United States
                                 Environmental Protection
                                 Agency
                                  Municipal Environmental Research
                                  Laboratory
                                  Cincinnati OH 45268
vvEPA
                                 Research and Development
                                  EPA-600/S2-81-175/1 76  Oct 1981
Project Summary
                                 Literature  Study of  the
                                 Biodegradability of
                                 Chemicals* in Water:
                                 Volumes  1  and  2
                                 John Geatmg
                                  This project was initiated to compile
                                 and review post-1974 literature refer-
                                 ences on aqueous biodegradability of
                                 chemicals to update a  previous EPA
                                 report.* Additionally, literature  back
                                 to  1913 was searched for inhibitory
                                 effects of specific chemicals on
                                 wastewater treatment processes.
                                 Results are presented as an in-depth
                                 hierarchical index and bibliography of
                                 600 references. The index is searchable
                                 at three levels: (1) chemical name or
                                 chemical class. (2) name of micro-
                                 organism or type of microbial popula-
                                 tion affecting or being affected by the
                                 chemical, and (3) wastewater treat-
                                 ment process.
                                  Also presented in the two-volume
                                 project report are the results  of a
                                 successful feasibility study for predicting
                                 biodegradabiiity solely from positive
                                 or negative values assigned to standard
                                 molecular  substructural  units  of a
                                 chemical compound. The predictability
                                 accuracy was 93% for known  bio-
                                 degraable compounds and  68% for
                                 nonbiodegradable compounds.
                                  Brief abstracts of recent advances in
                                 wastewater treatment technology
                                 plus a guide to current Japanese and
                                 West German commercial literature in
                                 the field are included as  a  separate
                                 section in the report.
                                  Appendix F of Volume 1 lists  430
                                 specific chemical compounds alphabet-
                                 ically by principal name and synonym
                                 classified from the literature search in
                                 one of three categories: (1) biodegrad-
                                 able, (2) nonbiodegradable,  or (3)
                                 nonbiodegradable/qualified.
                                   This Project Summary was devel-
                                 oped by EPA's  Municipal Environ-
                                 mental Research Laboratory, Cincin-
                                 nati. OH, to announce key findings of
                                 the research projects  that are fully
                                 documented in separate reports (see
                                 Project Reports ordering information
                                 at back).
                                 •Howard, P H , Saxena, J , Durkm, P R , and Ou, L -
                                 T Review and Evaluation of Available Techniques
                                 for Determining Persistence and Routes of
                                 Degradation of Chemical Substances in  the
                                 Environment  EPA-560/5-75-006, NTIS No PB
                                 243-825 May 1975

                                 Introduction
                                   A comprehensive search was made of
                                 the world's scientific and technical
                                 literature for articles  on applying
                                 methods for studying biodegradability of
                                 chemical substances in water. Also
                                 covered were the effects of  treating
                                 chemicals in water by all biological
                                 wastewater treatment processes,  in-
                                 cluding  both aerobic and anaerobic
                                 processes. After the literature search
                                 and information gathering phase were
                                 completed, the results were organized
                                 into a permutated index by chemical
                                 compounds or classes of compounds,
                                 types  of microorganisms involved in

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biodegradation, and by wastewater
treatment process  or  experimental
technique used. Volume 2 comprises
the complete index with 603 references.
  A major aspect of biodegradability of
waste chemical substances in'water is
the potential correlation  that may exist
between various structures, functional
groups,  or  positional  relationships
within  the  structure.  The  obvious
advantage of foretelling the potential of
any specific compound to degrade (or
not) in a specific wastewater treatment
system without extensive experimenta-
tion is sufficient reason to conduct such
a study. A structure-activity algorithm
for predicting biodegradability was
developed from data in the 603 refer-
ences ( in Volume 2) and from a search
of eight scientific data bases.
  Howard et al.'s previous report was
updated by including new or re-clustered
wastewater  treatment processes  and
equipment. These inclusions came from
searches of published literature reports,
review of manufacturers' advertise-
ments  and material  on  file with the
Water Pollution Control Federation, and
through  recommendations  resulting
from direct contact with professionals
(e.g., manufacturer's representatives,
consultants,  and operating engineers).
In addition, the literature on commercial
wastewater technology  from West
Germany and Japan  was searched for
relevant contributions (Volume 1).
  A table of chemical contaminants
with adverse effects on water treatment
processes (focusing on specific chemical
contaminants  found  in wastewaters
and reported  in earlier publications
(1913 to 1974) to have had negative
impact,  i.e.,  toxicity and/or inhibition,
within  municipal or  industrial waste-
water treatment systems) is compiled in
Volume 1. The chemicals, their CAS
Registry Number, their effects, and the
literature sources,  where  given, were
intermeshed alphabetically for ease of
accession by the user (Volume 1).


Structure-Activity Study
(Volume 1)
  The purpose of the structure-activity
work was to determine the feasibility of
developing a structure-activity model to
distinguish between biodegradable and
nonbiodegradable  chemicals. Similar
models have been developed in the past
for a  variety of biological endpoints,
including rat oral  LD50,  mutagenicity,
carcinogenicity, and teratogenicity.
  The data were originally intended to
be presented for substructural analysis
as  a  list  of compounds designated
degradable and a list designated non-
degradable. Unfortunately, the literature
in this field is  not presented in such a
manner as  to allow such  clear-cut
interpretations of results, so a third list
of compounds, designated nondegrad-
able/qualified,  was created. When
more  reliable data were  received, their
entries were transferred to  the other
two lists. The remaining  entries on this
third list were  not used in constructing
the predictability algorithm. The largest
number of compounds from the literature
survey were found to be biodegradable.
For this reason, a  subset  of  these
compounds was selected at random and
used in the structure-activity models.
  Three types of parameters were
considered  in the  biodegradability
models:  (1) molecular weight,  (2)
octanol-water  partition coefficient (log
p),  and  (3) Wiswesser  line Notation
(WLN)-based substructural  keys.  Mo-
lecular  weight  is,  of  course,  self-
evident.  The partition coefficient was to
be used initially, but was not used in the
finally developed models because of the
great  difficulty in  obtaining accurate
numbers for a sufficient number of
compounds  before completion of the
project.  The 336 WLN-based keys are
based on a  major modification of the
CROSSBOW program and  are  fully
described in Appendix B  of Volume 1.
  The statistical  methodology used in
developing  these  models consisted of
stepwise  discriminant  analysis  and
ridge  regression procedures. An initial
discriminant equation was  prepared
contrasting  the biodegradable com-
pounds with  the nonbiodegradable
chemicals. After multiple applications
of the statistical operations, those
substructural keys having the greatest
influence on  biodegradability were
identified,  those with least  influence
were eliminated, and a final discriminant
analysis was performed. The final result
is a table of classification functions with
two values (a degradability function and
a nondegradability function) listed for
molecular  weight and for each  sub-
structural key. These functions are used
in the Probability Equation as described
in Figure 1 to predict the probability that
a compound is biodegradable.
  The performance  of the  structure-
activity model on compounds of known
biodegradability is shown in Table 1. Of
292 degradable compounds, 270 or
92.5% were correctly classified whereas
39 of 57 (68.4%) nondegradable com-
pounds were correctly classified. A total
of 25 compounds could not be classified
by the model.
  A serious limitation on general use of
the model is that classification functions
could be derived for only 39 substruc-
tural  keys  from data available in  the
literature. Additionally, six keys were
found to have no significant influence
on biodegradability  and six others had
such  a  variable  influence that their
presence would not permit use of the
model.


Permutated  Index
(Volume  2)
  The in-depth hierarchical  index and
accompanying compilation of biblio-
graphic  citations  were created  to
provide the sanitary engineer, environ-
mental chemist, and microbiologist with
a concise and readily accessible source
of information on the biodegradation of
chemicals associated with wastewater
treatment plants.
  The online retrieval of pertinent world
literature covers the period from 1974
to 1979  as well as articles published
during 1970 to 1973 that did not appeal
m Howard et  al.'s previously published^
EPA study. Foreign language  articles
are included to emphasize the worldwide
interest  of this  increasing environ-
mental problem.
  The first level of the permutated index
is a  listing  of chemical names  or
chemical classes. The  final choice of
chemical names represents a third-
generation compromise involving utility
to professionals of widely diversified
chemical  background; industrial
importance;  an  awareness  of the
relative  insensitivity of the biodegrad-
ability of closely related homologues to
the presence  of nontoxic substituents;
and, finally, the traditional mechanics of
permutated index  creation.  Extensive
cross-indexing is included to assist the
investigator to locate readily the probable
sourcejs) of desired  information.
  The second level of the index consists
of the microbial populations responsible
for the biodegradation of the chemical
substances.  Major classes of these
microbial populations, created  to facil-
itate designation of the system with the
major role in the biodegradation process,
are as follows: activated sludge; micro-
bial population, mixed; microbial  pop-
ulations as  pure cultures;  and microbial

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 Compound:    2,4-Dmitrophenol

 Substructural Keys.

     Constant
     Molecular weight
     K3, Branching terminal nitro group - NO?
     K65, One - OH group
     K97, Aromatic 6-membered ring
     K137,  1 benzene ring
 Key
Degradable
Nondegradable
 Constant
 Molecular wt
 K3
 K65
 K97
 K137
  -6340
   0.023
   0111
   3 173
   4.259
   1.767
    -9.758
     0028
     3.306
     0.143
     6614
    -2.172
 Step 1.  Sum values for each key from degradable column
         constant + molecular wt. + K3 + K65 + K97 + K137 -6.340 + 0.023 +
         0 111 + 3.173 + 4.259 +  1.767 = 2.993
 Step 2.  Sum values for each key from nondegradable column
         -9.758 + 0.028 + 3.306 + 0.143 + 6.614 + (-) 2 172 = -1.839
 Step 3.  Insert values from Steps 1 and 2 in the Probability Equation
         P = exp (Step 1)/[exp (Step 1) + exp (Step 2)]
         P = exp 2 993/[exp 2 993 + exp (-) 1.839]
 Step 4.  By  inspect/on, the denominator is only slightly larger than the numerator,
         indicating that P >0.9, i e., a high probability  of biodegradation. In some
         cases the inspection  method of handling Step  3 will not work and the
         exponential terms will  have to be calculated. Probability values range
         from 0 to 1, thee larger the number, the greater the probability of biodegra-
         dation.
 Figure  1.    Example of calculation of probability of biodegradation
Table 1.    Degradable Versus Nondegradable Classification Matrix Classified by
           Discriminant Equation Evaluation
Actual
Classification
from Reference Literature
Degradable
Nondegradable
Degradable
(P > 0. 7)
N
270
9
%
92.5
15.8
Intermediate
(P = (0.3-0.6991)
N
16
9
%
5.5
15.8
Nondegradable
(P
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      John  Geating is with Franklin  Research Center,  Philadelphia,  PA  19103.
      Sidney A, Hannah is the EPA Project Officer (see below).
      The complete reports, entitled "Literature Study of the  Biodegradability of
        Chemicals in Water":
          Volume 1. Biodegradability Prediction, Advances in and Chemical Interfer-
          ences with Wastewater Treatment (Order No. PB 82-100 843; Cost: $18.50,
          subject to change)
          Volume 2. Permutated Index of Chemicals, Microbial Populations, and
          Wastewater Treatment Systems with Bibliography (Order No. PB 82-100850;
          Cost: $14.00, subject to change)
        will be available only from:
              National Technical Information Service
              5285 Port Royal Road
              Springfield. VA 22161
              Telephone:  703-487-4650
      The EPA Project Officer can be contacted at:
              Municipal Environmental Research Laboratory
              U.S.  Environmental Protection Agency
              Cincinnati,  OH 45268
     ~tt U S GOVERNMENT PRINTING OFFICE, 1981 — 559 01 7'7382
United States
Environmental Protection
Agency
Center for Environmental Research
Information
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