v'/EPA
                                United States
                                Environmental Protection
                                Agency
                                 Health Effects Research
                                 Laboratory
                                 Cincinnati OH 45268
                                Research and Development
                                 EPA-600/S1-81-016  Mar. 1981
Project  Summary
                                Assessment of  Mutagenic
                                Potential  of  Mixtures  of
                                Organic  Substances  in
                                Renovated  Water

                                M. W. Neal, L. Mason, D. J. Schwartz, and J. Saxena
                                 This study was conducted to deter-
                                mine the presence of mutagenic activity
                                in municipal wastewater and to evalu-
                                ate the performance of available ad-
                                vanced wastewater treatment systems
                                for removing such activity. Further,
                                the distribution of the described acti-
                                vity among various classes of chemical
                                compounds was studied in an attempt
                                to identify the active fractions. The
                                study was conducted utilizing rapid//?
                                vitro bioassays for detection of muta-
                                genic activity and, therefore, was
                                expected to  provide a preliminary
                                assessment regarding the mutagenic
                                hazards linked to the potential potable
                                use of reclaimed wastewater. The
                                results of this investigation should be
                                of value to the Environmental Protec-
                                tion Agency and others in identifying
                                the problem areas and in setting priori-
                                ties for in-depth and more specialized
                                toxicological  studies. Knowing that
                                certain wastewaters have toxic prop-
                                erties, treatment  systems may be
                                designed to remove the toxic compo-
                                nents or sources of such components,
                                for  example certain industries could
                                provide pretreatment measures.
                                 This Project Summary was develop-
                                ed by EPA's Health Effects Research
                                Laboratory, Cincinnati, OH, to an-
                                nounce key findings of the research
                                project which  is fully documented in a
                                separate report of the same title (see
                                Project Report ordering information at
                                back).
                                Introduction
                                  A full toxicological investigation of the
                                potential hazards from the consumption
                                of renovated wastewater is necessary
                                before considering it for potable reuse.
                                Wastewaters may contain  hazardous
                                chemicals for which currently no criteria
                                exist. Such pollutants may pass through
                                wastewater treatment plants in tracq
                                amounts, so an evaluation of the toxic-
                                ological properties of such effluents is
                                warranted.
                                Methods
                                  An investigation was undertaken to
                                evaluate the performance of selected
                                advanced wastewater treatment pro-
                                cesses for removing (introducing) muta-
                                genic substances and to determine the
                                distribution of the detected activity
                                among various classes of  chemical
                                compounds. The study utilized specially
                                constructed strains of Salmonella typhi-
                                murium and Saccharomyces  cerevisiae
                                to assess mutagenic  activity, and the
                                mammalian cell — BHK21 Cl 13 (to a
                                limited extent) to determine transform-
                                ing activity. In an effort to recover the
                                wide variety of organic contaminants
                                present in wastewater and  renovated
                                wastewater, three independent concen-
                                tration methods were utilized. These
                                included sorption on polyurethane foam
                                plugs, sorption on XAD resin, and
                                solvent extraction. Conditions suitable

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for recovery of organics of polyurethane
foam were: wastewater temperature 62
C, flow rate 250 ml/min, with a sample
volume of 10 I  for secondary effluent
and 20 I for intermediate or fully treated
wastewater. The conditions used for
XAD resin were: wastewater temperature
50 C, flow rate 100 ml/min, XAD-4 and
XAD-8 columns (1x10 cm) connected
in series, sample volume 51. For recovery
of organics by liquid-liquid  extraction,
15% methylene chloride in hexane (75
ml solvent/1 wastewater) was used.
The crude organic mixtures recovered
from wastewaters were separated into
seven major chemical classes of organic
compounds according to their solubility
under acidic, basic, and neutral condi-
tions, and each class  was tested for
mutagenic activity. The  classes of com-
pounds isolated were; ether insoluble,
water soluble, basic, amphoteric, strong
acid, weak acid, and neutral. Adsorption
chromatography with silica gel columns
was used to subfractionate the neutral
fraction into aliphatic, aromatic, and
oxygenated fractions.

  A mutagenic response by the waste-
water concentrates and separated frac-
tions was observed with the Ames Sal-
monella liquid suspension assay which
involved preincubation  of the test mix-
ture and  Salmonella tester strain in
liquid suspension prior  to plating. Con-
ventional  plate  incorporation and spot
tests failed to detect mutagens in crude
concentrates and separated fractions.
For detection of low concentrations of
active compounds in unconcentrated
wastewater, the assay was performed
by making filter sterilized test water into
media  (base agar layer). This modifica-
tion of the assay permitted incorporation
of up to 10 ml of test wastewater in the
Ames assay (70% v/v). The amino acid
histidine, which interferes with the
Ames assay by artifactually increasing
the  number of revertants, was not
detected  in wastewaters. The yeast
assay (forward and reverse mutagene-
sis, mitotic cross over, and gene conver-
sion) lacked the sensitivity for detection
of mutagens in wastewaters, wastewater
concentrates, or separated fractions.
Only a marginal response was obtained
with strain S288C (forward mutagene-
sis assay) with some samples. The
assay also lacked the capacity to detect
mutagenic compounds  which required
mammalian metabolic activation. The
BHK  cell system also proved to be
unsuitable for this study because of the
excessive time requirement and its erratic
behavior.
Physical-Chemical System
  The influent of the physical-chemical
AWT process at Piscataway, Maryland,
in unconcentrated form, showed mini-
mal mutagenesis in the base pair sub-
stitution mutants TA100 and TA1535 of S.
typhimurium. The activity was  lost by
incorporation of mammalian liver  en-
zymes in the assay. Wastewater samples
collected after the liming/recarbonation
steps showed increased activity over
that of the influent suggesting that
these treatment steps were capable of
introducing mutagenic substances.
Alternatively, the liming/recarbonation
steps  may have  removed toxicants
and/or masking agents, thereby permit-
ting detection of  mutagens already
present in the influent. The increased
activity observed  with the partially
treated sample was removed by break-
point chlorination and/or carbon filtra-
tion. However, the overall response
with the final effluent was no less than
that shown by the influent wastewaters.
Mutagens were not present as conjugates
in wastewaters since the presence of
the hydrolytic enzyme /3-glucuronidase
in the assay did not result in an increas-
ed mutagenicity. The organic mixtures
recovered from wastewater by  the
concentration methods showed muta-
genic activity, but not in the same tester
strains as with unconcentrated waste-
waters. Also, the activity could be
detected only when the indicator organ-
ism was incubated with the concentrates
in liquid suspension prior to the assay.
These findings suggested that the con-
centration methods employed failed to
recover all the active compounds from
wastewaters. The  recovered activity of
the purified effluent  was found to be
distributed mainly in weak acid, basic,
and aliphatic and aromatic  classes of
compounds. The combined activity of all
the separated fractions was greater
than that of the crude concentrate,
suggesting masking of activity in this
complex  mixture,  either  because of
toxicants or masking agents. The chemi-
cal separation scheme used in this
investigation resulted in the uncovering
of some of the activity but not all, since
many of the separated fractions remain-
ed toxic to the test organisms.  Only  a
small percent of the original organics,
as measured by total organic carbon,
was recovered by the three concentra-
tion methods and the  results must
tempered by this fact.
Biological With Physical-
Chemical System
  The influent and effluent from Bay
Park AWT Plant, at East Rockaway, New
York, which utilized combined biological
and physical-chemical treatment, show-
ed mutagenic response in the base pair
substitution mutants TA100 and TA1535.
A comparison of the mutagenic response
of AWT influent and effluent revealed
that  the AWT method employed at Bay
Park, as was observed with the Piscata-
way  treatment, not only failed to remove
certain mutagenic substances but also
added new mutagens to the final efflu-
ent.  Unlike the results with  unconcen-
trated wastewater, the organic mixtures
recovered from  Bay  Park wastewater
showed activity in the f rameshift mutant
TA1538. The mutagenic chemical class-
es derived from the influent were basic,
water soluble, and amphoteric. Activity
in these classes was partially reduced
as a result of treatment but activity
appeared in two new fractions: the
weak acid and ether insoluble.

                                  I

Industrial Waste  Plant
  Wastewaters from the physical-chem-
ical  Niagara Falls, New York AWT pro
cess, which consists of 60-70% indus
trial  wastes, showed weak to moderate
mutagenicity in  base pair substitutior
and  frameshift tester  strains of S
typhimurium.  Mammalian  metabolii
activation was required for mutagenesif
in frameshift mutants. The mutagenii
activity  was higher  in influent waste
water than in partially treated and fina
effluent suggesting removal of mutagen
during treatment. There were, however
mutagens still  present in the fina
effluent. The influent wastewaters a
the point samples had undergone partie
treatment including liming/pH  adjusl
ment, and the addition of mutagen
during these treatment steps may hav
been responsible for increased muta
genie activity of the influent.
 Domestic Wastes
  Influent and AWT effluent sample
 from the rapid sand filtration process i
 Lake George failed to cause mutagem
 sis in the Salmonella strains tested, bi

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showed an inhibitory  effect on the
spontaneous reversion rate of strain
TA98. Organic mixtures recovered from
these wastewaters were also free  of
mutagens. The data revealed that micro-
bial synthesis of mutagens did not occur
following prolonged contact with the
natural delta sand beds. Because of the
absence of mutagens in the influent
wastewater, efficiency of the process
for removing mutagens could not be
assessed. These wastewaters did not
contain  any industrial wastes and it is
significant that wastewaters strictly  of
domestic origin do not have mutagenic
properties.
ment steps themselves may contribute
mutagens. Further  toxicological and
analytical studies are  required to
determine the nature of potentially
hazardous compounds present in reno-
vated wastewater.
Sand Filtration System
  Information on removal of mutagens
by sand  filtration was obtained using
simulated laboratory sand columns
which were dosed with partially treated
primary effluent from the heavily indus-
trialized  area  of  Niagara  Falls.  The
primary effluent did not show mutagenic
activity in any of the chemical fractions
except for the strong acid fraction. This
was surprising since the wastewaters
from this facility, when tested in uncon-
centrated form, showed high mutagenic
response. After filtration of the waste-
waters,  through  one  half of the sand
column, the strong acid fraction became
less mutagenic, but  strong mutagenic
activity appeared in the water soluble
and ether insoluble fraction, and weak
mutagenicity was noted in weak acids,
basic, and amphoteric fractions. On
continued contact with sand, mutagens
of the amphoteric, weak acid, and basic
classes were removed to a nondetectable
level but mutagens of ether insoluble,
water soluble, and strong acid classes
were unaffected. The presence of sev-
eral new classes of  mutagens in the
midpoint and final effluent, not detected
in the influent, suggests synthesis of
mutagens  during  the sand filtration
process. Alternatively, the sand filtration
process may have removed toxicants
and/or masking agents thereby permit-
ting expression of the mutagens origi-
nally present in the influent.
Conclusions
  The study shows that the physical-
chemical, biological, and sand filtration
processes studied were unable to com-
pletely remove mutagenic activity from
wastewater. In several instances, treat-
  M. W. Neat, L Mason, D. J. Schwartz, and J. Saxena are with the Syracuse
    Research Corporation, Syracuse. NY 13210.
  Herbert R. Pahren is the EPA Project Officer (see below).
  The complete report, entitled "A ssessment of Mutagenic Potential of Mixtures of
    Organic Substances in Renovated Water," (Order No. PB 81-153 843; Cost:
    $11.00, 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:
          Health Effects Research Laboratory
          U.S. Environmental Protection Agency
          Cincinnati, OH 45268
                                                                                       US GOVERNMENT PRINTING OFFICE 1981-757-012/7011

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