United States      Office of Water       EPA 822-R-98-006
Environmental Protection   4304         July 1998
Agency
AMBIENT WATER QUALITY
CRITERIA FOR THE
PROTECTION OF HUMAN
HEALTH
Acrylonitnle

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    Ambient Water Quality Criteria for the Protection of Human Health:
                                   Acrylonitrile

NOTE TO READER

       The Agency is intending to develop streamlined criteria documents which focus on
critical lexicological and exposure-related studies only.  This is a departure from the past format
in which all existing lexicological and exposure studies were presented and evaluated in the 1980
criteria documents, with equal emphasis placed on exposure, pharmacokinetics, lexicological
effects, and criterion formulation. Due lo limited resources and a need to update criteria as
quickly as possible, EPA has decided lo develop more abbreviated versions of criteria documenls
wilh an emphasis on using existing risk assessments (on IRIS or other EPA health assessmenl
documenls) where available and still relevanl, and focusing lo a greater extenl on pertinenl
exposure and lexicological studies which may influence Ihe developmenl of a criterion (e.g.,
critical effecls studies which form the basis of RfD development or cancer assessmenl). EPA
will continue lo conducl a comprehensive review of Ihe literature for the latest studies, but will
not provide a summary or an evaluation of Ihose sludies in Ihe criteria documenls which are
deemed less significanl in the criteria developmenl process. Where there is a significanl amounl
of literature on an area of study (for instance, pharmacokinetics), EPA, lo the exlenl possible,
will reference the information or cite existing documenls (e.g., IRIS or other existing EPA risk
assessmenl documenls) which discuss Ihe information in greater delail.

       The overall objective of Ibis change in philosophy is lo allow EPA lo update 1980
AWQC al a greater frequency, while still maintaining Ihe scientific rigor which EPA requires
when developing an AWQC. EPA believes tiiese "new" criteria documenls will be jusl as
informative as previous criteria documenls and will continue lo serve as Ihe key scientific basis
for Slate and Tribal standards. EPA also believes Ihe documenls will provide Ihe necessary
scientific conlenl and scope lo allow a Stele or Tribe lo come lo an appropriate technical and/or
policy decision with regard lo setting water quality standards.

       EPA requests that commenters identify any relevanl information missing from this
criteria documenl which may resull in a differenl criteria calculation or scientific interpretation.
EPA also requests comments on the change in criteria documenl formal.  This criteria documenl
has undergone extensive external peer review.
1.
BACKGROUND
      Criteria for acrylonitrile were set in 1980 based on non-threshold carcinogenic effects (45
FR 79318). Because of Ihese carcinogenic effecls, Ihe levels of acrylonilrile in water should
ideally be zero. However, because Ihe zero level may nol be attainable, the following criteria
were set based on Ihree incremental increases of cancer risk:

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Risk Level
io-s
10-6
io-7
Criterion (ug/L)
Ingestion of Water and
Aquatic Organisms
0.58
0.058
0.006
Ingestion of Aquatic
Organisms Only
6.5
0.65
0.065
       Under the National Toxics Rule (USEPA, 1992), criteria were updated based on a new
cancer potency factor from IRIS.  At the 10'6 risk level, criteria for water and organisms and
organisms only were set at 0.059 and 0.66 ug/L, respectively.

       This criteria document updates national criteria for acrylonitrile using new methods and
information described in the Federal Register notice (USEPA, 1998a) and Technical Support
Document (TSD) (USEPA, 1998b) to calculate ambient water quality criteria. These new
methods include updated approaches to determine toxicity dose-response relationships for both
carcinogenic and non-carcinogenic effects, updated information for determining exposure
factors (e.g., values for fish consumption), new exposure assumptions used in the calculation,
and new procedures to determine bioaccumulation factors.

       In addition to new methods for deriving AWQC values, new data on the toxicity,
exposure, and bioaccumulation of acrylonitrile are also included in the criterion calculation.
Based on the most sensitive end point (cancer), the proposed criterion to protect against ingestion
from water and aquatic organisms is 0.055 fig/L, and the criterion to protect against ingestion of
aquatic organisms and incidental water exposure is 4.0 jag/L.  Both of these values are calculated
based on a lifetime risk of 10~6. The calculation is based on adults in the general population.

       The following sections include the toxicological, exposure, and bioaccumulation factor
evaluations, the calculation of the  criterion, and a discussion of site-specific adjustments to the
criterion.

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 2.
CHEMICAL NAME AND FORMULA
       The AWQC is being derived for acrylonitrile (CAS No. 107-13-1).  The chemical
 formula is C3H3N, and the chemical structure is
                              H
                              H
                                                 C=N
                                           H
       Synonyms include the following:  2-propenenitrile, acrylon, carbacryl, cyanoethene,
cyanoethylene, Acritet, Fumigrain, propenenitrile, VCN, Ventox, vinyl cyanide (U.S. EPA,
1983; Budavari, 1989).

       Physical and chemical properties (U.S. EPA, 1983; NTP, 1998)
       Chemical Formula
       Molecular Weight
       Physical State (25°C)
       Boiling Point
       Density (20°C)
       Vapor Pressure (20°C)
       Specific Gravity (20°C)
       Water Solubility (20°C)
       Log Octanol Water Partition
       Conversion Factor
                                        C3H3N
                                        53.06
                                        Clear colorless liquid
                                        77.3°C
                                        0.8060 g/mL
                                        SOmmHg
                                        0.8060
                                        7.35 weight %
                                        -0.92
3.
SUMMARY OF PHARMACOKINETICS
       Pharmacokinetic data were obtained from animal, but not human studies. The data
obtained from animal studies show that acrylonitrile is extensively absorbed from the
gastrointestinal tract.  Approximately 95% was absorbed in male rats receiving a single oral dose
of 0.1 or 10 mg/kg (Young et al., 1977). Acrylonitrile and its metabolites are distributed
throughout the body with the highest accumulation in the gastrointestinal tract, skin, and red
blood cells. These targets are maintained regardless of the route of delivery or level of exposure.
Accumulation also occurs in the liver, lung, kidney, mucosa, and adrenal cortex. (Ahmed et al.,
1982; Sandberg and Slanina, 1980; Silver et al., 1987; Young et al., 1977).

       Acrylonitrile undergoes various biotransformation and conjugation reactions. A major
product of metabolism is cyanide and many of the short-term toxic effects (acute toxicity) are

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due to cyanide formation. Acrylonitrile binds to nucleic acids and proteins and conjugates with
glutathione. The conjugation product is metabolized by glutathionase to form cyanoethylated
mercapturic acid which is excreted in urine (Dahm, 1977; Gut et al., 1975; Hashimoto and Kanai,
1965; Langvardt et al., 1979). Alternatively, acrylonitrile is converted by the microsomal mixed
function oxidase (MFO) system to 2-cyanoethylene oxide, a reactive intermediate. This is, in
turn, metabolized by several pathways including covalently binding with macromolecules or
conjugation with glutathione. The extent of conversion of acrylonitrile to cyanide and
thiocyanate is route and species dependent (Gut et al., 1975).

       A biphasic elimination dynamic has been observed in rats, indicative of a two-
compartment open model.  The half-lives observed were 3.5 to 5.8 hours in the  faster phase and
50 to 77 hours in the slower phase (Young et al., 1977).

4.     TOXICOLOGICAL BASIS FOR CRITERIA

4.1    Noncancer Data and Previous Evaluations

       4.1.1   Oral Exposure

       Human chronic exposure data are not available regarding oral exposure to acrylonitrile
(there are human inhalation exposure data, discussed in the following section).  Oral exposure
effects are reported hi numerous animal studies. An oral RfD was developed in 1993 by the RfD
Work Group, but is not yet available on the Integrated Risk Information System (IRIS). The
following summary of the oral non-carcinogenic effects reported in the literature is based on the
Work Group report (USEPA, 1993).

      A number of long-term animal studies have been carried out on oral exposure to
acrylonitrile:

      Tandon et al. (1988) studied effects on the male reproductive system in a gavage study in
      mice.  They found degenerative changes in reproductive structures (seminiferous
      tubules), as well as direct effects on sperm including decreases in the number of
      spermatozoa. Absence of effects was observed at the lowest dose tested (1 mg/kg-day for
      60 days).

      Chronic exposure studies by Biodynamics (1980a and b) in male and female rats found
      numerous blood disorders, food and water intake, body weight, and organ-specific weight
      disturbances, epithelial hyperplasia and hyperkeratosis in the stomach, gliosis and
      perivascular cuffing of the brain, and mammary gland hyperplasia. There were problems
      in these studies with premature mortality, as discussed below in the cancer section.

      A study of beagle dogs by Quast et al. (1975) for six months at doses of 10, 16, and 17
      mg/kg-day in males and 8,17, and 19 mg/kg-day in females found high toxicity at the

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      two highest dose levels with associated high mortality rates. The following effects were
      observed in the animals that died prematurely: lethargy, weakness, emaciation, and
      respiratory distress. No effects were observed at the lowest dose level.

      Bigner et al. (1986) observed neurological effects in a lifetime rat study with
      administration via drinking water at doses of 8 and 40 mg/kg-day in males and 8 and 50
      mg/kg-day in females.  These effects were observed at both dose levels and brain tumors
      were reported in the high dose group. Mortality was also observed in both dose groups.

      Beliles et al. (1980) observed rats over three generations dosed with 8 and 40 mg/kg-day
      in males and 8 and 50 mg/kg-day in females via drinking water.  Effects observed
      included reduced weight gain, food intake, and water consumption at both doses, reduced
      pup viability and reduced lactation. Microscopic evaluation of tissues was not done.

      Murray et al. (1978) evaluated developmental toxicity in rats exposed to 10,25, and 65
      mg/kg-day via gavage on days 6 through 15 of gestation. Maternal effects included
      hyperactivity, stomach abnormalities, reduced incidence of pregnancy, reduced body
      weight gain, and increased liver weights. Offspring effects included: missing vertebrae,
      shortened trunk, imperforate anus, and minor skeletal variants. The authors identified a
      LOAEL of 25 mg/kg-day. These findings are supported by an intraperitoneal study that
      also found skeletal abnormalities (Willhite et al., 1981).

      Additional studies have suggested effects on steroidogenesis (Szabo et al., 1984),
      however, the implications of these observations are not clear (Szalay et al., 1987).

      The RfD Work Group identified the Tandon et al. (1988) study as the principal study
with a NOAEL of 1 mg/kg-day.  The critical effects include seminiferous tubule degeneration
and a decrease in the sperm counts. An uncertainty factor of 1000 was applied, with a factor of
10 used to account for extrapolation from mice to humans, 10 to account for sensitive human
sub-populations, and 10 for the use of a sub-chronic study and data base deficiencies.  These
deficiencies include the lack of a chronic mouse study and the lack of adequate reproductive
toxicity studies. The calculated RfD for acrylonitrile from this study is 1 x 10'3 mg/kg-day
(USEPA, 1993). Confidence in the oral RfD is medium due to the small sample size of the
critical study and because only two dose levels were tested.

       4.1.2   Inhalation Exposure

       Acrylonitrile causes central nervous system depression and respiratory irritation.
Exposure has been reported to cause headaches, nausea, fatigue, and weakness in workers
chronically exposed via inhalation (USEPA, 1994b). It also causes dermal irritation with skin
contact  (Bakker, 1991). Numerous animal inhalation studies are available for acrylonitrile;
summaries of these studies are available on IRIS. A reference concentration (RfC) for inhalation
exposure of 2 x 10'3 mg/m3 was developed by EPA based upon degeneration and inflammation of

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 nasal respiratory epithelium and hyperplasia of mucous secreting cells. Results were obtained
 from a 2 year rat inhalation study (Quast et al., 1980b, as reported in IRIS), with no NOAEL and
 an adjusted LOAEL of 1.9 mg/m3. The uncertainty factors applied were: 10 to protect unusually
 sensitive individuals, 3 to adjust from a minimally adverse LOAEL to a NOAEL, 3 for
 interspecies variability, and 10 due to an incomplete data base including the lack of an inhalation
 bioassay in a second species and lack of reproductive data by the inhalation route (with the
 presence of reproductive effects in an oral study). Confidence in the RfC is medium.  The critical
 study was confounded by the early sacrifice of rats with large mammary gland tumors and
 limited examination of the target organ (nasal turbinates) at the end of the study. Other tumor
 data are also reported in the study (IRIS).

 4.2     Cancer Evaluation

              4.2.1  Human Data

        Several epidemiological studies have reported an increased incidence of lung cancer
 mortality in workers exposed to acrylonitrile (Thiess et al., 1980; Werner and Carter, 1981;
 Delzel and Manson, 1982; O'Berg et al., 1980,1985; Zhou and Wang, 1991 in Rothman,
 1994), but these excesses were not observed in other studies (Chen et al. 1987; Collins et al.,
 1989; Swaen et al., 1992). Most of the available studies have limitations, such as exposure levels
 not measured, exposure to other carcinogens, and/or lack of information on confounding factors
 such as cigarette smoking.  In addition, increased incidence of prostate cancer were reported in
 several cohorts (O'Berg et al., 1985; Collins et al., 1989; Chen et al., 1987; Swaen et al., 1992).
 A comprehensive review of the earlier health-related studies is available in a document entitled
 "Health Assessment Document for Acrylonitrile" (USEPA, 1983).

              4.2.1.1  Oral Exposure

       Human data are not available regarding chronic oral exposure to acrylonitrile.

              4.2.1.2  Inhalation Exposure

       Cancers observed in humans, associated primarily with inhalation exposure, included
lung cancer. The O'Berg study (O'Berg, 1980) was used as the basis for the estimation of the
inhalation cancer potency in IRIS.  In this study, 1345 male textile workers exposed to 5 to 20
ppm (0.011 to 0.04 ug/m3) acrylonitrile for an average of 9 years were followed for 10 or more
years. A maximum age at the end of the observation period of 60 years was assumed to calculate
an age-adjusted standardized mortality ratio in the cohort of 113. An exposure response trend
was observed with increased duration of exposure and follow-up associated with increased
cancer incidence.  A statistically significant increase in respiratory cancer was observed and the
analysis included controls for the contribution to cancer from smoking. Later, an update of the
study is reported (O'Berg et al., 1985). Thus, the IRIS information needs to be updated as well

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       Other studies have also found statistically significant associations between respiratory
cancer and acrylonitrile (Delzell and Monson, 1982; Thiess et al., 1980; Werner and Carter,
1981; Monson, 1978). These studies have problems associated with exposure quantification
and/or confounding exposures such as cigarette smoking and as a result are not appropriate for
use in dose-response analysis.

       4.2.2. Animal Data

       There is substantial evidence that acrylonitrile causes multiple rumor types following
oral and inhalation exposure to several strains of rats. Details are not provided here on animal
inhalation exposure studies, because human data are available on inhalation exposure, and
because the AWQC derivation focuses on the oral route rather than inhalation.

             4.2.2.1  Oral Exposure

       Animal tumors induced via oral exposure to acrylonitrile included stomach, tongue, small
intestine, mammary gland, and Zymbal gland (ear canal), and astrocytomas (the CNS) (Maltoni
et al., 1977; Biodynamics, 1980a; Biodynamics, 1980b; Quast et al., 1980a; Quast et al., 1980a;
Signer et al., 1986).  The study by Quast et al., (1980a) which provides data from a lifetime
study with large group sizes, is most applicable in this evaluation.  In the study, acrylonitrile was
administered in drinking water at doses of 35, 100, and 300 ppm (3.42, 8.53, and 21.18 mg/kg-
day respectively) to 48 served as controls. A statistically significant increase in tumors was
observed in the CNS  (astrocytomas), ear canal (Zymbal gland), stomach, tongue, and small
intestine of both male and female animals and in the mammary gland of females. In general, the
increase was dose-dependent.

       The tumor data from the Quast et al. (1980a)  study are listed in Table 4.2.1  with the
estimated equivalent human doses. The human equivalent dose was calculated two ways: using
the new proposed approach of scaling dose in proportion to body weight raised to the 3/4 power
and the current approach of scaling dose in proportion to body weight raised to the 2/3 power.
The tumor incidence  indicates the number of animals bearing tumors that were statistically
significant at any site divided by the total number of animals for the dose group.

       Exposure and follow-up periods were less than a lifetime for some animals in
Biodynamics (1980 a and b) and for all animals in Maltoni (1977). In the case of the
Biodynamics studies, interim sacrifices were carried out on thirty percent of the animals.
Premature mortality was also observed. It should be noted that the cancer potency factors
obtained from Biodynamics (1980a,b) were two times smaller than the factor obtained by Quast
et al. (1980a).  The Maltoni et al. (1977) study was planned as a one-year study.  In all these
studies, the shortened study duration (for some animals in the Biodynamics studies and all
animals in the Maltoni study) does not provide optimal information for determining the total
lifetime tumor risk by acrylonitrile. The Signer et al. (1986) study does not provide clear dose-
response data.

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    Table 4.2.1:  Human Equivalent Doses and Combined Tumor Incidence of a Lifetime
                                 Drinking Water Study*.
Administered Dose
(mg/kg-day)
0.00
3.42
8.53
21.18
Human Equivalent
Dose using Body
Weight374 Scaling
(mg/kg-day)
0.00
0.90
2.27
5.63
Human Equivalent
Dose using Body
Weight273 Scaling
(mg/kg-day)
0.00
0.58
1.46
3.62
Tumor
Incidence
4/80
18/47
36/48
45/48
 equivalent doses are computed (For detail, See the Draft FR and the Technical Support Document in USEPA
 1998a,b).
       4.2.3  Other Information Relevant to the Cancer Evaluation

              4.2.3.1   Mutagenicity

       Mutagenic studies of acrylonitrile are generally positive. Acrylonitrile causes mutations
in both Salmonella typhimurium (Venitt et al., 1977) and Escherichia coli (De Meester et al.,
1978). It has been shown to bind to DNA (Guengerich et al., 1981). It did induce an increase in
sister-chromatid exchange in CHO cells (Ved Brat and Williams, 1982). Acrylonitrile has been
shown to transform Syrian hamster embryo cells and to enhance transformation of these cells
infected with an oncogenic virus (Parent and Casto, 1979). On the other hand, a study has
reported negative results in Salmonella typhimurium (Ashby et al., 1985). In an in vivo test,
DNA adducts were identified in rat liver but not in rat brain (Hogy and Guengerich, 1986).
Acrylonitrile did not cause chromosomal aberrations in bone marrow cells of rats and mice
(Rabello-Gay and Ahmed, 1980; Leonard et al.,  1981), nor in peripheral blood lymphocytes of
exposed workers (Thiess and Fleig, 1978; IRIS,  1996).
             4.2.3.2    Summary of Cancer Data on Structural Analogue and Metabolite

       Like vinyl chloride, a metabolite of acrylonitrile, 2,3-epoxy-propionitrile, is mutagenic in
Salmonella (Kier, 1982).
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             4.2.3.3   Mode of Action

       The current scientific consensus is that there is virtually complete correspondence
between the ability of an agent to have a direct DNA activity and carcinogenicity. The data on
short-term studies as a whole support a mutagenic mode of action. Based on this assumption and
a lack of information supporting a non-linear approach for this chemical, a default low dose
linearity is assumed. (See further discussion of the use of mode of action data in USEPA, 1996
andUSEPA, 1998a,b).

       4.2.4   Previous Cancer Risk Evaluation

       Acrylonitrile has been classified as a Bl carcinogen (a probable human carcinogen) based
on the observation of a statistically significant increase in incidence of lung cancer in exposed
workers and observation of tumors, generally astrocytomas in the brain, in studies in two strains
of rats exposed by various routes (drinking water, gavage, and inhalation) (IRIS, 1996).
             4.2.4.1    Oral Exposure

       The oral cancer potency, entered into IRIS in 1987, was calculated by taking the
geometric mean of the individual cancer potencies obtained from three drinking water studies:
Biodynamics, 1980a; Biodynamics, 1980b, and Quast et al., 1980a. The overall risk was
determined from the number of animals having tumors that were statistically significant at any
site (i.e., the pooled tumor incidence of brain and spinal cord astrocytomas, Zymbal gland
carcinomas and stomach papillomas/carcinomas). The human equivalent dose was calculated
using the scaling approach of body weight raised to the 2/3 power (shown in Table 4.2.1). The
linearized multistage model was used to calculate the individual cancer potency factors for each
study.  The geometric mean was calculated by taking the cube root of the product of the three
cancer potency factors obtained from the these studies. The resulting factor, reported in IRIS, is
5.4 x 10'1 (mg/kg-day)'1. The approach used in the IRIS file is based on the  1986 Cancer
Guidelines (USEPA, 1986).

             4.2.4.2    Inhalation Exposure

       The unit risk was calculated from an average relative risk model adjusted for smoking
and based on a continuous lifetime equivalent  of occupational exposure using information from
O'Berg (1980) as discussed in section 4.2.1.2 above. The unit risk obtained was 6.8 xlO'5
(ug/m3)-1 (IRIS, 1996).

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       4.2.5   Cancer Risk Evaluation Using the New Proposed Methodology

       The proposed revision of the methodology for deriving ambient water quality criteria is
consistent with the principles of the proposed cancer guidelines to evaluate/describe the
carcinogenicity of chemicals (as described in USEPA, 1996, and USEPA, 1998a,b).

       Based on sufficient evidence from animal studies (multiple tumor types in several strains
of rats by several routes) and limited evidence from human studies (lung tumor in workers),
positive mutagenicity, acrylonitrile is considered as a likely human carcinogen by any route. A
linear approach is used for the low dose extrapolation.

              4.2.5.1   Rationale for Selecting the Cancer Assessment Approach

       In the new scheme of cancer  classification, acrylonitrile is considered a likely human
carcinogen based on sufficient evidence in animal studies and limited evidence in human studies.
See the Proposed Cancer Guidelines (USEPA, 1996) for additional information on the
classification scheme. Based on the  mutagenic mode of action of acrylonitrile, and the lack of
information that would support using a non-linear approach to this chemical, a linear low dose
approach is used.

              4.2.5.2       Calculation of the Cancer Potency Factor Using the New
                            Linear Method1

       The cancer potency factor for oral exposure to acrylonitrile was determined by following
the steps outlined in the FR notice (USEPA, 1998a) and the related Technical Support Document
(USEPA, 1998b). The Quast et al. (1980a) study, which provides data from a lifetime drinking
water study in rats with large group sizes, is used for the calculation of the slope  factor. The
Biodynamics (1980a,b) studies are not included in the calculation because of interim sacrifice
which would underestimate the risk (see section 4.2.2 under Oral Exposure and section 4.2.6
under Discussion of Confidence for more detail).  The following steps are carried out in the
calculations:

       1) The quantal polynomial model (using Global 86 multistage model software) was used
to model the Quast et al. (1980) dose response (tumor) data in the observed range using BW3/4 as
the dose scaling factor (see Table 4.2.1 for detail).  The LED102 (the lower 95th percent
        This section contains a discussion of the derivation of a cancer potency value based on oral exposure to acrylonitrile.
The focus of this criterion document is on waterborne exposure and the development of AWQC. While the contribution to
cancer risk from air sources may be important, it is not the primary subject of this analysis. Consequently, the inhalation cancer
potency value listed in IRIS, and described above, is not re-examined in this analysis.

        Use of the LED,0 as the point of departure is recommended with this methodology, as it is with the Proposed Cancer
Guidelines. Public comments were requested on the use of the LED10, ED,0, or other points. EPA is currently evaluating these
comments, and any changes in the Cancer Guidelines will be reflected in the final AWQC Methodology.

                                            10

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confidence limit on the dose at which 10 percent of the animals responded in significantly
elevated tumor incidence) was calculated to be 0.16 mg/kg-day.

       2) linear extrapolation was carried out from the LED!0 to the origin (the zero dose, zero
response point). The slope of this line, m (i.e., Ay/Ax), was estimated using the following
                                            0.10
                                        m=-
                                     (Equation 4.2.1)
The variable "m" is the low dose cancer potency value and was calculated to be 6.3 x 10'1
(mg/kg-day)'1.

       3) The risk specific dose (RSD) was calculated for the specific targeted lifetime cancer
risk (i.e., 10-4, 10'5 or 10'6),  using the equation:

                        _„     Target Incremental Cancer Risk
                        JK&JJ  —  	
                                              m


                                      (Equation 4.2.2)

where:

       RSD         =     risk specific dose (mg/kg-day),
       Target Risk  =     10'6 (lifetime incremental risk), and
       m           =     cancer potency factor of 6.3 x 10'1 (mg/kg-day)"1
       The calculated RSD is 1.6 x 10'6 mg/kg-day for a 10'6 lifetime cancer risk. When the
RSD (1.6 x 10'6) is substituted into Equation 7.1.1. in Section 7.1, an AWQC of 0.055 ug/L or
4.0 ug/L is calculated for ingestion of drinking water and aquatic organisms, or ingestion of
aquatic organisms alone (including incidental water ingestion from recreational activities),
respectively, for a lifetime risk of 10'6.

       4.2.6   Discussion of Confidence

       A large number of animals were evaluated in the Quast et al. (1980) study that serves as
the basis for the oral exposure cancer evaluation. This increases confidence hi the values

                                           11

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obtained. However, there are no human data regarding oral intake of acrylonitrile. Human
studies with exposure via the oral route could provide greater certainty regarding the
carcinogenicity and carcinogenic potency of acrylonitrile. Balancing this, the human evidence,
based on inhalation studies hi workers, indicates that acrylonitrile is carcinogenic via that route,
causing lung cancers. The animal studies are also persuasive regarding the carcinogenic
potential of acrylonitrile in humans, with multiple tumor types observed in multiple studies.

       A problem with the Biodynamics (1980a,b) studies is related to the use of interim
necropsy results at 6,12, and 18 months. The results from these animals were included with the
final sacrifice values  and they are counted in the overall incidence denominator, even though
they were not followed for the full lifespan.  This leads to an underestimate of incidence and
risk. The Quast et al. (1980a) study, which was not terminated prematurely, obtained a higher
incidence of tumors (e.g., 75% tumor response at 8 mg/kg-day versus 34% at the same dose in
Biodynamics (1980b). In addition, there were problems with premature mortality in both
Biodynamics (1980a,b) studies. As a result of the deficiencies in the Biodynamics studies, it was
determined that the Quast et al. (1980a) study should serve as the single source of dose-response
data for the cancer potency estimate and AWQC calculation.
5.
EXPOSURE ASSUMPTIONS
5.1    RSC Analysis

       When an ambient water quality criterion is set based on non-carcinogenic effects, or
carcinogenic effects evaluated by the margin of exposure (MOE) approach, anticipated
exposures from non-occupational sources (e.g., food, air) are taken into account. The amount of
exposure attributed to each source compared to total exposure is called the relative source
contribution (RSC) for that source. The allowable dose (typically, the RfD) is then allocated via
the RSC approach to ensure that the criterion is protective enough, given the other anticipated
sources of exposure.  Thus, accounting for non-water exposure sources results in a more stringent
ambient water quality criterion than if these sources were not considered. The method of
accounting for non-water exposure sources is described in more detail in the Federal Register
Notice (USEPA, 1998a) and hi the Technical Support Document (USEPA,  1998b). Available
information on exposure sources is discussed below. However, because the criterion is based on
the linear approach used to assess carcinogenicity, the information is not used to determine an
RSC for acrylonitrile.

       5.1.1  Overview of Potential for Exposure

       Acrylonitrile occurrence in environmental media is not well-documented. Several
regional and local drinking water surveys were found and one limited study analyzed ambient air
samples. Limited information is also available on acrylonitrile migration into foods from
packaging materials.  All of these studies are described in section 5.1.2 below.
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       Acrylonitrile is largely used in the manufacture of copolymers for the production of
acrylic and modacrylic fibers. Other major uses include the manufacture of acrylonitrile-
butadiene-styrene (ABS) and styrene acrylonitrile (SAN) (used hi production of plastics), and
nitrile elastomers and latexes. It is also used in the synthesis of antioxidants, pharmaceuticals,
dyes, and surface-active agents. Table 5.1.1 lists location of plants where acrylonitrile is
manufactured and the types of products made.

       According to the U.S. Environmental Protection Agency's (EPA) Toxic Release
Inventory, the total release of acrylonitrile into the environment in 1990 by manufacturers was
8,077,470 pounds.  The two largest pathways of release were underground injection, which
accounted for 61%  (or 4,925,276 pounds) of the total release, and emissions into the air, which
accounted for 39%  (or 3,148,049 pounds) of the total release. Release of acrylonitrile into water
bodies was reported at 3,877 pounds and release onto land was reported at 268 pounds.

       5.1.2   Occurrence in Environmental Media

       The following sections describe studies that measured concentrations of acrylonitrile in
environmental media.

              5.1.2.1    Exposure from Public Drinking Water Systems

       Acrylonitrile samples were taken from drinking water supplies in three different surveys,
two of which analyzed samples from groundwater supplies. In the early 1980's, 1,174
community wells and 617 private wells in Wisconsin were screened for 98 volatile organic
chemicals (VOCs), including acrylonitrile. Wells chosen were either located near known or
potential sources of VOC contamination or in areas of soil and geologic formation that would
permit transport of contaminants to the ground water.  There were no detections of acrylonitrile;
minimum reporting limits ranged from 0.1 to 3.0 |j.g/L (Krill and Sonzogni, 1986). In a more
recent survey, Ellingson and Redding (1988) reportedly sampled 40 randomly selected public
supply wells throughout Arizona for a variety of contaminants. Samples were collected from
July to September 1986 and wells were then re-sampled hi January of 1987. Acrylonitrile was
not detected above the detection limit of 8.1
                                           13

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Table 5.1.1: Acrylonitrile Manufacturing Locations and Products
Company
American Cyanamid

American Cyanamid
Borg-Warner
BP Chemicals
BP Chemicals
Copolymer Chemical &
Rubber
DuPont
DuPont
DuPont
Goodrich
Goodyear
Goodyear
Ketema
Miles, Inc.
Monsanto
Monsanto
Monsanto
Monsanto
Uniroyal
Uniroyal
Vistron
Zeon Chemicals
Zeon Chemicals
Manufacturing Site
New Orleans, LA
Linden, NJ
Avondale, LA
Washington, WV
Lima, OH
Green Lake, TX
Baton Rouge, LA
Lugoff, SC
Waynesboro, VA
Beaumont, TX
Louisville, KY
Houston, TX
Houston, TX
Odenton, MD
Orange, TX
Alvin, TX
Texas City, TX
Decatur, AL
Addyston, OH
Painesville, OH
Painesville, OH
Lima, OH
Louisville, KY
Pasadena, TX
Product
Acrylonitrile
Acrylonitrile
Acrylonitrile
ABS, SAN resins
Acrylonitrile
Acrylonitrile
Nitrile rubber
Acrylic fibers
Acrylic, modacrylic fibers
Acrylonitrile
Nitrile elastomers, ABS,
Nitrile latex
Nitrile rubber
ABS monofilament
Nitrile rubber
Acrylonitrile
Acrylonitrile
Acrylic, modacrylic fibers
ABS,SAN resins
Nitrile elastomers
Nitrile rubber
Acrylonitrile, Acrylamide
Nitrile rubber
Nitrile rubber
Source: SRI 1992; Going et al., 1978
                            14

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       The third study analyzed samples from surface water supplies. In a study of publicly-
owned treatment works (POTWs) in the R.M. Clayton sewage district near Atlanta, Georgia, tap
water samples were taken. Acrylonitrile was not detected in six daily composite samples based
on a reporting limit of 1 ug/L (Levins et al., 1979).

       In two ambient water studies, samples were taken and analyzed for acrylonitrile. The
first collected samples were from the Potomac River at Quantico, Virginia. Acrylonitrile was not
found based on a detection limit of 10 ug/L (Hall et al., 1987).  The second study examined
levels of acrylonitrile in surface water around eleven industrial sites that manufactured
acrylonitrile, acrylamide, acrylic and modacrylic fibers, ABS and SAN resin, and nitrile
elastomers. If possible, the liquid wastes of the manufacturing facilities were sampled.
Otherwise, the water was sampled at any observable uprising in the water body. The detection
limits ranged from 0.1 to 1.3 ug/L .  The results for  30 samples varied from <0.1 to 4,300 ug/L
as seen in Table 5.1.2. The two high values, 3,500  and 4,300 ug/L, were samples of the effluent
from the manufacturing facilities (Going et al., 1978).

       STORET, operated by the EPA, is a computerized data base comprised of water quality
data collected from states, EPA Regional offices, and other government  agencies.  It contains
over 130 million observations for over 700,000 sampling sites throughout the United States. It is
important to note that there are limitations in using STORET data to estimate representative
concentrations of contaminants in public water systems. The data in STORET were collected
from an array of studies conducted for various purposes. Analyses were conducted in different
laboratories employing different methodologies with a range of detection limits. In many cases
the detection limits were not reported.  A search of the data base located no positive detections of
acrylonitrile in ambient water (USEPA, 1992b).
                                           15

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     Table 5.1.2: Acrylonitrile Sampling in Ambient Water (Surface) for 11 Industrial
                                        Sites
Manufacturing Site
American Cyanamid
New Orleans, LA
American Cyanamid
Linden, NJ
Monsanto
Texas City, TX
Monsanto
Decatur, AL
DuPont
Lugoff, SC
DuPont
Waynesboro, VA
Borg-Wamer
Washington, WV
Goodrich
Louisville, KY
Monsanto
Addyston, OH
Uniroyal
Painesville, OH
Vistron
Lima, OH
Product
Acrylonitrile
Acrylamide
Acrylonitrile
Acrylic,
modacrylic fibers
Acrylic fibers
Acrylic,
modacrylic fibers
ABS, SAN resins
Nitrile
elastomers, ABS, SAN
resins
ABS, SAN resins
Nitrile elastomers
Acrylonitrile,
Acrylamide
Acrylonitrile (Surface Water)
No. of Samples
2
1
3
4
4
3
2
2
2
3
4
Range (ug/L)
<0.1
0.8
<0. 1-0.4
<0. 1-3,500
<0. 1-1 9.7
<1.3
1.4-1.9
<1. 4-2.0
<1. 4-8.0
9.3-4,300
<1.3
Source: Going et al., 1978
             5.1.2.2   Dietary and Fish Exposures

       Acrylonitrile can migrate from food packaging into foods.  The Chemistry Review
Branch (CRB) of the Department of Health and Human Services reviewed information submitted
by the Society of the Plastics Industry, Inc. (SPI) who modeled the migration of acrylonitrile into
foods for all currently regulated uses of acrylonitrile copolymers (DHHS, 1996).
                                          16

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       Information submitted included diffusion of acrylonitrile from a refrigerator into air and
subsequently into food, and from plastic dishes, bottles, and other containers into foods. From
these migrations, SPI calculated daily intakes. Based on a CRB review of these intakes, a
revised estimate of 20 fj.g/person/day was determined to be the dietary intake. This estimate is
based on reasonably conservative assumptions about modeling the migration into the food.

       Information on concentrations of acrylonitrile in fish tissues was not found.

              5.1.2.3   Respiratory Exposures

       Going et al. (1978) collected air samples from 11 industrial sites, chosen based on the
high probability that there would be sources of acrylonitrile emissions. As part of this study, a
total of 104 samples (24-hour composites) were collected from the perimeter of each site.
Concentrations reportedly ranged from < 0.1 to 325 |ag/m3. The limit of detection for the
analytical method was estimated to be 0.3  |ag/m3; however, lower limits were achieved during the
study.

       One of 16 studies included in a screening analysis of Urban Area Sources monitored for
ambient air concentrations of acrylonitrile. The study, conducted in Houston and Southeast
Texas, reported acrylonitrile concentrations at a minimum detection level of 2.0 ug/m3 at 12
monitoring sites (USEPA,  1994a).

5.2    Exposure Data Adequacy and Estimate Uncertainties

       As stated in the overview of exposure, environmental sampling for acrylonitrile is not
well-documented.  The few studies that sampled public drinking water supplies indicated that
acrylonitrile was not present at levels above detection limits.  Similarly, in one ambient water
study, acrylonitrile was not detected, although the detection limit was relatively high (10 |ag/L).
However, in surface waters near sites that manufacture acrylonitrile, levels were found and some
had very high concentrations. In general, based on rather limited data, it appears that
acrylonitrile is not a commonly occurring contaminant at significant levels in drinking water
supplies or ambient waters. However, more monitoring studies are needed to decrease the
uncertainty associated with this possible exposure route given the large amount of releases by
underground injection and  into water bodies.  The amount of information on acrylonitrile in
either fish or other dietary foods is more limited than that for the water medium. The only
estimate available is from the Society of the Plastics Industry, Inc., which indicates a
conservative daily intake of 20 U£/person/day. More information is needed to adequately assess
the potential for exposure to acrylonitrile from the diet. Additionally, the amount of data on
concentrations in ambient air is limited.  Two available studies indicate the potential for exposure
from air near industrial sites and from two urban air locations. The latter study could represent
levels that persons living in urban areas may be exposed to. However, more information is
necessary to adequately assess the likelihood and potential range of exposure to acrylonitrile
from ambient air, especially given the large amount of emissions into the air.

                                           17

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       The exposure parameters used for national criteria for acrylonitrile reflect exposures for
 the general adult population. Sufficient information on the toxicological susceptibility of
 specific high risk populations (i.e., pregnant women and children) is not available for
 acrylonitrile. In addition, it is not clear whether a particular population is likely to be more
 highly exposed than another population.  Although infants and children have a higher rate of
 water and food consumption per body weight compared to adults (USEPA, 1994c), the cancer
 estimates are based on lifetime exposures and, therefore, the criterion for acrylonitrile is
 evaluated using exposure factors applicable to adults, because individuals are adults over most of
 the course  of a lifetime.  Also, although certain water bodies may support populations of sport
 fishers and subsistence fishers who eat more fish than the general population, these national
 criteria are derived to protect the majority of the general population.

 5.3    Exposure Intake Parameters

       Exposure parameters (e.g., fish intake, drinking water intake, and body weight) used in
 the Ambient Water Quality Criterion equation should reflect the population to be protected.
 Default exposure parameters are available for the general population of adults as well as several
 specific populations that may be highly exposed or more toxicologically susceptible to  a given
 chemical. A full discussion of these exposure parameters is included in the Federal Register
 notice (USEPA, 1998a) and Technical  Support Document (USEPA, 1998b).

       The exposure parameters and values for the general population of adults are as follows:
       Fish intake (FI)
       Drinking water intake (DI)

       Incidental ingestion (II)

       Body Weight (BW)

       BIOACCUMULATION FACTORS
0.01780 kg/day
2 L/day (used for drinking water
sources)
0.01 L/day (used for non-drinking water
sources)
70kg
       This section describes the procedures and data sources used to calculate the
bioaccumulation factor (B AF) used for deriving an ambient water quality criterion for
acrylonitrile. Details and the scientific basis of U.S. EPA's recommended methodology for
deriving BAFs are described in USEPA (1998a) and USEPA (1998b).  When determining a BAF
for use in deriving ambient water quality criteria (AWQC) for nonpolar organic chemicals, two
general steps are required. The first step consists of calculating baseline BAFs for organisms at
appropriate trophic levels using available data from field and laboratory studies of the
bioaccumulation or bioconcentration of the chemical of interest. Since baseline BAFs are
normalized by important factors shown to affect bioaccumulation (e.g., the lipid content of
aquatic organisms on which they are based, the freely dissolved concentration of the chemical in
water), they are more universally applied to different sites compared to BAFs not adjusted for
                                           18

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these factors.  Once baseline BAFs have been calculated for the appropriate trophic levels, the
second step involves adjusting the baseline BAFs to reflect the expected conditions at the sites
that are applicable to the AWQC (e.g., lipid content of consumed organisms and the freely
dissolved fraction of the chemical in the site water). Application of both of these steps to the
derivation of a B AF for acrylonitrile is described below:

6.1    Baseline BAF

       Different procedures are recommended by EPA for determining the baseline BAF
depending on the type of bioaccumulation data available. As described in USEPA (1998b), the
data preference for deriving a BAF for non-polar organics is (in order of preference):

       1 .     Calculation of a baseline BAF from a reliable field-measured BAF,
       2.     Calculation of a baseline BAF from a reliable field-measured biota-sediment
             accumulation factor (BSAF),
       3 .     Calculation of a baseline BAF from a laboratory-measured bioconcentration
             factor (BCF) and food-chain multiplier (FCM), and
       4.     Calculation of a baseline BAF from a predicted BCF and FCM.

       For acrylonitrile, no acceptable measured BAF, BSAF, or BCF was found.  Given the
low KOW for this chemical, lack of field bioaccumulation data is not unexpected. Therefore,
method 4 above was chosen for determining the baseline BAF. This method is described further
in USEPA (1998b). According to this method, the baseline BAF is determined for each trophic
level as:
Baseline BAFd =
                         (BCF/d)-(FCM) - (Kw)-(FCM)
                                              ow
where:
       Baseline
       BCFd
       FCM
                                 (Equation 6.1.1)
                    predicted baseline BAF (L/kg-lipid) that if measured, would reflect
                    the lipid-normalized concentration in the biota divided by the
                    freely-dissolved concentration in the water for aquatic organisms
                    occupying a designated trophic level,
                    baseline BCF expressed on a freely-dissolved and lipid-normalized
                    basis
                    food-chain multiplier reflecting biomagnification at the designated
                    trophic level (unitless), and
                    octanol-water partition coefficient.
                                          19

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       Fish consumption rates determined from the USDA's Continuing Survey of Food Intakes
by Individuals (CSFII) indicate that on a national, average per capita basis, individuals in the
United States consume significant quantities offish and shellfish at trophic levels two (e.g.,
clams, oysters), three (e.g., crab, shrimp, flounder) and four (e.g., trout, pike, certain catfish
species) (USEPA, 1998c). Therefore, the national AWQC for acrylonitrile requires that baseline
BAFs be derived to reflect bioaccumulation in aquatic organisms at each of these three trophic
levels.

       For acrylonitrile, a baseline BAF of 1 .5 was calculated for organisms at trophic levels
two, three and four using Equation 6.1.1. These calculations are shown below for each trophic
level.

       Trophic Level Two:
              Baseline BAF[d= (KOW>(FCM2)
                           = (10°-"H1.000)
                           = 1.5 L/kg-lipid (expressed as 2 significant digits for convenience)

       Trophic Level Three:
              Baseline BAF[d=
                           = 1.5 L/kg-lipid (expressed as 2 significant digits for convenience)

       Trophic Level Four:
              Baseline BAF[d= (K^HFCNM)
                           = (10°-17H1.000)
                           = 1.5 L/kg-lipid (expressed as 2 significant digits for convenience)

       The calculated baseline BAFs do not differ at each trophic level because the relatively
low KOW of acrylonitrile (1.5 or log^R^ of 0.17) results in predicted FCMs of 1.000 at each
trophic level. A log K^ of 0.17 was selected as a typical value for acrylonitrile based on the
mean of two measured log K,,w values (0.09 from Tanii and Hashimoto, 1984; and 0.25 from
Pratesi et al., 1979). Values of 1.000 were selected as the FCMs at trophic levels two, three, and
four according to FCMs recommended in the Technical Support Document (TSD) for the
AWQC Methodology Revisions for organic chemicals with a log K,,w of 2.0 or less (USEPA,
1998b).

6.2    AWQC BAF

       After the derivation of trophic level-specific baseline BAFs for acrylonitrile (described in
the previous section), the next step is to calculate BAFs that will be used in the derivation of
AWQC.  This step is necessary to adjust the baseline BAFs to conditions that are expected to
affect the bioavailability of acrylonitrile at the sites applicable to the AWQC. Derivation of the
AWQC BAF requires information on: (1) the baseline BAF at appropriate trophic levels, (2) the

                                          20

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percent lipid of the aquatic organisms consumed by humans at the site(s) of interest (trophic level
specific), and (3) the freely dissolved fraction of the chemical in ambient water at the site(s) of
interest. For each trophic level, the equation for deriving a BAF to used in deriving AWQC is:
BAF for AWQC^ n) = [(Baseline BAFC
                                             fd
                                                             1] ' (Q
                                                                   fd
                                      (Equation 6.2.1)
where:
       BAF for AWQC (rLn) =
       Baseline BAFf (TL n)   =
                        BAF at trophic level "n" used to derive AWQC based on
                        site conditions for lipid content of consumed aquatic
                        organisms for trophic level "n" and the freely dissolved
                        fraction in the site water
                        BAF expressed on a freely dissolved and lipid-normalized
                        basis for trophic level "n"
                        Fraction lipid of aquatic species consumed at trophic level
                                  "n"
              ffd
                        Fraction of the total chemical in water that is freely
                        dissolved
Each of the equation components is discussed below.

       6.2.1  Baseline BAFs (Baseline BAFffd)

       The derivation of baseline BAFs at specific trophic levels is described in Section 6.1. For
acrylonitrile, a baseline BAF of 1.5 was derived for aquatic organisms at trophic levels two, three
and four.

       6.2.2  Lipid Content of Consumed Aquatic Species (ft)

       Accumulation of nonpolar organic chemicals in aquatic organisms has repeatedly been
shown to be a function of lipid content (e.g., Mackay, 1982; Connolly and Pedersen, 1988;
Thomann, 1989).  Therefore, baseline BAFs, which are lipid normalized for comparative
purposes, need to be adjusted to reflect the lipid content of aquatic organisms consumed by the
target population.  As discussed in USEPA (1998a, 1998b), EPA recommends that where
possible, lipid content of consumed aquatic species be determined on a consumption-weighted
average basis.

       For the purposes of deriving national ambient water quality criteria, EPA has established
national default, consumption-weighted lipid content values of 2.3% at trophic level two, 1.5% at
trophic level three, and 3.1% at trophic level four. These national default lipid content values are
based on a national survey offish and shellfish consumption rates and information on their lipid

                                           21

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 content (see USEPA (1998a, 1998b) for details of the determination of national default lipid
 content values). As discussed in USEPA (1998a, 1998b), EPA considers the use of national
 default lipid values as being appropriate in situations where local or regional data on lipid
 content and consumption rates are unavailable for the site(s) applicable to the AWQC. However,
 if local or regional data are available for the site(s) of interest, EPA recommends that States and
 Tribes use the local or regional data instead of the national default values because the type and
 quantity of consumed aquatic organisms and their lipid content may vary from one location to
 another.

        6.2.3  Freely-Dissolved Fraction Applicable to AWQC

        Information on the freely-dissolved fraction of the chemical expect at the site(s)
 applicable to the AWQC is important because the freely dissolved form of nonpolar organic
 chemicals is considered to represent the most bioavailable form in water and thus, the form that
 best predicts bioaccumulation (USEPA 1998a, 1998b). Freely dissolved chemical is defined as
 the portion of the chemical dissolved in water, excluding the portion sorbed on to particulate and
 dissolved organic carbon. The freely-dissolved fraction is estimated from the octanol-water
 partition coefficient and the dissolved and particulate organic carbon concentrations as shown
 below.
                        f   = _
                         fd                                  K
                              [1 + (POC  • Kow)  H- (DOC


                                     (Equation 6.2.2)
where:
       ffd     =      freely-dissolved fraction of chemical in water applicable to the AWQC
       POC   =      concentration of particulate organic carbon applicable to the AWQC
                     (kg/L)
       DOC  =      concentration of dissolved organic carbon applicable to the AWQC (kg/L)
       K<,w    =      n-octanol water partition coefficient for the chemical

In this equation, the terms "K^" and "K.,,/10" are used to estimate the partition coefficients to
POC and DOC, respectively, which have units of L/kg, the scientific basis of which is explained
in USEPA (1998b). Based on national default values of 2.9 mg/L for  DOC, 0.48 mg/L for POC,
and 1.5 for the K^ (Log K,,w of 0.17), the freely dissolved concentration of acrylonitrile is
calculated to be 1.000 (expressed as four significant digits for convenience). Calculation of the
default freely dissolved concentration is provided below.
                                           22

-------
                   .p   _
                    fd  ~
                         [1 + (POC • KJ  + (DOC  •
    t	:	L
         [1 + (4.8 x 1
-------
        AWOC BAF for Trophic Level Three
                      [(1.5 L/kg-lipid>(0.015)+1] • (1.000)
               =      1.02 L/kg-tissue (expressed as three significant digits for convenience)

        AWOC BAF for Trophic Level Four
                      [(1.5 L/kg-lipid)-(0.031) +1] • (1.000)
               =      1.05 L/kg-tissue (expressed as three significant digits for convenience)
 7.     AWQC CALCULATION

 7.1    For Ambient Waters Used as Drinking Water Sources

 The cancer-based AWQC was calculated using the RSD and other input parameters listed below:
                       AWQC =  RSD x
                                                   BW
                                               i=2
                                                      x BAF.)
                                                     '        '
 where:
                                   (Equation 7.1.1)
risk.
       RSD  =     Risk specific dose (1.6 x 10'6 mg/kg-day at 10'6 lifetime risk, see Section
                     4.2.5.2)
       BW   =     Human body weight assumed to be 70 kg
       DI    =     Drinking water intake assumed to be 2 L/day
       FIr    =     Fish intake at trophic level i, i=2, 3, and 4; total intake assumed to be
                     0.01780 kg/day3
       BAFj  =     Bioaccumulation factor equal to 1.03 L/kg-tissue for trophic level two,
                     1.02 L/kg-tissue for trophic level three, and 1.05 L/kg-tissue for trophic
                     level four.

       This yields a concentration of 5.5 x 10'5 mg/L (or 0.055  ug/L) for a 10'6 lifetime cancer
        Fish intake rates for each trophic level are: TL2=0.0011 kg/day; TL3=0.0115 kg/day; and TL4=0.0052 kg/day
(presented as four significant figures for convenience). For further information, see Section 2.4.8 of the TSD.

                                            24

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7.2    For Ambient Waters Not Used as Drinking Water Sources

       When the water body is to be used for recreational purposes and not as a source of
drinking water, the drinking water value (DI above) is eliminated from the equation and it is
substituted with an incidental ingestion value (II). The incidental intake is assumed to occur from
swimming and other activities. The fish intake value is assumed to remain the same. The default
value for incidental ingestion is 0.01 L/day.  When the above equation is used to calculate the
AWQC with the substitution of an incidental ingestion of 0.01 L/day an AWQC of 4.0 x 10'3
mg/L (or 4.0 p.g/L, rounded from 3.95 |ig/L) is obtained for a 10'6 lifetime cancer risk.
8.
SITE-SPECIFIC OR REGIONAL ADJUSTMENTS TO CRITERIA
       Several parameters in the AWQC equation can be adjusted on a site-specific or regional
basis to reflect regional or local conditions and/or specific populations of concern.  These include
fish consumption, incidental water consumption as related to regional/local recreational
activities, BAF (including factors used to derive BAFs such as POC/DOC, percent lipid offish
consumed by target population, and species representative of given trophic levels), and the
relative source contribution. States and Tribes are encouraged to make adjustments using the
information and instructions provided in the Technical Support Document (USEPA, 1998b).
9.
REFERENCES
Ahmed, A.E. and M.E. Abreu. 1982. Microsomal metabolism of acrylonitrile in liver and brain.
       Adv. Exp. Med. Biol.  136B: 1229-1238.

Ashby, J., F.J. deSerres, M. Draper, M. Ishidate, M. Margolin, B.H. Matter, and M.D. Shelby.
       1985. Evaluation of Short-Term Tests for Carcinogens. Prog. Mut. Res. 5, Elsevier,
       Amsterdam.

Bakker, J.G., M.J. Jongen, F.C. J.van Nerr, and J.M. Neis.  1991. Occupational contact
       dermatitis due to acrylonitrile.  Contact Dermatitis 24:50-53.

Biodynamics, Inc. 1980a. A twenty-four month oral toxicity/carcinogenicity study of
       acrylonitrile administered to Spartan rats in the drinking water. Final report, Vols. 1 -2.
       East Millstone, NJ: Bio/dynamics, Inc. Div. of Biol. and Safety Eval.  Bio/dynamics, Inc.
       Project No. 77-1745 (BDN-77-27) for Monsanto Company, St. Louis, MO.

Biodynamics, Inc. 1980b. A twenty-four month oral toxicity/ carcinogenicity study of
       acrylonitrile administered in the drinking water to Fischer 344 rats. Final report, Vols. 1-
       4. East Millstone, NJ: Biodynamics, Inc. Div. of Biol. and Safety Eval. Biodynamics,
       Inc. Project No. 77-1744 (BDN-77-27) for Monsanto Company, St. Louis, MO.
                                          25

-------
 Bellies, R., H. Paulin, N. Makris, and R. Weir. 1980. Three-generation study of rats receiving
       acrylonitrile in drinking water. Kensington, MD. Litton Bionetics, Inc., LBI Project No.
       2660 for the Chemical Manufacturing Association, Washington, D.C.

 Bigner, D., S. Bigner, J. Shelburne, and H. Friedman. 1986. Primary brain tumor in Fisher 344
       rats chronically exposed to acrylonitrile in their drinking water. Fd. Chem. Toxic.
       24:129-137.

 Budavari, S., ed. 1989. The Merck Index: An Encyclopedia of Chemicals, Drugs, and
       Biologicals. 11th ed. Rahway, New Jersey. Merck & Co, Inc.

 Chen, J.L., J. Walrath, M.T. O'Berg, C.A. Burke, and S. Pell.  1987.  Cancer incidence and
       mortality among workers exposed to acrylonitrile. Am. J. Ind. Med., 11:157-163.

 Collins, J.J., L.C. Page, J.C. Caporossi, H.M.  Utidjian, and LJ. Lucas. 1989. Mortality patterns
       among employees exposed to acylonitrile. J. Occup. Med. 31: 368-371.

 Connolly, H. and C. Pedersen.  1988.  A thermodynamic-based Evaluation of Organic Chemical
       Accumulation in Aquatic Organisms.  Environ. Sci. Technol. 22: 99-103.

 Dahm, K.J.  1977.  Identification of metabolites of acrylonitrile. Testimony before FDA.   '
       Reviewed in U.S. EPA, 1983.  Health  assessment document for acrylonitrile. EPA
       600/8-82-007F. Washington, DC.  Office of Health and Environmental Assessment.

 Delzell, E. and R.R. Monson. 1982. Mortality among rubber workers. VI. Men with exposure
       to acrylonitrile. J. Occup. Med. 24(10):767-769.

 DHHS. 1996. Department of Health and Human Services.  Acrylonitrile copolymer resins:
       Responses to ANPR. Memorandum to Indirect Additives Branch, Department of Health
       and Human Services. March 29, 1996.

De Meester, C.,  F. Poncelet, M. Ropberfroid, and M. Mecier. 1978.  Mutagencity of
       acrylonitrile. Toxicology, 11:19-27.

Ellingson, S.B. and Redding, M.B. 1988. Pesticides and inorganics in Arizona's drinking water
       wells. Proceedings of the FOCUS Conference of Southwestern Ground Water Issues,
       National Water Well Association. Dublin, OH. 223-247.

Going, J.E., et al. 1978. Environmental monitoring near industrial sites: Acrylonitrile. Midwest
       Research Institute. Prepared for the U.S. EPA, Washington, DC.  December.
                                         26

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 Guengerich, P.P., L.E. Geiger, L.L. Hogy, and P.L. Wright. 1981. In vitro metabolism of
       acrylonitrile to 2-cyanoethylene oxide, reaction with glutathione, and irreversible binding
       to proteins and nucleic acids. Cancer Res., 41: 4925-4933.

 Gut, I., J. Nerudova, J. Kopecky, and V. Holecek.  1975. Acrylonitrile biotransformation
       in rats, mice, and Chinese hamsters as influenced by the route of administration and by
       phenobarbital, SKF 525-A, cyteine, dimercaprol, or thiosulfate. Arch. Toxicol 33(2):
       151-161.

 Hall, L.W., W.S. Hall, S.J. Bushong, and R.L. Herman.  1987. In situ striped bass (Morone
       saxatilis) contaminant and water quality studies in the Potomac River. Aquatic
       Toxicology. 10:73-99.

 Hashimoto, K. and R.  Kanai.  1965. Studies on the toxicology of acrylonitrile: metabolism,
       mode of action, and therapy. Ind. Health (Kawasaki, Japan) 3(1-2): 30-56.

 Hogy, L.L. and  P.P. Guengerich. 1986. In vivo interaction of acrylonitrile and 2-cyanoethylene
       oxide with DNA in rats. Cancer Res. 46:3932-3938.

 IRIS, 1996 Integrated Risk Information System, U.S. EPA.  Available on line through Toxnet, or
       on disk via NTIS, EPA, Washington, D.C. The carcinogenicity assessment was
       verified  on 2/11/87.

 Kier, L.D. Monsanto Company.  1982. Ames/Salmonella mutagencity assay of acrylonitrile.
       St. Louis, MO: Monsanto Company, Report No. MSL-2063, Job/Project No. 800282-
       ML-80-441. Reviewed in U.S. EPA.  1983.  Health assessment document for
       acrylonitrile. EPA 600/8-82-007F.  Washington, DC: Office of Health and
       Environmental Assessment.

 Krill, R.M. and  W.C. Sonzogni.  1986. Chemical monitoring of Wisconsin's groundwater. J.
       Am Water Works. 78(9): 70-75.

Langvardt, P.W., C.L. Putzing, J.D. Young and W.H. Brawn. 1979. Isolation and identification
       of urinary metabolites of vinyl-type compounds: application to metabolites of
       acrylonitrile acrylamide.  Toxicol. Appl. Pharmacol. 48(1): 161.

Leonard, A., F. Gamy, F. Poncelet, and M. Mercier.  1981. Mutagenicity of acrylonitrile in
       mouse. Toxicol. Lett, 7:329-34.

Levins, P., J. Adams, P. Brenner, S. Coons, K. Thrun, and J. Varone. 1979. Sources of toxic
       pollutants found hi influents to sewage treatment plants: IV. R.M. Clayton Drainage
       Basin, Atlanta, Ga. Arthur D. Little, Inc. Prepared for U.S. EPA, Office of Water
       Planning and Standards, Washington, DC under Contract No. 68-01-3857, October.

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Mackay, D.  1982. Correlation of Bioconcentration Factors. Environ. Sci. Technol.  16:274-
       278.

Maltoni, C., A. Cilliberti, and V. DiMaio.  1977.  Carcinogenicity bioassays on rats of
       acrylonitrile administered by inhalation and by ingestion.  Med. Lavoro. 68(6): 401-411.

Monson, R.R. 1978. Mortality and cancer morbidity among chemical workers with potential
       exposure to acrylonitrile.  Report to the B.F. Goodrich Company and to the United
       Rubber Workers.  Prepared for submission to the post-hearing comment period to the
       OSHA Acrylonitrile Hearing.

Murray, F., Schwetz, B., Nitscheke, K., John, J., Morris, P., and Gehring, P., 1978.
       Teratogenicity of acrylonitrile given to rats by gavage or by inhalation.  Food Cosmet.
       Toxicol. 16(6):547 - 552.

NTP (National Toxicology Program). 1998. Chemical Health and Safety Database.

O'Berg, M. 1980. Epidemiologic study of workers exposed to acrylonitrile. J. Occup.  Med.
       22:245-252.

O'Berg, M., J.L. Chen, C.A. Berke, J. Walrath, and S. Pell.  1985. Epidemiologic study of
       workers exposed to Acrylonitrile: Update. J. Occup. Med.  27(11):835-840

Parent, R.A.  and B.C. Casto. 1979. Effect of acrylontrile on primary Syrian golden hamster
       embryo cells in culture: transformation and DNA fragmentation. J. Nat. Cancer Inst.
       6(4): 1025-29

Pratesi, P.L.V., V. Ferri, C. Demicheli, E. Grana, C. Silipo, and A. Vittoria. 1979. Additive-
       Constitutive Properties of Substituent Hydrophobic Parameters in a Set of Muscarinic
       Agents. II Farmaco. 34:580

Quast, J., C. Humiston, B. Schwetz, L. Frausaon, C. Wade, and J. Norris. 1975. A six-month
       oral study incorporating acrylonitrile in the drinking water of purebred beagle dogs.
       Prepared by Toxicology Research Laboratory, Health and Environmental Sciences, Dow
       Chemical USA, Midland, MI, for the chemical Manufacturers Association, Washington,
       D.C.

Quast, J.F., C.E. Wade, C.G. Humiston, R.M. Carreon, E.A. Hermann, C.N. Park, and B.A.
       Schwetz. Dow Chemical Company.  1980a. A two-year toxicity and oncogenicity study
       with acrylonitrile incorporated in the drinking water of rats.  Midland, MI: Dow Chemical
       Company, Toxicology Research Laboratory, Health and Environmental Research.
       Prepared by Dow Chemical Company for Chemical Manufacturers Association,
       Washington, DC.

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-------
Quast, J., D. Schwetz, M. Balmer, T. Gushow, C. Park, and M. McKenna.  1980b.  A two-year
      toxicity and oncogenicity study with acrylonitrile following inhalation exposure of rats.
      Dow Chemical Co., Toxicology Research Laboratory, Midland, Michigan.

Rabello-Gay, M.N. and A.E. Ahmed.  1980.  Acrylonitrile: in vivo cytogenic studies in mice
      and rats. Mutat. Res., 79:249-55.

Rothman, K.J. 1994.  Cancer occurrence among workers exposed to acrylonitrile. Scand. J.
      Work Environ. Health, 20:313:321.

Sandberg, E. C. and P. Slanina. 1980. Distribution of [l-14C]-acrylonitrile in rat and monkey.
      Toxicol. Lett. 6:187-191.

Silver, H., S. Szabo,  M. Cahill, and R.J. Jaeger.  1987. Time-course studies of the distribution
      of [1-14C] acrylonitrile in rats after intravenous administration. J. Appl. Toxicol. 7:303-
      306.

SRI. 1992. Directory  of Chemical Producers: United States of America. Stanford Research
      Institute, Menlo Park, CA.  443, 597, 598, 624-629.

Swaen, G.M.H., L.J.N Bloemen, J. Twisk, T. Scheffers, J.J.M. Slangen, and F. Sturmans.
       1992. Mortality of workers exposed to acrylonitrile. J. Occup. Med., 34(8): 801-9.

Szabo, S., G. Gallagher, E. Silver, E. Maull, H. Homer, P. Komanicky, T. Melby, D. McComb,
      andK. Kovacs 1984. Subacute and chronic action of acrylonitrile on adrenals and
      gastrointestinal tract: biochemical, functional and ultrastructural studies in the rat. J.
      Appl. Toxicol. 4: 131-140.

Szalay, K., D. Szabo, S. Szeberenyi, I. Toth, S. Szabo.  1987. Lack of direct effect of
      acrylonitrile on corticoid production of isolated zona fasciculata and zona glomerulosa
      cells. In vitro Toxicology,  1:163-169.

Tanii, H. and K. Hashimoto. 1984.  Studies on the Mechanism of Acute Toxicity of Nitriles in
      Mice. Arch. Toxicol. 55(l):47-54.

Tandon, R., D. Saxena, S. Chandra, P. Seth, and S.  Srivastava. 1988.  Testicular effects of
      acrylonitrile in mice. Toxicology Letters, 42:55-63.

Thiess, A.M. and A. Fleig.  1978. Analysis of chromosomes of workers exposed to acrylonitrile.
      Arch Toxicol., 41(2): 149-52.
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-------
 Thiess, A.M., R. Frentzel-Beyme, R. Link, and H. Wild. 1980. Mortalitats-studie bei
       chemiefacharbeitern verschiedener produkdtionsbetriebe mit exposition auch gegunuber
       acrylonitrile zentrabl.  Arbeitmed.  30:359-367. Reviewed in U.S. EPA. 1983. Health
       assessment document for acrylonitrile. EPA 600/8-82-007F. Washington, DC: U.S.
       Environmental Protection Agency, Office of Health and Environmental Assessment.

 Thomann, R.V. 1989. Bioaccumulation Model of Organic Chemical Distribution in Aquatic
       Food Chains.  Environ. Sci. Technol. 23:699-707.

 USEPA. 1983. Health Assessment Document for Acrylonitrile.  Prepared by the Office of
       Health and Environmental Asessment, Environmental Criteria and Assessment Office,
       Research Triangle Park, NC. October.

 USEPA. 1986. Guidelines for carcinogen risk assessment. Federal Register 51:33992-34003.

 USEPA. 1992. Water Quality Standards; Establishment of Numeric Criteria for Priority Toxic
       Pollutants; States' Compliance. Final Rule. Federal Register. 57 (246): 848-60923

 USEPA. 1992b. On-line search of EPA's STORET data base completed by Wade Miller
       Associates,  Inc., November 17.

 USEPA. 1994a. A Screening Analysis of Ambient Monitoring Data for the Urban Area Source
       Program.  Office of Air Quality Planning and Standards.  EPA-453/R-94-075.

 USEPA. 1994b. Review Draft of the Health Effects Notebook for Hazardous Air Pollutants.
       Air Risk Information Support Center (Air RISC), Research Triangle Park, North
       Carolina. Contract No. 68-F2-0065. Cited in Draft Toxic Air Contamination
       Identification List Compound Summaries, January, 1996, California Environmental
       Protection Agency, Air Resources Board.

 USEPA.  1994c. Draft Drinking Water Quantification of Toxicologic Effects for Acrylonitrile.
       January, Office of Science and Technology, Office of Water. Washington, D.C.

 USEPA.  1995. Great Lakes Water Quality Initiative Technical Support Document for the
       Procedure to Determine Bioaccumulation Factors.  EPA-820-B-95-005. U.S. EPA,
       Office of Water, Washington, DC.

USEPA. 1996. Proposed Guidelines for Carcinogen Risk Assessment (61 FR17960, April 23
       1996).

USEPA.  1998a. Federal Register Notice: Draft Revisions to the Methodology for Deriving
       Ambient Water Quality Criteria for the Protection of Human Health.
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-------
USEPA. 1998b. Ambient Water Quality Criteria Derivation Methodology; Human Health.
       Technical Support Document. EPA/822/B-98/005. July.

USEPA. 1998c. Daily Average Per Capita Fish Consumption Estimates Based on the Combined
       USDA 1989,1990,1991 Continuing Survey of Food Intakes by Individuals (CSFII).
       Volume I: Uncooked Fish Consumption National Estimates; Volume II: As Consumed
       Fish Consumption National Estimates.  Prepared by SAIC under Contract #68-C4-0046.
       March.

Ved Brat, S. and G.M. Williams.  1982. Hepatocyte-mediated production of sister chromatid
       exchange in co-cultured cells by acrylonitrile: evidence for extra cellular transport of a
       stable active intermediate.  Cancer Letters, 17:213-16.

Venitt, S., C.T. Bushell, and M. Osborne.  1977.  Mutagenicity of acrylonitrile (cyanoethylene)
       in Escherichia coli.  Mutat. Res., 45(2)283-88.

Werner, J.B. and J.T. Carter. 1981. Mortality of United Kingdom acrylonitrile polymerization
       workers. Brit.  J. Indus. Med. 38:247-253.

Willhite, C., Ferm, V., and Smith, R.  1981. Teratogenic effects of aliphatic nitriles. Teratology,
       23:317-323.

Young, J.D., R.W. Slauter, and R.J. Karbowski. 1977.  The pharmacokinetic and metabolic
       profile of C14 labeled - Acrylonitrile given to rats by three routes. Prepared by the
       Toxicology Research Laboratory, Health and Environmental Research, Dow Chemical,
       USA., Midland, MI for the Chemical Manufacturers Association, Washington D.C.

Zhou, B. and T. Wang. 1991. Historical cohort study of causes of death in a chemical fiber
       factory {in Chinese}. Chinese Med. Univ., 20:35-7 [cited in Rothman  1994].
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