  are  discharged.
     to a biological treatment system.

Alternate B: Measure at final effluent discharge point.

"R11  equals  the dilution ratio of the cyanide contaminated waste
streams to the total process wastewater discharge flow.

BAT COD limitations are being  reserved  for  promulgation  at  a
later date.  Additional information on the identity of pollutants
that contribute to COD and applicable COD removal technologies is
required before EPA can fully evaluate COD control options.
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                           SECTION XII

                NEW SOURCE PERFORMANCE STANDARDS
A.
GENERAL
New source performance standards   (NSPS)  are  established  under
Section  306  of  the  Act  and  are  based on the best available
demonstrated technology.  New  plants  have  the  opportunity   to
design  the  best and most efficient manufacturing and wastewater
treatment technologies.   Therefore,  Congress  directed  EPA   to
consider   the   best   demonstrated  process  changes,   in-plant
controls, and end-of-process treatment technologies  that  reduce
pollution   to   the  maximum  extent  feasible.   As  a  result,
limitations  for  NSPS  should  represent  the   most   stringent
numerical   values   attainable    through   the   application   of
demonstrated control technology for all pollutants (conventional,
nonconventional, and toxic).

The only pollutants regulated under NSPS at  this  time  are  the
toxic  pollutant cyanide and the conventional pollutant pH.  NSPS
for the conventional pollutants BOD5 and TSS are  being  proposed
in  a  separate  rulemaking.   Regulations for the control of the
nonconventional pollutant COD are  being deferred at this time.

NSPS for cyanide are being  promulgated  equal  to  BPT  and  BAT
effluent  limitations.  There are  no data available that indicate
that further levels of cyanide control can  be  achieved  by  new
sources.   The  technology basis,  the rationale for its selection
and the methodology for development of limitations are  discussed
in  Sections VIII and IX of this document.  NSPS requirements for
pH are established equal to those  for. BPT  and,  therefore,  will
have  no  resulting  cost  or impacts'.  A discussion of pH can  be
found in the Development  Document  for  Interim  Final  Effluent
Limitations   Guidelines  and  Proposed  New  Source  Performance
Standards  for  the  Pharmaceutical  Manufacturing  Point  Source
Category (U.S.  EPA,  December 1976).
B.
NSPS
Final NSPS which apply  to  subcategories  A,  B,  C  and  D  are
summarized below:
Parameter

Total Cyanide
     Alternate A
     Alternate B
                        Maximum
                     30-Day Average
                       9.4
                       9.4(.35)R
 Daily
Maximum
33.5
33. 5(
18)R
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Alternate  A:  Measure at effluent from cyanide destruction unit.
     Applies only when all cyanide-bearing wastes are diverted to
     a cyanide destruction unit and subsequently  are  discharged
     to a biological treatment system.

Alternate B: Measure at final effluent discharge point.

"R"  equals  the dilution ratio of the cyanide contaminated waste
streams to the total process wastewater discharge flow.

NSPS COD limitations are being reserved  for  promulgation  at  a
later date.  Additional information on the identity of pollutants
that contribute to COD and applicable COD removal technologies is
required before EPA can fully evaluate COD control options.

NSPS  BOD5,  and  TSS  limitations are being proposed concurrently
with  promulgation  of  these  final  regulations.   A   detailed
discussion  of  the proposed limitations is contained in Proposed
Development Document  for  Effluent  Limitations  Guidelines  and
Standards  for  the  Pharmaceutical  Manufacturing  Point  Source
Category (U.S. EPA, September 1983).
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A.
                     SECTION XIII

  PRETREATMENT STANDARDS FOR NEW AND EXISTING SOURCES


GENERAL
Section 307(b) of the Act requires EPA to promulgate pretreatment
standards for existing  sources   (PSES)  that  must  be  achieved
within three years of promulgation.  PSES are designed to  control
the discharge of pollutants that  pass through, interfere with, or
are  otherwise  incompatible  with  the  operation of POTWs.  The
Clean  Water  Act  of  1977  requires  pretreatment   for   toxic
pollutants  that  pass  through   the  POTW   in amounts that would
violate direct discharger effluent limitations or interfere  with
the  POTW's  treatment  process or chosen sludge disposal  method.
The  legislative  history  of  the  1977   Act   indicates  that
pretreatment  standards  are to be technology-based, analogous to
the best available technology for removal  of  toxic  pollutants.
EPA  has  generally  determined   that  there  is  pass through of
pollutants  if the  percent  of  pollutants  removed  by  a well-
operated  POTW  achieving  secondary  treatment  is less than the
percent removed by the BAT model  treatment system.   The   general
pretreatment  regulations,  which served as the framework  for the
categorical  pretreatment  regulations  for  the  Pharmaceuticals
industry  can  be found at 40 CFR Part 403 (43 FR 27736, June 26
1978; 46 FR 9462, January 28, 1981).

Section 307(c) of the Clean Water Act of  1977  requires   EPA  to
promulgate  pretreatment  standards for new sources (PSNS) at the
same time that it promulgates NSPS.   New  indirect  dischargers,
like  new direct dischargers, have the opportunity to incorporate
the best available demonstrated   technologies  including   process
changes, in-plant control measures, and end-of-pipe treatment and
to  use  plant site selection to  ensure adequate treatment system
installation.  Pretreatment standards  for  new  sources   (PSNS),
like  PSES  are  to control the discharge of pollutants that pass
through, interfere with,  or are otherwise incompatible  with  the
operation  of  POTWs.   The  Agency considers the same factors in
promulgating PSNS as it considers in promulgating PSES.

The only pollutant regulated under PSNS and  PSES  is  the  toxic
pollutant  cyanide.    PSES  and  PSNS  are  presented below.  The
technology basis for pretreatment standards as for BPT is  cyanide
destruction.  The rationale for the selection of that  technology
and  the  methodology for the development of effluent limitations
is discussed in Sections VIII and IX.

At proposal, the Agency stated it . was  considering  establishing
pretreatment   standards   to   control  TVO  discharges   because
available data indicated that pass  through  of  TVOs  occurs  at
POTWs.    A standard of 1.2 mg/1 for total toxic volatile organics
was suggested in the preamble to the proposed rules, pending  the
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availability  of  adequate  supporting data on the performance of
steam stripping technology.

One  POTW  and  one  State  Agency  commented  that  pretreatment
standards  controlling  TVOs  should  be  promulgated.   Industry
commenters questioned the need for TVO pretreatment standards  in
view of the low concentrations of toxic volatile organics in POTW
effluents.   They also questioned the achievability of a 1.2 mg/1
discharge level with steam stripping technology.

In the proposed regulation,  17  TVOs  were  listed  as  possible
candidates  for  regulation  by  pretreatment  standards.   After
reexamining all of the available data, EPA concluded  that,  with
the   exception  of  methylene  chloride  and  chloroform,  these
pollutants should be excluded from regulation by  the  provisions
of  paragraph  8  of the Settlement Agreement.  Thirteen of these
pollutants have been excluded because their amount and  toxicity,
taken together, are so insignificant as not to justify developing
uniformly  applicable  pretreatment regulations (see Section VI).
Of the remaining four, there are two (benzene and toluene) which,
while not as insignificant,  nonetheless  are  unlikely  to  pass
through POTWs.

To  address  the  issue  of  pass  through,  EPA studied 50 well-
operated POTWs that use biological  treatment  to  determine  the
extent  to  which  priority pollutants are reduced by such POTWs.
In the case of benzene and toluene, the data indicate that direct
discharger median percent reductions exceed POTW  median  percent
reductions  by  less  than  5  percent  (100  percent  for direct
dischargers versus 99 percent for  benzene  and  97  percent  for
toluene  at  POTWs).  In light of the fact that EPA had less data
in the POTW studies on benzene and toluene than it had  for  some
other  pollutants  and  in  light of the variability in analyzing
samples for organic priority  pollutants  at  the  concentrations
typically  found  in  end-of-pipe biological systems at POTWs and
pharmaceutical plants, EPA believes that differences of 5 percent
or less between the direct discharger and POTW data  for  benzene
and toluene are unlikely to reflect real differences in treatment
efficiency.   Therefore,  EPA  has  determined  that  benzene and
toluene do not pass through POTWs.

However, a potential interference problem could exist  for  these
two toxic volatile organics because of a potential fire/explosion
hazard.   Benzene  and  toluene  water  mixtures  have  low flash
points.  Relatively small concentrations  of  these  solvents  in
water  mixtures (about 180 mg/1) can cause spontaneous combustion
in  the  vapor  space  above  the  water  mixture  under  certain
conditions.   The  Agency's  latest  information  indicates  that
fire/explosions, while' not impossible, are unlikely.  Benzene and
toluene levels above the minimum concentrations required to cause
combustion have not been reported in discharges  from  plants  in
the pharmaceutical industry.  Because pass through does not occur
and  interference is unlikely, there is no basis for establishing
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nationally  applicable  categorical  pretreatment   standards   for
benzene  or  toluene.   However,   under   the  general pretreatment
regulation, 40 CFR  8403.5,  an   individual   POTW   may   establish
pretreatment  standards   if  benzene  and toluene discharges  from
pharmaceutical users result  in interference.   Section VIII  of  the
Development Document contains  suggested   pretreatment   standards
for   benzene   and   toluene,  based  on steam  stripping,   for
consideration by POTWs establishing standards under 8403.5.

At  direct  discharging  pharmaceutical    manufacturing   plants,
chloroform  is  reduced to levels  that are below its treatability
through   volatilization   in   biological   treatment    systems.
Therefore, EPA excluded chloroform from BAT regulations  under  the
provisions  of  paragraph  8(a)(iii) of the Settlement Agreement.
As for indirect dischargers, the Agency found that  POTWs to which
high concentrations of chloroform  are  discharged  achieve  high
chloroform  removal  (greater than 95 percent).  Therefore, POTWs
receiving high  concentrations  of chloroform as  a  result  of
pharmaceutical   discharges   are  unlikely   to  experience pass
through.  For the above reasons, EPA  decided not  to   establish
pretreatment   standards  controlling  chloroform   from   indirect
discharging   pharmaceutical   plants.     Suggested   chloroform
standards  may  be  found  in  Section  VIII   and   may be used by
municipalities  in  developing  pretreatment   standards   on   a
case-by-case basis where necessary.

EPA also considered the effect that other  toxic pollutants, which
were  found  in  significant  concentrations  in the wastewater of
pharmaceutical plants,  would have  on the  operation  of POTWs.  One
group  of  pollutants,   phenol  and  the   various   phenol   type
pollutants, is adequately biodegraded by  the  biological  treatment
systems of direct dischargers and  the evidence available from the
40-plant  POTW  study  (117) indicates that the concentrations of
these pollutants as discharged by  pharmaceutical  plants can  be
adequately  reduced  by  the  secondary treatment works  of  POTWs.
The  concentrations  of  toxic  metals  discharged  by    indirect
discharging  pharmaceutical  plants  are  low  enough that no pass-
through or interference problems result from   this  discharge  at
POTWs.   Therefore,  no  pretreatment  standards  are required to
control the discharge of toxic metals, phenol  and phenol  related
pollutants from pharmaceutical plants.

Through  this  process,  the Agency determined  that  only  methylene
chloride was a candidate for national PSES and PSNS  regulations.
The  Agency  found  that  the installation and operation of steam
strippers to reduce methylene chloride  discharges  to   POTWs  by
pharmaceutical   plants  would  result  in  costs   that   are  not
insignificant.   The Agency estimates that  25  indirect discharging
plants would incur capital  and  total  annual  costs  of   $0.748
million  and  $0.768  million  (1982  dollars), respectively,  per
plant.  EPA projects that one indirect discharging pharmaceutical
plant  would  close  if  required  to  install  steam    stripping
technology.  Steam strippers are also equally -energy intensive at
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indirect discharging plants as at direct dischargers.  The Agency
estimates  that the operation of steam strippers at the 25 plants
would increase energy usage by the equivalent of 315,000  barrels
of  oil  per  year.   For these reasons and because EPA concluded
that regulation of methylene chloride at  direct  dischargers  is
inappropriate,  the  Agency  decided not to establish categorical
PSES and PSNS for methylene chloride.

Data on the capabilities of steam stripping technology to  reduce
the discharge of methylene chloride and on the cost of installing
and  operating steam strippers to control toxic volatile organics
is presented in Section VII and  Appendix  A  of  this  document.
This  information  may  be  used  by municipalities in developing
pretreatment standards for methylene chloride on  a  case-by-case
basis where necessary.
B.
PSES and PSNS
Final PSES and PSNS which apply to subcategories A, B,
are summarized below:
                                                   C  and  D
Parameter
Total cyanide
     Alternate A
     Alternate B
                     PSES and PSNS

                     30-Day Maximum
                        Average
                         9.4
                         9.4R
 Daily
Maximum
33.5
33. 5R
Alternate  A:  Measured at effluent from cyanide destruction unit
     before dilution with other streams.  Applicable only if  all
     cyanide-containing   wastes  streams  are  diverted  to  the
     cyanide destruction unit.

Alternate B: Measured at final effluent discharge point.

"R" equals the dilution ratio of the cyanide  contaminated  waste
     stream to the total process wastewater flow.

C.   COST OF APPLICATION AND EFFLUENT REDUCTION BENEFITS

Only one out of the 277 indirect discharging plants  is  expected
to  incur costs; the estimated capital and annual costs are $0.42
million and $0.26 million, respectively (1982 dollars).  PSES for
cyanide will result in the removal of 148,000 pounds  of  cyanide
per year from the nation's waters.

Regulations  for  indirect discharging new sources (PSNS) are the
same as those for existing sources.   Therefore,  no  incremental
impacts  are expected from implementation of PSNS.  Since PSNS is
                                  190

-------
equal to PSES,
removal.
it  will  result  in  no  additional  incremental
D.   NONWATER QUALITY ENVIRONMENTAL IMPACTS

Cyanide PSES and PSNS limitations will result  in  no  additional
solid  waste  generation  or  discharge  of  air pollutants.  EPA
estimates that compliance with PSES to control cyanide discharges
to POTWs will increase overall energy use by 0.07 percent at  the
affected indirect discharging pharmaceutical plant.  Because PSNS
are  identical to PSES, there will be no incremental energy usage
resulting from compliance with PSNS.
                                  191

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                           SECTION XIV

                           REFERENCES
1 .




2.


3.


4.


5.


6.


7.


8.


9.


10.


1 1 .


12.



13.



14.
Anderson, Dewey  R.,  et  al_. ,  "Pharmaceutical  Wastewater:
Characteristics  and  Treatment,"  Industrial Wastes, March/
April 1971, pp. 2-6.

APHA  Project  Staff,  Factbook    '76,   Prescription   Drug
Industry, Pharmaceutical Manufacturers Association,  1976.

APHA  Project  Staff,  Handbook  of_  Nonprescroption  Drugs,
American Pharmaceutical Association, Washington, D.C.,  1977.

Breaz, Emil, "Drug Firm Cuts Sludge Handling  Costs,"   Water
and Wastes Engineering, January 1972, pp. 22-23.

Burns and Roe submittal to the  U.S.  EPA,  "Burns  and Roe
Review of TRC Data Base," May 8,1978, revised June 7, 1978  .
Burns and  Roe  submittal  to
Profile," February 15, 1978.
the  U.S.  EPA,  "Preliminary
Burns and Roe submittal to the U.S. EPA, "Profile Report No.
2, 308 Portfolio, Subcategory A Report," June 2, 1978.

Burns and Roe submittal to the U.S. EPA, "Profile Report No.
3, Industry Population," June 22,  1978.

Burns and Roe submittal to the U.S. EPA, "Profile Report No.
4, Fate of Industry Wastewater," August 18,1978.

Burns and Roe submittal to the U.S. EPA, "Profile Report No.
5, Treatment Technology," September 8,  1978.

Burns and Roe submittal to the U.S. EPA, "Profile Report No.
6A, Production Data by Plant Site," August 30,  1978.

Burns and Roe submittal to the U.S. EPA, "Summary Report No.
1,  Pharmaceutical  Manufacturing  Data  Base  Acquisition,"
February 14, 1978.

Burns and Roe submittal to the U.S. EPA, "Summary Report No.
1A,  308 '  Portfolio   Development,   Pharmaceutical   Manu-
facturing," May, 1978.

Burns and Roe submittal to the  U.S.  EPA,  "Summary  Report
No.2, 308 Portfolio Computerization, Phase I, Pharmaceutical
Manufacturing," February 24, 1978.
                           393.

-------
15.  Burns and Roe submittal to the U.S. EPA,  "Summary Report No.
     3, Industrial Subcategorization,  Review  of  Alternatives,"
     February 14, 1978.

16.  Burns and Roe submittal to the U.S. EPA,  "Summary Report No.
     4,  Pharmaceutical  Manufacturing  Point   Source   Category
     Definition," February 14, 1978.

17.  Burns and Roe submittal to the U.S. EPA,  "Summary Report No.
     5, 308 Portfolio Computerization, Phase   II,  Pharmaceutical
     Manufacturing," April 21, 1978.

18.  Burns and Roe submittal to the U.S. EPA,  "Screening  Plants
     Coverage  of  Pharmaceutical  Products,"  letter transmitted,
     December 12, 1978.

19.  Burns and Roe submittal to  the  U.S.  EPA,  "308  Treatment
     Plant  Performance  Data,"  letter report dated December 11,
     1978.

20.  Burns and Roe submittal to the U.S. EPA,  "Profile Report No.
     1A, " June 1.5, 1978.

21.  Crame, Leonard W., "Activated Sludge Enhancement:  A  Viable
     Alternative  to  Tertiary Carbon Adsorption," Proceedings of
     the Open Forum on Management of  Petroleum  Refinery  Waste-
     water, June 6-9, 1977.

22.  Dlouhy, P.E. and Dahlstrom, D.A., "Continuous Filtration  in
     Pharmaceutical  Production,"  Chemical Engineering Progress,
     Vol. 64, No. 4, April 1968, pp. 116-121.

23.  Dunphy, Joseph F. and Hall, Alan, "Waste Disposal:  Settling
     on  Safer  Solution  for Chemicals," Chemical Week, March 8,
     1978, pp. 28-32

24.  Echelberger, Wayne F., Jr., "Treatability Investigations for
     Pharmaceutical Manufacturing Wastes," presented at the  ASCE
     National  Environmental  Engineering  Conference, Vanderbilt
     University, July 13-15, 1977.

25.  Federal Register, Vol. 41,  No.31  -  Friday,  February  13,
     1976, pp. 6878-6894.

26.  Federal Register, Vol. 41, No. 106 - Tuesday, June 1,  1976,
     pp. 22202-22219.

27.  Federal Register, Vol.41, No. 223 - Wednesday, November  17,
     1976, pp. 50676-50686.

28.
Federal Register, Vol. 42, No. 20
pp. 5697.
Monday, January 31, 1977
                            194

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29.


30.


31 .


32.



33.



34.


35.
Federal Register, Vol. 42, No.  24  -
1977, pp. 6813-6814.

Federal Register, Vol. 42, No. 148,
1977, pp. 39182-39193.
Friday,  February  4,


 Tuesday,  August  2,
36.


37.




38.




40.


41 .



42.



43.
Federal Register, Vol. 42, No. 191,  -  Monday,  October  3,
1977, pp. 53804-53820.

Fox, Jeffrey L., "Ames Test Success Paves Way for Short-Term
Cancer Testing," Chemical and Engineering News, December 12,
1977, pp. 34-46.

Grieves, C.G., e_t al., "Powdered Carbon  Improves  Activated
Sludge  Treatment,"   Environmental Management, October  1977,
pp.  125-130.

Humphrey, Arthur E.,  "Current Developments  in Fermentation,"
Chemical Engineering, December 9,  1974, pp. 98-112.

Lawson, C.T.,  and  Hovious,  J.L.,  "Realistic  Performance
Criteria  for Activated Carbon Treatment of Wastewaters from
the  Manufacture of Organic Chemicals  and   Plastics,"   Union
Carbide Corporation,  February 14,1977.

Lund, Herbert F.,  Industrial  Pollution  Control  Handbook,
McGraw-Hill,  1971.

Marek,  Anton  C.,  Jr.,  and  Askins,  William,   "Advanced
Wastewater  Treatment for an Organic Chemicals Manufacturing
Complex,"  U.S./U.S.S.R.  Symposium   on    Physical/Chemical
Treatment, November 12-14, 1975.

Mohanrao, G.J., et al., "Waste Treatment at a Synthetic Drug
Factory  in   India,"   Journal   Water   Pollution   Control
Federation,  Vol.  42,  No.  8,  Part   1,   August  1970, pp.
1530-1543.

Natural Resources Defense  Council,  et  al..,  v.  Train,   8
E.R.C.  2120  (D.D.C. 1976).

PEDCo Environmental submittal to the U.S. EPA, "The  Presence
of  Priority Pollutants  in  the  Extractive Manufacture  of
Pharmaceuticals," October 1978.

PEDCo Environmental submittal to the U.S. EPA, "The  Presence
of   Priority  Pollutant  Materials   in   the    Fermentation
Manufacture of Pharmaceuticals," no date.

PEDCo Environmental submittal to the U.S. EPA, "The  Presence
of  Priority   Pollutants   in  the   Synthetic Manufacture  of
Pharmaceuticals," March 1979.
                             195

-------
44.  Shumaker, Thomas  P.,  "Carbon  Treatment   of   Complex   Organic
     Wastewaters,"  presented   at  Manufacturing  Chemists  Associ-
     ation, Carbon Adsorption Workshop, November  16,  1977.

45.  Stracke, R.J., and Bauman, E.R.,  "Biological  Treatment  of   a
     Toxic  Industrial Waste -  Performance of an  Activated Sludge
     and Trickling Filter  Plant:   Salisbury  Laboratories,"  1976.

46.  Struzeski,   E.J.,    Jr.,   "Waste    Treatment     in   the
     Pharmaceuticals   Industry/Part   1,"    Industrial    Wastes,
     July/August  1976, pp.  17-21.  pp. 17-21.

47.  Struzeski,   E.J.,    Jr.,   "Waste    Treatment     in   the
     Pharmaceuticals   Industry/Part   2,"    Industrial    Wastes,
     September/October 1976, pp. 40-43.

48.  Stumpf, Mark R.,  "Pollution Control at   Abbott",  Industrial
     Wastes, July/August 1973,  pp. 20-26.

49.  "Super Bugs Rescue Waste Plants,"  Chemical   Week,  November
     30, 1977, p. 47 (unauthored).

50.  The Directory of_ Chemical  Producers  -   U.S.A.,  Medicinals,
     Stanford Research Institute,  Menlo Park,  CA.,  1977.

51.  The Executive Directory  of.   U.S.  Pharmaceutical  Industry,
     Third Edition, Chemical Economics Services, Princeton,  NJ.

52.  U.S. EPA, "Assessment of the  Environmental   Effect   of  the
     Pharmaceutical  Industry," Contract No.  68-03-2510, December
     1978.

53.  U.S. EPA, "Characterization of Wastewaters from the  Ethical
     Pharmaceutical  Industry,"  Report  No.   670/2-74-057,  July
     1974.

54.  U.S. EPA, "Control Techniques for Volatile Organic Emissions
     from Stationary Sources," Contract No. 68-02-2608, Task  12,
     September, 1977.

55.  U.S. EPA, "Development Document for Interim   Final  Effluent
     Limitations  Guidelines  and  Proposed New Source Performance
     Standards for the Pharmaceutical Manufacturing Point  Source
     Category," Report No.  440/1-75/060,  December  1976.

56.  U.S. EPA, "Development Document for Proposed  Existing Source
     Pretreatment Standards for the Electroplating  Point  Source
     Category," Report No.  440/1-78/085,  February  1978.

57.  U.S. EPA, Draft  of   "Pretreatment  Standards  for  Ammonia,
     Phenols,  and Cyanides", Contract No.  68-01-3289, March  1976.
                              196

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58.  U.S. EPA, "Pharmaceutical  Industry:  Hazardous  Waste  Gen-
     eration, Treatment, and Disposal," Report No. SW-508,  1976.

59.  U.S. EPA, "Preliminary Evaluation of Sources and Control   of
     the    Wastewater    Discharges   of   Three   High   Volume
     Pharmaceutical Production Processes,"  Contract  No.  68-03-
     2870, November 1977.

60.  U.S. EPA, "Sampling and Analysis Procedures for Screening  of
     Industrial Effluents for Priority Pollutants," April  1977.

61.  U.S. EPA, ''Waste Treatment  and  Disposal  Methods  for  the
     Pharmaceutical  Industry," Report No. 330/1-75-001, February
     1975.

62.  Willey, William J.,  and  Vinnecombe,  Anne  T.,  Industrial
     Microbiology,  McGraw-Hill, 1976.

63.  Windholz, Martha, The Merck Index, 9th  Edition,  Merck  and
     Co., Rahway, NJ,  1976.

64.  Wu, Yeun C.  and Kao, Chiao F., "Activated  Sludge  Treatment
     of  Yeast  Industry  Wastewater,"  Journal  Water  Pollution
     Control Federation, Vol. 48,   No.  11,  November  1976,  pp.
     2609-2618.

65.  DeWalle, F.B., et a_l. , "Organic Matter Removal  .by  Powdered
     Activated  Carbon  Added to Activated Sludge," Journal Water
     Pollution Control Federation,  "April 1977.

66.  Grieves,  C.G.,   et   al.,   "Powdered   Activated   Carbon
     Enhancement   of   Activated   Sludge   for  BATEA  Refinery
     Wastewater Treatment," Proceedings  of  the  Open  Forum   on
     Management of Petroleum Refinery Wastewater, June 6-9, 1977.

67.  Grulich, G., e_t al_. , "Treatment of Organic  Chemicals  Plant
     Wastewater  with  DuPont  PACT  Process," presented at AICHE
     Meeting, February 1972.

68.  Heath,  H.W., Jr.,  "Combined  Powdered  Activated  Carbon  -
     Biological  ("PACT")  Treatment of 40 MGD Industrial Waste,"
     presented to Symposium on Industrial Waste Pollution Control
     at ACS National Meeting, March 24, 1977.

69.  Button, D.C., and Robertaccio, F.L., U.S. Patent  3,904,518,
     September 9, 1975.

70.  U.S. EPA, "Control  of  Volatile Organic  Emissions  from  the
     Manufacture  of Synthesized Pharmaceutical Products," Report
     No. 450/2-78-029, December 1978.
                             3.97

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71.  U.S. EPA, "Draft Development  Document  Including  the  Data
     Base for Effluent Limitations Guidelines (BATEA), New Source
     Performance  Standards,  and  Pretreatment Standards for the
     Inorganic Chemicals Manufacturing  Point  Source  Category,"
     Contract No. 68-01-4492, April 1979.

72.  Hwang, Seong T., and Fahrenthold, Paul, "Treatability of the
     Organic Priority Pollutants by Steam  Stripping,"  presented
     at A.I.Ch.E. meeting, August 1979.

73.  Burns and Roe submittal to the U.S EPA,  "Executive  Summary
     of  Effluent  Limitations  Guidelines for the Pharmaceutical
     Industry," July 1979.

74.  Burns and Roe submittal to the U.S. EPA, "Supplement to  the
     Draft  Contractors Engineering Report for the Development of
     Effluent  Limitations  Guidelines  for  the   Pharmaceutical
     Industry," July 1979.

75.  Fox,  C.R.,   "Removing  Toxic  Organics  from   Wastewater,"
     Chemical Engineering and Process, August 1979.

76.  Boznowski, J.H., and  Hanks,  D.L.,  "Low-Energy  Separation
     Processes,"  Chemical Engineering, May 7, 1979, pp. 65-71.

77.  Heist,  James   A.,   "Freeze   Crystallization,"   Chemical
     Engineering, May 7, 1979, pp. 72-82.

78.  Hanson,   Carl,    "Solvent    Extraction-An    Economically
     Competitive Process," Chemical Engineering, May 7, 1979, pp.
     83-87.

79.  Region 2 S&A Chemistry Section memo to William  Telliard  of
     Effluent Guidelines Division, "Quantitative. Organic Priority
     Pollutant   Analyses-Proposed   Modifications  to  Screening
     Procedures for Organics," December 12, 1978.

80.  Arthur D.  Little  submittal  to  the  U.S.  EPA,  "Economic
     Analyses  of  Interim  Final  Effluent  Guidelines  for  the
     Pharmaceutical Industry," August 1976.

81.  Arthur D. Little submittal to  the  U.S.  EPA,  "Preliminary
     Economic Assessment,of the Pharmaceutical Industry for BATEA
     Effluent Limitation Guidelines Studies," February 1978.

82.  Office of Quality Review to Robert B. Schaffer  of  Effluent
     Guidelines Division, "Treatability of "65" Chemicals Part B-
     Adsorption  of  Organic  Compounds  on  Activated Charcoal,"
     December 8,  1977.

83.  Waugh,  Thomas  H.,  "Incineration,  Deep  Wells  Gain   New
     Importance,"  Science,  Vol.  204,  June 15,  1979, pp. 1188-
     1190.
                              3.98

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84.



85.



86.


87.



88.



89.
90.


91 .



92.



93.


94.


95.


96.



97.
Wild, Norman H., "Calculator Program for Sour-Water-Stripper
Design," Chemical Engineering, February 12, 1979,  pp.   103-
113.

M & I preliminary submittal to the U.S. EPA,  "A Demonstrated
Approach  for  Improving  Performance  and  Reliability   of
Biological Wastewater Treatment Plants," December  1977.
Gibbobs,  J.  D.,   Nonparametric
McGraw-Hill, 1971.
Statistical   Inference,
Swan, Raymond, "Pharmaceutical Industry Sludge: Drug  Makers
Face  Waste  Management Headache," Sludge, July-August  1979,
pp. 21-25.

Robins,   Winston   K.,    "Representation   of    Extraction
Efficiencies,"   Analytical  Chemistry,  Vol.   51,  No.   11,
September 1979, pp. I860,  1861.

Dietz, Edward A., and Singley, Kenneth F., "Determination  of
Chlorinated  Hydrocarbons   in   Water   by   Headspace   Gas
Chromotography,"  Analytical  Chemistry,  Vol.  51,   No.  11,
September 1979, pp. 1809-1 81"4 .

U.S. EPA, "Indicatory Fate Study," Report No.   600/2-79-175,
August 1979.

U.S.   EPA,   "Biological   Treatment   of   High   Strength
Petrochemical  Wastewater," Report No. 600/2-179-172, August
1979.

U.S.  EPA,   "Activated  Carbon   Treatment   of   Industrial
Wastewaters:   Selected  Technical   Papers,"   Report   .No.
600/2-79-177, August  1979.

U.S.  EPA,   "Biodegradation  and  Treatability  of  Specific
Pollutants," Report No. 600/9-79-03, October  1979.

Interagency  Regulatory Liasion Group,  "Publications on  Toxic
Substances:  A Descriptive  Listing,"  1979.

Federal  Register, Vol. 44, No. 233   -  Monday,  December  3,
1979, pp. 69464-69575.

Engineering-Science,   Inc. submittal  to  the    U.S.    EPA,
"Effectiveness   of  Waste   Stabilization  Pond  Systems  for
Removal  of  the Priority Pollutants," December  1979.

U.S. EPA,   "Seminar   for   Analytical   Methods   for  Priority
Pollutants,"  May 1978.
                              3.99

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98.  Strier, Murray P., "Pollutant Treatability:  A     Molecular
     Engineering  Approach,"  Vol.  14, No. 1., January 1980, pp.
     28-31.

99.  U.S. EPA, "Fate of Priority  Pollutants  in  Publicly  Owned
     Treatment  Works  -  Pilot  Study," Report No. 440/1-79-300,
     October 1979.

100. Malina, Joseph F., Jr., "Biodisc Treatment," no date.

101. Gloyna, Earnest F., and Tischler, Lial F., "Design of  Waste
     Stabilization  Pond  Systems,"  presented  at  International
     Association  on  Water  Pollution  Research,  Conference  on
     Developments   on   Land  Methods  of  Waste  Treatment  and
     Utilization, October 1978.

102. Gulp, Russell L.,  "GAC  Water  Treatment  Systems,"  Public
     Works, February 1980, pp.  83-87.

103. Lawson, C.T.,  and  Hovious,  V.C.,  "Realistic  Performance
     Criteria  for Activated Carbon Treatment of Wastewaters from
     the Manufacture of Organic Chemicals  and  Plastics,"  Union
     Carbide Corporation,  February 14, 1977.

104. U.S. EPA, "Development of Treatment and  Control  Technology
     for  Refractory  Petrochemical Wastes," Report No. 600/2-79-
     080, April 1979.

105. Pharmaceutical  Manufacturers  Association,   "Administrative
     Officers  of  the  Member  Firms and Associates of the PMA,"
     October 1976.

106. Manufacturing  Chemists  Association   submittal   to   Paul
     Fahrenthold  of  Effluent  Guidelines Division, "Comments on
     the Molecular Engineering  Approach  to  Effluent  Guideline
     Development," January 23,  1979.

107. Chemical Manufacturers Association submittal to the U.S.  EPA
     "CMA  Comments  on  EPA's  Proposed  Leather   Tanning   and
     Finishing  Effluent  Limitations  Guidelines and Standards,"
     March 27, 1980.

108. U.S. EPA, "Ambient Water  Quality  Criteria,"  Criteria  and
     Standards Division, unpublished draft report.

109. U.S. EPA, "Development  Document  for  Effluent  Limitations
     Guidelines  and  New  Source  Performance  Standards for the
     Copper,  Nickel,  Chromium,   and   Zinc   Segment   of   the
     Electroplating Point  Source Category," Report No.   440/1-74-
     003a, March 1974.
                             200

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T10.  Walk,  Haydel and Associates, Inc., "Summary Report  for  the
     Pharmaceutical  BAT'/Priority  Pollutant  Orientation Study,"
     Contract No. 68-01-6024, Work  Assignment  No.,  3,  May  20,
     1980.

111.  Considine,  Douglas M, (ed.), Chemical and Process Technology
     Encyclopedia, McGraw Hill Book Co., New York, N.Y.,  1974.

112.  Hawley,  Gessner G.,  The Condensed Chemical  Dictionary,  9th
     edition, Van Nostrand Reinhold Co., New York, N.Y.,  1977.

113.  Calspan  Corp.,  "Addendum  to  Development   Document   for
     Effluent  Limitations  Guidelines and New Source Performance
     Standards,  Major Inorganic  Products  Segment  of  Inorganic
     Chemicals Manufacturing Point Source Category," Contract No.
     68-01-3281, 1978.

114.  Coleman, R.T., J..D.  Colley, R.F. Klausmeiser,  D.A.   Malish,
     N.P.    Meserole,   W.C.  Micheletti,  and  K.  Schwitzgebel,
     "Treatment  Methods   for   Acidic   Wastewater   Containing
     Potentially  Toxic Metal Compounds," EPA Contract No. 68-02-
     2608,  U.S.  Environmental Protection Agency, 1978. 220 pp.

115.  Colley,  J.D., C.A. Muela, M.L.  Owen,  N.P.  Meserole,  J.B.
     Riggs, and J.C. Terry, "Assessment of Technology for Control
     of  Toxic Effluents from the Electric Utility Industry," EPA
     600/7-78-090, U.S. Environmental Protection Agency,  1978.

116.  Hannah,  S.A., M. Jelus, and J.M. Cohen, "Removal of Uncommon
     Trace Metals by Physical and Chemical Treatment  Processes,"
     Journal  Water  Pjpillrut.ion  Control Federation, 49(11): 2297-
     2309,  1977.

117.  Larsen,  H.P., J.K. Shou, and L.W. Ross, "Chemical  Treatment
     of  Metal  Bearing  Mine  Drainage," Journal Water Pollution
     Control Federation,  45(8): 1682-1695, 1973.

118.  Maruvama, T., S.A. Hannah, and J.M. Cohen, "Metal Removal by
     Physical and Chemical Treatment  Processes,"  Journal  Water
     Pollution Control Federation, 47(5):962-975, 1975.

119.  Nilsson, R., "Removal of Metals  by  Chemical  Treatment  of
     Municipal Waste Water," Water Research, 5:51-60, 1971.

120.  Patterson,  J.W.,  and  R.A.  Minear,  "Wastewater  Treatment
     Technology," Illinois Institute of Technology, 1973.

121.  Patterson,   J.W.,  "Wastewater  Treatment  Technology,"  Ann
     Arbor Science Publishers, Inc., Ann Arbor, Micigan,  1975.

122.  Patterson,  J.W., H.E.  Allen,  and  J.J.  Scala,  "Carbonate
     Precipitation  for  Heavy  Metals Pollutants," Journal Water
     Pollution Control Federation, 49(12):2397-2410, 1977.
                             201

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123.  Schlauch,   R.M.,  and  A.C.  Epstein,  "Treatment  of  Metal
     Finishing   Wastes  by  Sulfide Precipitation," EPA-600/2-75-
     049,  U.S.  Environmental Protection Agency, 197?,, 89 pp.

124.  Scott, M.C., "Sulfex - A New Process Technology for  Removal
     of  Heavy  Metals from Waste Streams,"" The 32nd Annual Purdue
     Industrial Waste Conference, Lafayette,  Indiana,  1977,  17
     pp.

125.  Scott, M.C., "Heavy Metals  Removal  at  Phillips  Plating,"
     WWEMA  Industrial Pollution Conference, St. Louis, Missouri,
     1978, 16 pp.

126.  Sorg, T.J. O.T. Love, and G.S. Logsdon, "Manual of Treatment
     Techniques for Meeting the Interim  Primary  Drinking  Water
     Regulations,"     EPA-600/8-77-005,    U.S.    Environmental
     Protection Agency, 1977. 73 pp.

127.  U.S.   EPA,  "Development  Document  for  Proposed   Effluent
     Limitations  Guidelines,  New  Source Performance Standards,
     and  Pretreatment  Standards  for  the  Inorganic  Chemicals
     Manufacturing  Point  Source  Category," Contract No. 440/1-
     80/007-6,  June 1980.

128.  Sabadell,  J.E., "Traces of Heavy  Metals  in  Water  Removal
     Processes     and    Monitoring,"   EPA-902/9-74-001.     U.S.
     Environmental Protection Agency, 1973.

129.  U.S.  EPA,  "Analytical Methods for the Verification Phase  of
     the BAT Review," June 1977.

130.  The Research Corporation of New  England  subrnittal  to  the
     U.S.   EPA,  "Assessment  of  the Environmental Effect of the
     Pharmaceutical Industry," December 1978.

131.  Catalytic, Inc., "Computerized Wastewater Treatment  Model,"
     Prepared for U.S. EPA, 1980.

132.  Catalytic, Inc., Submittal to Burns and Roe, "Computer Print
     Out - Pharmaceutical Analysis," January 29, 1980.

133.  U.S.  EPA,  "Fate of Priority  Pollutants  in  Publicly  Owned
     Treatment  Works - Interim Report," October 1980.

134.  Roegner,   Russell,   "Statistical    Analysis    Supporting
     Subcategorization  for  the  Pharmaceutical  Industry," U.S.
     EPA,  September 14, 1983.

135.  "Statistical  Support  for   Pharmaceutical   Rulemaking
     September  1983," SRI International, September 1983.

136.  "Fate of Priority Pollutants  in  Publicly  Owned  Treatment
     Works - Final Report," U.S. EPA, September, 1983.
                               202

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137,  "Pretreatment Standards Evaluation  for  the  Pharmaceutical
     Manufacturing  Category,"  EPA Contract No. 68-01-6675, B.C.
     Jordan Co., August 1983.

138.  Treybal,, R.E., Mass - Transfer  Operations,  Third  Edition/
     McGraw-Hill Book Company, New York, NY, 1980.

139.  McCabe., W.L., and 3.C. Smith, Unit  Operations  of  Chemical
     Engineering,  Third  Edition,  McGraw-Hill Book Company, New
     York, NY, 1976.
140,
141
Peters,  M.S.,  and  K.D.  Timmerhaus,  Plant
Economics    for   Chemical   Engineers,
                                                Design   and
		Second   Edition,
McGraw-Hill Book Company, New York, NY, 1968.

Chemical Engineers Handbook, 4th Edition,  McGraw-Hill  Book
Company, New York, NY, 1963.
142. U.S. Environmental Protection Agency,  Proposed  Development
     Document  for  Effluent Limitations Guidelines and Standards
     for
      the   Pesticides
                         Point
Source
Category,
EPA
     440/1-82/D79-b, Washington, D.C., November 1982.
                            203

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                           SECTION XV

                     LEGEND OF ABBREVIATIONS
AA
A. C.
AE
atm
avg.
BADCT

BAT (BATEA)

bbl.
BCT
B-N
BOD5
BPT (BPCTA)

Btu
°C
C.A.
cal.
cc
cfm
cfs
cm
CN
COD
cone.
cu .m.
deg.
DO
E.Col.
Eq.
°F
Fig.
F/M

fpm
fps
ft
g
gal.
GC
GC/MS

gpd
gpm
hp
hp-hr
HPLC
atomic absorption
activated carbon
Acid extractables
atmosphere
average
Best Available Demonstrated Control
  Technology
Best Available Technology Economically
  Achievable
barrel
Best Conventional Control Technology
Base - Neutral Extractables
Biochemical Oxygen Demand, five day
Best Practicable Control Technology
  Currently Available
British Thermal Unit
degrees Centigrade
carbon adsorption
calorie
cubic centimeter
cubic feet per minute
cubic feet per second
centimeter
cyanide
Chemical Oxygen Demand
concentration
cubic meter
degree
dissolved oxygen
Escherichia coli - coliform bacteria
equation
degrees Fahrenheit
Figure
Food to microorganisms ratio
  (Ibs BOD/1bs MLSS)
feet per minute
feet per second
foot
gram
gallon
Gas chromatography
Gas chromatography/Mass
  Spectroscopy
gallon per day
gallon per minute
horsepower
horsepower-hour
High Pressure Liquid Chromatography
                                 205

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hr
in
kg
KW
KWh
1
1/kkg
Ib
m
M
mg
MGD
mg/1
inin
ml
MLSS
MLVSS

mm
MM
mole
mph
mu
NH3-N
N03-N
NPDES

NSPS
02
P04
P-
pH
POTW
pp.
ppb
ppm
PSES

psf
psi
PSNS
RBC
R.O.
rpm
RWL
sec.
Sec.
SIC
SOx
sg.
sq. ft.
 per day
liter
hour
inch
kilogram
kilowatt
kilowatt hour
liter
liters per 1000 kilograms
pound
meter
thousand
milligram
million gallons
milligrams per
minute
milliliter
mixed liquor suspended solids
mixed liquor volatile suspended
  solids
millimeter
million
gram molecular weight
mile per hour
millimicron
ammonia nitrogen
nitrate nitrogen
National Pollutant Discharge
  Elimination System
New Source Performance Standards
Oxygen
phosphate
page
potential hydrogen or hydrogen-ion
  index (negative logrithm of the
  hydrogen-ion concentration)
Publicly Owned Treatment Works
pages
parts per billion
parts per million
Pretreatment Standards for Existing
  Sources
pounds per square foot
pounds per square inch
Pretreatment Standards for New Sources
Rotating Biological Contactor
reverse osmosis
revolution per minute
raw waste load
second
Section
Standard Industrial
Oxides of Sulfur (e,
square
square foot
     Classification
    ,g. sulfate)
                                 206

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ss
STP
SRWL
TDS
TKN
TLM
TOC
TOD
TSS
VOA
vol
wt
yd
u
ug
ug/1
suspended solids
standard temperature and pressure
standard raw waste load
total dissolved solids
total Kjedahl nitrogen
median tolerance limit
total organic carbon
total oxygen demand
total suspended solids
Volatile Organic Analysis
volume
weight
yard
micron
microgram
microgram per liter
note:  symbols for chemical elements and compounds are in accordance
       with IUPAC and standard chemical nomenclature.
                                 207

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                            SECTION  XVI

                         ACKNOWLEDGMENTS
The U.S. Environmental  Protection  Agency   wishes   to  acknowledge
the  contributions   to   this  project  by Environmental  Science and
Engineering,  Inc.,- of Gainesville,  Florida.   The  key contributors
were John Crane, Bevin  Beaudet,  Susan Albrecht,   Russell   Bowen,
Leonard  Carter, and Margaret Parrel1.  We also wish to thank the
following personnel  of  the E.C.  Jordan Co.,  of  Portland,   Maine,
for  their  assistance:  Willard  Warren,   Conrad Bernier,  Robert
Steeves, Michael Crawford, and Neal Jannelle.

In the early  stages  of  this project,  the following members  of the
Burns  and  Roe  Industrial   Services Corp.   made   significant
contributions   to   the  data  base  development  and  technical
analysis: Arnold  Vernick,  Barry   Langer,   Jeffrey Arnold,   Tom
Fieldsend,  Thomas   Gunder,   Vaidyanathan  Ramaiah,  Mark Sadowski,
Mary  Surdovel,  Jeffrey  Walters,  and  Samuel   Zwickler.     The
following  personnel  at  Walk,  Haydel and  Associates,  Inc.  also
provided technical   support   for  this  regulatory  effort:   John
Beaver,  Forrest  Dryden,  E.  Jasper Westbrook,  Richard Melton,
Ronald  Rossi,  Miles   Seifert,  Efrain  Toro,  Fred  Zak,    Paul
Schneider, and Anita Junker.

The   assistance   of   PEDCo,   of   Cincinnati,   Ohio,  is   also
acknowledged  for their  technical   input  in   this  project.    The
efforts  of   the  Research  Corporation  of   New  England (TRC)  in
developing and maintaining an  open  literature data base are   also
appreciated.

We  wish  to acknowledge the  plant managers,  engineers,  and other
representatives of   the  pharmaceutical  industry  without  whose
cooperation   and  assistance  in  site  visits   and  information
gathering, the completion of  this project  would have been greatly
hindered.  We also thank  the  environmental  committees  of   the
Pharmaceutical Manufacturers  Association for  their  assistance.

The assistance of all personnel  at EPA Regional Offices  and State
environmental  departments who participated  in the  data  gathering
efforts is greatly appreciated.

Appreciation is  expressed  to   those  at  EPA  Headquarters   who
contributed  to  the completion  of this project,  including: Louis
DuPuis, Henry Kahn,  Russ Roegner, Joseph Yance, Rob  Ellis,   Jean
Noroian,   Susan  Green,   John  Ataman, and Kathleen  Ehrensberger,
Office of Analysis and Evaluation,  Office  of  Water  Regulations
and  Standards;  Alexander McBride, Rod Frederick, Richard Healy,
William Kaschak,  Rich Silver,  and  Ruth  Wilbur,   Monitoring   and
Data Support Division,  Office of Water Regulations and  Standards,
Susan  Lepow  and  Catherine  Winer,  Office  of  General Counsel;
                                 209

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Mahesh Podar, Office of Policy and Resource Management; and Bruce
Newton, Office of Water Enforcement.

Within the Effluent Guidelines Division,  Jeffery  Denit,  Joseph
Vitalis, Gregory Aveni, Glenda Colvin, Kointheir Ok, Pearl. Smith,
Glenda  Nesby,  Carol  Swann,  Linda  Wilbur, Marvin Rubin, James
Gallup, Devereaux Barnes,  Kaye  Storey,  Robert  Schaffer,  Paul
Fahrenthold, Michael Kosakowski, Dan Lent, and Susan Delpero made
significant contributions to this project.
                                  210

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                            APPENDIX A

            COST,  ENERGY,  AND NON-WATER QUALITY ASPECTS
 A.
INTRODUCTION
 Previous  sections  describe the respective BPT,  BAT,   NSPS,   PSES,
 and   PSNS  control  options that  were  considered as  the basis for
 final  rules.   This section summarizes  the cost,  energy,  and other
 non-water quality  impacts  (including  implementation   requirements
 and   the   generation of  air pollution,  noise pollution,  and iolid
 waste)  of these  various  treatment options.

 As explained previously, this  document  does   not  address   Agency
 efforts  to establish BCT  effluent limitations  guidelines  for the
 pharmaceutical industry.   EPA  is  also postponing a final decision
 on appropriate BAT limitations and NSPS for  COD until   more  data
 are    obtained   and  appropriate   COD   removal   technologies  are
 identified.  The reader  is referred to  the   development  document
 supporting the  November   1982 proposal  for the latest published
 information on cost,  energy, and  non-water quality aspects  of BCT
 technology options and technology options for control  of  COD  at
 direct  discharging plants.  Additionally, EPA  decided to propose
 rather  than to promulgate  new  source  performance standards  for
 the   conventional   pollutants  BOD5_ and  TSS.    For   the   latest
 information, on    NSPS  technology  options   for    controlling
 conventional  pollutants,   see Proposed  Development Document for
 New   Source Performance    Standards    for    the  Pharmaceutical
 Manufacturing Point Source Category (U.S. EPA,  September 1983).

 B.'   METHODOLOGY FOR DEVELOPMENT  OF COSTS              -
 1 .
Introduction
This  section  describes  how   estimates   of   the   costs   of
implementation  of  the  technology  options were developed.  The
actual cost of implementing these treatment options can  vary  at
each  individual  facility, depending on the design and operation
of the  production  facilities  and  on  local  conditions.   EPA
developed  treatment  costs  that  are  representative  of  costs
anticipated to be incurred at existing and new source direct  and
indirect  discharging plants in the pharmaceutical industry.  The
methodology for development of costs  is  summarized  below.   To
develop  the cost estimates presented in this section, the Agency
relied  on  information  contained  in  Section   VIII   of   the
Development  Document  for  Interim  Final  Effluent  Limitations
Guidelines and Proposed New Source Performance Standards for  the
Pharmaceutical  Manufacturing  Pofnt  Source  Category (U.S. EPA7
December 1976) and  Supplement  A  to  that  document  (55),  the
Catalytic  Treatment  Model,  and on information contained in the
April 5,  1982, issue of Chemical  Engineering.   These  materials
can be found in the record of the final rulemaking.
                             211

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2.   Model Plant Approach

EPA estimated the costs of implementing the control and treatment
options discussed in Sections VII and VIII in order to  determine
the  economic  impact  of  each technology option.  EPA based  its
cost estimates for cyanide and TVO control and treatment on model
plant raw waste characteristics.  However, in the case of the  BPT
TSS limitations, plant specific cost  estimates  were  developed.
EPA  selected  model  plant  sizes  that  cover  the range of  the
anticipated  sizes  of   new   and   existing   plants   in    the
pharmaceutical   industry.   From  the  model  plant  costs,   EPA
constructed cost curves that were  used  to  predict  costs  that
would  be  incurred  at  each  individual pharmaceutical plant in
complying with the technology options considered as the basis   of
final  regulations.   These  individual plant cost estimates were
then used to estimate the potential  economic  impact  associated
with each technology option.

3.   Cost Estimating Criteria

In order to develop cost  estimates  for  the  treatment  options
under consideration, criteria were developed relating to capital,
operating,  and  energy  costs.   These criteria are presented in
Table A-l.  EPA's estimates are pre-engineering estimates and  are
expected to have a  variability  consistent  with  this  type   of
estimate, on the order of plus or minus 30 percent.
                                                  *
All  costs  presented  are  in  terms  of  1982  dollars.   Since
construction costs escalate,  these  estimates  may  be  adjusted
through  the  use of appropriate cost indices.  The most accepted
and widely-used cost  index  in  the  engineering  field  is   the
Engineering  News  Record  (ENR) construction cost  index.  The  ENR
Index for cost data presented in this  document  is  3,825.    All
total  annual  costs stated herein  include capital recovery costs
equal to  22 percent  of  the  total  capital  costs.   All  total
capital   costs  include  engineering  and contingency costs along
with equipment and installation costs.

C.   COSTS FOR IMPLEMENTATION OF BPT OPTIONS CONTROLLING BODS,
     COD, AWTSS

As  explained  in  Section  VIII,   EPA  considered  the option of
modifying existing BPT BOD5.  and  COD  effluent  limitations   for
subcategories B, D, and  E.  The modified BOD5_ and  COD  limitations
would,   in  certain instances, relax the  1976 BPT  limitations  for
those pollutants to be consistent with EPA's  assessment  of   the
minimum   concentration   levels attainable through  the application
of the best practicable  control technology  currently   available,
as  defined in the  1976  rulemaking.  No costs are  associated with
this option  because  it  involves   the   relaxation  of   existing
limits.
                              212

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                                TABLE A-l

                         COST ESTIMATING CRITERIA
 1.  Capital costs are for 1982:                  ENR = 3825
 2.  Steam stripping capital cost:  4.74 times purchased equipment cost
 3.  Miscellaneous Construction Costs:
4.



5.

6.
                Piping:
                Electrical:
                Instrumentation:
                Site Preparation:
                                    20% of installed equipment  cost2
                                    14% of installed equipment  cost2
                                     8% of installed equipment  cost2
                                     6% of installed equipment  cost2
Engineering and Contingencies are 30%
including installed equipment, piping,
and site preparation costs.
of total  installed costs,
 electrical,  instrumentation,
Annual fixed costs are 22% of capital  expenditures.

Operation/Maintenance Costs:
                Labor:
                               steam stripping,  $29,000/man-year
                               including taxes  and  fringe benefits^
                               (Eng. Tech.  level  V)  $24,000/man-year
                               including taxes  and  fringe benefits^
                               (Eng. Tech.  level  IV)
1.  Cran, John, Chemical  Engineering,  April  6,  1981.
2.  Development Document  for Interim Final Effluent Limitations Guidelines
    and Proposed New Source Performance Standards  for  the  Pharmaceutical
    Manufacturing Point Source Category,  U.  S.  EPA, Washington, D. C.,
    December 1976.  (TJT
3.  "National  Survey of Professional,  Administrative,  Technical, and
    Clerical Pay, March 1981," U.  S. Department of Labor,  September 1981.   (7)
4-  Proposed Development  Document  for  Effluent  Limitations Guidelines and
    Standards  for the Pharmaceutical Point Source  Category, U. S. EPA,
    Washington, D.C., November 1982..   (2)
5.  Vendor and Supplier Quotations to  Environmental Science and Engineering,
    Inc., Gainesville, Florida,  1982 and  1983.   (8)
                                213

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                                   -2-
                                   3% of total  capital  costs4
                                   $8.64/cubic  yard (non-hazardous)5
                                   $0.046/kilowatt-hour6
                                   $5.73/1000 pounds7
Maintenance:
Sludge Disposal:
Electricity:
Steam:
Chemicals:
       hydrated lime:              $51/ton8
       sulfuric acid (66°):        $85/ton8
       anhydrous ammonia:          $392/ton|
       phosphoric acid (80%):       $618/torP
       chlorine gas:               $441/ton8
       polymer:                    $2.54/lb8
6.  "Electric Utility Company Monthly Statement,"  March  1980  -  Forward:
    Federal Energy Regulatory Commission.,  Form 5,  as  cited  in Monthly
    Energy Review, U. S. Department of Energy, Energy Information Administration,
    DOE/EIA-0035 (81/12), December 1981.   (9)
7.  Treatability Manual, Volume IV.  Cost  Estimating, EPA-60018-80-042d,
    U. S. Environmental  Protection Agency, Office  of  Research and Development,
    July 1980.
8.  Innovative and Alternative Technology  Assessment  Manual,  U. S. EPA,
    Office of Water Program Operations, Washington, D. C.,  February  1980.
    (10)
                                214

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EPA  also  considered  the  option:  of modifying, the existing BPT
effluent TSS limitations  for  subcategories  B,  D,  and  E  and
establishing a BPT TSS limitation for subcategories A and C.  EPA
based the new and. modified BPT TSS limitations on the application
of biological treatment, which is the same technology that formed
the  basis of BPT effluent limitations for subcategories A, B, C,
D, and E.  Thus, in general,  EPA  expects  that  no  incremental
costs will be incurred in meeting limitations based on biological
treatment.   However, EPA identified five plants that comply with
the 1976 BPT BOD5. limits that would not comply with  the  new  or
modified  TSS  limits  that  EPA  believes  are characteristic of
well-designed and  well-operated  biological  treatment  systems.
Therefore,   EPA   developed  plant  specific  estimates  of  the
incremental costs that would be incurred at these five plants  to
meet  the  new and modified TSS limits.  These costs are shown in
Table A-2 and include total capital  and  annual  costs  for  the
installation and operation of clarification technology, including
polymer  addition  for  the five plants.  The design criteria for
these clarifiers are identical to those specified in Supplement A
to the 1976 BPT Development Document.  Total annual costs include
costs for sludge  disposal,  polymer  addition,  maintenance  and
labor.   Total  capital costs include costs for two clarifiers to
be operated in parallel, polymer feed facilities and pumps.

D.  COSTS FOR IMPLEMENTATION OF TOXIC POLLUTANT CONTROLS

Agency  analyses  indicate  that  toxic   pollutant   raw   waste
concentrations  are  likely  to be similar for plants in all four
subcategories where toxic pollutants are used or generated in the
manufacturing process.  For this reason, EPA developed one  model
treatment  system  for removal of cyanide and one model treatment
system for control of toxic volatile organics.  These models  can
be applied uniformly to plants in all subcategories.
1
Cyanide Control
The cost estimates for cyanide  control  were  generated   by   the
Catalytic  Treatment Model based on the design criteria specified
in Section VIII of the November 1982 Development Document.  Table
A-3 presents design criteria for a cyanide destruction unit.   The
cyanide removal mechanism assumed for purposes of developing  cost
estimates  is  oxidation  with  hypochlorite   in   an    alkaline
environment.   The  Agency  assumed  that the cyanide destruction
unit  would  be  employed  in-plant  to   treat   waste    streams
contaminated   with   cyanide   prior   to   dilution   by other
non-contaminated  streams.   Capital  costs   for   the    cyanide
destruction  unit include costs for a two-stage concrete  reaction
vessel, a pH control system,  an  oxidation  reduction  potential
control  system,  a  chlorinator, a vaporizer, circulation pumps,
two reagent  feed  systems  (sodium  hypochlorite   and  caustic),
detention  tanks  and mixers.  The annual costs include costs for
chemicals, energy, maintenance and labor.
                              215

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                                TABLE A-2
               INCREMENTAL COST REQUIREMENTS FOR ACHIEVING
                           BPT TSS LIMITATIONS
PLANT CODE

12098
12160
12248
12462
1 2471
TOTAL
CAPITAL COSTS

$92,000
$92,000
$92,000
$102,000
$92,000
$470,000
ANNUAL COSTS*
O&M COSTS
1
$24,000
$25,000
$27,000
$37,000
$27,000
$140,000
$19,000
$19,500
$21,000
$29,000
$21 ,000
$109,500
*A11 annual costs assume 22% capital recovery,
                                 216

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                                TABLE A-3

                      DESIGN CRITERIA FOR CN REMOVAL
                         BY ALKALINE CHLORINATION
EFFECTIVENESS:  Cyanide destruction by sodium hypochlorite addition

APPLICATION LIMITATIONS:  Inf. TSS <^ 50 mg/1

DESIGN BASIS:  Mean Flow 26,000 gal/day subcategory C continuous operation

               CONTACT TIME:

                       FIRST STAGE    10 minutes
                       SECOND STAGE   30 minutes

               CHEMICAL REQUIREMENTS:

                       15 parts HYPOCHLORITE per part CN

                       17 parts NaOH* per part CN

                       pH 8-9.5

MAJOR EQUIPMENT:

     Two stage, concrete reaction vessel  with mixer

     pH control system

     ORP control system

     Oxidation - chemical feed system
''or chemical equivalent
                                217

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Table A-4 presents estimates of the  installation  and  operating
costs of the cyanide destruction unit in treating three different
wastewater  flow  rates.   EPA  used  these  three  sets  of cost
estimates to develop the cost curves presented in Figures A-l and
A-2.  The curves  were  used  to  predict  costs  that  would  be
incurred  at individual plants in meeting cyanide limitations and
standards  based  on  the  application  of  cyanide   destruction
technology.  In estimating plant-specific costs, EPA assumed that
the process stream to be treated would be 10 percent of the total
plant  process wastewater flow rate.  This is the same assumption
that was made  in  estimating  total  industry  costs  that  were
presented  in  the  development  document supporting the November
1982 proposed rules.  The Agency received no comments  addressing
this aspect of the proposed regulation.

2.   Toxic Volatile Organics Control

Table A-5 presents design criteria for a steam stripper to reduce
the discharge of toxic volatile  organics.   The  Agency  assumed
that the steam stripper would be employed in-plant to treat waste
streams  contaminated  with  toxic, volatile  organics  prior  to
dilution  by  other  non-contaminated   waste   streams.    Batch
treatment  was  assumed  in  the  estimation  of installation and
operating costs for the treatment of low volume TVO waste streams
(less than 57,600 GPD), while continuous systems were costed  for
the  treatment  of  high  volume  TVO waste streams (greater than
57,600 GPD).
performance  of  this
suggested  limitations
presented  in  Section
The design criteria presented in Table A-5; were developed  for  a
packed column-type stripper.  The Agency decided to develop costs
based on the design of a packed column steam stripper because the
                       type  of  stripper  forms the basis of the
                        for  methylene  chloride  and  chloroform
                        VIII.   The design characteristics of the
packed column stripper include a packing volume of 63 percent,  a
19  foot tray to tray packed column and packing consisting of one
inch porcelain saddles.  The design assumes a  hydraulic  loading
of  18.3 gpm per sq. ft.  Whenever the design diameter calculated
from the flow and hydraulic loading was greater  than  3.5  feet,
multiple  columns  were  costed assuming parallel operation.  The
capital costs include costs  for  the  following  equipment:  the
column(s),  the packing, the feed preheater (heat exchanger), the
filter, the overhead condenser,  tanks  and  pumps.   The  annual
costs  include  costs  for  steam,  electricity,  cooling  water,
maintenance and labor.

Table A-6 presents estimates of the  installation  and  operating
costs of the steam stripper in treating nine different wastewater
flow  rates.   EPA  used  these  nine  sets  of cost estimates to
develop the capital and annual cost curves shown in  Figures  A-3
and  A-4,  respectively.   The  curves were used to predict costs
that would be  incurred  at  individual  plants  in  'meeting  TVO
limitations  and  standards  based  on  the  application of steam
                             218

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       TABLE A-4



  CYANIDE DESTRUCTION



CAPITAL AND ANNUAL COSTS
FLOW VARIATION
1982 CAPITAL COSTS
CHEMICALS
Hypochlorite
Caustic
ENERGY
LABOR
MAINTENANCE
CAPITAL AMORTIZATION
1982 ANNUAL COSTS
13,000 gpd
$67,200

5,000
1,100
200
7,200
2,200
14,800
$30,500
26,000 gpd
$105,000

9,900
2,300
300
7,200
3,300
23,100
$46,100
52,000 gpd
$165,200

19,800
4,600
600
7,200
5,200
36,300
$73,700
       219

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     FIGURE  A-l
 CYANIDE DESTRUCTION
   CAPITAL COSTS
                  '   *  6  7  * ' 1°00
   FLOW RATE  (1000 GPD)
220

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     FIGURE  A-2
CYANIDE  DESTRUCTION
     Annual  COSTS
                            • 10
                            100
                                            a   4  5 • 7 » 9 TO
   FLOW RATE  (1000 GPD)
           221

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                               TABLE A-5

                   DESIGN CRITERIA FOR STEAM STRIPPER
EFFECTIVENESS: Reduction of toxic volatile organics concentrations by
               steam stripping

APPLICATION LIMITATIONS:  Concentration of the organic volatile in the
                          entering wastewater feed is at or near saturation

DESIGN BASIS:  19 ft. tray to tray packed column.
               1 inch porcelain saddles packing
               63% packing volume
               18.3 gpm/ft  hydraulic loading
               TSS of influent stream less than or equal to 50 mg/1
               Diameter > 3.5 ft., multiple columns, costed for parallel
               operation 316 stainless steel

MAJOR EQUIPMENT:  Column (continuous operation, spare column costed)

                  packing
                  feed preheater
                  feed prefilter
                  overhead condenser
                  tanks
                  pumps

STEAM REQUIREMENTS:  0.156 pound steam/pound feed
                                   222

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                                TABLE A-6
                CAPITAL ITEMIZED COSTS FOR BATCH OPERATION
FLOW (GPD)
COLUMNS
PACKING
FEED PREHEATER
OVERHEAD CONDENSER
PRE FILTER
TANKS
PUMPS
TOTAL EQUIPMENT
(4.74 x Equipment)
TOTAL CAPITAL
JAN 1978 $
TOTAL CAPITAL COST
1982 $
500
15,620
2,88'6
31 ,800
4,500
1,200
11,400
2,000
69,406
328,984
470,945
1000
15,620
2,886
31 ,800
4,500
1,200
12,000
2,000
70,506
334,198
478,408
5000
15,620
2,886
31 ,800
4,500
1,200
12,500
2,000
70,506
334,198
478,408
10,000
15,620
1,511
33,500
5,200
1,200
16,500
2,100
75,631
358,491
513,184
50,000
19,454
2,336
41,900
6,000
1,200
23,200
2,300
96,390
456,900
654,058
ENR Jan 1978 = 2672
    Aug 1978 = 3825
                                223

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                           TABLE A-6 (cont'd)
            CAPITAL ITEMIZED COSTS FOR CONTINUOUS OPERATION
FLOW (MGD)
COLUMNS
PACKING
FEED PREHEATER
OVERHEAD CONDENSER
PRE FILTER
TANKS
PUMPS
TOTAL EQUIPMENT
TOTAL CAPITAL (1/78 $)
4.74 x Equipment Costs
TOTAL CAPITAL COST
1982 $
0.0576
31 ,240
1,511 *
15,600
7,100
1,200
19,000
3,100
78,751
373,280

534,355

0.288
35,571
5,046
47,700
10,800
1,200
38,700
5,100
144,117
683,115

977,887

0.576
59,285
8,410
87,500
15,900
2,400
58,200
5,700
237,395
1,125,252

1,610,812

1.152
106,713
15,074
167,100
23,900
2,400
91 ,400
7,100
413,687
1,960,876

2,807,017

ENR Jan 1978 = 2672
    Aug 1978 = 3825
                                224

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                           TABLE A-6  (cont'd)

                 ANNUAL  ITEMIZED COSTS FOR BATCH OPERATON
FLOW (GPD)
1978 CAPITAL COSTS
STEAM
STEAM FOR PREHEATING
COOLING WATER
ELECTRICITY
LABOR
MAINTENANCE
(3% of Capital)
CAPITAL RECOVERY
(22% Capital)
TOTAL ANNUAL
Jan. 1978 $
TOTAL ANNUAL COST
1982 $
500
328,984
609.55
341 .28
29.20
60.23
7,628.5
9,870
72,376
90,915
130,146
1,000
334,198
1,219.10
682.55
58.4
120.45
7,628.5
10,026
73,524
93,259
133,501
5,000
334,198
6,095.5
3,412.8
292
602.3
39,967.5
10,026
73,524
133,920
191,708
10,000
358,491
12,191
6,825.5
584
1,204.5
40,150
10,755
78,868
150,578
215,554
50,000
456,900
60,955
34,128
2,920
6,023
80,300
13,707
100,518
298,551
427,379
ENR:  Jan. 1978 - 2672
      Avg. 1982 - 3825
                                225

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                            TABLE A-6  (cont'd)

              ANNUAL  ITEMIZED  COSTS  FOR CONTINUOUS OPERATON
FLOW (MGD)
1978 CAPITAL COSTS
STEAM
STEAM FOR PREHEATING
COOLING WATER
ELECTRICITY
LABOR
MAINTENANCE
(Z% of Capital)
CAPITAL RECOVERY
(22% Capital )
TOTAL ANNUAL
Jan. 1978 $
TOTAL ANNUAL COST
1982 $
0.0576
373,280
70,220
39,315
3,364
6,938
88,301
11,198
82,122
301 ,458
431,541
0.288
683,115
351,101
196,574
16,819
34,690
88,301
20,493
150,285
858,263
1,228,614
0.576
1,125,252
702,202
393,150
33,638
69,379
88,301
33,758
247,555
1,567,983
2,244,586
1.152
1,960,876
1,404,403
786,298
67,277
138,758
88,301
58,826
431 ,393
2,975,256
4,259,115
ENR:  Jan. 1978 - 2672
      Avg. 1982 - 3825
                                226

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stripping technology.  In estimating  plant-specific  costs,  EPA
assumed that the process stream to be treated would be 26 percent
of  the  total  plant  process  wastewater  flow  rate.   This is
different from the assumption that was made in  estimating  total
industry  costs  that  were presented in the development document
supporting the November 1982 proposed rules.

The Agency received comments contending  that  its  estimates  of
steam  stripping  costs  that  were  presented  in  the  proposed
development document were understated.  As part of  the  Agency's
review   of  . its   cost   estimating  procedures,  EPA  obtained
information on the  percentage  of  process  wastewater  that  is
contaminated with toxic volatile organics.  The Agency determined
that  26  percent is a representative estimate of the quantity of
process wastewater flow contaminated by toxic  volatile  organics
when  these  compounds  are  used  or generated at pharmaceutical
plants..

E.   ENERGY AND NONWATER QUALITY IMPACTS

The  implementation  of  the  control   and   treatment   options
considered  as the basis of final rules are expected to have only
a small effect on current energy demand, solid waste  generation,
air pollutant generation, and noise potential. .The one exception
is  the substantial steam requirement for removing toxic volatile
organics from pharmaceutical wastewaters through the  application
of  steam  stripping  technology.   This  section  addresses  the
non-water quality aspects of the control  and  treatment  options
considered by EPA in developing final BPT and BAT limitations and
NSPS,  PSES,  and PSNS for the pharmaceutical manufacturing point
source category.

1.   Energy Requirements
a.
BPT
Incremental  energy  associated  with   the   treatment   options
considered  as  the  basis of modified and new BPT limitations is
limited to power requirements for additional pumps and agitators.
The  1976  BPT  regulations  are  based  on  the  application  of
biological  treatment.   The  technology option considered as the
basis for new BPT TSS  limits  for  subcategories  A  and  C  and
modified  BPT  TSS limits for subcategories B and D. is biological
treatment.   Therefore,  in  general,  the  Agency   expects   no
additional  energy demand to result from attainment of TSS limits
based on the application of biological  treatment.   However,  as
discussed  previously,  EPA identified five pharmaceutical plants
that comply with the 1976 BPT BOD_5 limits that would  not  comply
with the TSS limits presented in Section IX that EPA believes are
characteristic  of  well-designed  and  well-operated  biological
treatment  systems.   Therefore,  EPA  developed   plant-specific
estimates of the incremental technology that would be required to
meet the new and modified TSS limits considered for subcategories
                              229

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A  and  C  and  for  subcategories  B  and  D, respectively.  EPA
estimates that the incremental energy use at  these  five  plants
will be 0.01 percent more than the current energy usage at direct
discharging pharmaceutical plants.

Table  A-7  summarizes  Agency  estimates of total energy used at
existing direct discharging plants  for  the  baseline  case  and
after  the  application  of  cyanide  removal  technology.  Total
energy is presented in terms of equivalent barrels of No. 6 fuel;
purchased electrical energy (kwh) required is converted  to  heat
energy  (BTU)  at  a conversion of 10,500 BTU/kwh, which reflects
the average efficiency of electrical power generation.
b.
BAT and NSPS
No technology options were identified to effect a further removal
of cyanide from wastewaters discharged by existing or new  direct
discharging   pharmaceutical  plants.   Therefore,  there  is  no
incremental energy usage  associated  with  BAT  cyanide  removal
technology options.

Table  A-8  summarizes  Agency  estimates of total energy used at
existing and new direct discharging pharmaceutical plants for the
baseline case  and  after  the  application  of  steam  stripping
technology to remove toxic volatile organics.
c.
     PSES and PSNS
Table A-9 summarizes Agency estimates of  total  energy  used  at
existing  indirect  discharging  pharmaceutical  plants  for  the
baseline case  and  after  the  application  of  cyanide  removal
technology.   No  technology  options were identified to effect a
further removal of cyanide from  wastewaters  discharged  by  new
indirect  discharging pharmaceutical plants.  Therefore, there is
no  incremental  energy  usage  associated  with  PSNS  technology
options.

Table  A-10  summarizes  Agency estimates of total  energy used at
existing and new  indirect discharging pharmaceutical  plants  for
the baseline  case  and after the  application of steam stripping
technology to remove toxic volatile organics.

2.   Solid Waste  Generation

No  significant incremental solid waste  generation   is  associated
with  the  treatment  options considered as  the  basis of modified
and new BPT  limitations, BAT  limitations, NSPS,  PSES,  or  PSNS.
No  appreciable quantities of  sludge will be  generated through the
application  of   steam  stripping or cyanide  removal technologies.
A small amount of solid waste will be generated   at  the five
plants  that are  now  in compliance  with the  1976 BPT BOD5.  limits,
but do not comply with  the TSS limits presented   in Section   IX.
The Agency  estimates  that  the  incremental  solid waste generated
                              230

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                         TABLE A-7
                  BPT CYANIDE DESTRUCTION
                    ENERGY REQUIREMENTS
  BASE  LINE
   ENERGY
(BBL oil/yr)

  110,560
 INCREMENTAL
   ENERGY
(BBL oil/yr)

     65
    TOTAL
   ENERGY
(BBL oil/yr)

   110,625
                           231

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                          TABLE  A-8
                     BAT STEAM STRIPPING
                     ENERGY REQUIREMENTS
  BASE LINE
   ENERGY
(BBL oil/yr)

  110,560
 INCREMENTAL
   ENERGY
(BBL oil/yr)

   94,300
    TOTAL
   ENERGY
(BBL oil/yr)

   204,860
                          232

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                          TABLE A-9
                   PSES CYANIDE DESTRUCTION
                     ENERGY REQUIREMENTS
  BASE LINE
   ENERGY
(BBL oil/yr)

  110,560
 INCREMENTAL
   ENERGY
(BBL oil/yr)

     75
    TOTAL
   ENERGY
(BBL oil/yr)

  110,635
                          233

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                         TABLE A-10
                     PSES  STEAM  STRIPPING
      ENERGY REQUIREMENTS  FOR METHYLENE CHLORIDE REMOVAL
  BASE LINE
   ENERGY
(BBL oil/yr)

  110,560
 INCREMENTAL
   ENERGY
(BBL oil/yr)

   315,000
    TOTAL
   ENERGY
(BBL oll/yr)
   425,560
                          234

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at these  five  plants  will  be    42  percent  more  than  that
currently  generated  at  these five plants in complying with the
1976 BPT BOD5_ limitation.

3.  Air Pollution and Noise Pollution

The technologies under consideration are not a significant source
of noise  pollution  or  air  pollution.   EPA  anticipates  that
implementation   of  the  control  and  treatment  options  under
consideration will have no direct  impact  on  air  pollution  or
noise  pollution.  Some reduction in air pollution is expected at
facilities  that  are  in  compliance  with  the  suggested   TVO
limitations,  when  steam  stripping technology is employed.  EPA
estimates that if all pharmaceutical plants were  in  conformance
with  the  suggested  TVO  limits,  the  emissions  of  methylene
chloride, chloroform toluene and  benzene  would  be  reduced  by
about 5000, 800,  180, and 160 pounds per day, respectively.
                              235

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                           APPENDIX B

                            GLOSSARY
Abatement.  The measures taken to reduce or eliminate pollution.

Absorption.  The penetration of  one  substance  (the  absorbent)
into  the inner structure of another (the absorbate) resulting  in
the formation of a homogeneous mixture having the attributes of a
solution.

Acclimation.  The ability of an organism to adapt to  changes   in
its immediate environment.

Acid.  A substance which dissolves in water with the formation  of
hydronium ions.

Acidulate.  To make somewhat acidic.

Act.   The  Clean  Water Act (the Federal Water Pollution Control
Act amendments of 1972, 33 USC 1251 et seq., as  amended  by  the
Clean Water Act of 1977, P.L. 95-217 and the Settlement Agreement
in  Natural  Resources Defense Council, Inc. v. Train, 8-ERC 2120
(D.D.C. 1976), modified, 12 ERC 1833 (D.D.C. 1979),  modified   by
Orders dated October 26, 1982,  and August 2, 1983).
Activated   Carbon.
Carbon  which  has  been  heated  by  high
temperature steam or carbon dioxide to produce an internal porous
particle structure.

Activated Sludge Process.   A  wastewater  treatment  process  in
which   microorganisms  absorb  dissolved  or  suspended  organic
matter.  The significant feature of the process is the recycle of
a   biologically-active   sludge   formed   by    settling    the
micro-organism   population   from  the  aeration  process  in  a
clarifier.  Waste is treated in a  matter  of  hours  instead  of
days.

Active  Ingredient.  The chemical constituent in a medicine which
is responsible for its activity.

Adsorption.  Adherence of one substance to the surface of another
substance called the "adsorbent."

Advanced  Waste  Treatment.   Any  treatment   process   employed
following  biological  treatment  for  the  purpose of increasing
pollutant removal.  Advanced waste  treatment  is  also  used  to
produce  a  high-quality  effluent  suitable for reuse.  The term
"tertiary treatment" is commonly used .to  denote  advanced  waste
treatment methods.
                             237

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Aeration.   The  process   of   impregnating   a   liquid  with  air  by
spraying the  liquid  in  the air,   bubbling   the   air  through  the
liquid,  or agitating the  liquid  to promote surface  absorption  of
air  (in waste treatment, liquid from   the   primary   clarifier   is
mixed with compressed air  and  with biologically active sludge).

Aerobic.   Descriptive  of a chemical  reaction  or a  microorganism
that requires the presence of  air or oxygen.

Algae.  Chlorophyll-bearing organisms  occurring in both salt  and
fresh  water;  algae  release  oxygen   into water and  are used  in
treatment of  sewage and plant  effluent in a flocculation process.

Alqicide.  Chemical  agent added to   water to destroy   algae.
Copper sulfate is commonly used in large water  systems.
Alkali.
strongly.
A  water-soluble  metallic  hydroxide  that  ionizes
Alkalinity.  The  presence  of  salts  of  alkali  metals   (e.g.,
hydroxides,  carbonates,  and bicarbonates of  calcium, sodium and
magnesium) and usually  expressed   in  terms   of   the  amount  of
calcium  carbonate  that  would  have  an  equivalent  capacity to
neutralize strong acids.

Alkaloids.  Basic (alkaline) nitrogenous botanical products which
produce a marked physiological action when administered  to  ani-
mals or humans.

Alkylation.  The addition of a aliphatic group to  a molecule.

Ammonia  Nitrogen.   A  substance produced by  the  microbiological
decay of plant and animal  protein.   When  ammonia  nitrogen  is
found in waters, it is  indicative of incomplete treatment.

Ampu1e.   A sealed glass or plastic bulb containing solutions for
hypodermic injection.                     :

Anaerobic.  Descriptive of a chemical reaction or  a microorganism
that does not require the presence of air or   oxygen   (e.g.,  the
decomposition of sewage sludge by anaerobic bacteria).

Anion.  Ion with a negative charge.

Antagonistic  Effect.  The simultaneous action of  separate agents
opposing each other.

Antibiotic.  A substance produced by a  microorganism  which  has
the  power,  in  dilute  solution,  to  inhibit  or destroy other
organisms.

Aqueous Solution.  A solution containing water.
                            238

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Arithmetic Mean.  The arithmetic mean, or
of  items  is  obtained  by  adding   all
dividing the total by the number of items.
                                           average", of a  number
                                           the items together and
Autoclave.  A  heavy
chemical   reactions
equipment using steam
                      vessel  with  thick  walls  for
                      under  high  pressure  or  for
                      under pressure.
 conducting
sterilizing
Azeotrope.  A liquid mixture of  two  or  more  substances  which
behaves  like  a  single  substance in that the vapor produced by
partial evaporation of liquid has the  same  composition  as  the
liquid.   The  constant boiling mixture exhibits either a maximum
or minimum boiling point as compared with that of other  mixtures
of the same substances.

Bacteria.   A  type  of  microorganism often composed of a single
cell  with  round,  rodlike,  spiral,  or   filamentous   bodies.
Bacteria  exist in soil, water, organic matter, and  in the bodies
of plants and animals and are primarily composed of  protein  and
nucleic acids.
Bacteriophage.
bacteria.
                    type  of   virus  which   attacks   and  destroys
BADCT.  Best Available Demonstrated Control Technology.

Base.  A substance that  in  aqueous  solution   turns   red   litmus
blue,  furnishes  hydroxyl ions,  and reacts with an  acid  to  form  a
salt  and water only.

BAT Effluent Limitations.  Limitations  for point sources,   other
than   publicly  owned  treatment  works,  which  are  based  on  the
application  of   the  best  available    technology    economically
achievable.   These  limitations must be achieved by  July  1,  1983
and are the principal means of  controlling the   direct  discharge
of toxic and non-conventional pollutants to navigable waters.

Batch Process.   A process which has an intermittent flow  of  raw
materials  into the the process  and a resultant  intermittent  flow
of product from the process.
 BCT    Effluent   Limitations.     Limitations
 conventional   pollutant   control   technology
                                                establishing  best
                                               for  discharges  of
 conventional  pollutants from existing direct dischargers.

 Bioassay.   A  determination made on an organism to determine its
 reaction to another substance.

 Biochemical  Oxygen  Demand  (BOD5).    The  quantity  of   oxygen
 required   to  oxidize  the  organic  material  in  a  sample  of
 wastewater in a  specified  time  (5  days)   and  at  a  specific
 temperature (120 degrees C).  This quantity  is not related to the
 oxygen  requirements  in chemical combustion but is determined by
                           239

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the biodegradability  of  the  material  and  by  the  amount  of   oxygen
utilized   by   the  microorganisms  during  oxidation.   This  test  is
universally   accepted as  the   yardstick of  pollution   and   is
utilized   to   determine  the degree   of   treatment   in a  waste
treatment  process.

Biota.  The flora and fauna  (plant and animal  life)  of  a body   of
water.

Biological  Products.    In the pharmaceutical  industry, medicinal
products derived from animals or humans (e.g., vaccines, toxoids,
antisera,  and human blood fractions).

Biological Treatment  System.  A  system that  uses microoganisms  to
remove organic pollutants from a wastewater.
Blood Fractionation.  The separation  of
various protein fractions.
human  blood  into  its
Slowdown.   The   liquid  and solid waste materials ejected from a
vessel such as a  boiler.

BODS. Biochemical oxygen demand.

Botanicals.  Drugs made from a part of a plant,  such  as  roots,
bark, or leaves.

BPT  Effluent  Limitations.  Limitations for point sources, other
than publicly owned treatment  works,  which  are  based  on  the
application  of the best practicable control technology currently
available.  These limitations must be achieved by July 1,1977.

Brine.  Water saturated with a salt.

Buffer.  A solution containing both a weak acid and its conjugate
weak base whose pH changes only slightly on the addition of  acid
or alkali.                              ;

Capsule.  A gelatinous shell used to contain medicinal chemicals.

Carbohydrate.   A  compound  of  carbon, hydrogen, and oxygen, in
which the ratio of hydrogen to oxygen is usually two to one.

Carbonaceous.  Containing or composed of carbon.

Catalyst.  A substance which changes the rate of a chemical reac-
tion without undergoing a permanent chemical change itself.

Cation.  The ion  in an electrolyte  which  carries  the  positive
charge  and which migrates toward the cathode under the influence
of a potential difference.
                           240

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Cellulose.  The major polysaccharide component of the cell  walls
of  all  woods,  straws,  bast fibers, and seed hairs.  It  is the
principal raw material of pulp, paper, and paperboard.

Chemical Oxygen Demand  (COD).    A  measure  of  oxygen-consuming
capacity  of  organic  and  inorganic  matter present in water or
wastewater.  It is expressed as the  amount  of  oxygen  consumed
from a chemical oxidant in a specific test.

Chemical  Synthesis.   The process of chemically combining  two or
more constituent substances into a single substance.

Chlorination.  The application of chlorine to water,  sewage,  or
industrial wastes, generally for the purpose of disinfection.

Coagulation.    Irreversible   combination   or   aggregation  of
semisolid particles to form a clot or mass.  This can be  brought
about  by  the addition of certain chemicals, such as lime, alum,
or polyelectrolytes.

Combined Sewer.   A sewer which carries  both  sewage  and  storm
water run-off.

Composite  Sample.   A  mixture  of grab samples collected  at the
same sampling point at different times.

Comprehensive  Pharmaceutical  Data  Base.   Combined  data  base
containing  the  first 308 survey of PMA-member companies and the
second, or supplemental 308 survey.

Concentration.  The amount of a given substance in a stated  unit
of a mixture or solution.

Conductivity.   The  property  of  a  substance  or  mixture that
describes its ability to transfer heat or electricity.

Contact Process Wastewaters.  Process-generated wastewaters which
have come in contact with the  reactants  used  in  the  process.
These  include  such streams as contact cooling water, filtrates,
concentrates, wash waters, etc.
Continuous Process.
materials , into
product from the process.
_   A process which has a constant flow  of  raw
the  process  and  a  resultant constant flow of
Contract Disposal.
party for a fee.
    Disposal of waste  products  by  an  outside
Crustaceae.    Small  animals  ranging  in  size  form 0.2 to 0.3
millimeters long which move very rapidly . through  the  water  in
search  of  food.  They have recognizable head and posterior sec-
tions and are a principal source of food for small fish.
                            241

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Crystallization.   The formation  of  solid  particles  within  a
homogeneous phase.  Formation of crystals separates a solute from
a  solution  and generally leaves impurities behind in the mother
liquid.

Culture.   A mass of microorganisms growing in a medium.

Cyanide,  Total.    Total  cyanide  as  determined  by  the  test
prodecure  specified  in  40 CFR Part 136 (Federal Register, Vol.
38, no. 199, October 16,1973).

Cyanide A.   Cyanides amenable to chlorination  as  described  in
"1972  Annual  Book  of  ASTM Standards" 1972:  Standard 2036-72,
Method B, p. 553.
Derivative.
substance.
A  substance  extracted  from  another   body   or
Desorption.    The opposite of adsorption.  A phenomenon where an
adsorbed molecule leaves the surface of the adsorbent.

Diluent.  A diluting agent.

Direct Discharge.   The discharge of process wastewaters to navi-
gable waters such as rivers, streams and  lakes.

Disinfectant.   A chemical agent which kills bacteria.
Disinfection.   The process of killing the   larger
not   necessarily   all)   of   the   harmful  and
microorganisms in or on a medium.
                                     portion  (but
                                     objectionable
Dissolved Oxygen   (DO).    The  amount  of  oxygen  dissolved  in
sewage,  water  or other liquids, usually expressed in milligrams
per liter or percent of saturation.

Distillation.   A  method  of  separating  a  liquid  mixture  by
vaporizing  it into components or groups of components.

Effluent.   A liquid which  leaves a unit operation or process.

Elution.  (1) The process  of washing out or removing with the use
of  a  solvent.   (2) In an ion exchange process, the stripping of
adsorbed ions from an  ion  exchange resin by  passing  a  solution
through   the   resin  solutions  which  contain  other  ions  in
relatively  high concentrations.

Emulsion.   A stable mixture of two  or  more  immiscible  liquids
held in suspension.
                             242

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Equalization  Basin.  A holding basin in which variations in flow
and composition of  a liquid are averaged.  Such basins are  used
to  provide  a  flow  of  uniform  volume  and  composition  to a
treatment unit.

Esterification.  The combination of an alcohol  and  an   organic
acid  to produce an ester and water.  The reaction is carried out
in the liquid phase, with aqueous sulfuric acid as a catalyst.

Ethical Products.  Pharmaceuticals promoted by advertising to the
medical, dental, and veterinary professions.

Fatty  Ac_:Lds.    An  organic  acid  obtained  by  the  hydrolysis
(saponification)  of  natural  fats  and  oils, e.g., stearic and
palmitic acids.  These  acids,  which  contain  sixteen  or  more
carbon  atoms,  are  monobasic  and  and  may contain some double
bonds.

Fauna.   The  animal  life  adapted  for  living  in  a  specified
environment.

Fermentation.   A chemical change induced by a living organism or
enzyme, specifically bacteria, or the microorganisms occurring in
unicellular plants such as yeast, molds, or fungi.

Fermentor Broth.  A slurry of microorganisms in water  containing
nutrients    (carbohydrates,    nitrogen)   necessary   for   the
microorganisms' growth.

Filter Cakes.
from a
or  a
diatomaceous
filtration.
	   Wet solids generated by the filtration  of  solids
liquid.  This filter cake may be a pure material  (product)
waste  material  containing  additional fine solids (i.e.,
       earth)  that  have  been  added  to  aid   in   the
Fines.   Crushed  solids  sufficiently  fine  to  pass  through a
screen, etc.

Flocculant.   A  substance  that  induces  the   aggregation   of
suspended" solids  particles  in  such a way that they form small
clumps.  Inorganic flocculants are lime, alum or ferric chloride;
polyelectrolytes are examples of organic flocculants.

Flora.  The plant life characteristic of a region.

Flotation.  A process for  separating  suspended  solids  from  a
liquid  where  the  suspended  matter  (as scum) is raised to the
surface of the liquid in a tank by aeration, vacuum, evolution of
gas, chemicals, electrolysis, heat  or  bacterial  decomposition.
The scum is then removed by skimming.
                            243

-------
Fractionation  (or  Fractional  Distillation).   The separation of
constituents of a mixture by vaporization and recondensation over
specific boiling point ranges.

Fungus.  Any of a plant-like group of  organisms  that  does  not
produce chlorophyll; they derive their food either by decomposing
organic  matter  from  dead  plants  and  animals or by parasitic
attachment to living organisms, thus often causing infections and
disease.  Examples of fungi are molds,  mildews,  mushrooms,  and
the  rusts  and  smuts  that infect grain and other plants.  They
grow best in a moist environment at, temperatures of  about  25°C,
with little or no light being required.  In sanitary engineering,
fungi  are  considered  to  be  multicellular,  nonphotosynthetic,
heterotrophic protists.

Gland.  A device of soft wear-resistant material used to minimize
leakage between a rotating shaft and the stationary portion of  a
vessel such as a pump.
Gland  Water.   Water used to lubricate a gland.
"packing water."
      Sometimes called
Grab Sample.  (1) Instantaneous sampling.
a random time.
(2)   A sample taken at
Grease.  In sewage,  grease  includes  fats,  waxes,  free  fatty
acids,  calcium  and magnesium soaps, mineral oils and other non-
fatty materials.

Hardness.  The proportion of calcium carbonate or calcium sulfate
contained in a given sample of water.

Hormone.   Any of a number of substances formed in the body  which
activate  specifically  receptive organs when transported to them
by the body fluids.   A  material  secreted  by  ductless  glands
(endocrine glands).  Most hormones as well as synthetic analogues
have in common the cyclopentanophenanthrene nucleus.

Indirect  Discharge.   The  discharge of (process) wastewaters to
publicly owned treatment works (POTW).
Injectables.  Medicinals prepared in a  sterile
suitable for administration by injection.
      (buffered)   form
Mycelia.   The filamentous material which makes up the vegetative
body of a fungus.

New Source.  Any facility  from  which  there  is  or  may  be  a
discharge  of  pollutants, the construction of which is commenced
after the  publication  of  proposed  regulations  prescribing  a
standard of performance under section 306 of the Act.
                            244

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Non-Contact  Cooling Water.  Water used for cooling that does not
come into direct contact with any raw material, intermediate pro-
duct, waste product or finished product.

Non-Contact Process  Wastewaters.   Wastewaters  generated  by  a
manufacturing  process which have not come in direct contact with
the reactants used in the process.  These include such streams as
noncontact  cooling  water,  cooling   tower   blowdown,   boiler
blowdown, etc.

NSPS. New Source Performance Standards.

NPDES.    National  Pollution  Discharge  Elimination  System.   A
federal program requiring industry to obtain permits to discharge
plant effluents to the nation's water courses.

Nutrient.   Any  substance  assimilated  by  an  organism   which
promotes growth and replacement of cellular constituents.

Operation   and  Maintenance.   Costs  required  to  operate  and
maintain pollution abatement equipment including labor, material,
insurance, taxes, solid waste disposal, etc.

.Organic Loading.  In the activated  sludge  process,the  food  to
microorganisms  (F/M) ratio defined as the amount of biodegradable
material  available  to a given amount of microorganisms per unit
of time.

Oxidation.  At one time, the term  oxidation  was  restricted  to
reactions  involving  oxygen, but its usage has been broadened to
include all reactions where electrons are transferred.

Oxidation Reduction  (OR).  A class of chemical reactions in which
one of the reacting species gives up electrons (oxidation)  while
another species in the reaction accepts electrons  (reductions).

Oxidation   Reduction   Potential    (ORP).   A  measurement  that
indicates the  activity  ratio  of  the  oxidizing  and  reducing
species present.

Oxygen,  Available.  The quantity of atmospheric oxygen dissolved
in the water of  a  stream;  the  quantity  of  dissolved  oxygen
available for the oxidation of organic matter  in sewage.

Oxygen,   Dissolved.   The  oxygen   (usually   designated   as  DO)
dissolved  in  sewage,  water  or  another  liquid  and    usually
expressed in mg/1, parts per million, or percent of saturation.

Parts  Per Million  (ppm).  Parts  by weight  in  sewage analysis;ppm
by weight is  equal  to  milligrams  per   liter  divided   by  the
specific gravity.   It should be noted that  in  water analysis, ppm
is   always understood to imply a  weight/weight ratio,  even though
in practice volume may be measured instead  of  a weight.
                              245

-------
Pathogenic.  Disease  producing.

pH.  The value   representing   the   acidity  or   alkalinity  of '  a
solution  and   defined  as  the  negative  logarithm of  the hydronium
ion concentration  or  activity  in   a   solution.  ' The  number   7
indicates  neutrality,   numbers  less   than  7  indicate increasing
acidity  and  numbers  greater  than    7    indicate   increasing
alkalinity.

Photosynthes is.     The   mechanism   by   which  chlorophyll-bearing
plants utilize  light  energy to produce  'carbohydrate  and   oxygen
from carbon dioxide and water(the reverse  'of respiration.).

Physical/Chemical   Treatment   System.    A  system that utilizes
physical  (i.e.,    sedimentation,    filtration,   centrifugation,
activated  carbon,  reverse  osmosis, etc.)  and/or chemical  means
(i.e.  coagulation,   oxidation,  precipitation,   etc.)   to  treat
wastewaters.

Plasma.   The   fluid  part  of blood,  lymph,: or  intramuscular  fluid
in which cells  are  suspended.

PMA.   Pharmaceutical Manufacturers  Association.

Point Source.   Any  discernible,  confined and discrete  conveyance,
including but not  limited  to any pipe,   ditch,   channel,   tunnel,
conduit,   well,  discrete  fissure,  container,  rolling   stock,
concentrated  animal  feeding  operation,  or  vessel   or    other
floating craft,   from  which pollutants are  or may  be  discharged.

Potable Water.   Drinking water sufficiently  pure  for human use.

Potash.   Potassium   compounds   used in  agriculture  and industry.
Potassium carbonate can be obtained  from wood ashes.   The  mineral
potash is usually a muriate (chloride).  Caustic  potash   is  its
hydrated form.

Preaeration.    A process  where sewage   is aerated to replenish
dissolved oxygen prior  to primary sedimentation.   The   objective
is to improve the treatability of the wastewater.

Precipitation.   The  phenomenon where small particles  settle out
of a liquid or  gaseous  suspension by gravity or when a   substance
held in solution passes out of that solution into solid form as a
result of a chemical  reaction.

Pretreatment.   Any wastewater  treatment process used to partially
reduce  the  pollution  load   before the wastewater  is  introduced
into a main sewer system or delivered to a   treatment   plant  for
substantial  reduction of the pollution load.
                            246

-------
Process  Waste  Water.
    	    Any water which, during manufacturing or
comes into direct contact with or  results  from  the
or  use  of  any  raw material, intermediate product,
processing
production
finished product, by-product, or waste product.
Process Water.  Any.water(solid,  liquid or vapor)  which,  during
the manufacturing process, comes  into direct contact with  any  raw
material,  intermediate  product,  by-product,  waste product,  or
finished product.

Proprietary Products.  Pharmaceuticals manufactured and sold only
by the owner of a patent, trademark, etc.

PSES.  Pretreatment Standards for Existing Sources.

PSNS.  Pretreatment Standards for New Sources.

Raw Waste Load (RWL).   The  quantity  (kg)  of  pollutant  being
discharged  in  a  plant's  wastewater  measured in terms of some
common denominator  (i.e., kkg of production or sq. ft.  of  floor
area).

Receiving Waters.  Rivers, lakes, oceans or other bodies of water
that receive treated or untreated wastewaters.

Reduction.   A process in which an atom (or group of atoms) gains
electrons.

Refractory Orqanics.   Organic materials that are only  partially
biodegradable    in   biological   waste   treatment   processes.
Refractory organics include detergents,  pesticides,  color-  and
odor-causing agents, tannins, lignins, ethers, olefins, alcohols,
amines, aldehydes, ketones, etc.

Residual  Chlorine.  The amount of chlorine left in treated water
that  can  oxidize  contaminants  if  they  enter   the   stream.
Hypochlorite  ion  concentration  alone  is called "free chlorine
residual"; the  hypochlorite  ion  and  chloramine  concentration
together are called "combined chlorine residual."

Retort.   A  vessel,  commonly a glass bulb with a long neck bent
downward,used for distilling or decomposing substances by heat.

Sanitary Sewers.   In a separate system,  pipes  in  a  city  that
carry  only  domestic  wastewater.   The  storm  water  runoff  is
handled by a separate system of pipes.
Saprophytic Organism.
matter.
           One that lives on dead or decaying organic
Secondary Treatment.  The second step  in  most  waste  treatment
systems in which bacteria consume the organic part of the wastes.
                              247

-------
Seed.  To  introduce microorganisms  into a culture medium.

Serum.   A fluid  extracted  from  an  animal for the purpose of
innoculation to effect the cure of  a disease.

Settleable Solids.  Suspended solids which will settle out  of  a
liquid waste in a given period of time.

Sewage,  Storm.  The liquid flowing in sewers during or following
a period of heavy rainfall.

Sewerage.  A comprehensive term  which  includes  facilities  for
collecting,  pumping,  treating  and  disposing  of  sewage;  the
sewerage system and the sewage treatment works.

SIC Codes.  Standard Industrial Classification.  Numbers used  by
the U.S. Department of Commerce to denote segments of industry.

Sludge, Activated.  Sludge floe produced in raw or settled sewage
by  the growth of bacteria and other organisms in the presence of
dissolved  oxygen.

Sludge, Age.  The ratio of the weight of volatile solids  in  the
digester   to  the weight of volatile solids added per day.  There
is a maximum sludge age beyond which no significant reduction  in
the concentration of volatile solids will occur.

Sludge,  Digested.   Sludge  digested  under anaerobic conditions
until  the  volatile  content  has  been  reduced,   usually   by
approximately 50 percent or more.

Solution.   A  homogeneous  mixture  of two or more substances of
dissimilar molecular  structure.   In  a  solution,  there  is  a
dissolving medium (solvent) and a dissolved substance (solute).
Solvent  Extraction.
The  treatment of a mixture of two or more
components by a solvent that preferentially dissolves one or more
of the components in the mixture.

Steam Distillation.  Fractionation process in which steam is used
to provide the heat of the system.

Sterilization.  The complete destruction of all living  organisms
in  or on a medium accomplished by heating to 121°C at 5 psig for
15 minutes.

Steroid.  Any one of  a  large  group  of  substances  chemically
related to various alcohols found in plants and animals.

Still  Bottom.   The  residue  remaining  after distillation of a
material.
                             248

-------
Stlllwell.   A pipe, chamber, or compartment with small inlets  to
a  main  body of water.  Its purpose is to dampen waves or surges
while permitting the water level within the well to rise and fall
with the major fluctuations of the main body of water.
Stoichiometric.   Characterized  by   being
proportion   of
substances exactly right for a specific chemical reaction with no
excess of any reactant or product.

Stripper.   A  device in which relatively volatile components are
removed from a mixture by distillation or  by  passage  of  steam
through the mixture.

Supernatant.   Floating above or on the surface.

Surge  Tank.    A  tank  for  absorbing and dampening the wavelike
motion of a volume of liquid; an  in-process  storage  tank  that
acts as a flow buffer between process tanks.

Suspended  Solids.   The  wastes  that will not sink or settle in
sewage.  The quantity of material deposited on a  filter  when  a
liquid is drawn through a Gooch crucible.

Synergistic.   An effect produced by a group of contributors which
is  greater  than  the  sum of the individual contributors acting
individually.

Tablet.  A small, disc-like mass of medicinal powder  used  as  a
dosage form for administering medicine.

Tertiary  Treatment.   A  treatment process added after secondary
treatment to remove practically all  solids  and  organic  matter
from wastewater.

Thermal  Oxidation.   The combustion of organic materials through
the application of heat in the presence of oxygen.

Total Organic Carbon (TOO.  A measure of the amount of carbon in
a sample originating from organic matter only.  The test  is  run
by burning the sample and measuring the carbon dioxide produced.

Total Solids.  The total amount of solids in a wastewater both in
solution and suspension.

Toxoid.   Toxin  treated so as to destroy its toxicity, but still
capable of inducing formation of antibodies.

Vaccine.  A killed or modified live virus or bacteria prepared in
suspension for inoculation to prevent or treat certain infectious
diseases.
                            249

-------
Viruses.   (1) An obligate intracellular  parasitic  microorganism
smaller than bacteria.  Most can pass through filters that retain
bacteria.  (2)  The smallest (10-300 urn in diameter) form capable
of producing  infection  and  diseases  in  man  or  other  large
species.    Occurring in a variety of shapes, viruses consist of a
nucleic acid core surrounded by an  outer  shell  (capsid)  which
consists  of numerous protein subunits (capsomeres).  Some of the
larger viruses contain additional chemical 'substances.  The  true
viruses  are  insensitive  to antibiotics.  They multiply only in
living cells where they are assembled as  complex  macromolecules
utilizing  the  cells' biochemical systems.  They do not multiply
by division as do intracellular bacteria.
Volatile Suspended  Solids  (VSS]
                 The  quantity  of  suspended
solids lost after the ignition of total suspended solids.

Water  Quality  Criteria.  Those specific values of water quality
associated with an identified beneficial us(e of the  water  under
consideration.
Zero  Discharge.
Plants  that  do not discharge wastewaters to
either publicly owned treatment works or to navigable waters.
                             250

-------
                           APPENDIX C
                     PHARMACEUTICAL.  INDUSTRY
                  WASTEWATER DISCHARGE METHODS
 Plant
Code Ho.

1 2.0-0,0
12001
1:2003
12004
12005
12006
12007
12011
12012
12014
12015
12016
12018
120-19
12021
12022
12023
12024
12026
12030
12031
12035
12036
12037
12038
12040
12042
12043
12044
12048
120.51
12052
12053
120.54
12055
12056
12057
12058
12060
12061
12062
12063
12065
lad-irect

    X

    X
    X
    x

    X
    X
    X
    X
    X
    X
    X
    X

    X
    X
    X
    X
    X
    X
    X
    X
    X
    X
    X
    X
    X
    X
    X
    X
    X
Direct
   X
   X.
               X
               X
Zero
Comment
           X
                       X
        Reey/c 1 e/Reuse

        Land Application

        No Process Wastewater
  POTW1
Treatment
  Level
                                   P
                                   S
                                   S

                                   S
                                   S
                                   T
                                              S
                                              S
               x
               X

               X
                  Re cy c1e/Reus e

                  Private Treatment  System



                  Evaporation
                  Subsurface Discharge
                  Subsurface Discharge
                              Subsurface Discharge
                       X
                  Subsurface Discharge
                  Septic System
                                   T
                                   T

                                   S

                                   S

                                   S
                                   S
                                   S
                                   S
                                              S
                                              P
                                              S
                                              S
                                              S
                                              S
                             251

-------
12066
12068
12069
12073
12074
12076
12077
12078
12080
12083
12084
12085
12087
12088
12089
12093
12094
12095
12097
12098
12099
12100
12102
12104
12107
12108
12110
12111
12113
12115
12117
12118
12119
12120
12122
12123
12125
12128
12129
12131
12132
12133
12135
12141
12143
12144
12145
12147
12155
12157
12159
12160
12161
X
X
X

X
X
X
X
X
X
X

X
X

X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
               Private Treatment System
:x
X
           X
           X
               Contract Disposal
                   X

                   X
           X

           X
               Deep Well Injection

               Contract Disposal

               Ocean Discharge


               Ocean Discharge
               Private Treatment System
               Subsurface Discharge
           X
                   X
               Land Application
               No Process Wastewater
                                          T

                                          S
P
P
P
S
P
T

S
P

S
T
P
P
S
S

'S

S

S
                                          S
                                          S
                                          S

                                          T
                                          S
                                          S
                   X
           X
           X
               Recycle/Reuse
               Private Treatment System
                             252

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12166
12168
12171
12172
12173
12174
12175
12177
12178
12183
12185
12186
12187
12191
12194
12195
12198
12199
12201
12204
12205
12206
12207
12210
1221 1
12212
12217
12219
12224
12225
12226
12227
12230
12231
12233
12235
12236
12238
12239
12240
12243
12244
12245
12246
12247
12248
12249
12250
12251
12252
12254
12256
12257
X
X
X
X
X
X
X

X
X
X
X
X
X
X
X
X

X
X
X
X
X
X
X
X

X
X
X
X
X
X
X
X
X
X
X

X
X
X
X
X
X
X
                   X
                   X
               Evaporation
               No Process Wastewater
               Evaporation
               Private Treatment System
               Ocean Discharge

               (Also Contract Disposal)

               Private Treatment System
                           S
                           S
                   X
           X
           X
               Land Application


               Contract Disposal


               No Process Wastewater


               Subsurface Discharge

               Ocean Discharge



               Contract Disposal
               Evaporation
               Contract Disposal

               Private Treatment System
                           S
                           S

                           S
                           S
                           S

                           S
                           S
                           S
                           S
                           S

                           S
                           p
                           S

                           p
                           S
                           p
                           S
X
(Also Land Application)
Land Application
S
P
T
S
P
S

S
S
S
S
S
S
T
                              253

-------
12260
12261
12263
12264
12265
12267
12268
12269
12273
12275
12277
12281
12282
12283
12287
12289
12290
12294
12295
12296
12297
12298
12300
12302
12305
12306
12307
12308
12309
12310
12311
12312
12317
12318
12322
12326
12330
12331
12332
12333
12338
12339
12340
12342
12343
12345
12375
12384
12385
12392
12401
12405
12406
X
X

X
X
X
X
X
X
X

X
X
X

X
X
X
X
X
X
X
X
X

X
X

X
X
X
X

X
X
X
X
X
X
X
X
X
X
X
                   X
               Septic System
               Septic System
X
X
                   X
                   X
           X
           X
               Contract  Disposal
               Septic  System
               Septic  System
               Land Application
               Land Application
                                          S
                                          S
P
T

S
S
                                         P
                                         S
                                         T
                                         S
                                         S
P
S
S

S
P

P
S
S
P
P
S
P
S
S
S
T
                             254

-------
12407
12409
1241 1
12414
12415
12417
12419
12420
12427
12429
12433
12438
12439
12440
12441
12444
12447
12454
12458
12459
12460
12462
12463
12464
12465
12466
12467
12468
12470
12471
12472
12473
12474
12475
12476
12477
12479
12481
12482
12495
12499
20006
20008
20012
20014
20015
20016
20017
20020
20026
20030
20032
20033
X
X
X
X
X
X
X
X
X
X
X

X
X
X
X
X
X
               Contract Disposal
X
X

X
X
X

X
X
X
X
X
X
X
X
X

X
X
X
X
X

X
X
        X
Land Application
               Deep Well Injection
           X

           X
           X
               Land Application
               Septic System
X
                   X
                   X
                   X
                   X
                   X
               Land Application
               Land Application

               Ocean Discharge
               No Process Wastewater
               Evaporation
               No Process Wastewater
               No Process Wastewater
               Evaporation
                           S
                           S
                           T

                           T
                           T
                           S
                           S
                           S
                           S
                           S
                           S

                           S
                           S
                                          S
                                          S
                                          p
                                          p
                                          S
                           p
                           S
                           p
                              255

-------
20034
20035
20037
20038
20040
20041
20045
20048
20049
20050
20051
20052
20054
20055
20057
20058
20062
20064
20070
20073
20075
20078
20080
20081
20082
20084
20087
20089
20090
20093
20094
20099
20100
20103
20106
20108
20115
20117
20120
20125
20126
20134
20139
20141
20142
20147
20148
20151
20155
20159
20165
20169
20173
                           No  Process  Wastewater
X

X
X
X
X
X
X
X

X

X

X
X


X
X
X
X
X
X
X

X

X
X
                   X
                   X
                   X
                   X
                   X

                   X
                   X
                   X

                   X
                   X
                   X
                   X
                   X
                   X
                   X
                   X
                   X
X

X

X
X
X
                           No  Process
                           No  Process
                           No  Process
                           No  Process
                           No  Process
                           No  Process
           Wastewater
           Wastewater
           Wastewater
           Wastewater
           Wastewater
           Wastewater
No Process Wastewater
Septic System
Contract Disposal
No Process Wastewater
       No Process
       No Process
       No Process
       No Process
       No Process
           Wastewater
           Wastewater
           Wastewater
           Wastewater
           Wastewater
           X
       No Process Wastewater
       No Process Wastewater
       No Process Wastewater

       No Process Wastewater
       No Process Wastewater
       No Process Wastewater
       No Process Wastewater
       No Process Wastewater
       No Process Wastewater
       No Process Wastewater
       Evaporation
       Septic System
No Process Wastewater

No Process Wastewater

No Process Wastewater
Contract Disposal

No Process Wastewater
No Process Wastewater

No Process Wastewater
Contract Disposal

No Process Wastewater
                             256

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20174
201 76
20177
20178
20187
20188
20195
20197
20201
20203
20204
20205
20206
20208
20209
20210
2021 5
2021 6
20218
20220
20224
2022.5
20226
20228
20229
20231
20234
20235
20.236
20237
20240
20241
20242
20244
20245
20246
20247
'20249
20254
20256
20.257
2.0258
20261
20263
20264
20266
20267
20269
20270
20271
20273
20282
X

X

X
X



X

X
X

X
x
X
X
X
X
X
X

X
X
X
X
X

X
X
X

X
X
x
X
           X
           X
           X
        X

        X
        X
        X
        X
        X
        X
        ,x
        X

        X
                   X
                   X
                   X
                   X
                   X
                   X
                   X
        X

        X
        X
        X
No Process Wastewater

No Process Wastewater
Evaporation
No Process Wastewater

Land Application
Land Application

Land Application
No Process Wastewater
No Process Wastewater
No Process Wastewater
No Process Wastewater

No Process Wastewater
               No Process Wastewater
               No Process Wastewater
               No Process Wastewater
               No Process Wastewater
               Contract Disposal
               No Process Wastewater
               No Process Wastewater
No Process Wastewater

No Process Wastewater
Contract Disposal
No Process Wastewater
Mo Process Wastewater
                              257

-------
20294
20295
20297
20298
20300
20303
20305
20307
20308
20310
20311
20312
20316
20319
20321
20325
20328
20331
20332
20333
20338
20339
20340
20342
20346
20347
20349
20350
20353
20355
20356
20359
20361
20362
20363
20364
20366
20370
20371
20373
20376
20377
20385
20387
20389
20390
20394
20396
20397
20400
20402
20405
20413
           X
           X
X

X

X
X
X


X

X
X
X
X

X
X
X
X
X
X
X
X
X
X
X
X
X
           X
                   X
                   X
X

X

X



X
X

X

X


X
X

X
                   X
                   X
X
X
X
X

X

X
       No Process Wastewater
       No Process Wastewater
No Process Wastewater

No Pro-cess Wastewater

No Process Wastewater
Contract Disposal


No Process Wastewater


No Process Wastewater


No Process Wastewater

No Process Wastewater

Evaporation


No Process Wastewater
       Contract Disposal

       Land Application
       Evaporation
                          Contract Disposal

                          No Process Wastewater
                          No Process Wastewater
                          No Process Wastewater
                          No Process Wastewater
                          Contract Disposal
                              258

-------
20416
20421
20423
20424
20425
20435
20436
20439
20440
20441
20443
20444
20446
20448
20450
20452
20453
20456
20460
20462
20464
20465
20466
20467
20470
20473
20476
20483
20485
20486
20490
20492
20494
20496
20498
20500
20502
20503
20504
20507
20509
20511
20518
20519
20522
20526
20527
20529
11111
33333
44444
55555
X

X
X

X

X

X
X
X
X
X
X
X
X
X
X
X
X
X
X

X
X
X
X

X
X

X

X
                   X
                   X
                   X
                   X
                   X
                   X
                   X
X
X
X
X

X
X
X
X
X

X
X

X
No Process Wastewater
No Process Wastewater
Evaporation
No Process Wastewater
No Process Wastewater
No Process Wastewater
No Process Wastewater

No Process Wastewater
No Process Wastewater

No Process Wastewater

No Process Wastewater
       No Process Wastewater
       No Process Wastewater
       Subsurface Discharge
       No Process Wastewater
       Deep Well Injection

       No Process Wastewater
       No Process Wastewater
       No Process Wastewater
                          No Process Wastewater
                          No Process Wastewater
                          No Process Wastewater
                          No Process Wastewater
                          No Process
                          No Process
                          No Process
                          No Process
                          No Process
           Wastewater
           Wastewater
           Wastewater
           Wastewater
           Wastewater
 No  Process  Wastewater
 Contract  Disposal

 No  Process  Wastewater
           X
           X
           X
           X
                              259

-------
IpOTW Treatment Level Symbols:
  P - Primary
  S - Secondary
  T - Tertiary


^ Data on  POTW treatment  level  was  not  requested from the
 Supplemental 308  (20000 series) plants
                             260

-------