United States
Environmental Protection
1=1 m m Agency
Provisional Peer-Reviewed Toxicity Values for
/V-Ni tr o s opyrr o 1 i di n e
(CASRN 930-55-2)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

Benchmark Dose
Integrated Risk Information System
inhalation unit risk
lowest-observed-adverse-effect level
LOAEL adjusted to continuous exposure duration
LOAEL adjusted for dosimetric differences across species to a human
no-ob served-adverse-effect level
NOAEL adjusted to continuous exposure duration
NOAEL adjusted for dosimetric differences across species to a human
no-ob served-effect level
oral slope factor
provisional inhalation unit risk
provisional oral slope factor
provisional inhalation reference concentration
provisional oral reference dose
inhalation reference concentration
oral reference dose
uncertainty factor
animal to human uncertainty factor
composite uncertainty factor
incomplete to complete database uncertainty factor
interhuman uncertainty factor
LOAEL to NOAEL uncertainty factor
subchronic to chronic uncertainty factor

On December 5, 2003, the U.S. Environmental Protection Agency's (U.S. EPA) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1)	U.S. EPA's Integrated Risk Information System (IRIS).
2)	Provisional Peer-Reviewed Toxicity Values (PPRTVs) used in U.S. EPA's Superfund
3)	Other (peer-reviewed) toxicity values, including
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in U.S. EPA's IRIS. PPRTVs are developed according to a
Standard Operating Procedure (SOP) and are derived after a review of the relevant scientific
literature using the same methods, sources of data, and Agency guidance for value derivation
generally used by the U.S. EPA IRIS Program. All provisional toxicity values receive internal
review by two U.S. EPA scientists and external peer review by three independently selected
scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multiprogram consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all U.S. EPA programs, while PPRTVs are developed
specifically for the Superfund Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a 5-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV documents conclude that
a PPRTV cannot be derived based on inadequate data.
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and Resource Conservation and Recovery Act (RCRA) program offices are advised to
carefully review the information provided in this document to ensure that the PPRTVs used are
appropriate for the types of exposures and circumstances at the Superfund site or RCRA facility
in question. PPRTVs are periodically updated; therefore, users should ensure that the values
contained in the PPRTV are current at the time of use.

It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV document and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the U.S. EPA
Office of Research and Development's National Center for Environmental Assessment,
Superfund Health Risk Technical Support Center for OSRTI. Other U.S. EPA programs or
external parties who may choose of their own initiative to use these PPRTVs are advised that
Superfund resources will not generally be used to respond to challenges of PPRTVs used in a
context outside of the Superfund Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the U.S. EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
No RfD or RfC assessment for A-nitrosopyrrolidine (chemical structure shown in
Figure 1) is available on IRIS (U.S. EPA, 2009), the Drinking Water Standards and Health
Advisories list (U.S. EPA, 2006), or in the HEAST (U.S. EPA, 1997). The Chemical
Assessments and Related Activities (CARA) database (U.S. EPA, 1994, 1991a) lists an Ambient
Water Quality Criteria Document (AWQCD) for nitrosamines (U.S. EPA, 1980) that includes
A'-nitrosopyrrolidine, but they did not attempt noncancer assessments. A Health Environmental
Effects Profile (HEEP) for nitrosamines (U.S. EPA, 1986a) has also been located, but it does not
include data for iV-nitrosopyrrolidine. ATSDR (2009) has not published a toxicological profile
for iV-nitrosopyrrolidine. Neither CalEPA (2009a, b) nor the World Health Organization
(WHO, 2009) have attempted to derive noncancer toxicity values for A-nitrosopyrrolidine.
Occupational exposure limits for Af-nitrosopyrrolidine have not been recommended or
established by the American Conference of Governmental Industrial Hygienists (ACGIH, 2008),
the National Institute for Occupational Safety and Health (NIOSH, 2009), or the Occupational
Safety and Health Administration (OSHA, 2009).
Figure 1. Chemical Structure of N-Nitrosopyrrolidine

A cancer assessment for iV-nitrosopyrrolidine is available on IRIS (U.S. EPA, 1991b).
The chemical is classified under the U.S. EPA (1986b) Guidelines for Carcinogen Assessment as
"Group B2 — Probable Human Carcinogen" based on oral studies in two rodent species in which
tumors occurred at more than one site (Preussmann et al., 1977; Greenblatt and Lijinsky,
1972a, b). IRIS (U.S. EPA, 1991b) reports an Oral Slope Factor (OSF) of 2.1 per mg/kg-day
based on hepatocellular carcinomas or adenomas in Sprague-Dawley rats administered
A'-nitrosopyrrolidine in drinking water for life (Preussmann et al., 1977). IRIS also reports an
Inhalation Unit Risk (IUR) of 6.1 x 10"4 per |ig/m3 based on the same oral data
(Preussmann et al., 1977). The AWQCD (U.S. EPA, 1980) and HEEP (U.S. EPA, 1986a) for
nitrosamines are cited as source documents for the IRIS assessment.
The National Toxicology Program (NTP, 2009) has not tested the toxicity or
carcinogenicity of A'-nitrosopyrrolidine. However, the 11th Report on Carcinogens (NTP, 2005)
concludes that iV-nitrosopyrrolidine is "reasonably anticipated to be a human carcinogen" based
on sufficient evidence in experimental animals. The International Agency for Research on
Cancer (IARC, 1978) classified A-nitrosopyrrolidine as "Group B2 — Probable Human
Carcinogen" based on sufficient evidence of carcinogenicity in experimental animals and
inadequate evidence of carcinogenicity in humans. CalEPA (2009c) has adopted an IUR of
6.0 x 10"4 (iig/m3)"1 and OSF of 2.1 x 10° (mg/kg-day)"1 based on the IRIS values.
Due to the presence of a quantitative cancer assessment for A'-nitrosopyrrolidine on IRIS
(U.S. EPA, 2009), no provisional cancer assessment is necessary or performed in this document.
Literature searches were conducted from the 1960s through January 2009 for studies
relevant to provisional noncancer toxicity values for iV-nitrosopyrrolidine. The databases
GENETOX, CHEMABS, BIOSIS, and Current Contents (last 6 months).
Human Studies
No pertinent data have been located regarding health effects of iV-nitrosopyrrolidine in
humans following oral or inhalation exposure
Animal Studies
Oral Exposure
Numerous animal studies have been conducted in which iV-nitrosopyrrolidine was
administered in drinking water. However, all of these studies (Anderson et al., 1993 [lung
tumors in mice]; Gray et al., 1991 [liver tumors in rats]; Berger and Schmaehl, 1988 [liver tumors
in rats]; Berger et al., 1987 [dose-dependent incidence of liver tumors in rats];
Chung et al., 1986 [hepatocellular carcinomas, liver neoplastic nodules, altered liver cell foci in
rats]; Hoos et al., 1985 [liver tumors in rats]; Peto and Gray, 1984 [dose-dependent incidence of
liver tumors in rats]; Ketkar et al., 1982 [liver tumors in hamsters]; Crampton, 1980 [unspecified
tumor incidence]; Habs et al., 1980 [liver and other tumors in rats]; Preussmann et al., 1976
[liver tumors in rats], 1977 [liver and other tumors in rats]; Takatori et al., 1977 [carcinogenicity
by iV-nitrosopyrrolidine derivatives]; Lijinsky and Taylor, 1976 [hepatocellular and olfactory

carcinoma in rats]; Greenblatt and Lijinsky, 1972a [hepatocellular carcinoma in rats; genital
tumors in some male rats]; and Druckrey et al., 1969 [review for organtropic and transplacental
carcinogenesis by /V-nitroso compounds]) were either designed as cancer bioassays with limited
or no evaluation and reporting of noncancer endpoints, or they did not note or observe
independent noncancer effects (not as part of tumor progression). Only a subset of these studies
(Gray et al., 1991; Berger and Schmaehl, 1988; Berger et al., 1987; and Chung et al., 1986) did
report potential noncancer endpoints, such as the incidence of altered liver foci. However, these
foci formations did not occur at any dose in the absence of hepatocellular cancer. Since altered
liver hepatocytes are widely considered to be progenitors to hepatocellular neoplasias, and there
was no further information to verify them as independent noncancer events, these studies have
not been considered further for assessment of noncancer endpoints.
A noteworthy study was conducted by Zerban and Bannasch (1983). Sprague-Dawley
rats (137 males/dose) were administered 0.5 mg/kg-day /V-nitrosopyrrolidine (purity not
specified) via drinking water for 460 days and followed for 100 days after treatment. An
additional 133 male Sprague-Dawley rats served as controls. Three control animals and three
treated animals were killed at 8-week intervals for up to 560 days. Liver tissues were fixed,
stained for cytochemical analysis, and examined microscopically for spongiosis hepatis (a
degenerative lesion of hepatic perisinusoidal cells generally considered to be related to tumor
formation). No other toxicological evaluations were performed. No information on mortality
was reported. Spongiosis hepatis was not observed in any control or treated animals sacrificed
during the treatment period, but was found in 1/73 (1%) control animals and 4/79 (5%) treated
animals examined during the observation period following treatment, a difference that was not
statistically significant (p = 0.209; Fisher's exact test performed for this review). Some
spongiotic lesions were associated with morphologically normal tissue, while others were
associated with hepatic foci (clear, acidophilic, basophilic, or mixed), neoplastic hepatic nodules,
or hepatocellular carcinomas (incidences were not reported, although it was reported that the
"majority" of spongiotic lesions occurred outside of neoplastic nodules and carcinomas for
A'-nitrosopyrrolidine). This study evaluated insufficient endpoints to establish effect levels for
noncancer effects of A'-nitrosopyrrolidine.
Male albino rats (six of unspecified strain and age) were administered a
hypercholesterolemic diet containing A-nitrosopyrrolidine at 100 ppm and sacrificed after
4 weeks (Mittal et al., 2007). Another treatment group of six rats received the same diet plus
5% chickpea seed coat fiber (intended to reduce absorption of A-nitrosopyrrolidine). Six rats
that received the hypercholesterolemic diet alone served as controls. Due to effects of
A'-nitrosopyrrolidine treatment on feed intake and body weight, and incomplete reporting of
these data in the study, the ingested dose of A'-ni trosopyrrolidine in the treated group could not
be reliably estimated. Blood samples collected at 4 weeks were analyzed for hematology
(hemoglobin [Hgb] and osmotic fragility of erythrocytes) and serum chemistry (creatinine, urea,
aspartate aminotransferase [AST], and alanine aminotransferase [ALT]). Organ weights of the
heart, liver, lungs, spleen, and kidneys were noted, and these tissues were subject to
histopathological examination. Oxidation status in these tissues and in erythrocytes was assessed
by measuring lipid peroxidation (LPO) and the activity levels of the antioxidant enzymes
catalase (CAT), peroxidase (Px), and superoxide dismutase (SOD).

It was not reported whether any mortality was observed in this study (Mittal et al., 2007).
Food intake of rats administered A-nitrosopyrrolidine was considerably reduced to less than half
that of control animals (see Table 1). While control animals experienced no change in body
weight over the course of the study, the treated animals lost an average of 10 g. The researchers
characterized the change in food intake as "substantial" and the change in body weight as
"marginal." However, the actual body weights were not reported. Serum creatinine, urea, ALT,
and AST were all significantly increased (p < 0.01) in treated animals (see Table 1). Hgb levels
were unchanged, but the osmotic fragility of erythrocytes (hemolysis) was increased. Relative
liver weight was significantly decreased (p < 0.05) in the treated group, while relative weights of
the other organs were all increased (statistically significant for heart (p < 0.01) and spleen
p < 0.05); however, the absolute organ weights were not reported. The authors reported
histopathological lesions in the heart (lipid droplets and degenerative changes in myocardial
fibers), coronary vessel (accumulation of fat droplets in walls, periarterial edema, degenerative
changes in muscle fibers), lungs (chronic interstitial pneumonia together with infiltration of
leukocytes), spleen (congestion, hemorrhage, severe depletion of lymphoid cells), liver
(accumulation of lipid droplets in hepatocytes, severe granular degeneration with infiltration of
fibroblasts), and kidneys (severe granular degeneration). However, no incidence data were
provided. LPO was significantly increased (p < 0.05) compared with the control in erythrocytes
and in the heart, lung, liver, spleen, and kidney. SOD activity was significantly decreased
(p < 0.05) in erythrocytes and increased in the heart. Px activity was significantly increased
(p < 0.05) in erythrocytes, heart, lung, and liver, but decreased in spleen. CAT activity was
significantly decreased (p < 0.05) in erythrocytes, lung, and liver, but increased in spleen.
Differences from control were reduced (to varying degrees for the different endpoints) in rats fed
the diet supplemented with 5% chickpea seed coat fiber.
Table 1. Selected Changes in Albino Rats Treated
with jV-Nitrosopyirolidinein the Diet for 4 Weeks3
100 ppm
Number of animals examined
Food intake/day (g)
11.5 ± 0.99b
5.5 ± 0.40°
Change in body weight (g)
- (10.0 ± 1.69)
Serum chemistry
8.96 ±0.64
14.50 ±0.35c
5.77 ±0.62
13.67 ±0.58c
Urea (mg/dL)
45.41 ±2.50
58.45 ±4.91c
Creatinine (mg/dL)
0.410 ±0.05
0.888 ±0.10c
aMittal et al. (2007).
bValues are presented as means ± standard deviation
Statistically significantly different from control atp< 0.01

Interpretation of this study (Mittal et al., 2007) is confounded by the cholesterol-rich diet,
severely reduced feed intake in the treated animals, and incomplete reporting of results. Given
the experimental conditions, it cannot be concluded with confidence that the observed changes
were due to the administration of A'-nitrosopyrrolidine alone. In addition, effect levels and
dose-response can not be identified. This study is not considered further for the assessment of
noncancer endpoints.
Inhalation Exposure
No pertinent data were located regarding effects of A'-nitrosopyrrolidine in animals
following inhalation exposure.
Other Studies
Other Routes
Female Wistar-derived rats (number not unspecified) were administered
A'-nitrosopyrrolidine (99% purity) subcutaneously at 0-30 mg/kg-day for up to 12 weeks and
sacrificed at 4-week intervals (Hendy and Grasso, 1977). Body weights were recorded weekly.
The livers of sacrificed animals were weighed, fixed, and examined microscopically. Staining
was employed to ascertain the activity of glucose-6-phosphatase and lysosomal acid phosphatase
in liver sections. Liver tissues were subject to histopathological examination. No other
toxicological evaluations were performed.
Mortality, body weights, and liver weights were not reported. After treatment with
30 mg/kg-day/V-nitrosopyrrolidine for 4 weeks, inflammatory cell infiltrate and necrosis were
detected in the liver tissues of sacrificed animals (Hendy and Grasso, 1977). Enlarged nuclei and
the presence of an iron-containing, PAS-positive pigment were detected in affected hepatocytes.
Centrilobular loss of glucose-6-phosphatase and lysosomal phosphatase activities were reported.
Hypertrophy of the Golgi apparatus and SER were noted, and relative liver weights increased
(actual weights not specified). Histopathological observations from animals sacrificed after
8 weeks of treatment showed enlarged hepatocytes with small lysosomes. By 12 weeks, bile
duct proliferation and individual cell necrosis were apparent. Lysosomes were present, and
glucose-6-phosphatase activity was markedly reduced. Relative liver weights sharply increased
(data not shown). In rats treated with 10 mg/kg-day for up to 12 weeks, the same histochemical,
ultrastructural, and cytochemical liver changes were noted—but to a lesser degree. Rats
administered 3 mg/kg-day for up to 12 weeks had decreased relative liver weights, but did not
otherwise differ from control animals.
Provisional RfD values for /V-nitrosopyrrolidine cannot be derived because of the lack of
suitable oral toxicity data. Chronic oral studies were conducted as cancer bioassays primarily
and do not provide suitable endpoints for noncancer assessment. The 4-week study
(Mittal et al., 2007) in hypercholesterolemic rats is not useful in the derivation of the RfD
because of the short duration (28 days) with only one dose group. No effect levels could be
identified due to the lack of dose-response relationship. In addition, the Mittal et al. (2007) study

is confounded by the cholesterol-rich diet with "mild to severe pathological changes among the
control and experimental groups," severely reduced feed intake in the treated animals, and
incomplete reporting of results.
Provisional RfC values for /V-nitrosopyrrolidine cannot be derived because no inhalation
data are available.
Due to the presence of a quantitative cancer assessment for A'-nitrosopyrrolidine on IRIS
(U.S. EPA, 2009), no provisional cancer assessment is necessary or performed in this document.
ACGIH (American Conference of Governmental Industrial Hygienists). (2008) Threshold limit
values for chemical substances and physical agents and biological exposure indices. Cincinnati,
Anderson, LM; Carter, JP; Driver, CL; et al. (1993) Enhancement of tumorigenesis by
A'-nitrosodi ethyl amine, A'-nitrosopyrrolidine and N6-(methylnitroso)-adenosine by ethanol.
Cancer Lett 68:61-66.
ATSDR (Agency for Toxic Substances and Disease Registry). (2009) Toxicological profile
information sheet. U.S. Department of Health and Human Services, Public Health Service.
Available online at http://www.atsdr.cdc.eov/toxprofiles/index.asp.
Berger, MR; Schmahl D; Zerban, H. (1987) Combination experiments with very low doses of
three genotoxic nitrosamines with similar organotropic carcinogenicity in rats. Carcinogen
Berger, MR; Schmahl D. (1988) Combination effects of low doses of genotoxic carcinogens with
similar organotropism. In: Schmahl, D; ed. Combination effects in chemical carcinogenesis.
New York, NY: VCH Publishers, pp. 93-123.
CalEPA (California Environmental Protection Agency). (2009a) Search chronic RELs. Office
of Environmental Health and Hazard Assessment. Available online at
http://www.oehha.ca.gov/air/chronic rets/index.html.

CalEPA (California Environmental Protection Agency). (2009b) Search toxicity criteria
database. Office of Environmental Health and Hazard Assessment. Available online at
CalEPA (California Environmental Protection Agency). (2009c) Hot spots unit risk and cancer
potency values. Available online at
http://www.oehha.ca.gov/air/hot spots/pdf/TSDlookup2002.pdf.
Chung, FL; Tanaka, T; Hecht, SS. (1986) Induction of liver tumors in F344 rats by
crotonaldehyde. Cancer Res 46:1285-1289.
Crampton, RF. (1980) Carcinogenic dose-related response to nitrosamines. Oncology
Druckrey, H; Preussmann, R; Ivankovic, S. (1969) A'-nitroso compounds in organotropic and
transplacental carcinogenesis. Ann NY Acad Sci 163:676-696.
Gray, R; Peto, R; Brantom, P; et al. (1991) Chronic nitrosamine ingestion in 1040 rodents: the
effect of the choice of nitrosamine, the species studied, and the age of starting exposure. Cancer
Res 51:6470-6491.
Greenblatt, M; Lijinsky, W. (1972a) Nitrosamine studies: Neoplasms of liver and genital
mesothelium in nitrosopyrrolidine-treated MRC rats. J Natl. Cancer Inst. 48(6): 1687-1696.
Greenblatt, M; Lijinsky, W. (1972b) Failure to induce tumors in Swiss mice after concurrent
administration of amino acids and sodium nitrite. J Natl. Cancer Inst. 48(5): 1389-1392.
Habs, M; Habs, H; Schmahl, D. (1980) Effect of the intermittent administration of
A'-nitrosopyrrolidine on the tumor incidence in Sprague-Dawley rats. Int J Cancer 26:47-51.
Hendy, R; Grasso, P. (1977) Hepatotoxic response to single or repeated injections of
n-nitrosopyrrolidine in the rat. Chem Biol Interact 18:309-326.
Hoos, A; Habs, M; Schmahl, D. (1985) Comparison of liver tumor frequencies after intermittent
oral administration of different doses of A'-ni trosopyrrolidine in Sprague-Dawley rats. Cancer
Lett 26:77-82.
IARC (International Agency for Research on Cancer). (1978). Some N-Nitroso Compounds.
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Lyon, France.
17: 226-255.
IARC (International Agency for Research on Cancer). (2009) Search IARC monographs.
Available online at http://monographs.iarc.fr/index.php.
Ketkar, MB; Schneider, P; Preussmann, R; et al. (1982) Carcinogenic effect of low doses of
A'-nitrosopyrrolidine administered in drinking water to Syrian Golden hamsters. J Cancer Res
Clin Oncol 104:75-79.

Lijinsky, W; Taylor, HW. (1976) The effect of substituents on the carcinogenicity of
A'-nitrosopyrrolidine in Sprague-Dawley rats. Cancer Res 36:1988-1990.
Mittal, G; Vadhera, S; Brar, A; et al. (2007) Protective role of dietary fibre on
A'-nitrosopyrrolidine-induced toxicity in hypercholesterolemic rats. Hum Exp Toxicol 26:91-98.
NIOSH (National Institute for Occupational Safety and Health). (2009) NIOSH pocket guide to
chemical hazards. Index by CASRN.
NTP (National Toxicology Program). (2005) 11th Report on carcinogens. U.S. Department of
Health and Human Services, Public Health Service, National Institutes of Health, Research
Triangle Park, NC. Available online at http://ntp-server.niehs.nih.gov.
NTP (National Toxicology Program). (2009) Management status report. Available online at
OSHA (Occupational Safety and Health Administration). (2009) OSHA Standard 1910.1000
Table Z-l. Part Z, toxic and hazardous substances. Available online at
https://www.osha.gov/pls/oshaweb/owadisp.show doeument?p table standards&p id=9992.
Peto, R; Gray, R. (1984) Nitrosamine carcinogenesis in 5120 rodents: chronic administration of
16 different concentrations of NDEA, NDMA, NPYR and NPIP in the water of 4440 inbred rats,
with parallel studies on NDEA alone of the effect of age of starting (3, 6, or 20 weeks) and of
species (rats, mice, or hamsters). IARC Sci Publ 57:627-665.
Preussmann, R; Eisenbrand, G; Schmahl, D. (1976) Carcinogenicity testing of low doses of
nitrosopyrrolidine and of nitrosobenzthiazuron and nitrosocarbaryl in rats. IARC Sci Publ.
Preussmann, R; Schmahl, D; Eisenbrand, G. (1977) Carcinogenicity of /V-nitrosopyrrolidine:
Dose-response study in rats. Z. Krebsforsch. 90:161-166.
Takatori, K; Mori, H; Kato, T; et al. (1977) Research on the carcinogenic activities of
A'-nitrosopyrrolidine, A'-nitroso-2-pyrrolidone, and A'-nitroso-5-methyl-2-pyrrolidone. Yakugaku
Zasshi 97:320-323.
U.S. EPA (Environmental Protection Agency). (1980) Ambient water quality criteria for:
nitrosamines. Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Water Regulations and
Standards, Washington, DC.
U.S. EPA (Environmental Protection Agency). (1986a) Health and environmental effects profile
for nitrosamines. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and
Emergency Response, Washington, DC.
U.S. EPA (Environmental Protection Agency). (1986b) Guidelines for carcinogen risk
assessment. Washington, DC.

U.S. EPA (Environmental Protection Agency). (1991a) Chemical Assessments and Related
Activities (CARA). Office of Health and Environmental Assessment, Washington, DC.
U.S. EPA (Environmental Protection Agency). (1991b) Integrated Risk Information System
(IRIS). IRIS Summary of/V-Nitrosopyrrolidine (CASRN 930-55-2). Office of Research and
Development, National center for Environmental Assessment, Washington, DC. Available online
at http://www.epa.gov/iris/.
U.S. EPA (Environmental Protection Agency). (1994) Chemical Assessments and Related
Activities (CARA). Office of Health and Environmental Assessment, Washington, DC.
U.S. EPA (Environmental Protection Agency). (1997) Health Effects and Assessment Summary
Tables. FY-1997 update. Prepared by the Office of Research and Development, National Center
for Environmental Assessment, Cincinnati, OH for the Office of Emergency and Remedial
Response, Washington, DC; EPA/540/R-97/036. NTIS PB97-921199.
U.S. EPA (Environmental Protection Agency). (2006) 2006 Edition of the drinking water
standards and health advisories. Office of Water, Washington, DC; EPA 822-R-06-013.
Available online at http://www.epa.gov/waterscience/drinkine/standards/dwstandards.pdf.
U.S. EPA (Environmental Protection Agency). (2009) Integrated Risk Information System
(IRIS). Office of Research and Development, National center for Environmental Assessment,
Washington, DC. Available online at http://www.epa.gov/iris/.
WHO (World Health Organization). (2009) Online catalogs for the Environmental Health
Criteria series. Available online at
http://www.who.int/ipcs/publications/ehc/ehc alphabetical/en/index.html.
Zerban, H; Bannasch, P. (1983) Spongiosis hepatis in rats treated with low doses of hepatotropic
nitrosamines. Cancer Lett 19:247-252.