NTP TECHNICAL REPORT
 

ON THE
 

TOXICOLOGY AND CARCINOGENESIS
 

STUDIES OF
 

POLYVINYL ALCOHOL
 

(Molecular Weight .24,000)
#

(CAS NO. 9002-89-5)
#

IN FEMALE B6C3F1 MICE

(INTRAVAGINAL STUDIES) 

NATIONAL TOXICOLOGY PROGRAM
 

P.O. Box 12233
#

Research Triangle Park, NC 27709
#

May 1998 

NTP TR 474 

NIH Publication No. 98-3964 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

National Institutes of Health
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

FOREWORD

The National Toxicology Program (NTP) is made up of four charter agencies of the U.S. Department of

Health and Human Services (DHHS): the National Cancer Institute (NCI), National Institutes of Health; the

National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health; the National

Center for Toxicological Research (NCTR), Food and Drug Administration; and the National Institute for

Occupational Safety and Health (NIOSH), Centers for Disease Control. In July 1981, the Carcinogenesis

Bioassay Testing Program, NCI, was transferred to the NIEHS. The NTP coordinates the relevant

programs, staff, and resources from these Public Health Service agencies relating to basic and applied

research and to biological assay development and validation. 

The NTP develops, evaluates, and disseminates scientific information about potentially toxic and hazardous

chemicals. This knowledge is used for protecting the health of the American people and for the primary

prevention of disease. 

The studies described in this Technical Report were performed under the direction of the NIEHS and were

conducted in compliance with NTP laboratory health and safety requirements and must meet or exceed all

applicable federal, state, and local health and safety regulations. Animal care and use were in accordance

with the Public Health Service Policy on Humane Care and Use of Animals. The prechronic and chronic

studies were conducted in compliance with Food and Drug Administration (FDA) Good Laboratory Practice

Regulations, and all aspects of the chronic studies were subjected to retrospective quality assurance audits

before being presented for public review. 

These studies are designed and conducted to characterize and evaluate the toxicologic potential, including

carcinogenic activity, of selected chemicals in laboratory animals (usually two species, rats and mice). 

Chemicals selected for NTP toxicology and carcinogenesis studies are chosen primarily on the bases of

human exposure, level of production, and chemical structure. The interpretive conclusions presented in this

Technical Report are based only on the results of these NTP studies. Extrapolation of these results to other

species and quantitative risk analyses for humans require wider analyses beyond the purview of these

studies. Selection per se is not an indicator of a chemical’s carcinogenic potential. 

Listings of all published NTP reports and ongoing studies are available from NTP Central Data

Management, NIEHS, P.O. Box 12233, MD E1-02, Research Triangle Park, NC 27709 (919-541-3419). 

The Abstracts and other study information for 2-year studies are also available at the NTP’s World Wide

Web site: http://ntp-server.niehs.nih.gov. 
 

 

 

 

 

 

 

 

NTP TECHNICAL REPORT
 

ON THE
 

TOXICOLOGY AND CARCINOGENESIS
 

STUDIES OF
 

POLYVINYL ALCOHOL
 

(Molecular Weight .24,000)
#

(CAS NO. 9002-89-5)
#

IN FEMALE B6C3F1 MICE

(INTRAVAGINAL STUDIES) 

NATIONAL TOXICOLOGY PROGRAM
 

P.O. Box 12233
#

Research Triangle Park, NC 27709
#

May 1998 

NTP TR 474
#

NIH Publication No. 98-3964
#

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

National Institutes of Health
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

2 Polyvinyl Alcohol, NTP TR 474 

CONTRIBUTORS
 

National Toxicology Program

Evaluated and interpreted results and reported findings

A. Radovsky, D.V.M., Ph.D., Study Scientist

D.A. Bridge, B.S. 

J.R. Bucher, Ph.D. 

R.E. Chapin, Ph.D. 

J.R. Hailey, D.V.M. 

J.K. Haseman, Ph.D. 

R.R. Maronpot, D.V.M. 

G.N. Rao, D.V.M., Ph.D. 

J.H. Roycroft, Ph.D. 

C.S. Smith, Ph.D. 

G.S. Travlos, D.V.M. 

D.B. Walters, Ph.D. 

K.L. Witt, M.S., Oak Ridge Associated Universities

Arthur D. Little, Inc. Conducted studies, evaluated pathology findings

J.K. Marquis, Ph.D., Principal Investigator (30-day study) 

C.L. Berman, Ph.D., Principal Investigator (2-year study) 

M.E.P. Goad, D.V.M., Ph.D. 

Experimental Pathology Laboratories, Inc. Provided pathology quality assurance

J.F. Hardisty, D.V.M., Principal Investigator

C.C. Shackelford, D.V.M., M.S., Ph.D. 

Dynamac Corporation

Prepared quality assurance audits

S. Brecher, Ph.D., Principal Investigator

NTP Pathology Working Group

Evaluated slides, prepared pathology report on mice (2 May 1996) 

L.L. Lanning, D.V.M., Chairperson

Pathology Associates International

M. Butt, D.V.M. Pathology Associates International

B.J. Davis, D.V.M., Ph.D. North Carolina State University

D. Dixon, D.V.M., Ph.D. National Toxicology Program

J.K. Hailey, D.V.M. National Toxicology Program

R.A. Herbert, D.V.M., Ph.D. National Toxicology Program

A. Nyska, D.V.M. National Toxicology Program

A. Radovsky, D.V.M., Ph.D. National Toxicology Program

C.C. Shackelford, D.V.M., M.S., Ph.D. Experimental Pathology Laboratories, Inc. 

Analytical Sciences, Inc. Provided statistical analyses

R.W. Morris, M.S., Principal Investigator

S.R. Lloyd, M.S. 

N.G. Mintz, B.S. 

Biotechnical Services, Inc. Prepared Technical Report

S.R. Gunnels, M.A., Principal Investigator

J.R. Carlton, B.A. 

L.M. Harper, B.S. 

A.M. Macri-Hanson, M.A., M.F.A. 
 

 

 

 

 

 

 

 

 

 

 

3 

CONTENTS
 

ABSTRACT ............................................................ 5 
 #

EXPLANATION OF LEVELS OF EVIDENCE OF CARCINOGENIC ACTIVITY ............ 8 
 #

TECHNICAL REPORTS REVIEW SUBCOMMITTEE ............................... 9 
 #

SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS ......... 10 
 #

INTRODUCTION ........................................................ 11 
 #

MATERIALS AND METHODS ............................................... 15 
 #

RESULTS .............................................................. 23 
 #

DISCUSSION AND CONCLUSIONS ........................................... 29 
 #

REFERENCES .......................................................... 31 
 #

APPENDIX A Summary of Lesions in Female Mice in the 2-Year Intravaginal Study
 

of Polyvinyl Alcohol ............................................ 35 
 #

APPENDIX B Chemical Characterization and Dose Formulation Studies .................. 95 
 #

APPENDIX C Ingredients, Nutrient Composition, and Contaminant Levels
 

in NIH-07 Rat and Mouse Ration .................................. 103 
 #

APPENDIX D Sentinel Animal Program ........................................ 107 
 #
4 Polyvinyl Alcohol, NTP TR 474 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

5 

ABSTRACT
 

CH2	 CH 

OH n 

POLYVINYL ALCOHOL

CAS No. 9002-89-5 

Chemical Formula: (CHO 2 4 ) n Molecular Weight: approximately 24,000

Synonyms:	# Ethenol homopolymer, PVA

Trade names:	#Akwa Tears, Alcotex, Alvyl, Aracet, Cipoviol, Covol, Elvanol, Ethenol, Gelvatol, Gohsenol, Ivalon, Kuralon, Kurare, Lemol, 

Liquifilm, Mowiol, Polydesis, Polysizer, Polyvinol, Polyviol, Poval, Resistoflex, Rhodoviol, Sno Tears, Solvar, Sumitex, 

Vibatex, Vinacol, Vinalak, Vinarol, Vinarole, Vinavilol, Vinol, Vinylon

Polyvinyl alcohol is produced primarily for use in

textile sizing, adhesives, polymerization aids, and

paper coatings. It is also used in surgical drapes, 

towels, and gauze sponges; protective gloves; cosmetic formulations; topical ophthalmic preparations; 

plastic sponge implants for reconstructive surgery; 

and intravaginal contraceptive foam and film. In

addition, polyvinyl alcohol is used with magnesium

sulfate to dilate the cervix of women prior to induction of labor. It is estimated that hundreds of thousands of women in the United States use an intravaginal product containing polyvinyl alcohol each

year. The Food and Drug Administration nominated

low-viscosity polyvinyl alcohol for a 2-year study

because of concern about the lack of information

about the long-term toxic and carcinogenic effects by

the intravaginal route. Female B6C3F1 mice received

polyvinyl alcohol (approximately 99% pure) in

deionized water by intravaginal administration for

30 days or 2 years. 

30-DAY STUDY IN MICE

Three groups of 50 female B6C3F1 mice were used in

this intravaginal study. The vehicle control group

received only 20 μL of a deionized water vehicle. 

The other two groups each received 20 μL of 25% 

polyvinyl alcohol in deionized water. Animals in one

dose group were returned to their cages after dosing; 

animals in the other dose group were restrained in a

vertical nose-down position in restraint bags for

several minutes after dosing. Animals were dosed

daily for 30 consecutive days. All mice survived to

the end of the study. The final mean body weights

and body weight gains of dosed mice were similar to

those of the vehicle control group. Abnormalities

noted in the vaginal area after dosing included vaginal

plugs, secretions, and swelling. These vaginal

changes were minimal to mild and occurred in vehicle

controls as well as in dosed mice. Restraint of mice

after dosing appeared to eliminate vaginal secretions

but increased both the incidence of vaginal irritation
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

__________

 

 

6 Polyvinyl Alcohol, NTP TR 474 

and the severity of vaginal opening swelling. At

necropsy, mildly enlarged uterine horns were observed in 10 vehicle control mice, three 25% mice, 

and seven 25% (restrained) mice. No chemicalrelated lesions were observed. 

2-YEAR STUDY IN MICE

Three groups of 100 female B6C3F1 mice were used

in this intravaginal study: an untreated control group, 

a vehicle control group receiving 20 μL deionized

water vehicle only, and a dosed group receiving

20 μL 25% polyvinyl alcohol in deionized water. 

Animals were dosed 5 days per week, excluding

holidays, for 104 to 105 weeks. 

Survival, Body Weights, and Clinical Findings

Survival of dosed mice was similar to that of the two

control groups. The final mean body weight of

vehicle control mice was less than that of the untreated control group. The mean body weights of the

dosed mice were less than those of the untreated

controls from week 17 until the end of the study. The

only clinical finding was vaginal irritation, observed

in six mice in the vehicle control group and 11 mice

in the dosed group. 

Pathology Findings

No neoplasms or nonneoplastic lesions related to

chemical treatment were observed. The incidences of

reproductive tract nonneoplastic lesions in the dosed

group did not differ significantly from those in the

vehicle control group; similarly, the incidences of

reproductive tract nonneoplastic lesions in the vehicle

control group did not differ significantly from those in

the untreated control group. 

CONCLUSIONS

Under the conditions of this 2-year study, there was

no evidence of carcinogenic activity* of polyvinyl

alcohol (molecular weight approximately 24,000) in

female B6C3F1 mice administered 20 μL of a 25% 

solution intravaginally. There were no neoplasms or

nonneoplastic lesions considered related to treatment

with polyvinyl alcohol. 

* Explanation of Levels of Evidence of Carcinogenic Activity is on page 8. A summary of the Technical Reports Review Subcommittee

comments and the public discussion on this Technical Report appears on page 10. 
 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 7 

Summary of the 2-Year Carcinogenesis Study of Polyvinyl Alcohol in Female B6C3F1 Mice

Doses Untreated control, vehicle control receiving 20 μL deionized water only, and dosed group receiving

20 μL 25% polyvinyl alcohol in deionized water

Body weights Vehicle control and dosed groups slightly less than untreated control group

2-Year survival rates 47/100, 51/100, 61/100 

Nonneoplastic effects None

Neoplastic effects None

Level of evidence of No evidence

carcinogenic activity
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

8 Polyvinyl Alcohol, NTP TR 474 

EXPLANATION OF LEVELS OF EVIDENCE OF CARCINOGENIC ACTIVITY

The National Toxicology Program describes the results of individual experiments on a chemical agent and notes the strength of the evidence for

conclusions regarding each study. Negative results, in which the study animals do not have a greater incidence of neoplasia than control

animals, do not necessarily mean that a chemical is not a carcinogen, inasmuch as the experiments are conducted under a limited set of

conditions. Positive results demonstrate that a chemical is carcinogenic for laboratory animals under the conditions of the study and indicate that

exposure to the chemical has the potential for hazard to humans. Other organizations, such as the International Agency for Research on Cancer, 

assign a strength of evidence for conclusions based on an examination of all available evidence, including animal studies such as those conducted

by the NTP, epidemiologic studies, and estimates of exposure. Thus, the actual determination of risk to humans from chemicals found to be

carcinogenic in laboratory animals requires a wider analysis that extends beyond the purview of these studies. 

Five categories of evidence of carcinogenic activity are used in the Technical Report series to summarize the strength of the evidence observed

in each experiment: two categories for positive results (clear evidence and some evidence); one category for uncertain findings (equivocal

evidence); one category for no observable effects (no evidence); and one category for experiments that cannot be evaluated because of major

flaws (inadequate study). These categories of interpretative conclusions were first adopted in June 1983 and then revised in March 1986 for

use in the Technical Report series to incorporate more specifically the concept of actual weight of evidence of carcinogenic activity. For each

separate experiment (male rats, female rats, male mice, female mice), one of the following five categories is selected to describe the findings. 

These categories refer to the strength of the experimental evidence and not to potency or mechanism. 

•	 Clear evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing a dose-related

(i) increase of malignant neoplasms, (ii) increase of a combination of malignant and benign neoplasms, or (iii) marked increase of

benign neoplasms if there is an indication from this or other studies of the ability of such tumors to progress to malignancy. 

•	 Some evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing a chemical-related increased

incidence of neoplasms (malignant, benign, or combined) in which the strength of the response is less than that required for clear

evidence. 

•	 Equivocal evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing a marginal increase of

neoplasms that may be chemical related. 

•	 No evidence of carcinogenic activity is demonstrated by studies that are interpreted as showing no chemical-related increases in

malignant or benign neoplasms. 

•	 Inadequate study of carcinogenic activity is demonstrated by studies that, because of major qualitative or quantitative limitations, 

cannot be interpreted as valid for showing either the presence or absence of carcinogenic activity. 

When a conclusion statement for a particular experiment is selected, consideration must be given to key factors that would extend the actual

boundary of an individual category of evidence. Such consideration should allow for incorporation of scientific experience and current

understanding of long-term carcinogenesis studies in laboratory animals, especially for those evaluations that may be on the borderline between

two adjacent levels. These considerations should include: 

• adequacy of the experimental design and conduct;
#

• occurrence of common versus uncommon neoplasia;
#

•	 progression (or lack thereof) from benign to malignant neoplasia as well as from preneoplastic to neoplastic lesions; 

•	 some benign neoplasms have the capacity to regress but others (of the same morphologic type) progress. At present, it is

impossible to identify the difference. Therefore, where progression is known to be a possibility, the most prudent course is to

assume that benign neoplasms of those types have the potential to become malignant; 

•	 combining benign and malignant tumor incidence known or thought to represent stages of progression in the same organ or tissue; 

•	 latency in tumor induction; 

•	 multiplicity in site-specific neoplasia; 

•	 metastases; 

•	 supporting information from proliferative lesions (hyperplasia) in the same site of neoplasia or in other experiments (same lesion in

another sex or species); 

•	 presence or absence of dose relationships; 

•	 statistical significance of the observed tumor increase; 

•	 concurrent control tumor incidence as well as the historical control rate and variability for a specific neoplasm; 

•	 survival-adjusted analyses and false positive or false negative concerns; 

•	 structure-activity correlations; and

• in some cases, genetic toxicology. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

___________

 

Polyvinyl Alcohol, NTP TR 474 9 

NATIONAL TOXICOLOGY PROGRAM BOARD OF SCIENTIFIC COUNSELORS
 

TECHNICAL REPORTS REVIEW SUBCOMMITTEE

The members of the Technical Reports Review Subcommittee who evaluated the draft NTP Technical Report on polyvinyl alcohol on

12 December 1996 are listed below. Subcommittee members serve as independent scientists, not as representatives of any institution, company, 

or governmental agency. In this capacity, subcommittee members have five major responsibilities in reviewing NTP studies: 

• to ascertain that all relevant literature data have been adequately cited and interpreted, 

• to determine if the design and conditions of the NTP studies were appropriate, 

• to ensure that the Technical Report presents the experimental results and conclusions fully and clearly, 

• to judge the significance of the experimental results by scientific criteria, and

• to assess the evaluation of the evidence of carcinogenic activity and other observed toxic responses. 

Gary P. Carlson, Ph.D., Chairperson Irma Russo, M.D., Principal Reviewer

School of Health Sciences Fox Chase Cancer Center

Purdue University Philadelphia, PA

West Lafayette, IN

Louise Ryan, Ph.D. Arnold L. Brown, M.D. Division of Biostatistics

University of Wisconsin Medical School Dana-Farber Cancer Institute

Madison, WI Boston, MA

Thomas L Robert E. Taylor, M.D., Ph.D., Principal Reviewer . Goldsworthy, Ph.D. Department Department of Pharmacology of Experimental Pathology and Toxicology Howard University College of Medicine Chemical Industry Institute of Toxicology Washington, DC Research Triangle Park, NC

Robert LeBoeuf Frederick L. Tyson, Ph.D. , Ph.D. St. Mary’s Hospital and Medical Center Corporate Professional and Regulatory Services

Human Cancer Research Institute Safety Department Grand Junction, CO The Procter & Gamble Company

Cincinnati, OH

Jerrold M. Ward, D.V.M., Ph.D.* 

Janardan K. Reddy, M.D. National Cancer Institute

Department of Pathology
 Frederick, MD

Northwestern University Medical School
 

Chicago, IL
 

* Did not attend
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

10 Polyvinyl Alcohol, NTP TR 474 

SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS
 

On 12 December 1996, the draft Technical Report on Dr. Taylor, the second principal reviewer, agreed

the toxicology and carcinogenesis studies of polyvinyl with the proposed conclusions. He said it would have

alcohol received public review by the National been of merit to have developed innovative ways to

Toxicology Program’s Board of Scientific Counselors’ administer higher doses. Dr. Radovsky said the probTechnical Reports Review Subcommittee. The review lem with handling of the 25% solution of polyvinyl

meeting was held at the National Institute of alcohol was not so much solubility as viscosity. The

Environmental Health Sciences, Research Triangle dose used was the maximum concentration that could

Park, NC. be consistently administered with the available dosing

equipment. 

Dr. A. Radovsky, NIEHS, introduced the toxicology

and carcinogenesis studies of polyvinyl alcohol by dis- Dr. W. Allaben, Food and Drug Administration

cussing the uses of the chemical and rationale for (FDA), said that the FDA was involved in the study

study, describing the experimental design, reporting design and the agency thought the information needed

on survival and body weight effects, and commenting was obtained in spite of the technical difficulties. 

on the lack of compound-related neoplasms or non- Dr. Goldsworthy asked whether Glaxo-Wellcome, in

neoplastic lesions in female mice. The proposed its studies of AZT in rats, observed similar responses

conclusion was no evidence of carcinogenic activity in with systemic versus intravaginal administration. 

female B6C3F mice. No neoplasms or nonneoplastic Dr. Radovsky replied that vaginal neoplasms were 1 

lesions were considered related to treatment with induced when AZT was administered by oral gavage

polyvinyl alcohol. or vaginal administration. Dr. Tyson asked whether

there was any leakage after intravaginal administraDr. Russo, a principal reviewer, agreed with the pro- tion. Dr. Radovsky said there was some, but it was

posed conclusions. She had concerns about the lack not quantifiable. Dr. H. Matthews, NIEHS, reported

of testing in the rat and not having more than one that his group studied disposition of radiolabeled

dose. This was in view of studies reporting develop- polyvinyl alcohol in the rat using measures to avoid

ment of sarcomas at the site of subcutaneous implants ingestion through grooming. He said there was very

of polyvinyl sponges in rats that led the International slight absorption without bioaccumulation after either

Agency for Research on Cancer to recommend further single or multiple doses. 

studies in animals. Dr. Russo wondered if the chemical could be administered in a sponge or tampon. Dr. Russo moved that the Technical Report on polyDr. Radovsky said the 3N-azido-3N-deoxythymidine vinyl alcohol be accepted with revisions discussed and

(AZT) studies had shown the mouse to be susceptible the conclusions as written for female mice, no evito developing vaginal neoplasms. She said the possi- dence of carcinogenic activity. Dr. Taylor seconded

bility of using a pessary or tampon could be con- the motion, which was accepted unanimously with

sidered in a future study. eight votes. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

11 

INTRODUCTION
 

CH2	 CH 

OH n 

POLYVINYL ALCOHOL

CAS No. 9002-89-5 

Chemical Formula: (CHO 2 4 ) n Molecular Weight: approximately 24,000

Synonyms:	# Ethenol homopolymer, PVA

Trade names:	#Akwa Tears, Alcotex, Alvyl, Aracet, Cipoviol, Covol, Elvanol, Ethenol, Gelvatol, Gohsenol, Ivalon, Kuralon, Kurare, Lemol, 

Liquifilm, Mowiol, Polydesis, Polysizer, Polyvinol, Polyviol, Poval, Resistoflex, Rhodoviol, Sno Tears, Solvar, Sumitex, 

Vibatex, Vinacol, Vinalak, Vinarol, Vinarole, Vinavilol, Vinol, Vinylon

CHEMICAL PRODUCTION, USE, 

AND PHYSICAL PROPERTIES AND HUMAN EXPOSURE

Polyvinyl alcohol is a synthetic polymer with a wide Polyvinyl alcohol is produced by the controlled hyrange of molecular weights (from less than 15,000 to drolysis of polyvinyl acetate. In 1991, 114,000 tons

over 430,000). The physical properties of polyvinyl of polyvinyl alcohol was produced in the United

alcohol polymers are dependent on the molecular States, primarily for use in textile sizing, adhesives, 

weight, degree of hydrolysis, and water content of the polymerization aids, and paper coatings (Chemical

polymers (IARC, 1979). The water solubility of poly- Economics Handbook, 1996). The four production

vinyl alcohol polymer increases as the molecular grades of polyvinyl alcohol are super-high viscosity

weight decreases (Merck Index, 1976); it is practically (molecular weight 250,000–300,000); high viscosity

insoluble in organic solvents (Lefaux, 1968). The (molecular weight 170,000–220,000); medium viscoscurrent study is of an aqueous solution of polyvinyl ity (molecular weight 120,000–150,000); and low visalcohol polymer with a molecular weight of about cosity (molecular weight 25,000–35,000) (Hawley’s, 

24,000. Prior to dissolution, this material is an off- 1987). The Food and Drug Administration permits

white crystalline solid that is 88% hydrolyzed. It has the use of polyvinyl alcohol in contact with food

a pH of 5.9 and a viscosity of 4.82 cps. Its density is (IARC, 1979), and it has been used in grease-resistant

1.006 g/mL and its melting point is 194E C. As a coatings for containers such as potato chip bags. 

20% aqueous solution, the polyvinyl alcohol polymer Surgical drapes, towels, and gauze sponges made of

used in this study has a density of 1.07 g/mL. polyvinyl alcohol which dissolve in hot water have
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

12 Polyvinyl Alcohol, NTP TR 474 

been developed to simplify hospital waste disposal

(Fisher, 1996). Protective gloves composed of polyvinyl alcohol have been used to protect the hands of

workers from organic solvents (Lefaux, 1968). 

Polyvinyl alcohol is used in many cosmetic formulations such as facial masks, eye shadow and brow

products, and lipliners. Concentrations of polyvinyl

alcohol in cosmetics are as high as 13% in paste

masks (mud packs) (CIR, 1996). Polyvinyl alcohol is

also used in topical ophthalmic preparations to increase viscosity. A relatively insoluble form of

polyvinyl alcohol is used for plastic sponge implants

in reconstructive surgery (Grant, 1974). Polyvinyl

alcohol foam spheres have been injected intravascularly for elective embolization of vascular malformations in the brain (Lanman et al., 1988). 

Pessaries composed of polyvinyl alcohol with incorporated magnesium sulfate have been used in pregnant

women for dilatation of the cervix prior to the induction of labor (Johnson et al., 1985). An over-thecounter intravaginal contraceptive foam (Delfen, 

Ortho Pharmaceutical Corporation) contains less than

1% polyvinyl alcohol. The manufacturer of an overthe-counter soluble intravaginal contraceptive film

estimates that over 500,000 women in the United

States use their product annually (VCF; Apothecus, 

Inc., Great Neck, NY); the product is composed of a

spermicide, glycerol, and 67% polyvinyl alcohol

(molecular weight 25,000). 

ABSORPTION, DISTRIBUTION, 

METABOLISM, AND EXCRETION

In general, synthetic macromolecular polymers such

as polyvinyl alcohol are chemically inert and not

orally absorbed, but injected polymers could possibly

be metabolized (Lefaux, 1968). 

Experimental Animals125 The distribution of five [ I]-radiolabeled polyvinyl

alcohol polymers with molecular weights of 15,000, 

70,000, 120,000, 200,000, and 430,000 was determined at up to 30 hours after intravenous administration into 8- to 12-week-old female BALB/cCrSlc mice

(Yamaoka et al., 1995). The polymer with a molecular weight of 15,000 had a circulating half-life of

90 minutes compared to 23 hours for the polymer

with a molecular weight of 430,000. Almost 80% of

the 15,000 molecular weight polymer was excreted by

the kidney within 30 minutes after injection. 

14 [ C]-Radiolabeled polyvinyl alcohol with a molecular

weight less than or equal to 50,000 was given orally, 

intravenously, or intravaginally to Fischer 344 rats

(Sanders and Matthews, 1990). Following oral administration, greater than 98% of the dose was excreted in the feces within 48 hours and only a trace

was detected in the urine. No evidence of polyvinyl

alcohol was detected in the tissues. Following intravenous administration, systemic distribution of

polyvinyl alcohol was evident with the highest concentrations detected in the liver. Intravenous dosing also

resulted in most of the dose being excreted in the

urine, thus indicating that the oral dose was not

absorbed. Following intravaginal administration of

3 mg/kg polyvinyl alcohol for 1, 3, or 10 days, less

than 1% of the dose of polyvinyl alcohol-derived

radioactivity was detected in the tissues. The highest

concentrations were seen in the liver, but even after

10 doses the concentration in the liver was less than

2 ppm. Polyvinyl alcohol-derived material was

slowly cleared, and 0.3 ppm remained in liver tissue

30 days after the last of 10 daily doses. 

Twenty-eight consecutive daily doses of 1 mL of

5% polyvinyl alcohol polymers with average molecular weights of 37,000, 133,000, or 185,000 in

physiological saline were injected subcutaneously into

female Holtzman rats (Hall and Hall, 1963). Using a

special stain (Congo red) on histologic tissue sections, 

the polymers with molecular weights of 133,000 and

185,000, but not the polymer with a molecular weight

of 37,000, were found in the liver, spleen, and

kidney. 

Humans

No specific data on the absorption, distribution, 

metabolism, or excretion of polyvinyl alcohol in

humans were found in the literature. 

TOXICITY

In general, macromolecules such as polyvinyl alcohol

are considered to have little or no oral or cutaneous

toxicity due to their chemical inertness (Lefaux, 

1968). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 13 

Experimental Animals

Oral LD50s greater than 20 g polyvinyl alcohol/kg

body weight for rats and 14.7 g/kg for mice have

been reported (Zaitsev et al., 1986). 

Polyvinyl alcohol polymers with average molecular

weights of 37,000, 133,000, or 185,000 were injected

subcutaneously into female Holtzman rats (Hall and

Hall, 1963). Twenty-eight consecutive daily doses of

1 mL of 5% polyvinyl alcohol in physiological saline

resulted in elevated blood pressure in some rats from

each treatment group. The polymer with a molecular

weight of 133,000 was associated with widespread

cardiovascular lesions, severe polydipsia, severe

glomerulonephritis, and enlargement of the heart, 

kidney, liver, and spleen. The polymer with a molecular weight of 185,000 was associated with renal

glomerular swelling and enlargement of the heart, 

kidney, liver, and spleen. The polymer with a molecular weight of 37,000 was not associated with lesions. 

The authors concluded that the pathologic effects

following subcutaneous injections of polyvinyl alcohol

in rats, particularly in the kidney and in production of

the nephrotic syndrome, were dependent on the

molecular weight rather than on the chemical structure

of the polymer. 

Intraocular injection of a 1.4% solution of polyvinyl

alcohol (unspecified molecular weight) in isotonic

saline was made into the eyes of rabbits by the subconjunctival, intracameral (into the anterior chamber), 

and intravitreal routes (Krishna and Mitchell, 1965). 

Eyes were examined grossly and microscopically, and

intraocular pressures were measured for 6 weeks after

injection. Polyvinyl alcohol injections were concluded to be nonirritating. Solid subconjunctival

implants of polyvinyl alcohol produced inflammation

and fibroblastic proliferation in rabbit eyes (Anderson

and Shea, 1961). Five-week dermal toxicity tests with

undiluted polyvinyl alcohol and 13-week studies with

a peel-off facial mask containing 13% polyvinyl

alcohol were conducted in rats by the Cosmetic, 

Toiletry and Fragrance Association. No significant

toxic effects were noted in clinical pathology or

clinical or necropsy observations (CIR, 1996). 

Humans

Intravascularly injected polyvinyl alcohol foam

spheres for elective embolization of vascular malformations resulted in inflammation and necrosis of the

blood vessels in which they lodged, but this property

was considered efficacious in this application (Lanman

et al., 1988). Foamed polyvinyl alcohol has been

used in reconstructive surgery for over 40 years for

conditions such as rectal prolapse and repair of large

hernias without reported toxic effects (Hulman and

Kirkham, 1990). Three-week dermal irritation tests

using topical formulations containing 13% polyvinyl

alcohol resulted in classification of polyvinyl alcohol

as a “mild material” for dermal use (CIR, 1996). 

Sixteen human volunteers used a topical ophthalmic

solution containing 1.4% polyvinyl alcohol in saline

three times daily on alternate days in a 6-day study of

tear replacement solutions without experiencing any

ocular discomfort (Fassihi and Naidoo, 1989). 

REPRODUCTIVE

AND DEVELOPMENTAL TOXICITY

No data on the reproductive or developmental toxicity

of polyvinyl alcohol by any route of administration in

experimental animals or humans were found in the

literature. 

CARCINOGENICITY

Experimental Animals

Subcutaneously implanted polyvinyl alcohol sponges

in rats have been associated with the appearance of

local sarcomas in some studies (Oppenheimer et al., 

1955; Dasler and Milliser, 1963; Walter and

Chiaramonte, 1965) but not in others (Russell et al., 

1959). Dukes and Mitchley (1962) and Roe et al. 

(1967) reported that substantially more local sarcomas

resulted from the subcutaneous implantation of 2-mmthick versus 5-mm-thick polyvinyl alcohol sponges in

rats. This suggests that the physical form and the

thickness of the polyvinyl alcohol implant may be

important in carcinogenicity just as molecular weight

is thought to be important in the toxicity of polyvinyl

alcohol. No neoplasms were noted at the site of subcutaneous implantation of polyvinyl alcohol powder in

a group of 25 Bethesda black rats in a 2-year study

(Hueper, 1959). The International Agency for

Research on Cancer (IARC, 1979) reviewed these and

other data and concluded that further studies were

needed before an evaluation of the carcinogenicity of

polyvinyl alcohol in animals could be made. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

14 Polyvinyl Alcohol, NTP TR 474 

Humans

Implantation of polyvinyl alcohol sponge as a breast

prosthesis has been associated with fibrosis (Hamit, 

1957). Biopsy of a polyvinyl alcohol foam sponge

implanted 20 years earlier for rectal prolapse showed

extensive fibrosis around the implant (Hulman and

Kirkham, 1990). IARC (1979) concluded that available data were not adequate to determine the possible

carcinogenicity of polyvinyl alcohol in humans. 

GENETIC TOXICITY

There is only one published report concerning the

mutagenicity of polyvinyl alcohol, and the authors

concluded that the results of their in vitro and in vivo

investigations were negative (Shibuya et al., 1985). 

Three assays, the Salmonella assay (employing strains

TA98, TA100, and TA1537, with and without induced rat liver S9 activation enzymes), the Chinese

hamster V79 cell chromosomal aberrations test without S9, and a female mouse bone marrow micronucleus test, were used in the study. Independent

evaluation of the results is precluded because no data

were presented for polyvinyl alcohol from the latter

two assays, and there were some departures from

standard protocols in these tests. 

STUDY RATIONALE

It is estimated that hundreds of thousands of women

in the United States use an intravaginal product

containing polyvinyl alcohol each year. The Food

and Drug Administration nominated low-viscosity

polyvinyl alcohol for a 2-year study because of

concern about the lack of information about the longterm toxic and carcinogenic effects by the intravaginal

route. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

15 

MATERIALS AND METHODS
 

PROCUREMENT

AND CHARACTERIZATION

OF POLYVINYL ALCOHOL

Polyvinyl alcohol was obtained from Marubeni

America Corporation (New York, NY) in one lot

(N082889). Identity, purity, and stability analyses

were conducted by the analytical chemistry laboratory, Midwest Research Institute (Kansas City, MO) 

(Appendix B). Reports on analyses performed in

support of the polyvinyl alcohol studies are on file at

the National Institute of Environmental Health

Sciences. 

The chemical, an off-white crystalline solid, was

identified as polyvinyl alcohol by infrared, ultraviolet/ 

visible, and nuclear magnetic resonance spectroscopy. 

Purity of lot N082889 was determined by elemental

analyses, United States Pharmacopeia (USP) analyses, 

and high-performance liquid chromatography. Results

of elemental analyses were slightly high for carbon

and slightly low for hydrogen when compared with

the theoretical values for polyvinyl alcohol. All

results of USP analyses indicated that lot N082889 

met the USP specifications for polyvinyl alcohol. 

High-performance liquid chromatography revealed a

major peak and three impurities with a combined area

of 1.1% relative to the major peak area. The overall

purity was determined to be approximately 99%. 

Stability studies of the bulk chemical were performed

by the analytical chemistry laboratory using highperformance liquid chromatography. These studies

indicated that polyvinyl alcohol was stable as a bulk

chemical for 2 weeks when stored protected from light

at temperatures up to 60E C. To ensure stability, the

bulk chemical was stored at room temperature protected from light. 

Stability was monitored during the 30-day and 2-year

studies by high-performance liquid chromatography. 

No degradation of the bulk chemical was detected. 

PREPARATION AND ANALYSIS

OF DOSE FORMULATIONS

The dose formulation was prepared twice during the

30-day study and approximately every 4 weeks during

the 2-year study by mixing polyvinyl alcohol with

heated, charcoal-filtered, deionized water to give the

required concentration (Table B1). Stability studies of

the dose formulation were performed by the analytical

chemistry laboratory using high-performance liquid

chromatography. The stability of the dose formulation was confirmed for at least 4 weeks when stored

at room temperature protected from light and for

3 weeks when stored open to air and light. 

Periodic analyses of the dose formulations of polyvinyl alcohol were conducted at the study laboratory

using high-performance liquid chromatography. 

During the 2-year study, the dose formulations were

analyzed every 4 to 8 weeks (Table B2). All dose

formulations analyzed and used during the 2-year

study were within 10% of the target concentration; all

animal room samples were also within 10% of the

target concentration. 

30-DAY STUDY

The 30-day study was conducted to evaluate the

cumulative toxic effects of repeated exposure to

polyvinyl alcohol and to determine the appropriate

doses to be used in the 2-year study. 

Female B6C3F1 mice were obtained from Taconic

Farms (Germantown, NY). On receipt, the mice

were 4 weeks old. Animals were quarantined for

11 days and were 6 weeks old on the first day of the

study. There were three groups of 50 females in this

intravaginal study. The vehicle control group received only 20 μL of deionized water. The other two

groups each received 20 μL of a 25% solution of

polyvinyl alcohol in deionized water, resulting in an

average dose of 250 mg polyvinyl alcohol/kg body
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

16 Polyvinyl Alcohol, NTP TR 474 

weight at the start of the study when mice averaged

20 g in weight and 213 mg/kg at the end of the study. 

The dose volume was delivered by an Eppendorf

repeater pipette with a 0.5 mL Combitip inserted

approximately 1 mm into the vaginal opening. 

Animals in one dosed group were returned to their

cages after dosing; animals in the other dosed group

were restrained in a vertical nose-down position in restraint bags for several minutes after dosing. Animals

were dosed daily for 30 consecutive days. Feed and

water were available ad libitum. The animals were

housed individually. Clinical findings were recorded

weekly. The animals were weighed initially, weekly, 

and at the end of the study. Details of the study

design and animal maintenance are summarized in

Table 1. Histopathologic examinations were performed on all mice, but were limited to the uterus and

vagina. 

2-YEAR STUDY

Study Design

There were three groups of 100 female mice in this

intravaginal study: an untreated control group, a

vehicle control group receiving 20 μL of deionized

water vehicle, and a dosed group receiving 20 μL of

25% polyvinyl alcohol in deionized water, which

resulted in doses of 250 mg/kg in mice at the beginning of the study and 83 mg/kg when mice weighed

60 g. The dose volume was delivered by an Eppendorf repeater pipette with a 0.5 mL Combitip inserted

approximately 1 mm into the vaginal opening. 

Source and Specification of Animals

Female B6C3F1 mice were obtained from Taconic

Farms (Germantown, NY) for use in the 2-year study. 

Mice were quarantined for 12 days before the beginning of the study. Ten mice were randomly selected

for parasite evaluation and gross observation of

disease. Mice were 6 to 7 weeks old at the beginning

of the study. The health of the animals was monitored

during the study according to the protocols of the

NTP Sentinel Animal Program (Appendix D). 

Animal Maintenance

The animals were housed individually. Feed and

water were available ad libitum. Cages and racks

were rotated once every 2 weeks. Further details of

animal maintenance are given in Table 1. Information

on feed composition and contaminants is provided in

Appendix C. 

Clinical Examinations and Pathology

All animals were observed twice daily. Body weights

were recorded initially, weekly for the first 13 weeks, 

monthly thereafter, and at study termination; clinical

findings were recorded monthly. 

A complete necropsy and microscopic examination

were performed on all mice. At necropsy, all organs

and tissues were examined for grossly visible lesions, 

and all major tissues were fixed and preserved in

10% neutral buffered formalin, processed and

trimmed, embedded in paraffin, sectioned to a thickness of 5 to 6 μm, and stained with hematoxylin and

eosin for microscopic examination. For all paired

organs (i.e., adrenal gland, kidney, ovary), samples

from each organ were examined. Tissues examined

microscopically are listed in Table 1. 

Microscopic evaluations were completed by the study

laboratory pathologist, and the pathology data were

entered into the Toxicology Data Management

System. The slides, paraffin blocks, and residual wet

tissues were sent to the NTP Archives for inventory, 

slide/block match, and wet tissue audit. The slides, 

individual animal data records, and pathology tables

were evaluated by an independent quality assessment

laboratory. The individual animal records and tables

were compared for accuracy, the slide and tissue

counts were verified, and the histotechnique was

evaluated. For the 2-year study, a quality assessment

pathologist reviewed the clitoral gland, liver, ovary, 

glandular stomach, thyroid gland, uterus, and vagina. 

The quality assessment report and the reviewed slides

were submitted to the NTP Pathology Working Group

(PWG) chairperson, who reviewed the selected tissues

and addressed any inconsistencies in the diagnoses

made by the laboratory and quality assessment pathologists. Representative histopathology slides containing examples of lesions related to chemical administration, examples of disagreements in diagnoses

between the laboratory and quality assessment pathologist, or lesions of general interest were presented by

the chairperson to the PWG for review. The PWG

consisted of the quality assessment pathologist and

other pathologists experienced in rodent toxicologic
 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 17 

pathology. This group examined the tissues without

any knowledge of dose groups or previously rendered

diagnoses. When the PWG consensus differed from

the opinion of the laboratory pathologist, the diagnosis

was changed. Final diagnoses for reviewed lesions

represent a consensus between the laboratory pathologist, reviewing pathologist(s), and the PWG. Details

of these review procedures have been described, in

part, by Maronpot and Boorman (1982) and Boorman

et al. (1985). For subsequent analyses of the pathology data, the decision of whether to evaluate the

diagnosed lesions for each tissue type separately or

combined was generally based on the guidelines of

McConnell et al. (1986). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

18 Polyvinyl Alcohol, NTP TR 474 

TABLE 1 

Experimental Design and Materials and Methods in the Intravaginal Studies of Polyvinyl Alcohol

30-Day Study 2-Year Study

Study Laboratory

Arthur D. Little, Inc. (Cambridge, MA) Arthur D. Little, Inc. (Cambridge, MA) 

Strain and Species

B6C3F1 mice B6C3F1 mice

Animal Source

Taconic Farms (Germantown, NY) Taconic Farms (Germantown, NY) 

Time Held Before Studies

11 days 12 days

Average Age When Studies Began

6 weeks 6-7 weeks

Date of First Dose

17 December 1991 18 February 1992 

Duration of Dosing

7 days per week for 30 consecutive days 5 days per week, excluding holidays, for 104 to 105 weeks

Date of Last Dose

15 January 1992 16 February 1994 

Necropsy Dates

16 January 1992 15-17 February 1994 

Average Age at Necropsy

11 weeks 111-112 weeks

Size of Study Groups

50 females 100 females

Method of Distribution

Animals were distributed randomly into groups of approximately

equal initial mean body weights. 

Same as 30-day study

Animals per Cage

1 1 

Method of Animal Identification

Tail tattoo Same as 30-day study

Diet

NIH-07 open formula pelleted diet (Zeigler Brothers, Inc., Gardners, 

PA), available ad libitum, changed once per week

Same as 30-day study

Water

Tap water (Cambridge municipal supply) via clear glass bottles with

plastic Teflon-lined caps and stainless steel sipper tubes, available

ad libitum, changed twice per week

Same as 30-day study

Cages

Polycarbonate (Allentown Caging, Allentown, NJ), changed once per

week

Same as 30-day study
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 19 

TABLE 1 

Experimental Design and Materials and Methods in the Intravaginal Studies of Polyvinyl Alcohol

30-Day Study 2-Year Study

Bedding

Heat-treated hardwood chips (Northeastern Products, Warrensburg, 

NY), changed once per week

Cage Filters

Reemay spun-bonded polyester (Allentown Caging, Allentown, NJ), 

changed once every 2 weeks

Racks

Stainless steel (Allentown Caging, Allentown, NJ), changed once

every 2 weeks

Animal Room Environment

Temperature: 13E-24E C

Relative humidity: 32%-70% 

Room fluorescent light: 12 hours/day

Room air changes: 10-15/hour

Doses

Vehicle control group receiving 20 μL of deionized water vehicle

only and two dosed groups receiving 20 μL of 25% polyvinyl alcohol

in deionized water (250 mg/kg). The dose volume was delivered by

an Eppendorf repeater pipette with a 0.5 mL Combitip inserted

approximately 1 mm into the vaginal opening. Animals in one dosed

group were returned to their cages after dosing; animals in the other

dosed group were restrained in a vertical nose-down position in

restraint bags for several minutes after dosing. 

Type and Frequency of Observation

Observed twice daily; animals were weighed initially, weekly, and at

the end of the studies; clinical findings were recorded weekly. 

Method of Sacrifice

CO2 asphyxiation

Necropsy

Necropsy performed on all animals. 

Histopathology

Histopathologic examination was performed on all mice, but was

limited to the uterus and vagina. 

Same as 30-day study

Same as 30-day study, except changed once per week

Same as 30-day study, except changed once per week

Temperature: 16E-28E C

Relative humidity: 23%-78% 

Room fluorescent light: 12 hours/day

Room air changes: 10-15/hour

Untreated control, vehicle control receiving 20 μL of deionized water

vehicle only, and dosed group receiving 20 μL of 25% polyvinyl

alcohol in deionized water (250 mg/kg in 20 g mice; 83 mg/kg in 60 g

mice). The dose volume was delivered by an Eppendorf repeater

pipette with a 0.5 mL Combitip inserted approximately 1 mm into the

vaginal opening. 

Observed twice daily; animals were weighed initially, weekly for

13 weeks, monthly thereafter, and at the end of the studies; clinical

findings were recorded monthly. 

Same as 30-day study

Necropsy performed on all animals

Complete histopathology was performed on all mice. In addition to

gross lesions and tissue masses, the following tissues were examined: 

adrenal gland, bone with marrow, brain, clitoral gland, esophagus, 

gallbladder, heart and aorta, large intestine (cecum, colon, rectum), 

small intestine (duodenum, jejunum, ileum), kidney, liver, lungs and

bronchi, mammary gland, nose, ovary, pancreas, pancreatic islets, 

pituitary gland, salivary gland, skin, spinal cord with sciatic nerve, 

spleen, stomach (forestomach and glandular), thymus, thyroid gland, 

trachea, urinary bladder, uterus, and vagina. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

20 Polyvinyl Alcohol, NTP TR 474 

STATISTICAL METHODS

Survival Analyses

The probability of survival was estimated by the

product-limit procedure of Kaplan and Meier (1958) 

and is presented in the form of graphs. Animals

found dead of other than natural causes or missing

were censored from the survival analyses; animals

dying from natural causes were not censored. Statistical analyses for possible treatment-related effects on

survival used Cox’s (1972) method for testing two

groups for equality. All reported P values for the

survival analyses are two sided. 

Calculation of Incidence

The incidences of neoplasms and nonneoplastic

lesions as presented in Tables A1 and A4 are given as

the number of animals bearing such lesions at a

specific anatomic site and the number of animals with

that site examined microscopically. For calculation of

statistical significance, the incidences of most neoplasms (Tables A3a, A3b, and A3c) and all nonneoplastic lesions are given as the numbers of animals

affected at each site examined microscopically. However, when macroscopic examination was required to

detect neoplasms in certain tissues (e.g., harderian

gland, intestine, mammary gland, and skin) before

microscopic evaluation, or when neoplasms had

multiple potential sites of occurrence (e.g., leukemia

or lymphoma), the denominators consist of the number of animals on which a necropsy was performed. 

Tables A3a, A3b, and A3c also give the survivaladjusted neoplasm rate for each group and each sitespecific neoplasm, i.e., the Kaplan-Meier estimate of

the neoplasm incidence that would have been observed

at the end of the study in the absence of mortality

from all other competing risks (Kaplan and Meier, 

1958). 

Analysis of Neoplasm Incidences

The majority of neoplasms in this study were considered to be incidental to the cause of death or not

rapidly lethal. Thus, the primary statistical method

used was logistic regression analysis, which assumed

that the diagnosed neoplasms were discovered as the

result of death from an unrelated cause and thus did

not affect the risk of death. In this approach, neoplasm prevalence was modeled as a logistic function

of chemical exposure and time. Both linear and

quadratic terms in time were incorporated initially, 

and the quadratic term was eliminated if the fit of the

model was not significantly enhanced. The neoplasm

incidences of dosed and control groups were compared on the basis of the likelihood score test for the

regression coefficient of dose. This method of adjusting for intercurrent mortality is the prevalence analysis of Dinse and Lagakos (1983), further described

and illustrated by Dinse and Haseman (1986). When

neoplasms are incidental, this comparison of the timespecific neoplasm prevalences also provides a comparison of the time-specific neoplasm incidences

(McKnight and Crowley, 1984). 

In addition to logistic regression, other methods of

statistical analysis were used, and the results of these

tests are summarized in the appendixes. These methods include the life table test (Cox, 1972; Tarone, 

1975), appropriate for rapidly lethal neoplasms, and

the Fisher exact test (Armitage, 1971; Gart et al., 

1979), a procedure based on the overall proportion of

neoplasm-bearing animals. 

Tests of significance included pairwise comparisons of

the dosed group with each group of controls. 

Continuity-corrected tests were used in the analysis of

neoplasm incidence, and reported P values are one

sided. The procedures described in the preceding

paragraphs were also used to evaluate selected nonneoplastic lesions. For further discussion of these

statistical methods, refer to Haseman (1984). 

Analysis of Nonneoplastic Lesion Incidences

Because all nonneoplastic lesions in this study were

considered to be incidental to the cause of death or not

rapidly lethal, the primary statistical analysis used was

a logistic regression analysis in which nonneoplastic

lesion prevalence was modeled as a logistic function

of chemical exposure and time. 

Analysis of Continuous Variables

Body weight data, which have approximately normal

distributions, were analyzed with the parametric multiple comparison procedures of Dunnett (1955) and

Williams (1971, 1972). Average severity values were

analyzed for significance with the Mann-Whitney U

test (Hollander and Wolfe, 1973). 
 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 21 

QUALITY ASSURANCE METHODS

The 2-year study was conducted in compliance with

Food and Drug Administration Good Laboratory

Practice Regulations (21 CFR, Part 58). In addition, 

as records from the 2-year study were submitted to the

NTP Archives, this study was audited retrospectively

by an independent quality assurance contractor. Separate audits covering completeness and accuracy of

the pathology data, pathology specimens, final pathology tables, and a draft of this NTP Technical Report

were conducted. Audit procedures and findings are

presented in the reports and are on file at NIEHS. 

The audit findings were reviewed and assessed by

NTP staff, so all comments had been resolved or were

otherwise addressed during the preparation of this

Technical Report. 
22 Polyvinyl Alcohol, NTP TR 474 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

23 

RESULTS
 

MICE

30-DAY STUDY

All mice survived to the end of the study (Table 2). 

The final mean body weights and body weight gains

of the dosed groups were similar to those of the

vehicle control group. Abnormalities noted in the

vaginal area after dosing included vaginal plugs, 

secretions, and swelling. These vaginal changes were

TABLE 2 

minimal to mild and occurred in vehicle controls as

well as in dosed mice. Restraint of mice after dosing

appeared to eliminate vaginal secretions but increased

both the incidence of vaginal irritation and the severity

of vaginal opening swelling. At necropsy, mildly

enlarged uterine horns were observed in 10 vehicle

control mice, in three 25% mice, and in seven

25% (restrained) mice. No chemical-related lesions

were observed. 

Survival and Body Weights of Mice in the 30-Day Intravaginal Study of Polyvinyl Alcohol

Mean Body Weightb (g) Final Weight

Dose Survivala Initial Final Change Relative to Controls

(%) (%) 

Female

0 50/50 19.8 ± 0.1 23.0 ± 0.2 3.3 ± 0.2 

25 50/50 20.0 ± 0.1 23.2 ± 0.2 3.2 ± 0.2 101 

25 (restrained) 50/50 19.9 ± 0.2 23.4 ± 0.2 3.5 ± 0.2 102 

a Number of animals surviving at 30 days/number initially in group b Weights and weight changes are given as mean ± standard error. Differences from the control group were not significant by Dunnett’s test. 

Dose Selection Rationale: A one-species study was solution of polyvinyl alcohol (molecular weight

considered adequate to indicate possible toxicity or approximately 24,000) was the maximum dose volcarcinogenicity from intravaginal polyvinyl alcohol ume and concentration that could be administered

administration. The mouse rather than the rat was based on the viscosity of the material and the size of

chosen as the most appropriate rodent species because the vagina in 6- to 7-week-old mice. There was no

it was felt that retention time of the dissolved poly- evidence of adverse effects from this maximum dose

vinyl alcohol might be better in the smaller vagina of volume and concentration in the 30-day study. 

the mouse. An untreated control group in addition to Administration of 20 μL of a 25% solution resulted in

a vehicle control group was used in the 2-year study an average dose of 250 mg/kg at the start of the study

in order to determine whether there were effects from when the average weight of the mice was 20 g and an

intravaginal dosing alone because this dosing route average dose of 83 mg/kg on week 85 when the

had not been used previously. The 30-day study average weight of the mice was 60 g. 

established that 0.02 mL (20 μL) of a 25% aqueous
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

24 

c

Polyvinyl Alcohol, NTP TR 474 

2-YEAR STUDY
 

Survival survival curves (Figure 1). Survival of dosed mice

Estimates of 2-year survival probabilities for female was similar to that of the untreated control and vehicle

mice are shown in Table 3 and in the Kaplan-Meier control groups. 

TABLE 3 

Survival of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol

Untreated Control Vehicle Control 25% 

Animals initially in study 100 100 100 

Accidental deathsa 10 4 5 

Moribund 19 25 13 

Natural deaths 24 20 21 

Animals surviving to study termination

Percent probability of survival at end of studyb

47 

53 

51 

53 

61 

64 

Mean survival (days)

c 645 674 676 

Survival analysisd

Survival analysise P ̆0.142N

P ̆0.158N

a Censored from survival analyses b Kaplan-Meier determinations

Mean of all deaths (uncensored, censored, and terminal sacrifice) d The result of the life table pairwise comparison (Cox, 1972) with the untreated control group. Lower mortality in the dosed group is

indicated by N. e The result of the life table pairwise comparison (Cox, 1972) with the vehicle control group. Lower mortality in the dosed group is indicated

by N. 

Body Weights and Clinical Findings

The final mean body weight of vehicle control mice controls from week 17 until the end of the study. The

was less than that of the untreated control group only clinical finding was vaginal irritation, observed

(Figure 2 and Table 4). The mean body weights of in six mice in the vehicle control group and 11 mice

the dosed mice were less than those of the untreated in the dosed group. 
Polyvinyl Alcohol, NTP TR 474 25 

FIGURE 1 

Kaplan-Meier Survival Curves for Female Mice Administered
 

Polyvinyl Alcohol Intravaginally for 2 Years
 
26 Polyvinyl Alcohol, NTP TR 474 

FIGURE 2 

Growth Curves for Female Mice Administered
 

Polyvinyl Alcohol Intravaginally for 2 Years
 
 

 

Polyvinyl Alcohol, NTP TR 474 27 

TABLE 4 

Mean Body Weights and Survival of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol

Weeks Untreated Control Vehicle Control 25% 

on Av. Wt. No. of Av. Wt. Wt. (% of No. of Av. Wt. Wt. (% of No. of

Study (g) Survivors (g) untreated Survivors (g) untreated Survivors

controls) controls) 

1 20.2 100 19.6 97 100 19.7 98 100 

2 21.1 100 20.7 98 100 20.8 99 100 

3 21.8 100 21.1 97 100 21.4 98 100 

4 22.7 100 22.0 97 100 22.2 98 100 

5 23.7 100 23.3 98 100 23.4 99 100 

6 24.0 100 23.5 98 100 23.6 98 100 

7 25.1 100 24.6 98 100 24.8 99 100 

8 26.1 100 25.5 98 100 25.5 98 100 

9 27.4 100 26.7 97 100 26.6 97 100 

10 28.2 100 27.4 97 100 27.3 97 100 

11 28.9 99 28.2 98 100 27.8 96 100 

12 29.5 99 28.3 96 100 28.1 95 99 

13 30.9 99 29.9 97 100 29.6 96 99 

17 35.2 98 33.7 96 100 33.1 94 98 

21 39.4 98 37.0 94 100 36.5 93 98 

25 42.6 97 39.8 93 100 39.1 92 98 

29 44.6 96 42.1 94 100 41.4 93 98 

33 47.5 96 44.9 95 99 44.2 93 98 

37 50.5 96 47.8 95 99 46.8 93 98 

41 53.3 96 50.5 95 99 49.3 93 98 

45 54.3 96 51.3 95 99 49.7 92 98 

49 56.4 96 52.8 94 96 51.5 91 96 

53 55.2 94 51.8 94 96 50.3 91 96 

57 57.6 93 54.5 95 96 53.0 92 96 

61 59.1 91 56.2 95 96 54.7 93 95 

65 60.8 90 58.1 96 96 56.1 92 95 

69 60.7 88 58.3 96 95 56.5 93 95 

73 60.7 87 58.6 97 95 56.5 93 94 

77 62.9 84 60.1 96 94 58.8 94 92 

81 64.5 82 61.7 96 90 59.6 92 90 

85 63.7 80 61.0 96 88 59.8 94 90 

89 62.6 77 59.7 95 83 56.4 90 90 

93 60.2 73 58.1 97 76 55.2 92 80 

97 57.6 63 54.3 94 69 53.7 93 74 

101 57.8 57 53.5 93 59 53.5 93 66 

104 58.0 47 53.2 92 52 52.2 90 61 

Mean for weeks

1-13 25.4 24.7 97 24.7 97 

14-52 47.1 44.4 94 43.5 92 

53-104 60.1 57.1 95 55.5 92 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

28 

c

Polyvinyl Alcohol, NTP TR 474 

Pathology and Statistical Analyses

This section describes the statistically significant or

biologically noteworthy changes in the incidences of

nonneoplastic lesions of the reproductive tract (clitoral

gland, ovary, uterus, and vagina) and other organs. 

There were no neoplasms that were considered

possibly related to polyvinyl alcohol. Summaries of

the incidences of neoplasms and nonneoplastic lesions, 

individual animal tumor diagnoses, and statistical

analyses of primary neoplasms that occurred with an

incidence of at least 5% in at least one animal group

are presented in Appendix A. 

TABLE 5 

Reproductive Tract: There were no neoplasms

observed in the reproductive tract of mice that were

considered related to polyvinyl alcohol treatment. 

The incidences and severities of nonneoplastic lesions

of the reproductive tract of mice in the dosed group

were similar to those in the vehicle control and

untreated control groups (Tables 5 and A4). None of

the reproductive tract nonneoplastic lesions were

related to chemical treatment. 

Incidences of Selected Nonneoplastic Lesions of the Reproductive Tract of Female Mice

in the 2-Year Intravaginal Study of Polyvinyl Alcohol

Untreated Control Vehicle Control 25% 

Clitoral glanda

Atrophyb

Hyperplasia

Chronic inflammation

89 

29 

4 

2 

(1.8)c

(1.8) 

(4.0) 

81 

26 

8 

1 

(1.6) 

(2.0) 

(4.0) 

83 

18 

10 

0 

(1.8) 

(1.5) 

Ovary

Cyst

Lymphoid hyperplasia

Tubulostromal hyperplasia

Acute or chronic inflammation

Thrombosis

95 

13 

0 

0 

1 

2 

(2.2) 

(4.0) 

(4.0) 

97 

13 

1 

0 

2 

2 

(2.7) 

(3.0) 

(4.0) 

(3.5) 

97 

15 

0 

1 

2 

1 

(2.4) 

(3.0) 

(4.0) 

(3.0) 

Uterus 100 100 100 

Hydrometra

Chronic inflammation

Endometrial angiectasis

Endometrial cystic hyperplasia

7 

3 

1 

90 

(3.9) 

(2.7) 

(2.0) 

(2.9) 

2 

1 

1 

97 

(4.0)

(3.0) 

(3.0) 

(3.1)

 2 

0 

0 

98 

(3.0) 

(3.0) 

Vagina

Acute, chronic, or epithelial inflammation

Epithelial hyperplasia

97

0 

0 

99 

5 

1 

(2.6) 

(3.0) 

99 

1 

0 

(3.0) 

a Number of animals with organ examined microscopically b	 Number of animals with lesion. Incidences in the 25% group were not significantly different from those in the vehicle control group; incidences

in the vehicle control group were not significantly different from those in the untreated control group. 

Average severity grade of lesions in affected animals: 1 ̆minimal, 2 ̆mild, 3 ̆moderate, 4 ̆marked

Other Organs: Incidences of chronic inflammation of (Table A4). Neither of these increased incidences of

the pancreas (untreated control, 18/97; vehicle con- nonneoplastic lesions were considered related to

trol, 40/95; 25%, 36/98) and thymic atrophy (66/98, chemical treatment, but because they occurred in

82/93, 79/99) in the vehicle control and dosed groups intravaginally dosed mice, they may have been

were greater than those in the untreated control group associated with the dosing method. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

__________

 

 

29 

DISCUSSION AND CONCLUSIONS
 

It is estimated that hundreds of thousands of women

in the United States use a vaginal contraceptive film

(VCF) each year (Apothecus, Inc.). VCF is composed of 67% polyvinyl alcohol along with a spermicide

and is designed to rapidly dissolve in the vagina. The

average dose of polyvinyl alcohol from a single use of

intravaginal VCF in a 55-kg woman is 3 mg/kg. In

the present 30-day and 2-year studies, daily doses of

intravaginal polyvinyl alcohol solution in female mice

ranged from 83 to 250 mg/kg. There were no significant differences in survival, body weights, clinical

findings, or neoplasms or nonneoplastic lesions between vehicle control and dosed mice in the current

study. 

The NTP historical database at present does not list

any agents for which the vagina was a target for

neoplasm induction. However, current studies of

AZT in mice indicate that the mouse is susceptible to

neoplasm induction at this site (NTP, 1998). The

18 studies in the historical database in which either the

uterus or cervix was the site of neoplasm induction

were equally distributed between mice and rats. In

the current study there was no evidence of neoplasm

induction in the reproductive tract or other organs of

mice administered a daily intravaginal dose of 20 μL

of a 25% solution of polyvinyl alcohol (molecular

weight approximately 24,000) for 2 years. Nonneoplastic lesions of the reproductive tract in dosed mice

were few in number and did not differ in severity or

incidence from those in the vehicle control group. 

In addition to concern about the reproductive tract, 

systemic absorption studies in rats suggested that the

liver and kidneys might also be exposed to polyvinyl

alcohol after intravaginal administration (Hall and

Hall, 1963; Sanders and Matthews, 1990). In the

current study, incidences of neoplasms and nonneoplastic lesions of the liver in dosed mice were not

significantly greater than those in the vehicle control

mice. Incidences of atrophy, clear cell foci, and glycogen depletion of the liver were greater in vehicle

control and dosed mice than in untreated control mice, 

but these lesions commonly occur spontaneously and

their biologic significance is unknown. In rats, subcutaneous injection of polyvinyl alcohol (molecular

weight 35,000 to 240,000) has been used to create a

condition of benign glomerulopathy with thickening of

the glomerular basement membrane but without alteration of the glomerular filtration rate (Sterzel et al., 

1983; Mauer et al., 1985). In the current study with

intravaginally administered polyvinyl alcohol in mice, 

no differences between the kidneys of untreated controls, vehicle controls, and dosed mice were detected

by light microscopy. 

Incidences of chronic inflammation of the pancreas

and of thymic atrophy in untreated controls were less

than those in either vehicle control or dosed mice. 

Both are common spontaneous lesions. Body weights

of untreated controls were greater than those of either

vehicle control or dosed mice throughout most of the

study, perhaps indicative of an effect associated with

intravaginal dosing. 

CONCLUSIONS

Under the conditions of this 2-year study, there was

no evidence of carcinogenic activity* of polyvinyl

alcohol (molecular weight approximately 24,000) in

female B6C3F1 mice administered 20 μL of a 25% 

solution intravaginally. There were no neoplasms or

nonneoplastic lesions considered related to treatment

with polyvinyl alcohol. 

* Explanation of Levels of Evidence of Carcinogenic Activity is on page 8. A summary of the Technical Reports Review Subcommittee

comments and the public discussion on this Technical Report appears on page 10. 
30 Polyvinyl Alcohol, NTP TR 474 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

31 

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34 Polyvinyl Alcohol, NTP TR 474 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

35 

APPENDIX A

SUMMARY OF LESIONS IN FEMALE MICE

IN THE 2-YEAR INTRAVAGINAL STUDY

OF POLYVINYL ALCOHOL

TABLE A1 

TABLE A2 

TABLE A3a

TABLE A3b

TABLE A3c

TABLE A4 

Summary of the Incidence of Neoplasms in Female Mice

in the 2-Year Intravaginal Study of Polyvinyl Alcohol ....................... 

Individual Animal Tumor Pathology of Female Mice

in the 2-Year Intravaginal Study of Polyvinyl Alcohol ....................... 

Statistical Analysis of Primary Neoplasms in Female Mice

in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control vs. Vehicle Control .................................. 

Statistical Analysis of Primary Neoplasms in Female Mice

in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control vs. 25% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Statistical Analysis of Primary Neoplasms in Female Mice

in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control vs. 25% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice

in the 2-Year Intravaginal Study of Polyvinyl Alcohol ....................... 

36 

40 

80 

83 

86 

89 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

36 Polyvinyl Alcohol, NTP TR 474 

TABLE A1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohola

Untreated Control Vehicle Control 25% 

Disposition Summary

Animals initially in study 100 100 100 

Early deaths

Accidental deaths 10 4 5 

Moribund 19 25 13 

Natural deaths 24 20 21 

Survivors

Terminal sacrifice 47 51 61 

Animals examined microscopically 100 100 100 

Alimentary System

Gallbladder (76) (87) (79) 

Hepatocholangiocarcinoma, metastatic, liver 1 (1%) 

Intestine small, duodenum (88) (90) (92) 

Polyp adenomatous 1 (1%) 1 (1%) 

Intestine small, jejunum (89) (90) (91) 

Squamous cell carcinoma, metastatic, stomach, forestomach 1 (1%) 

Intestine small, ileum (88) (90) (92) 

Liver (99) (99) (100) 

Hepatocellular carcinoma 11 (11%) 18 (18%) 20 (20%) 

Hepatocellular adenoma 25 (25%) 43 (43%) 36 (36%) 

Hepatocellular adenoma, multiple 30 (30%) 13 (13%) 19 (19%) 

Hepatocholangiocarcinoma 2 (2%) 

Histiocytic sarcoma 4 (4%) 2 (2%) 1 (1%) 

Serosa, fibrosarcoma, metastatic, skeletal muscle 1 (1%) 

Mesentery (33) (25) (36) 

Carcinoma, metastatic, islets, pancreatic 1 (4%) 

Hepatocholangiocarcinoma, metastatic, liver 2 (6%) 

Histiocytic sarcoma 1 (3%) 

Rhabdomyosarcoma, metastatic, skeletal muscle 1 (3%) 

Sarcoma 1 (3%) 

Squamous cell carcinoma, metastatic, stomach, forestomach 1 (3%) 

Yolk sac carcinoma, metastatic, ovary 1 (3%) 

Pancreas (97) (95) (98) 

Adenoma 1 (1%) 

Carcinoma 1 (1%) 

Fibrosarcoma, metastatic, skeletal muscle 1 (1%) 

Hepatocholangiocarcinoma, metastatic, liver 1 (1%) 

Squamous cell carcinoma, metastatic, stomach, forestomach 1 (1%) 

Salivary glands (99) (97) (100) 

Stomach, forestomach (94) (93) (97) 

Squamous cell carcinoma 1 (1%) 

Squamous cell papilloma 2 (2%) 

Stomach, glandular (93) (93) (96) 

Leiomyosarcoma 1 (1%) 

Cardiovascular System

Heart (100) (99) (100) 

Hemangiosarcoma 1 (1%) 

Hepatocellular carcinoma, metastatic, liver 1 (1%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 37 

TABLE A1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol

Untreated Control Vehicle Control 25% 

Endocrine System

Adrenal cortex (100) (94) (97) 

Carcinoma, metastatic, islets, pancreatic 1 (1%) 

Hepatocellular carcinoma, metastatic, liver 1 (1%) 

Histiocytic sarcoma 1 (1%) 

Squamous cell carcinoma, metastatic, stomach, forestomach 1 (1%) 

Capsule, adenoma 1 (1%) 

Capsule, carcinoma 1 (1%) 

Adrenal medulla (99) (94) (92) 

Hepatocholangiocarcinoma, metastatic, liver 1 (1%) 

Pheochromocytoma benign 2 (2%) 

Islets, pancreatic (97) (94) (97) 

Adenoma 3 (3%) 1 (1%) 

Hepatocholangiocarcinoma, metastatic, liver 1 (1%) 

Parathyroid gland (59) (59) (69) 

Adenoma 1 (1%) 

Pituitary gland (88) (86) (84) 

Pars distalis, adenoma 13 (15%) 9 (10%) 10 (12%) 

Pars intermedia, adenoma 1 (1%) 

Thyroid gland (100) (96) (100) 

C-cell, adenoma 1 (1%) 

Follicular cell, adenoma 8 (8%) 9 (9%) 11 (11%) 

Follicular cell, carcinoma 1 (1%) 

General Body System

Tissue NOS (1) 

Squamous cell carcinoma, metastatic, stomach, forestomach 1 (100%) 

Genital System

Ovary (95) (97) (97) 

Cystadenoma 6 (6%) 5 (5%) 3 (3%) 

Granulosa cell tumor benign 1 (1%) 2 (2%) 

Hemangiosarcoma 1 (1%) 

Hepatocellular carcinoma, metastatic, liver 1 (1%) 1 (1%) 

Hepatocholangiocarcinoma, metastatic, liver 1 (1%) 

Histiocytic sarcoma 3 (3%) 1 (1%) 

Liposarcoma 1 (1%) 

Luteoma 1 (1%) 2 (2%) 

Squamous cell carcinoma, metastatic, stomach, forestomach 1 (1%) 

Teratoma benign 1 (1%) 

Yolk sac carcinoma 2 (2%) 

Uterus (100) (100) (100) 

Carcinoma 1 (1%) 

Deciduoma NOS 1 (1%) 

Granular cell tumor benign 1 (1%) 1 (1%) 

Hamartoma 1 (1%) 

Hepatocellular carcinoma, metastatic, liver 1 (1%) 

Histiocytic sarcoma 4 (4%) 2 (2%) 1 (1%) 

Leiomyoma 1 (1%) 

Polyp stromal 1 (1%) 3 (3%) 

Sarcoma stromal 2 (2%) 

Squamous cell carcinoma, metastatic, stomach, forestomach 1 (1%) 

Serosa, fibrosarcoma, metastatic, skeletal muscle 1 (1%) 

Vagina (97) (99) (99) 

Histiocytic sarcoma 1 (1%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

38 Polyvinyl Alcohol, NTP TR 474 

TABLE A1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol

Untreated Control Vehicle Control 25% 

Hematopoietic System

Bone marrow (100) (98) (100) 

Histiocytic sarcoma 1 (1%) 

Lymph node (15) (21) (21) 

Liposarcoma 1 (5%) 

Plasma cell tumor benign 1 (5%) 

Squamous cell carcinoma, metastatic, stomach, forestomach 1 (7%) 

Iliac, histiocytic sarcoma 1 (7%) 1 (5%) 

Inguinal, fibrosarcoma, metastatic, skeletal muscle 1 (7%) 

Mediastinal, fibrosarcoma, metastatic, skeletal muscle 1 (7%) 

Mediastinal, histiocytic sarcoma 1 (7%) 

Mediastinal, sarcoma, metastatic, uncertain primary site 1 (5%) 

Renal, histiocytic sarcoma 1 (7%) 1 (5%) 

Lymph node, mandibular (92) (94) (93) 

Plasma cell tumor benign 1 (1%) 

Lymph node, mesenteric (90) (93) (93) 

Fibrosarcoma, metastatic, skeletal muscle 1 (1%) 

Hepatocellular carcinoma, metastatic, liver 1 (1%) 1 (1%) 

Hepatocholangiocarcinoma, metastatic, liver 1 (1%) 

Histiocytic sarcoma 4 (4%) 

Rhabdomyosarcoma, metastatic, skeletal muscle 1 (1%) 

Sarcoma, metastatic, uncertain primary site 1 (1%) 

Squamous cell carcinoma, metastatic, stomach, forestomach 1 (1%) 

Spleen (98) (96) (98) 

Fibrosarcoma, metastatic, skeletal muscle 1 (1%) 

Histiocytic sarcoma 2 (2%) 

Sarcoma, metastatic, uncertain primary site 1 (1%) 

Thymus (98) (93) (99) 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 (1%) 

Fibrosarcoma, metastatic, skin 1 (1%) 

Fibrosarcoma, metastatic, skeletal muscle 1 (1%) 

Hepatocellular carcinoma, metastatic, liver 1 (1%) 

Hepatocholangiocarcinoma, metastatic, liver 1 (1%) 

Thymoma benign 1 (1%) 1 (1%) 

Integumentary System

Mammary gland (93) (92) (91) 

Adenoma 1 (1%) 

Carcinoma 1 (1%) 

Skin (98) (98) (100) 

Fibrosarcoma 1 (1%) 

Sarcoma 1 (1%) 

Subcutaneous tissue, fibrosarcoma 1 (1%) 2 (2%) 

Subcutaneous tissue, fibrous histiocytoma 1 (1%) 

Subcutaneous tissue, pinna, fibrosarcoma 1 (1%) 

Musculoskeletal System

Bone (100) (100) (100) 

Pelvis, sarcoma 1 (1%) 

Skeletal muscle (9) (10) (8) 

Fibrosarcoma, metastatic, skeletal muscle 1 (11%) 

Hepatocholangiocarcinoma, metastatic, liver 1 (13%) 

Rhabdomyosarcoma 2 (22%) 2 (20%) 2 (25%) 

Sarcoma 1 (13%) 

Squamous cell carcinoma, metastatic, stomach, forestomach 1 (11%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 39 

TABLE A1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol

Untreated Control Vehicle Control 25% 

Nervous System

Brain (100) (99) (100) 

Respiratory System

Lung (100) (98) (100) 

Alveolar/bronchiolar adenoma 6 (6%) 7 (7%) 8 (8%) 

Alveolar/bronchiolar carcinoma 3 (3%) 3 (3%) 5 (5%) 

Carcinoma, metastatic, harderian gland 1 (1%) 

Fibrosarcoma, metastatic, skin 1 (1%) 

Hepatocellular carcinoma, metastatic, liver 4 (4%) 2 (2%) 

Hepatocholangiocarcinoma, metastatic, liver 2 (2%) 

Histiocytic sarcoma 2 (2%) 1 (1%) 

Osteosarcoma, metastatic, tissue NOS 1 (1%) 

Sarcoma, metastatic, uncertain primary site 1 (1%) 1 (1%) 

Yolk sac carcinoma, metastatic, ovary 1 (1%) 

Nose (100) (100) (100) 

Carcinoma 1 (1%) 

Special Senses System

Harderian gland (5) (11) (6) 

Adenoma 4 (80%) 9 (82%) 4 (67%) 

Carcinoma 1 (20%) 2 (18%) 1 (17%) 

Zymbal’s gland (3) 

Carcinoma 1 (33%) 

Urinary System

Kidney (100) (98) (100) 

Adenoma 1 (1%) 

Histiocytic sarcoma 1 (1%) 

Urinary bladder (96) (96) (98) 

Histiocytic sarcoma 1 (1%) 

Systemic Lesions

Multiple organsb (100) (100) (100) 

Histiocytic sarcoma 4 (4%) 2 (2%) 1 (1%) 

Lymphoma malignant 13 (13%) 14 (14%) 18 (18%) 

Neoplasm Summary

Total animals with primary neoplasmsc 78 82 88 

Total primary neoplasms 145 160 161 

Total animals with benign neoplasms 67 72 69 

Total benign neoplasms 103 109 102 

Total animals with malignant neoplasms 38 40 51 

Total malignant neoplasms 42 51 58 

Total animals with metastatic neoplasms 11 7 4 

Total metastatic neoplasms 33 13 15 

Total animals with malignant neoplasms

of uncertain primary site 2 1 

Total animals with uncertain neoplasms—

benign or malignant 1 

Total uncertain neoplasms 1 

a

b

Number of animals examined microscopically at the site and the number of animals with neoplasm

Number of animals with any tissue examined microscopically c Primary neoplasms: all neoplasms except metastatic neoplasms
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

40 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

0111333444444555555555666 

Number of Days on Study 6167556014778123338999023 

7085075001363190891255654 

0000000000000000000000000 

Carcass ID Number 7192377082710557044503380 

6968031541466018819579371 

Alimentary System

Esophagus +++++++++++++++++++++++++ 

Gallbladder + + A + + A + AAA I + A A + I A +++ AAA + A

Intestine large, colon +++++ A +++ A + + A + + A A ++++ A A ++ 

Intestine large, rectum + + A + + A + + A A + + A + + A A ++++ A A ++ 

Intestine large, cecum + + A + + A + + A A + + A A + A A ++++ A A ++ 

Intestine small, duodenum + + A + + A + + A A + + A A + A A ++++ A A ++ 

Polyp adenomatous X

Intestine small, jejunum + + A + + A +++ A + + A A + A A ++++ A A ++ 

Squamous cell carcinoma, metastatic, 

stomach, forestomach X

Intestine small, ileum + + A + + A + + A A + + A A + A A ++++ A A ++ 

Liver ++++++++++++++++++++++ A ++ 

Hepatocellular carcinoma X

Hepatocellular adenoma X X X X X

Hepatocellular adenoma, multiple

Histiocytic sarcoma X

Serosa, fibrosarcoma, metastatic, 

skeletal muscle

Mesentery + + + + + + 

Histiocytic sarcoma

Rhabdomyosarcoma, metastatic, 

skeletal muscle

Sarcoma

Squamous cell carcinoma, metastatic, 

stomach, forestomach X

Pancreas +++++ A ++++++ A +++++++++ A ++ 

Adenoma

Fibrosarcoma, metastatic, skeletal muscle

Squamous cell carcinoma, metastatic, 

stomach, forestomach X

Salivary glands +++++++++++++++++++++++++ 

Stomach, forestomach +++++ A +++ A +++ A + + A ++++ A +++ 

Squamous cell carcinoma X

Squamous cell papilloma

Stomach, glandular +++++ A +++ A +++ A + + A ++++ A A ++ 

Cardiovascular System

Blood vessel

Heart +++++++++++++++++++++++++ 

Hemangiosarcoma

Hepatocellular carcinoma, metastatic, liver X

+: Tissue examined microscopically M: Missing tissue X: Lesion present

A: Autolysis precludes examination I: Insufficient tissue Blank: Not examined
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 41 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

6666666666666666667777777 

Number of Days on Study 4445555556667888990000111 

0362557796885226063449148 

0000000000000000000000000 

Carcass ID Number 2166161907299688538892520 

6506350230343985883089442 

Alimentary System

Esophagus +++++++++++++++++++++++++ 

Gallbladder + I +++ I A A + AAA ++++++ A ++++++ 

Intestine large, colon +++++++++++++++++++++++ A + 

Intestine large, rectum +++++++++++++++++++++++ A A

Intestine large, cecum +++++++++++++++++++++++ A A

Intestine small, duodenum +++++++++++++++++++++++ A A

Polyp adenomatous

Intestine small, jejunum +++++++++++++++++++++++ A A

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Intestine small, ileum +++++++++++++++++++++++ A A

Liver +++++++++++++++++++++++++ 

Hepatocellular carcinoma X X X X

Hepatocellular adenoma X X X X XXX

Hepatocellular adenoma, multiple X X X X X X

Histiocytic sarcoma X X X

Serosa, fibrosarcoma, metastatic, 

skeletal muscle X

Mesentery + +++ + ++ ++ ++ ++ 

Histiocytic sarcoma X

Rhabdomyosarcoma, metastatic, 

skeletal muscle

Sarcoma X

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Pancreas +++++++++++++++++++++++++ 

Adenoma

Fibrosarcoma, metastatic, skeletal muscle X

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Salivary glands +++++++++++++++++++++++++ 

Stomach, forestomach +++++++++++++++++++++++ A + 

Squamous cell carcinoma

Squamous cell papilloma X

Stomach, glandular +++++++++++++++++++++++ A + 

Cardiovascular System

Blood vessel

Heart +++++++++++++++++++++++++ 

Hemangiosarcoma

Hepatocellular carcinoma, metastatic, liver
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

42 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

7777777777777777777777777 

Number of Days on Study 2222222222222222222233333 

1559999999999999999900000 

0000000000000000000000000 

Carcass ID Number 2460112344445677789911233 

7219785505679225711912226 

Alimentary System

Esophagus +++++++++++++++++++++++++ 

Gallbladder +++++++++++++++++++++++++ 

Intestine large, colon +++++++++++++++++++++++++ 

Intestine large, rectum +++++++++++++++++++++++++ 

Intestine large, cecum +++++++++++++++++++++++++ 

Intestine small, duodenum +++++++++++++++++++++++++ 

Polyp adenomatous

Intestine small, jejunum +++++++++++++++++++++++++ 

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Intestine small, ileum +++++++++++++++++++++++++ 

Liver +++++++++++++++++++++++++ 

Hepatocellular carcinoma X X X

Hepatocellular adenoma X X X X X X

Hepatocellular adenoma, multiple X X X XXXXXXX X X X

Histiocytic sarcoma

Serosa, fibrosarcoma, metastatic, 

skeletal muscle

Mesentery + +++ ++ ++ 

Histiocytic sarcoma

Rhabdomyosarcoma, metastatic, 

skeletal muscle X

Sarcoma

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Pancreas +++++++++++++++++++++++++ 

Adenoma X

Fibrosarcoma, metastatic, skeletal muscle

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Salivary glands ++ I ++++++++++++++++++++++ 

Stomach, forestomach +++++++++++++++++++++++++ 

Squamous cell carcinoma

Squamous cell papilloma X

Stomach, glandular +++++++++++++++++++++++++ 

Cardiovascular System

Blood vessel

Heart +++++++++++++++++++++++++ 

Hemangiosarcoma

Hepatocellular carcinoma, metastatic, liver
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 43 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

7777777777777777777777777 

Number of Days on Study 3333333333333333333333333 

0000000000001111111111111 

0000000000000000000000001 Total

Carcass ID Number 3445566688890123345567990 Tissues/ 

7383747826954401442639070 Tumors

Alimentary System

Esophagus +++++++++++++++++++++++++ 100 

Gallbladder ++++++++++++ I ++++++ I +++++ 76 

Intestine large, colon +++++++++++++++++++++++++ 92 

Intestine large, rectum +++++++++++++++++++++++++ 89 

Intestine large, cecum +++++++++++++++++++++++++ 88 

Intestine small, duodenum +++++++++++++++++++++++++ 88 

Polyp adenomatous 1 

Intestine small, jejunum +++++++++++++++++++++++++ 89 

Squamous cell carcinoma, metastatic, 

stomach, forestomach 1 

Intestine small, ileum +++++++++++++++++++++++++ 88 

Liver +++++++++++++++++++++++++ 99 

Hepatocellular carcinoma X X X 11 

Hepatocellular adenoma X X X X X X X 25 

Hepatocellular adenoma, multiple XXXX XXX X X X X 30 

Histiocytic sarcoma 4 

Serosa, fibrosarcoma, metastatic, 

skeletal muscle 1 

Mesentery ++ + ++ + 33 

Histiocytic sarcoma 1 

Rhabdomyosarcoma, metastatic, 

skeletal muscle 1 

Sarcoma 1 

Squamous cell carcinoma, metastatic, 

stomach, forestomach 1 

Pancreas +++++++++++++++++++++++++ 97 

Adenoma 1 

Fibrosarcoma, metastatic, skeletal muscle 1 

Squamous cell carcinoma, metastatic, 

stomach, forestomach 1 

Salivary glands +++++++++++++++++++++++++ 99 

Stomach, forestomach +++++++++++++++++++++++++ 94 

Squamous cell carcinoma 1 

Squamous cell papilloma 2 

Stomach, glandular +++++++++++++++++++++++++ 93 

Cardiovascular System

Blood vessel + 1 

Heart +++++++++++++++++++++++++ 100 

Hemangiosarcoma X 1 

Hepatocellular carcinoma, metastatic, liver 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

44 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

0111333444444555555555666 

Number of Days on Study 6167556014778123338999023 

7085075001363190891255654 

0000000000000000000000000 

Carcass ID Number 7192377082710557044503380 

6968031541466018819579371 

Endocrine System

Adrenal cortex +++++++++++++++++++++++++ 

Histiocytic sarcoma

Squamous cell carcinoma, metastatic, 

stomach, forestomach X

Adrenal medulla +++++++++++++++++++++++++ 

Islets, pancreatic +++++ A ++++++++++++++++ A ++ 

Parathyroid gland ++ III ++++ I + IIII + I I ++ I + III

Pituitary gland +++++ A M I + + M +++ M ++++++++++ 

Pars distalis, adenoma

Pars intermedia, adenoma

Thyroid gland +++++++++++++++++++++++++ 

Follicular cell, adenoma

General Body System

Tissue NOS + 

Squamous cell carcinoma, metastatic, 

stomach, forestomach X

Genital System

Clitoral gland +++++++ I +++++ M + I +++++ I +++ 

Ovary +++++ A +++++++++++++++ M +++ 

Cystadenoma X

Granulosa cell tumor benign

Hemangiosarcoma X

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma X

Luteoma

Squamous cell carcinoma, metastatic, 

stomach, forestomach X

Uterus +++++++++++++++++++++++++ 

Granular cell tumor benign

Hamartoma

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma X

Squamous cell carcinoma, metastatic, 

stomach, forestomach X

Serosa, fibrosarcoma, metastatic, 

skeletal muscle

Vagina ++++++ ++++++++++++++++++ 

Hematopoietic System

Bone marrow +++++++++++++++++++++++++ 

Lymph node ++ + 

Squamous cell carcinoma, metastatic, 

stomach, forestomach X

Iliac, histiocytic sarcoma

Inguinal, fibrosarcoma, metastatic, 

skeletal muscle

Mediastinal, fibrosarcoma, 

metastatic, skeletal muscle

Mediastinal, histiocytic sarcoma

Renal, histiocytic sarcoma
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 45 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

6666666666666666667777777 

Number of Days on Study 4445555556667888990000111 

0362557796885226063449148 

Carcass ID Number

0000000000000000000000000 

2166161907299688538892520 

6506350230343985883089442 

Endocrine System

Adrenal cortex +++++++++++++++++++++++++ 

Histiocytic sarcoma X

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Adrenal medulla ++++++++++++++++ I ++++++++ 

Islets, pancreatic +++++++++++ A +++++++++++++ 

Parathyroid gland +++++++ I I +++++ I I ++ III + I ++ 

Pituitary gland +++++++ M +++ M +++++++++++ I + 

Pars distalis, adenoma X X X

Pars intermedia, adenoma

Thyroid gland +++++++++++++++++++++++++ 

Follicular cell, adenoma X

General Body System

Tissue NOS

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Genital System

Clitoral gland I ++++++++ I I ++++++++++++++ 

Ovary ++++++++++ I ++++++++++++++ 

Cystadenoma X X

Granulosa cell tumor benign

Hemangiosarcoma

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma X X

Luteoma

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Uterus +++++++++++++++++++++++++ 

Granular cell tumor benign

Hamartoma

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma X X X

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Serosa, fibrosarcoma, metastatic, 

skeletal muscle X

Vagina + ++++++++ ++++++++++++++ 

Hematopoietic System

Bone marrow +++++++++++++++++++++++++ 

Lymph node + + + + ++ + 

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Iliac, histiocytic sarcoma X

Inguinal, fibrosarcoma, metastatic, 

skeletal muscle X

Mediastinal, fibrosarcoma, 

metastatic, skeletal muscle X

Mediastinal, histiocytic sarcoma X

Renal, histiocytic sarcoma X
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

46 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

7777777777777777777777777 

Number of Days on Study 2222222222222222222233333 

1559999999999999999900000 

Carcass ID Number

0000000000000000000000000 

2460112344445677789911233 

7219785505679225711912226 

Endocrine System

Adrenal cortex +++++++++++++++++++++++++ 

Histiocytic sarcoma

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Adrenal medulla +++++++++++++++++++++++++ 

Islets, pancreatic +++++++++++++++++++++++++ 

Parathyroid gland + I I + I ++++ I ++++++ IIII ++ III

Pituitary gland +++++++ M +++ M ++++++++ M +++ M

Pars distalis, adenoma X X X

Pars intermedia, adenoma

Thyroid gland +++++++++++++++++++++++++ 

Follicular cell, adenoma X X X X

General Body System

Tissue NOS

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Genital System

Clitoral gland ++++++++++++++++++++++++ I

Ovary +++++++ M +++++++++++++++++ 

Cystadenoma X

Granulosa cell tumor benign X

Hemangiosarcoma

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma

Luteoma

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Uterus +++++++++++++++++++++++++ 

Granular cell tumor benign

Hamartoma X

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Serosa, fibrosarcoma, metastatic, 

skeletal muscle

Vagina +++++++++++++++++++++++++ 

Hematopoietic System

Bone marrow +++++++++++++++++++++++++ 

Lymph node + + + 

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Iliac, histiocytic sarcoma

Inguinal, fibrosarcoma, metastatic, 

skeletal muscle

Mediastinal, fibrosarcoma, 

metastatic, skeletal muscle

Mediastinal, histiocytic sarcoma

Renal, histiocytic sarcoma
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 47 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

7777777777777777777777777 

Number of Days on Study 3333333333333333333333333 

0000000000001111111111111 

0000000000000000000000001 Total

Carcass ID Number 3445566688890123345567990 Tissues/ 

7383747826954401442639070 Tumors

Endocrine System

Adrenal cortex +++++++++++++++++++++++++ 100 

Histiocytic sarcoma 1 

Squamous cell carcinoma, metastatic, 

stomach, forestomach 1 

Adrenal medulla +++++++++++++++++++++++++ 99 

Islets, pancreatic +++++++++++++++++++++++++ 97 

Parathyroid gland +++++ I +++ I + I I +++ I ++++ I + I I 59 

Pituitary gland +++++++++++++++++++++++++ 88 

Pars distalis, adenoma X X X X X X X 13 

Pars intermedia, adenoma X 1 

Thyroid gland +++++++++++++++++++++++++ 100 

Follicular cell, adenoma X X X 8 

General Body System

Tissue NOS 1 

Squamous cell carcinoma, metastatic, 

stomach, forestomach 1 

Genital System

Clitoral gland +++++++ M + I ++++++ I ++++++++ 89 

Ovary +++++++++++++ I +++++++++++ 95 

Cystadenoma X X 6 

Granulosa cell tumor benign 1 

Hemangiosarcoma 1 

Hepatocellular carcinoma, metastatic, liver 1 

Histiocytic sarcoma 3 

Luteoma X 1 

Squamous cell carcinoma, metastatic, 

stomach, forestomach 1 

Uterus +++++++++++++++++++++++++ 100 

Granular cell tumor benign X 1 

Hamartoma 1 

Hepatocellular carcinoma, metastatic, liver 1 

Histiocytic sarcoma 4 

Squamous cell carcinoma, metastatic, 

stomach, forestomach 1 

Serosa, fibrosarcoma, metastatic, 

skeletal muscle 1 

Vagina +++++++++++++++++++++++++ 97 

Hematopoietic System

Bone marrow +++++++++++++++++++++++++ 100 

Lymph node + + 15 

Squamous cell carcinoma, metastatic, 

stomach, forestomach 1 

Iliac, histiocytic sarcoma 1 

Inguinal, fibrosarcoma, metastatic, 

skeletal muscle 1 

Mediastinal, fibrosarcoma, 

metastatic, skeletal muscle 1 

Mediastinal, histiocytic sarcoma 1 

Renal, histiocytic sarcoma 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

48 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

0111333444444555555555666 

Number of Days on Study 6167556014778123338999023 

7085075001363190891255654 

0000000000000000000000000 

Carcass ID Number 7192377082710557044503380 

6968031541466018819579371 

Hematopoietic System (continued) 

Lymph node, mandibular +++ I + + M ++++ I ++++++ I ++++++ 

Lymph node, mesenteric +++++ A +++ A + + A A +++++++ A A I + 

Fibrosarcoma, metastatic, skeletal muscle

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma X

Rhabdomyosarcoma, metastatic, 

skeletal muscle

Squamous cell carcinoma, metastatic, 

stomach, forestomach X

Spleen +++++ A ++++++++++++++++ A ++ 

Fibrosarcoma, metastatic, skeletal muscle

Histiocytic sarcoma

Thymus +++++++ I +++++++++++++++++ 

Alveolar/bronchiolar carcinoma, 

metastatic, lung X

Fibrosarcoma, metastatic, skeletal muscle

Hepatocellular carcinoma, metastatic, liver X

Thymoma benign

Integumentary System

Mammary gland +++++++++++++++++++++ A +++ 

Adenoma

Skin +++++++++++++++++++++ A +++ 

Fibrosarcoma

Sarcoma

Subcutaneous tissue, fibrosarcoma

Subcutaneous tissue, fibrous histiocytoma

Musculoskeletal System

Bone +++++++++++++++++++++++++ 

Skeletal muscle + + + 

Fibrosarcoma, metastatic, skeletal muscle

Rhabdomyosarcoma

Squamous cell carcinoma, metastatic, 

stomach, forestomach X

Nervous System

Brain +++++++++++++++++++++++++ 
 #

Peripheral nerve + +
#

Spinal cord +
#

Respiratory System

Lung +++++++++++++++++++++++++ 

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar carcinoma X

Carcinoma, metastatic, harderian gland

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma X

Osteosarcoma, metastatic, tissue NOS

Nose +++++++++++++++++++++++++ 

Trachea +++++++++++++++++++++++++ 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 49 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

6666666666666666667777777 

Number of Days on Study 4445555556667888990000111 

0362557796885226063449148 

0000000000000000000000000 

Carcass ID Number 2166161907299688538892520 

6506350230343985883089442 

Hematopoietic System (continued) 

Lymph node, mandibular +++++ I +++++++++++++++ I +++ 

Lymph node, mesenteric +++++ I ++++++++ I +++++++++ I

Fibrosarcoma, metastatic, skeletal muscle X

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma X X X

Rhabdomyosarcoma, metastatic, 

skeletal muscle

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Spleen +++++++++++++++++++++++++ 

Fibrosarcoma, metastatic, skeletal muscle X

Histiocytic sarcoma X X

Thymus + I +++++++++++++++++++++++ 

Alveolar/bronchiolar carcinoma, 

metastatic, lung

Fibrosarcoma, metastatic, skeletal muscle X

Hepatocellular carcinoma, metastatic, liver

Thymoma benign

Integumentary System

Mammary gland +++++++++++++++++++++++++ 

Adenoma X

Skin +++++++++++++++++++++++ A + 

Fibrosarcoma X

Sarcoma

Subcutaneous tissue, fibrosarcoma X

Subcutaneous tissue, fibrous histiocytoma

Musculoskeletal System

Bone +++++++++++++++++++++++++ 

Skeletal muscle + +++ 

Fibrosarcoma, metastatic, skeletal muscle X

Rhabdomyosarcoma

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Nervous System

Brain +++++++++++++++++++++++++ 

Peripheral nerve + 

Spinal cord + 

Respiratory System

Lung +++++++++++++++++++++++++ 

Alveolar/bronchiolar adenoma X X

Alveolar/bronchiolar carcinoma X

Carcinoma, metastatic, harderian gland X

Hepatocellular carcinoma, metastatic, liver X X

Histiocytic sarcoma X

Osteosarcoma, metastatic, tissue NOS

Nose +++++++++++++++++++++++++ 
 #

Trachea +++++++++++++++++++++++++ 
 #
 

 

 

 

 

 

 

 

 

 

 

 

 

 

50 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

7777777777777777777777777 

Number of Days on Study 2222222222222222222233333 

1559999999999999999900000 

0000000000000000000000000 

Carcass ID Number 2460112344445677789911233 

7219785505679225711912226 

Hematopoietic System (continued) 

Lymph node, mandibular ++ I ++++++++ I +++++++++++++ 

Lymph node, mesenteric +++++++++++++++++++++++++ 

Fibrosarcoma, metastatic, skeletal muscle

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma

Rhabdomyosarcoma, metastatic, 

skeletal muscle X

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Spleen +++++++++++++++++++++++++ 

Fibrosarcoma, metastatic, skeletal muscle

Histiocytic sarcoma

Thymus +++++++++++++++++++++++++ 

Alveolar/bronchiolar carcinoma, 

metastatic, lung

Fibrosarcoma, metastatic, skeletal muscle

Hepatocellular carcinoma, metastatic, liver

Thymoma benign X

Integumentary System

Mammary gland I + I + I I ++++++ I ++++++++++++ 

Adenoma

Skin +++++++++++++++++++++++++ 

Fibrosarcoma

Sarcoma

Subcutaneous tissue, fibrosarcoma

Subcutaneous tissue, fibrous histiocytoma

Musculoskeletal System

Bone +++++++++++++++++++++++++ 

Skeletal muscle + + 

Fibrosarcoma, metastatic, skeletal muscle

Rhabdomyosarcoma X X

Squamous cell carcinoma, metastatic, 

stomach, forestomach

Nervous System

Brain +++++++++++++++++++++++++ 

Peripheral nerve

Spinal cord

Respiratory System

Lung +++++++++++++++++++++++++ 

Alveolar/bronchiolar adenoma X X X

Alveolar/bronchiolar carcinoma X

Carcinoma, metastatic, harderian gland

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma

Osteosarcoma, metastatic, tissue NOS X

Nose +++++++++++++++++++++++++ 

Trachea +++++++++++++++++++++++++ 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 51 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

7777777777777777777777777 

Number of Days on Study 3333333333333333333333333 

0000000000001111111111111 

0000000000000000000000001 Total

Carcass ID Number 3445566688890123345567990 Tissues/ 

7383747826954401442639070 Tumors

Hematopoietic System (continued) 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 92 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 90 

Fibrosarcoma, metastatic, skeletal muscle 1 

Hepatocellular carcinoma, metastatic, liver X 1 

Histiocytic sarcoma 4 

Rhabdomyosarcoma, metastatic, 

skeletal muscle 1 

Squamous cell carcinoma, metastatic, 

stomach, forestomach 1 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 98 

Fibrosarcoma, metastatic, skeletal muscle 1 

Histiocytic sarcoma 2 

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 98 

Alveolar/bronchiolar carcinoma, 

metastatic, lung 1 

Fibrosarcoma, metastatic, skeletal muscle 1 

Hepatocellular carcinoma, metastatic, liver 1 

Thymoma benign 1 

Integumentary System

Mammary gland ++++++++++++++++++++++ I + + 93 

Adenoma 1 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 98 

Fibrosarcoma 1 

Sarcoma X 1 

Subcutaneous tissue, fibrosarcoma 1 

Subcutaneous tissue, fibrous histiocytoma X 1 

Musculoskeletal System

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 100 

Skeletal muscle 9 

Fibrosarcoma, metastatic, skeletal muscle 1 

Rhabdomyosarcoma 2 

Squamous cell carcinoma, metastatic, 

stomach, forestomach 1 

Nervous System

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 100 

Peripheral nerve 3 

Spinal cord 2 

Respiratory System

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 100 

Alveolar/bronchiolar adenoma X 6 

Alveolar/bronchiolar carcinoma 3 

Carcinoma, metastatic, harderian gland 1 

Hepatocellular carcinoma, metastatic, liver 4 

Histiocytic sarcoma 2 

Osteosarcoma, metastatic, tissue NOS 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 100 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 100 
 

 

 

 

 

 

52 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

Number of Days on Study

0111333444444555555555666 

6167556014778123338999023 

7085075001363190891255654 

Carcass ID Number

0000000000000000000000000 

7192377082710557044503380 

6968031541466018819579371 

Special Senses System

Eye

Harderian gland

Adenoma

Carcinoma

Urinary System

Kidney

Histiocytic sarcoma

Urinary bladder

+++++++++++++++++++++++++ 

X

++++++++++++ I ++++++++++++ 

Systemic Lesions

Multiple organs

Histiocytic sarcoma

Lymphoma malignant

+++++++++++++++++++++++++ 

X
 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 53 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

Number of Days on Study

6666666666666666667777777 

4445555556667888990000111 

0362557796885226063449148 

Carcass ID Number

0000000000000000000000000 

2166161907299688538892520 

6506350230343985883089442 

Special Senses System

Eye + + + 

Harderian gland + + + 

Adenoma X X

Carcinoma X

Urinary System

Kidney

Histiocytic sarcoma

Urinary bladder

+++++++++++++++++++++++++ 

++++ I ++++++++++++++++++ A + 

Systemic Lesions

Multiple organs

Histiocytic sarcoma

Lymphoma malignant

+++++++++++++++++++++++++ 

X X X

X X X X X
 

 

 

 

 

 

 

54 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

7777777777777777777777777 

Number of Days on Study 2222222222222222222233333 

1559999999999999999900000 

0000000000000000000000000 

Carcass ID Number 2460112344445677789911233 

7219785505679225711912226 

Special Senses System

Eye + 

Harderian gland + 

Adenoma X

Carcinoma

Urinary System

Kidney +++++++++++++++++++++++++ 

Histiocytic sarcoma

Urinary bladder +++++++++++++++++++++++++ 

Systemic Lesions

Multiple organs +++++++++++++++++++++++++ 

Histiocytic sarcoma

Lymphoma malignant X X X X
 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 55 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control

7777777777777777777777777 

Number of Days on Study 3333333333333333333333333 

0000000000001111111111111 

0000000000000000000000001 Total

Carcass ID Number 3445566688890123345567990 Tissues/ 

7383747826954401442639070 Tumors

Special Senses System

Eye 4 

Harderian gland + 5 

Adenoma X 4 

Carcinoma 1 

Urinary System

Kidney +++++++++++++++++++++++++ 100 

Histiocytic sarcoma 1 

Urinary bladder + M +++++++++++++++++++++++ 96 

Systemic Lesions

Multiple organs +++++++++++++++++++++++++ 100 

Histiocytic sarcoma 4 

Lymphoma malignant X X X X 13 
 

 

 

 

 

 

 

 

 

 

 

 

56 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

Number of Days on Study

2333455555556666666666666 

0111634444880111122333444 

5344222888889111307479036 

Carcass ID Number

1111111111111111111111111 

3078188889062455043644371 

5973826593777814640630457 

Alimentary System

Esophagus

Gallbladder

Intestine large, colon

Intestine large, rectum

Intestine large, cecum

Intestine small, duodenum

Polyp adenomatous

Intestine small, jejunum

Intestine small, ileum

Liver

Hepatocellular carcinoma

Hepatocellular adenoma

Hepatocellular adenoma, multiple

Histiocytic sarcoma

Mesentery

Carcinoma, metastatic, islets, pancreatic

Pancreas

Carcinoma

Salivary glands

Stomach, forestomach

Stomach, glandular

+++++++++++++++++++++++++ 

+ A A + A +++++ AAA +++ A ++++ A +++ 

+ + A + + A ++++ AAA ++++++++++++ 

+ + AAAA ++++ AAA ++++++++++++ 

+ + A A + A ++++ AAA ++++++++++++ 

+ + AAAA ++++ AAA ++++++++++++ 

+ + AAAA ++++ AAA ++++++++++++ 

+ + AAAA ++++ AAA ++++++++++++ 

+++++++++++ A +++++++++++++ 

X X X X

X X XXX

X X

+ + + + + 

+++++++ I +++ A A ++++++++ A +++ 

++++++++++ M A +++++++++++++ 

+ + AAA +++++ AAA ++++++++++++ 

+ + AAA +++++ AAA ++++++++++++ 

Cardiovascular System

Heart +++++++++++ A +++++++++++++ 

Endocrine System

Adrenal cortex +++++++ I +++ A A +++++++++ M ++ 

Carcinoma, metastatic, islets, pancreatic

Hepatocellular carcinoma, metastatic, liver X

Capsule, adenoma

Adrenal medulla +++++++ I +++ A A +++++++++ M ++ 

Pheochromocytoma benign

Islets, pancreatic + + A ++++ I +++ A A ++++++++ A +++ 

Adenoma X

Parathyroid gland + I A I I I + I +++ A +++ I +++ I +++++ 

Pituitary gland ++++ M ++ I M + + A A +++++++++ M ++ 

Pars distalis, adenoma X X X

Thyroid gland + + A I +++++++ A +++++++++++++ 

C-cell, adenoma

Follicular cell, adenoma X

Follicular cell, carcinoma

General Body System

None
 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 57 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

Number of Days on Study

6666666666666666777777777 

5556677777779999011122222 

4481815555990004511712289 

Carcass ID Number

1111111112111111111111111 

1602371190060359127051980 

0038341270194295322576888 

Alimentary System

Esophagus

Gallbladder

Intestine large, colon

Intestine large, rectum

Intestine large, cecum

Intestine small, duodenum

Polyp adenomatous

Intestine small, jejunum

Intestine small, ileum

Liver

Hepatocellular carcinoma

Hepatocellular adenoma

Hepatocellular adenoma, multiple

Histiocytic sarcoma

Mesentery

Carcinoma, metastatic, islets, pancreatic

Pancreas

Carcinoma

Salivary glands

Stomach, forestomach

Stomach, glandular

+++++++++++++++++++++++++ 

+++++ A +++++ A ++++++++ A + A ++ 

+++++++++++ A + + A ++++++++++ 

+++++++++++ A + + A ++++++++++ 

+++++++++++ A + + A ++++++++++ 

++++++++++ A A + + A ++++++++++ 

++++++++++ A A + + A ++++++++++ 

++++++++++ A A + + A ++++++++++ 

+++++++++++++++++++++++++ 

X X X X X

X X X X XXXXX X

X X X X

++ + + + ++ + 

X

+++++++++++ A +++++++++++++ 

X

+++++++++++ A +++++++++++++ 

+++++++++++ A +++++++++++++ 

+++++++++++ A +++++++++++++ 

Cardiovascular System

Heart +++++++++++++++++++++++++ 

Endocrine System

Adrenal cortex +++++++++++ A +++++++++++++ 

Carcinoma, metastatic, islets, pancreatic X

Hepatocellular carcinoma, metastatic, liver

Capsule, adenoma

Adrenal medulla +++++++++++ A +++++++++++++ 

Pheochromocytoma benign

Islets, pancreatic +++++++++++ A +++++++++++++ 

Adenoma

Parathyroid gland ++ I I + I + I +++ A ++ I I + I I + I I + I I

Pituitary gland M + + M +++++++ A ++++++++ I ++++ 

Pars distalis, adenoma X X

Thyroid gland +++++++++++ A +++++++++++++ 

C-cell, adenoma

Follicular cell, adenoma X X X

Follicular cell, carcinoma

General Body System

None
 

 

 

 

 

 

 

 

 

 

 

 

58 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

Number of Days on Study

7777777777777777777777777 

2222222222222222223333333 

9999999999999999990000000 

Carcass ID Number

1111111111111111111111111 

1344556677888999990122233 

9825381518147012462434916 

Alimentary System

Esophagus

Gallbladder

Intestine large, colon

Intestine large, rectum

Intestine large, cecum

Intestine small, duodenum

Polyp adenomatous

Intestine small, jejunum

Intestine small, ileum

Liver

Hepatocellular carcinoma

Hepatocellular adenoma

Hepatocellular adenoma, multiple

Histiocytic sarcoma

Mesentery

Carcinoma, metastatic, islets, pancreatic

Pancreas

Carcinoma

Salivary glands

Stomach, forestomach

Stomach, glandular

+++++++++++++++++++++++++ 

+++++ I +++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

X X X

X X XXXXXX X X X X X X

X X X X

+ +++ + + 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

Cardiovascular System

Heart +++++++++++++++++++++++++ 

Endocrine System

Adrenal cortex ++++++++++++++++ M ++++++++ 

Carcinoma, metastatic, islets, pancreatic

Hepatocellular carcinoma, metastatic, liver

Capsule, adenoma

Adrenal medulla ++++++++++++++++ M ++++++++ 

Pheochromocytoma benign X

Islets, pancreatic +++++++++++++++++++++++++ 

Adenoma X

Parathyroid gland ++ I ++ I I +++ I + I I +++++++++++ 

Pituitary gland I ++++++++++++++++++++++ M + 

Pars distalis, adenoma X

Thyroid gland +++++++++++++++++++++++++ 

C-cell, adenoma

Follicular cell, adenoma X X X X X

Follicular cell, carcinoma

General Body System

None
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 59 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

Number of Days on Study

7777777777777777777777777 

3333333333333333333333333 

0000000000000011111111111 

Carcass ID Number

1111111111111111111111111 

3344445566677812222556779 

7916790523869050156264039 

Total

Tissues/ 

Tumors

Alimentary System

Esophagus

Gallbladder

Intestine large, colon

Intestine large, rectum

Intestine large, cecum

Intestine small, duodenum

Polyp adenomatous

Intestine small, jejunum

Intestine small, ileum

Liver

Hepatocellular carcinoma

Hepatocellular adenoma

Hepatocellular adenoma, multiple

Histiocytic sarcoma

Mesentery

Carcinoma, metastatic, islets, Pancreatic

Pancreas

Carcinoma

Salivary glands

Stomach, forestomach

Stomach, glandular

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

X

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

X X X X X X

X X X XXXX X X X X X X X

X X X X X

+ + + + + + 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

100 

87 

93 

91 

92 

90 

1 

90 

90 

99 

18 

43 

13 

2 

25 

1 

95 

1 

97 

93 

93 

Cardiovascular System

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 99 

Endocrine System

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 94 

Carcinoma, metastatic, islets, pancreatic 1 

Hepatocellular carcinoma, metastatic, liver 1 

Capsule, adenoma X 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 94 

Pheochromocytoma benign X 2 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 94 

Adenoma X 3 

Parathyroid gland I +++ I + I I +++ I I ++ I I ++ I + IIII 59 

Pituitary gland ++++++++++++ M +++++++++++ M 86 

Pars distalis, adenoma X X X 9 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 96 

C-cell, adenoma X 1 

Follicular cell, adenoma 9 

Follicular cell, carcinoma X 1 

General Body System

None
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

60 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

2333455555556666666666666 

Number of Days on Study 0111634444880111122333444 

5344222888889111307479036 

1111111111111111111111111 

Carcass ID Number 3078188889062455043644371 

5973826593777814640630457 

Genital System

Clitoral gland + IIII ++++++ A I + I I ++++++ I ++ 

Ovary +++++++++++ A A ++++++++++++ 

Cystadenoma

Granulosa cell tumor benign

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma X

Liposarcoma

Uterus +++++++++++++++++++++++++ 

Granular cell tumor benign

Histiocytic sarcoma X X

Leiomyoma

Polyp stromal

Sarcoma stromal

Vagina +++++++++++ A +++++++++++++ 

Hematopoietic System

Bone marrow +++++++++++ A +++++++++++++ 

Histiocytic sarcoma X

Lymph node + + + + + + 

Liposarcoma

Iliac, histiocytic sarcoma X

Mediastinal, sarcoma, metastatic, 

uncertain primary site

Renal, histiocytic sarcoma X

Lymph node, mandibular ++++++++++ M A A ++++++++++++ 

Lymph node, mesenteric + I A ++++ I + + AAA ++++++++++++ 

Hepatocellular carcinoma, metastatic, liver

Sarcoma, metastatic, uncertain primary site

Spleen + + A ++++++++ A A ++++++++++++ 

Sarcoma, metastatic, uncertain primary site

Thymus +++++++ I M + AAA ++++++++++++ 

Fibrosarcoma, metastatic, skin

Integumentary System

Mammary gland ++++ I I ++ I + + A +++ I +++++++++ 

Skin +++++++++++ A +++++++++++++ 

Subcutaneous tissue, fibrosarcoma

Musculoskeletal System

Bone +++++++++++++++++++++++++ 

Skeletal muscle + ++ + 

Rhabdomyosarcoma X

Nervous System

Brain +++++++++++++++++++++++++ 

Peripheral nerve + + 

Spinal cord + 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 61 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

6666666666666666777777777 

Number of Days on Study 5556677777779999011122222 

4481815555990004511712289 

1111111112111111111111111 

Carcass ID Number 1602371190060359127051980 

0038341270194295322576888 

Genital System

Clitoral gland +++++++ I I ++ I +++++++++++++ 

Ovary +++++++++++ A +++++++++++++ 

Cystadenoma X

Granulosa cell tumor benign

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma

Liposarcoma X

Uterus +++++++++++++++++++++++++ 

Granular cell tumor benign

Histiocytic sarcoma

Leiomyoma

Polyp stromal

Sarcoma stromal

Vagina +++++++++++++++++++++++++ 

Hematopoietic System

Bone marrow +++++++++++++++++++++++++ 

Histiocytic sarcoma

Lymph node + + + + + 

Liposarcoma X

Iliac, histiocytic sarcoma

Mediastinal, sarcoma, metastatic, 

uncertain primary site

Renal, histiocytic sarcoma

Lymph node, mandibular +++++++++++ A +++++++++++++ 

Lymph node, mesenteric +++++++++++ A +++++++++++++ 

Hepatocellular carcinoma, metastatic, liver

Sarcoma, metastatic, uncertain primary site

Spleen +++++++++++ A +++++++++++++ 

Sarcoma, metastatic, uncertain primary site

Thymus +++++++++++ A + I +++++++++++ 

Fibrosarcoma, metastatic, skin X

Integumentary System

Mammary gland ++++ I ++++++ A +++++++++++++ 

Skin +++++++++++ A +++++++++++++ 

Subcutaneous tissue, fibrosarcoma X X

Musculoskeletal System

Bone +++++++++++++++++++++++++ 

Skeletal muscle + + + + + 

Rhabdomyosarcoma X

Nervous System

Brain +++++++++++ A +++++++++++++ 

Peripheral nerve + + 

Spinal cord + + 
 

 

 

 

 

 

 

 

 

 

 

 

 

62 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

7777777777777777777777777 

Number of Days on Study 2222222222222222223333333 

9999999999999999990000000 

1111111111111111111111111 

Carcass ID Number 1344556677888999990122233 

9825381518147012462434916 

Genital System

Clitoral gland +++++++++++ I I +++ I I ++++++ I

Ovary +++++++++++++++++++++++++ 

Cystadenoma X

Granulosa cell tumor benign

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma

Liposarcoma

Uterus +++++++++++++++++++++++++ 

Granular cell tumor benign X

Histiocytic sarcoma

Leiomyoma

Polyp stromal X

Sarcoma stromal X X

Vagina +++++++++++++++++++++++++ 

Hematopoietic System

Bone marrow +++++++++++++++++++++++++ 

Histiocytic sarcoma

Lymph node + + + 

Liposarcoma

Iliac, histiocytic sarcoma

Mediastinal, sarcoma, metastatic, 

uncertain primary site

Renal, histiocytic sarcoma

Lymph node, mandibular ++++++++++++++++ I ++++++++ 

Lymph node, mesenteric +++++++++++++++++++++++++ 

Hepatocellular carcinoma, metastatic, liver

Sarcoma, metastatic, uncertain primary site

Spleen +++++++++++++++++++++++++ 

Sarcoma, metastatic, uncertain primary site

Thymus +++++++++++++++++++++++++ 

Fibrosarcoma, metastatic, skin

Integumentary System

Mammary gland +++++++++++++++++++++++++ 

Skin +++++++++++++++++++++++++ 

Subcutaneous tissue, fibrosarcoma

Musculoskeletal System

Bone +++++++++++++++++++++++++ 

Skeletal muscle + 

Rhabdomyosarcoma

Nervous System

Brain +++++++++++++++++++++++++ 

Peripheral nerve

Spinal cord
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 63 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

7777777777777777777777777 

Number of Days on Study 3333333333333333333333333 

0000000000000011111111111 

1111111111111111111111111 Total

Carcass ID Number 3344445566677812222556779 Tissues/ 

7916790523869050156264039 Tumors

Genital System

Clitoral gland +++++++++ I +++++++++++++ I + 81 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 97 

Cystadenoma X X X 5 

Granulosa cell tumor benign X X 2 

Hepatocellular carcinoma, metastatic, liver 1 

Histiocytic sarcoma 1 

Liposarcoma 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 100 

Granular cell tumor benign 1 

Histiocytic sarcoma 2 

Leiomyoma X 1 

Polyp stromal 1 

Sarcoma stromal 2 

Vagina + + + + + + + + + + + + + + + + + + + + + + + + + 99 

Hematopoietic System

Bone marrow +++++++++ I + + + + + + + + + + + + + + + 98 

Histiocytic sarcoma 1 

Lymph node ++ ++ + + + 21 

Liposarcoma 1 

Iliac, histiocytic sarcoma 1 

Mediastinal, sarcoma, metastatic, 

uncertain primary site X 1 

Renal, histiocytic sarcoma 1 

Lymph node, mandibular ++++++++++++++++++ I + + + + + + 94 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 93 

Hepatocellular carcinoma, metastatic, liver X 1 

Sarcoma, metastatic, uncertain primary site X 1 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 96 

Sarcoma, metastatic, uncertain primary site X 1 

Thymus + + + + + + + + + + + + + + + + + + + + + + + + + 93 

Fibrosarcoma, metastatic, skin 1 

Integumentary System

Mammary gland ++++++ I + + + + + + + + + + + + + + + + + + 92 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 98 

Subcutaneous tissue, fibrosarcoma 2 

Musculoskeletal System

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 100 

Skeletal muscle 10 

Rhabdomyosarcoma 2 

Nervous System

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 99 

Peripheral nerve 4 

Spinal cord 3 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

64 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

2333455555556666666666666 

Number of Days on Study 0111634444880111122333444 

5344222888889111307479036 

1111111111111111111111111 

Carcass ID Number 3078188889062455043644371 

5973826593777814640630457 

Respiratory System

Lung +++++++++++ A A ++++++++++++ 

Alveolar/bronchiolar adenoma X

Alveolar/bronchiolar carcinoma X

Fibrosarcoma, metastatic, skin

Hepatocellular carcinoma, metastatic, liver X

Histiocytic sarcoma X

Sarcoma, metastatic, uncertain primary site

Nose +++++++++++++++++++++++++ 

Carcinoma X

Pleura

Trachea +++++++++++++++++++++++++ 

Special Senses System

Eye + + 

Harderian gland + + 

Adenoma

Carcinoma X X

Zymbal’s gland

Carcinoma

Urinary System

Kidney +++++++++++ A A ++++++++++++ 

Adenoma

Urinary bladder + + A + + M + I +++ A +++++++++++++ 

Histiocytic sarcoma X

Systemic Lesions

Multiple organs +++++++++++++++++++++++++ 

Histiocytic sarcoma X X

Lymphoma malignant X X
 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 65 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

6666666666666666777777777 

Number of Days on Study 5556677777779999011122222 

4481815555990004511712289 

1111111112111111111111111 

Carcass ID Number 1602371190060359127051980 

0038341270194295322576888 

Respiratory System

Lung +++++++++++++++++++++++++ 

Alveolar/bronchiolar adenoma X X X

Alveolar/bronchiolar carcinoma

Fibrosarcoma, metastatic, skin X

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma

Sarcoma, metastatic, uncertain primary site X

Nose +++++++++++++++++++++++++ 

Carcinoma

Pleura

Trachea +++++++++++++++++++++++++ 

Special Senses System

Eye + + + 

Harderian gland + + + + 

Adenoma X X X X

Carcinoma

Zymbal’s gland

Carcinoma

Urinary System

Kidney +++++++++++++++++++++++++ 

Adenoma X

Urinary bladder +++++++++++++++++++++++++ 

Histiocytic sarcoma

Systemic Lesions

Multiple organs +++++++++++++++++++++++++ 

Histiocytic sarcoma

Lymphoma malignant X X X X
 

 

 

 

 

 

 

 

 

 

 

66 Polyvinyl Alcohol, NTP TR 474 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

7777777777777777777777777 

Number of Days on Study 2222222222222222223333333 

9999999999999999990000000 

1111111111111111111111111 

Carcass ID Number 1344556677888999990122233 

9825381518147012462434916 

Respiratory System

Lung

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar carcinoma

Fibrosarcoma, metastatic, skin

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma

Sarcoma, metastatic, uncertain primary site

Nose

Carcinoma

Pleura

Trachea

+++++++++++++++++++++++++ 

X

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

Special Senses System

Eye

Harderian gland

Adenoma

Carcinoma

Zymbal’s gland

Carcinoma

+ 

X

+ 

+ 

X

+ 

X

+ 

Urinary System

Kidney

Adenoma

Urinary bladder

Histiocytic sarcoma

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

Systemic Lesions

Multiple organs

Histiocytic sarcoma

Lymphoma malignant

+++++++++++++++++++++++++ 

X X X X
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 67 

TABLE A2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control

7777777777777777777777777 

Number of Days on Study 3333333333333333333333333 

0000000000000011111111111 

1111111111111111111111111 Total

Carcass ID Number 3344445566677812222556779 

7916790523869050156264039 

Tissues/ 

Tumors

Respiratory System

Lung

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar carcinoma

Fibrosarcoma, metastatic, skin

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma

Sarcoma, metastatic, uncertain primary site

Nose

+++++++++++++++++++++++++ 

X X X

X

X

+++++++++++++++++++++++++ 

98 

7 

3 

1 

2 

1 

1 

100 

Carcinoma 1 

Pleura + 1 

Trachea +++++++++++++++++++++++++ 100 

Special Senses System

Eye

Harderian gland

Adenoma

+ 

X

+ 

X

6 

11 

9 

Carcinoma 2 

Zymbal’s gland

Carcinoma

+ 

X

+ 3 

1 

Urinary System

Kidney

Adenoma

+++++++++++++++++++++++++ 98 

1 

Urinary bladder

Histiocytic sarcoma

+++++++++++++++++++++++++ 96 

1 

Systemic Lesions

Multiple organs

Histiocytic sarcoma

Lymphoma malignant

+++++++++++++++++++++++++ 

X X X X

100 

2 

14 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

68 Polyvinyl Alcohol, NTP TR 474 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

0133355555666666666666666 

Number of Days on Study 7112700145122222333444556 

2234247423900447478066181 

2222222222222222222222222 

Carcass ID Number 5413083823806194297416163 

8089828596114311240363490 

Alimentary System

Esophagus +++++++++++++++++++++++++ 

Gallbladder + + A + + A + I +++++ I AAAA ++++ A A + 

Hepatocholangiocarcinoma, metastatic, liver X

Intestine large, colon +++++++++++++++ AAA +++++++ 

Intestine large, rectum + + A ++++++++++++ AAA +++++++ 

Intestine large, cecum + + A ++++++++++++ AAA +++++++ 

Intestine small, duodenum + + A +++++++++++++ A A ++++ A ++ 

Intestine small, jejunum + + A + + A ++++++++++ A A ++++ A ++ 

Intestine small, ileum + + A +++++++++++++ A A ++++ A ++ 

Liver +++++++++++++++++++++++++ 

Hepatocellular carcinoma X X X X X

Hepatocellular adenoma XXX X X XXX

Hepatocellular adenoma, multiple

Hepatocholangiocarcinoma X X

Histiocytic sarcoma

Mesentery + + + ++ + ++ + 

Hepatocholangiocarcinoma, metastatic, liver X X

Yolk sac carcinoma, metastatic, ovary X

Oral mucosa

Pancreas ++++++++++++++++ I A +++++++ 

Hepatocholangiocarcinoma, metastatic, liver X

Salivary glands +++++++++++++++++++++++++ 

Stomach, forestomach ++++++++++++++++ A A ++++ A ++ 

Stomach, glandular +++++ A ++++++++++ A A ++++ A ++ 

Leiomyosarcoma X

Cardiovascular System

Blood vessel

Heart

+ 

+++++++++++++++++++++++++ 

Endocrine System

Adrenal cortex +++ I +++++++++++++++++++++ 

Capsule, carcinoma

Adrenal medulla +++ I +++++++++++++++++++++ 

Hepatocholangiocarcinoma, metastatic, liver X

Islets, pancreatic ++++++++++++++++ I A +++++++ 

Adenoma

Hepatocholangiocarcinoma, metastatic, liver X

Parathyroid gland ++ I +++ I + I ++++ I ++ I + I ++++++ 

Adenoma

Pituitary gland ++++ M + M ++++++++ M +++++++++ 

Pars distalis, adenoma X X X

Thyroid gland +++++++++++++++++++++++++ 

Follicular cell, adenoma X

General Body System

None
 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 69 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

6666666677777777777777777 

Number of Days on Study 6788899900012222222222222 

8526806714841199999999999 

2222222222222222222222222 

Carcass ID Number 1605844368724900112234445 

0797924318185547596726895 

Alimentary System

Esophagus +++++++++++++++++++ I +++++ 

Gallbladder ++++ A + + AAA + A A ++++++++++ I + 

Hepatocholangiocarcinoma, metastatic, liver

Intestine large, colon +++++++++++++++++++++++++ 

Intestine large, rectum +++++++++++++++++++++++++ 

Intestine large, cecum +++++++++++++++++++++++++ 

Intestine small, duodenum +++ A +++ A A + + A +++++++++++++ 

Intestine small, jejunum +++ A +++ A A + + A +++++++++++++ 

Intestine small, ileum +++ A +++ A A + + A +++++++++++++ 

Liver +++++++++++++++++++++++++ 

Hepatocellular carcinoma X X X X X X

Hepatocellular adenoma X X X X X X X X X X

Hepatocellular adenoma, multiple X X X X XXX X X

Hepatocholangiocarcinoma

Histiocytic sarcoma X

Mesentery + ++++ + ++ ++ 

Hepatocholangiocarcinoma, metastatic, liver

Yolk sac carcinoma, metastatic, ovary

Oral mucosa

Pancreas +++++++++++++++++++++++++ 

Hepatocholangiocarcinoma, metastatic, liver

Salivary glands +++++++++++++++++++++++++ 

Stomach, forestomach +++++++++++++++++++++++++ 

Stomach, glandular +++++++++++++++++++++++++ 

Leiomyosarcoma

Cardiovascular System

Blood vessel

Heart +++++++++++++++++++++++++ 

Endocrine System

Adrenal cortex +++ M +++++++++++++++++++++ 

Capsule, carcinoma

Adrenal medulla +++ M +++++++++++++++++++++ 

Hepatocholangiocarcinoma, metastatic, liver

Islets, pancreatic ++ I ++++++++++++++++++++++ 

Adenoma

Hepatocholangiocarcinoma, metastatic, liver

Parathyroid gland ++ I I + I ++ I ++ III + I +++++++++ 

Adenoma

Pituitary gland M +++++++ M ++++++++++++++++ 

Pars distalis, adenoma X X X

Thyroid gland +++++++++++++++++++++++++ 

Follicular cell, adenoma X X

General Body System

None
 

 

 

 

 

 

 

 

 

 

 

 

 

 

70 Polyvinyl Alcohol, NTP TR 474 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

7777777777777777777777777 

Number of Days on Study 2222222222333333333333333 

9999999999000000000000000 

2222222223222222222222222 

Carcass ID Number 5677799990001122223345555 

6556723790352701454770149 

Alimentary System

Esophagus +++++++++++++++++++++++++ 

Gallbladder ++++++++++ I ++++++ I +++++++ 

Hepatocholangiocarcinoma, metastatic, liver

Intestine large, colon +++++++++++++++++++++++++ 

Intestine large, rectum +++++++++++++++++++++++++ 

Intestine large, cecum +++++++++++++++++++++++++ 

Intestine small, duodenum +++++++++++++++++++++++++ 

Intestine small, jejunum +++++++++++++++++++++++++ 

Intestine small, ileum +++++++++++++++++++++++++ 

Liver +++++++++++++++++++++++++ 

Hepatocellular carcinoma X X X

Hepatocellular adenoma X X X X X XXXX X

Hepatocellular adenoma, multiple X X X X

Hepatocholangiocarcinoma

Histiocytic sarcoma

Mesentery + ++++++ +++ 

Hepatocholangiocarcinoma, metastatic, liver

Yolk sac carcinoma, metastatic, ovary

Oral mucosa

Pancreas +++++++++++++++++++++++++ 

Hepatocholangiocarcinoma, metastatic, liver

Salivary glands +++++++++++++++++++++++++ 

Stomach, forestomach +++++++++++++++++++++++++ 

Stomach, glandular +++++++++++++++++++++++++ 

Leiomyosarcoma

Cardiovascular System

Blood vessel

Heart

+ 

+++++++++++++++++++++++++ 

Endocrine System

Adrenal cortex +++++++++++++++++++++++++ 

Capsule, carcinoma X

Adrenal medulla ++++++++++++ I + I ++++++++++ 

Hepatocholangiocarcinoma, metastatic, liver

Islets, pancreatic +++++++++++++++++++++++++ 

Adenoma

Hepatocholangiocarcinoma, metastatic, liver

Parathyroid gland + I + I +++ I I +++ I + I I ++++ I ++ I + 

Adenoma X

Pituitary gland ++++ M ++++ I +++ M I ++++++++++ 

Pars distalis, adenoma X X

Thyroid gland +++++++++++++++++++++++++ 

Follicular cell, adenoma X X X

General Body System

None
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 71 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

7777777777777777777777777 

Number of Days on Study 3333333333333333333333333 

0000000001111111111111111 

2222222222222222222222222 Total

Carcass ID Number 6666778890012335577788899 Tissues/ 

0268283402613152334906768 Tumors

Alimentary System

Esophagus +++++++++++++++++++++++++ 99 

Gallbladder ++++++++ I +++++++++++++++ I 79 

Hepatocholangiocarcinoma, metastatic, liver 1 

Intestine large, colon +++++++++++++++++++++++++ 97 

Intestine large, rectum +++++++++++++++++++++++++ 96 

Intestine large, cecum +++++++++++++++++++++++++ 96 

Intestine small, duodenum +++++++++++++++++++++++++ 92 

Intestine small, jejunum +++++++++++++++++++++++++ 91 

Intestine small, ileum +++++++++++++++++++++++++ 92 

Liver +++++++++++++++++++++++++ 100 

Hepatocellular carcinoma X X X XXX 20 

Hepatocellular adenoma X X X X X XXX 36 

Hepatocellular adenoma, multiple X X XXX X 19 

Hepatocholangiocarcinoma 2 

Histiocytic sarcoma 1 

Mesentery + + + + + + + 36 

Hepatocholangiocarcinoma, metastatic, liver 2 

Yolk sac carcinoma, metastatic, ovary 1 

Oral mucosa + 1 

Pancreas +++++++++++++++++++++++++ 98 

Hepatocholangiocarcinoma, metastatic, liver 1 

Salivary glands +++++++++++++++++++++++++ 100 

Stomach, forestomach +++++++++++++++++++++++++ 97 

Stomach, glandular +++++++++++++++++++++++++ 96 

Leiomyosarcoma 1 

Cardiovascular System

Blood vessel

Heart +++++++++++++++++++++++++ 

2 

100 

Endocrine System

Adrenal cortex ++++++++ M ++++++++++++++++ 97 

Capsule, carcinoma 1 

Adrenal medulla +++ I ++++ M +++++ I +++++++++ I 92 

Hepatocholangiocarcinoma, metastatic, liver 1 

Islets, pancreatic +++++++++++++++++++++++++ 97 

Adenoma X 1 

Hepatocholangiocarcinoma, metastatic, liver 1 

Parathyroid gland I + I + I + I ++++ I +++ I + I ++++++ I 69 

Adenoma 1 

Pituitary gland M +++++++ M +++++ M ++++ I + I I + M 84 

Pars distalis, adenoma X X 10 

Thyroid gland +++++++++++++++++++++++++ 100 

Follicular cell, adenoma X X X X X 11 

General Body System

None
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

72 Polyvinyl Alcohol, NTP TR 474 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

0133355555666666666666666 

Number of Days on Study 7112700145122222333444556 

2234247423900447478066181 

2222222222222222222222222 

Carcass ID Number 5413083823806194297416163 

8089828596114311240363490 

Genital System

Clitoral gland + I +++++ I +++++++ I A + I + I I + I + 

Ovary ++++++++++++++++ A ++++++++ 

Cystadenoma

Hepatocholangiocarcinoma, metastatic, liver X

Luteoma X

Teratoma benign

Yolk sac carcinoma X

Uterus +++++++++++++++++++++++++ 

Carcinoma X

Deciduoma NOS

Histiocytic sarcoma

Polyp stromal X

Vagina ++ ++++++++++++++++++++++ 

Histiocytic sarcoma

Hematopoietic System

Bone marrow +++++++++++++++++++++++++ 

Lymph node ++ + + 

Plasma cell tumor benign X

Lymph node, mandibular +++++ I +++++ I ++++ I ++++++++ 

Plasma cell tumor benign

Lymph node, mesenteric ++++++++++++++++ A M +++++++ 

Hepatocholangiocarcinoma, metastatic, liver X

Spleen ++++++++++++++++++++++ A ++ 

Thymus +++++ I +++++++++++++++++++ 

Hepatocholangiocarcinoma, metastatic, liver X

Thymoma benign

Integumentary System

Mammary gland I +++++++++++ I ++ I +++ I +++++ 

Carcinoma X

Skin +++++++++++++++++++++++++ 

Subcutaneous tissue, pinna, fibrosarcoma

Musculoskeletal System

Bone +++++++++++++++++++++++++ 

Pelvis, sarcoma X

Skeletal muscle +++ + + + 

Hepatocholangiocarcinoma, metastatic, liver X

Rhabdomyosarcoma

Sarcoma X

Nervous System

Brain +++++++++++++++++++++++++ 
 #

Peripheral nerve + + + +
#

Spinal cord + + + +
#
 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 73 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

6666666677777777777777777 

Number of Days on Study 6788899900012222222222222 

8526806714841199999999999 

2222222222222222222222222 

Carcass ID Number 1605844368724900112234445 

0797924318185547596726895 

Genital System

Clitoral gland ++++ I I +++++++++++ I ++++ I ++ 

Ovary +++++++++++++++++++++++++ 

Cystadenoma X

Hepatocholangiocarcinoma, metastatic, liver

Luteoma

Teratoma benign

Yolk sac carcinoma

Uterus +++++++++++++++++++++++++ 

Carcinoma

Deciduoma NOS

Histiocytic sarcoma X

Polyp stromal

Vagina +++++++++++++++++++++++++ 

Histiocytic sarcoma X

Hematopoietic System

Bone marrow +++++++++++++++++++++++++ 

Lymph node + + + ++ 

Plasma cell tumor benign

Lymph node, mandibular +++++++ I +++++ I +++++++++++ 

Plasma cell tumor benign X

Lymph node, mesenteric +++ A +++ I ++ I ++++++++++++++ 

Hepatocholangiocarcinoma, metastatic, liver

Spleen +++ A +++++++++++++++++++++ 

Thymus +++++++++++++++++++++++++ 

Hepatocholangiocarcinoma, metastatic, liver

Thymoma benign

Integumentary System

Mammary gland ++++++++++++ I ++++++++++++ 

Carcinoma

Skin +++++++++++++++++++++++++ 

Subcutaneous tissue, pinna, fibrosarcoma

Musculoskeletal System

Bone +++++++++++++++++++++++++ 

Pelvis, sarcoma

Skeletal muscle

Hepatocholangiocarcinoma, metastatic, liver

Rhabdomyosarcoma

Sarcoma

Nervous System

Brain +++++++++++++++++++++++++ 

Peripheral nerve

Spinal cord
 

 

 

 

 

 

 

 

 

 

 

74 Polyvinyl Alcohol, NTP TR 474 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

7777777777777777777777777 

Number of Days on Study 2222222222333333333333333 

9999999999000000000000000 

2222222223222222222222222 

Carcass ID Number 5677799990001122223345555 

6556723790352701454770149 

Genital System

Clitoral gland +++++++ I + I +++++++++++++ I + 

Ovary ++ I +++++++++++++++ M ++++++ 

Cystadenoma

Hepatocholangiocarcinoma, metastatic, liver

Luteoma X

Teratoma benign X

Yolk sac carcinoma

Uterus +++++++++++++++++++++++++ 

Carcinoma

Deciduoma NOS

Histiocytic sarcoma

Polyp stromal X

Vagina +++++++++++++++++++++++++ 

Histiocytic sarcoma

Hematopoietic System

Bone marrow +++++++++++++++++++++++++ 

Lymph node + + + + + + 

Plasma cell tumor benign

Lymph node, mandibular +++++++++++++++++++++++++ 

Plasma cell tumor benign

Lymph node, mesenteric ++++ I + I ++++++++++++++++++ 

Hepatocholangiocarcinoma, metastatic, liver

Spleen +++++++++++++++++++++++++ 

Thymus +++++++++++++++++++++++++ 

Hepatocholangiocarcinoma, metastatic, liver

Thymoma benign

Integumentary System

Mammary gland ++++++++++ I +++++++++++++ I

Carcinoma

Skin +++++++++++++++++++++++++ 

Subcutaneous tissue, pinna, fibrosarcoma X

Musculoskeletal System

Bone +++++++++++++++++++++++++ 

Pelvis, sarcoma

Skeletal muscle + 

Hepatocholangiocarcinoma, metastatic, liver

Rhabdomyosarcoma X

Sarcoma

Nervous System

Brain +++++++++++++++++++++++++ 

Peripheral nerve

Spinal cord
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 75 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

7777777777777777777777777 

Number of Days on Study 3333333333333333333333333 

0000000001111111111111111 

2222222222222222222222222 Total

Carcass ID Number 6666778890012335577788899 Tissues/ 

0268283402613152334906768 Tumors

Genital System

Clitoral gland +++++++ I +++++ I +++++++++++ 83 

Ovary +++++++++++++++++++++++++ 97 

Cystadenoma X X 3 

Hepatocholangiocarcinoma, metastatic, liver 1 

Luteoma 2 

Teratoma benign 1 

Yolk sac carcinoma X 2 

Uterus +++++++++++++++++++++++++ 100 

Carcinoma 1 

Deciduoma NOS X 1 

Histiocytic sarcoma 1 

Polyp stromal X 3 

Vagina +++++++++++++++++++++++++ 99 

Histiocytic sarcoma 1 

Hematopoietic System

Bone marrow +++++++++++++++++++++++++ 100 

Lymph node + + + + ++ 21 

Plasma cell tumor benign 1 

Lymph node, mandibular +++++++ I +++++++++++++++ I + 93 

Plasma cell tumor benign 1 

Lymph node, mesenteric +++++++++++++++++++++++++ 93 

Hepatocholangiocarcinoma, metastatic, liver 1 

Spleen +++++++++++++++++++++++++ 98 

Thymus +++++++++++++++++++++++++ 99 

Hepatocholangiocarcinoma, metastatic, liver 1 

Thymoma benign X 1 

Integumentary System

Mammary gland I I +++++++++++++++++++++++ 91 

Carcinoma 1 

Skin +++++++++++++++++++++++++ 100 

Subcutaneous tissue, pinna, fibrosarcoma 1 

Musculoskeletal System

Bone +++++++++++++++++++++++++ 100 

Pelvis, sarcoma 1 

Skeletal muscle + 8 

Hepatocholangiocarcinoma, metastatic, liver 1 

Rhabdomyosarcoma X 2 

Sarcoma 1 

Nervous System

Brain +++++++++++++++++++++++++ 100 

Peripheral nerve 4 

Spinal cord 4 
 

 

 

 

 

 

 

 

 

 

 

76 Polyvinyl Alcohol, NTP TR 474 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

Number of Days on Study

0133355555666666666666666 

7112700145122222333444556 

2234247423900447478066181 

Carcass ID Number

2222222222222222222222222 

5413083823806194297416163 

8089828596114311240363490 

Respiratory System

Lung

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar carcinoma

Hepatocholangiocarcinoma, metastatic, liver

Sarcoma, metastatic, uncertain primary site

Yolk sac carcinoma, metastatic, ovary

Nose

Trachea

+++++++++++++++++++++++++ 

X X

X X

X

X

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

Special Senses System

Eye

Harderian gland

Adenoma

Carcinoma

+ 

+ 

X

Urinary System

Kidney

Urinary bladder

+++++++++++++++++++++++++ 

++++++++++++++++++ I ++++++ 

Systemic Lesions

Multiple organs

Histiocytic sarcoma

Lymphoma malignant

+++++++++++++++++++++++++ 

XXX
 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 77 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

Number of Days on Study

6666666677777777777777777 

6788899900012222222222222 

8526806714841199999999999 

Carcass ID Number

2222222222222222222222222 

1605844368724900112234445 

0797924318185547596726895 

Respiratory System

Lung

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar carcinoma

Hepatocholangiocarcinoma, metastatic, liver

Sarcoma, metastatic, uncertain primary site

Yolk sac carcinoma, metastatic, ovary

Nose

Trachea

+++++++++++++++++++++++++ 

X

X X X

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

Special Senses System

Eye

Harderian gland

Adenoma

Carcinoma

+ 

+ 

X

Urinary System

Kidney

Urinary bladder

+++++++++++++++++++++++++ 

+++ A +++++++++++++++++++++ 

Systemic Lesions

Multiple organs

Histiocytic sarcoma

Lymphoma malignant

+++++++++++++++++++++++++ 

X

X X X X
 

 

 

 

 

 

 

 

78 Polyvinyl Alcohol, NTP TR 474 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

7777777777777777777777777 

Number of Days on Study 2222222222333333333333333 

9999999999000000000000000 

2222222223222222222222222 

Carcass ID Number 5677799990001122223345555 

6556723790352701454770149 

Respiratory System

Lung

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar carcinoma

Hepatocholangiocarcinoma, metastatic, liver

Sarcoma, metastatic, uncertain primary site

Yolk sac carcinoma, metastatic, ovary

Nose

Trachea

+++++++++++++++++++++++++ 

X X X

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

Special Senses System

Eye

Harderian gland

Adenoma

Carcinoma

Urinary System

Kidney

Urinary bladder

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

Systemic Lesions

Multiple organs

Histiocytic sarcoma

Lymphoma malignant

+++++++++++++++++++++++++ 

X X X XXX X X
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 79 

TABLE A2
#

Individual Animal Tumor Pathology of Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 25%
#

7777777777777777777777777 

Number of Days on Study 3333333333333333333333333 

0000000001111111111111111 

2222222222222222222222222 Total

Carcass ID Number 6666778890012335577788899 

0268283402613152334906768 

Tissues/ 

Tumors

Respiratory System

Lung

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar carcinoma

Hepatocholangiocarcinoma, metastatic, liver

Sarcoma, metastatic, uncertain primary site

Yolk sac carcinoma, metastatic, ovary

Nose

+++++++++++++++++++++++++ 

X X

X X

+++++++++++++++++++++++++ 

100 

8 

5 

2 

1 

1 

100 

Trachea +++++++++++++++++++++++++ 100 

Special Senses System

Eye + 3 

Harderian gland + + + + 6 

Adenoma X X X 4 

Carcinoma 1 

Urinary System

Kidney

Urinary bladder

+++++++++++++++++++++++++ 

+++++++++++++++++++++++++ 

100 

98 

Systemic Lesions

Multiple organs

Histiocytic sarcoma

Lymphoma malignant

+++++++++++++++++++++++++ 

X X X

100 

1 

18 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

80 Polyvinyl Alcohol, NTP TR 474 

TABLE A3a

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control vs. Vehicle Control

Untreated Control Vehicle Control

Harderian Gland: Adenoma a Overall rate 4/100 (4%) 9/100 (9%) 

Adjusted rateb 7.1% 15.0% c Terminal rate 2/47 (4%) 5/51 (10%) 

First incidence (days) 640 668 

d Life table test P ̆0.160 

d Logistic regression test P ̆0.152 

d Fisher exact test P ̆0.125 

Harderian Gland: Adenoma or Carcinoma

Overall rate 5/100 (5%) 11/100 (11%) 

Adjusted rate 8.3% 17.1% 

Terminal rate 2/47 (4%) 5/51 (10%) 

First incidence (days) 640 620 

Life table test P ̆0.130 

Logistic regression test P ̆0.115 

Fisher exact test P ̆0.096 

Liver: Hepatocellular Adenoma

Overall rate 55/99 (56%) 56/99 (57%) 

Adjusted rate 80.3% 80.5% 

Terminal rate 34/47 (72%) 38/51 (75%) 

First incidence (days) 365 611 

Life table test P ̆0.384N

Logistic regression test P ̆0.355N

Fisher exact test P ̆0.500 

Liver: Hepatocellular Carcinoma

Overall rate 11/99 (11%) 18/99 (18%) 

Adjusted rate 18.6% 27.5% 

Terminal rate 5/47 (11%) 9/51 (18%) 

First incidence (days) 538 548 

Life table test P ̆0.175 

Logistic regression test P ̆0.143 

Fisher exact test P ̆0.114 

Liver: Hepatocellular Adenoma or Carcinoma

Overall rate 59/99 (60%) 61/99 (62%) 

Adjusted rate 82.6% 82.9% 

Terminal rate 35/47 (74%) 39/51 (76%) 

First incidence (days) 365 548 

Life table test P ̆0.421N

Logistic regression test P ̆0.402N

Fisher exact test P ̆0.442 

Lung: Alveolar/bronchiolar Adenoma

Overall rate 6/100 (6%) 7/98 (7%) 

Adjusted rate 11.0% 11.8% 

Terminal rate 4/47 (9%) 3/51 (6%) 

First incidence (days) 643 611 

Life table test P ̆0.558 

Logistic regression test P ̆0.542 

Fisher exact test P ̆0.485 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 81 

TABLE A3a

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control vs. Vehicle Control

Untreated Control Vehicle Control

Lung: Alveolar/bronchiolar Adenoma or Carcinoma

Overall rate 9/100 (9%) 10/98 (10%) 

Adjusted rate 15.2% 16.4% 

Terminal rate 4/47 (9%) 5/51 (10%) 

First incidence (days) 473 548 

Life table test P ̆0.571 

Logistic regression test P ̆0.525 

Fisher exact test P ̆0.481 

Ovary: Cystadenoma

Overall rate 6/95 (6%) 5/97 (5%) 

Adjusted rate 11.1% 9.4% 

Terminal rate 3/45 (7%) 4/51 (8%) 

First incidence (days) 529 711 

Life table test P ̆0.428N

Logistic regression test P ̆0.437N

Fisher exact test P ̆0.486N

Pituitary Gland (Pars Distalis): Adenoma

Overall rate 13/88 (15%) 9/86 (10%) 

Adjusted rate 26.2% 14.9% 

Terminal rate 9/43 (21%) 4/47 (9%) 

First incidence (days) 657 620 

Life table test P ̆0.196N

Logistic regression test P ̆0.210N

Fisher exact test P ̆0.266N

Thyroid Gland (Follicular Cell): Adenoma

Overall rate 8/100 (8%) 9/96 (9%) 

Adjusted rate 16.3% 15.8% 

Terminal rate 7/47 (15%) 6/51 (12%) 

First incidence (days) 686 634 

Life table test P ̆0.566 

Logistic regression test P ̆0.555 

Fisher exact test P ̆0.464 

Thyroid Gland (Follicular Cell): Adenoma or Carcinoma

Overall rate 8/100 (8%) 10/96 (10%) 

Adjusted rate 16.3% 17.6% 

Terminal rate 7/47 (15%) 7/51 (14%) 

First incidence (days) 686 634 

Life table test P ̆0.469 

Logistic regression test P ̆0.456 

Fisher exact test P ̆0.368 

All Organs: Malignant Lymphoma

Overall rate 13/100 (13%) 14/100 (14%) 

Adjusted rate 23.1% 23.0% 

Terminal rate 7/47 (15%) 8/51 (16%) 

First incidence (days) 652 627 

Life table test P ̆0.578N

Logistic regression test P ̆0.580 

Fisher exact test P ̆0.500 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

82 

c

Polyvinyl Alcohol, NTP TR 474 

TABLE A3a

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control vs. Vehicle Control

Untreated Control	 Vehicle Control

All Organs: Benign Neoplasms

Overall rate 67/100 (67%) 72/100 (72%) 

Adjusted rate 90.3% 92.1% 

Terminal rate 40/47 (85%) 45/51 (88%) 

First incidence (days) 365 588 

Life table test P ̆0.533N

Logistic regression test P ̆0.540N

Fisher exact test P ̆0.270 

All Organs: Malignant Neoplasms

Overall rate 39/100 (39%) 42/100 (42%) 

Adjusted rate 52.7% 55.9% 

Terminal rate 14/47 (30%) 21/51 (41%) 

First incidence (days) 410 548 

Life table test P ̆0.545N

Logistic regression test P ̆0.557 

Fisher exact test P ̆0.387 

All Organs: Benign or Malignant Neoplasms

Overall rate 78/100 (78%) 82/100 (82%) 

Adjusted rate 93.9% 96.4% 

Terminal rate 42/47 (89%) 48/51 (94%) 

First incidence (days) 365 548 

Life table test P ̆0.449N

Logistic regression test P ̆0.464N

Fisher exact test P ̆0.298 

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for liver, lung, ovary, 

pituitary gland, and thyroid gland; for other tissues, denominator is number of animals necropsied. b	 Kaplan-Meier estimated neoplasm incidence at the end of the study after adjustment for intercurrent mortality

Observed incidence at terminal kill

d	 Beneath the vehicle control group incidence are the P values corresponding to pairwise comparisons between the untreated control group and the vehicle

control group. The life table test regards neoplasms in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. The logistic

regression test regards these lesions as nonfatal. The Fisher exact test compares directly the overall incidence rates. For all tests, a lower incidence in the

vehicle control group is indicated by N. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 83 

TABLE A3b
 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control vs. 25%
#

Untreated Control 25% 

Harderian Gland: Adenoma or Carcinoma a Overall rate 5/100 (5%) 5/100 (5%) 

Adjusted rateb 8.3% 7.4% c Terminal rate 2/47 (4%) 3/61 (5%) 

First incidence (days) 640 646 

d Life table test P ̆0.507N

d Logistic regression test P ̆0.583N

d Fisher exact test P ̆0.626N

Liver: Hepatocellular Adenoma

Overall rate 55/99 (56%) 55/100 (55%) 

Adjusted rate 80.3% 69.2% 

Terminal rate 34/47 (72%) 37/61 (61%) 

First incidence (days) 365 514 

Life table test P ̆0.081N

Logistic regression test P ̆0.239N

Fisher exact test P ̆0.525N

Liver: Hepatocellular Carcinoma

Overall rate 11/99 (11%) 20/100 (20%) 

Adjusted rate 18.6% 28.0% 

Terminal rate 5/47 (11%) 13/61 (21%) 

First incidence (days) 538 507 

Life table test P ̆0.181 

Logistic regression test P ̆0.088 

Fisher exact test P ̆0.062 

Liver: Hepatocellular Adenoma or Carcinoma

Overall rate 59/99 (60%) 62/100 (62%) 

Adjusted rate 82.6% 73.4% 

Terminal rate 35/47 (74%) 39/61 (64%) 

First incidence (days) 365 507 

Life table test P ̆0.143N

Logistic regression test P ̆0.416N

Fisher exact test P ̆0.420 

Lung: Alveolar/bronchiolar Adenoma

Overall rate 6/100 (6%) 8/100 (8%) 

Adjusted rate 11.0% 11.7% 

Terminal rate 4/47 (9%) 6/61 (10%) 

First incidence (days) 643 313 

Life table test P ̆0.548 

Logistic regression test P ̆0.410 

Fisher exact test P ̆0.391 

Lung: Alveolar/bronchiolar Carcinoma

Overall rate 3/100 (3%) 5/100 (5%) 

Adjusted rate 4.7% 7.8% 

Terminal rate 0/47 (0%) 4/61 (7%) 

First incidence (days) 473 675 

Life table test P ̆0.474 

Logistic regression test P ̆0.383 

Fisher exact test P ̆0.360 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

84 Polyvinyl Alcohol, NTP TR 474 

TABLE A3b
 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control vs. 25%
#

Untreated Control 25% 

Lung: Alveolar/bronchiolar Adenoma or Carcinoma

Overall rate 9/100 (9%) 13/100 (13%) 

Adjusted rate 15.2% 19.3% 

Terminal rate 4/47 (9%) 10/61 (16%) 

First incidence (days) 473 313 

Life table test P ̆0.434 

Logistic regression test P ̆0.274 

Fisher exact test P ̆0.249 

Ovary: Cystadenoma

Overall rate 6/95 (6%) 3/97 (3%) 

Adjusted rate 11.1% 4.8% 

Terminal rate 3/45 (7%) 2/59 (3%) 

First incidence (days) 529 690 

Life table test P ̆0.157N

Logistic regression test P ̆0.204N

Fisher exact test P ̆0.238N

Pituitary Gland (Pars Distalis): Adenoma

Overall rate 13/88 (15%) 10/84 (12%) 

Adjusted rate 26.2% 16.5% 

Terminal rate 9/43 (21%) 6/50 (12%) 

First incidence (days) 657 634 

Life table test P ̆0.206N

Logistic regression test P ̆0.293N

Fisher exact test P ̆0.372N

Thyroid Gland (Follicular Cell): Adenoma

Overall rate 8/100 (8%) 11/100 (11%) 

Adjusted rate 16.3% 16.7% 

Terminal rate 7/47 (15%) 8/61 (13%) 

First incidence (days) 686 637 

Life table test P ̆0.528 

Logistic regression test P ̆0.445 

Fisher exact test P ̆0.315 

All Organs: Malignant Lymphoma

Overall rate 13/100 (13%) 18/100 (18%) 

Adjusted rate 23.1% 25.8% 

Terminal rate 7/47 (15%) 12/61 (20%) 

First incidence (days) 652 624 

Life table test P ̆0.451 

Logistic regression test P ̆0.324 

Fisher exact test P ̆0.217 

All Organs: Benign Neoplasms

Overall rate 67/100 (67%) 69/100 (69%) 

Adjusted rate 90.3% 81.9% 

Terminal rate 40/47 (85%) 46/61 (75%) 

First incidence (days) 365 313 

Life table test P ̆0.076N

Logistic regression test P ̆0.332N

Fisher exact test P ̆0.440 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

85 

c

Polyvinyl Alcohol, NTP TR 474 

TABLE A3b
 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Untreated Control vs. 25%
#

Untreated Control	 25% 

All Organs: Malignant Neoplasms

Overall rate 39/100 (39%) 51/100 (51%) 

Adjusted rate 52.7% 60.9% 

Terminal rate 14/47 (30%) 30/61 (49%) 

First incidence (days) 

Life table test

Logistic regression test

Fisher exact test

410 324 

P ̆0.393 

P ̆0.088 

P ̆0.059 

All Organs: Benign or Malignant Neoplasms

Overall rate 78/100 (78%) 88/100 (88%) 

Adjusted rate 93.9% 91.6% 

Terminal rate 42/47 (89%) 53/61 (87%) 

First incidence (days) 

Life table test

Logistic regression test

Fisher exact test

365 313 

P ̆0.257N

P ̆0.135 

P ̆0.045 

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for liver, lung, ovary, 

pituitary gland, and thyroid gland; for other tissues, denominator is number of animals necropsied. b	 Kaplan-Meier estimated neoplasm incidence at the end of the study after adjustment for intercurrent mortality

Observed incidence at terminal kill

d	 Beneath the dosed group incidence are the P values corresponding to pairwise comparisons between the untreated control group and the dosed group. The life

table test regards neoplasms in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. The logistic regression test regards these

lesions as nonfatal. The Fisher exact test compares directly the overall incidence rates. For all tests, a lower incidence in the dosed group is indicated by N. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

86 Polyvinyl Alcohol, NTP TR 474 

TABLE A3c
 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control vs. 25%
#

Vehicle Control 25% 

Harderian Gland: Adenoma a Overall rate 9/100 (9%) 4/100 (4%) 

Adjusted rateb 15.0% 6.3% c Terminal rate 5/51 (10%) 3/61 (5%) 

First incidence (days) 668 690 

d Life table test P ̆0.081N

d Logistic regression test P ̆0.107N

d Fisher exact test P ̆0.125N

Harderian Gland: Adenoma or Carcinoma

Overall rate 11/100 (11%) 5/100 (5%) 

Adjusted rate 17.1% 7.4% 

Terminal rate 5/51 (10%) 3/61 (5%) 

First incidence (days) 620 646 

Life table test P ̆0.063N

Logistic regression test P ̆0.091N

Fisher exact test P ̆0.096N

Liver: Hepatocellular Adenoma

Overall rate 56/99 (57%) 55/100 (55%) 

Adjusted rate 80.5% 69.2% 

Terminal rate 38/51 (75%) 37/61 (61%) 

First incidence (days) 611 514 

Life table test P ̆0.147N

Logistic regression test P ̆0.373N

Fisher exact test P ̆0.468N

Liver: Hepatocellular Carcinoma

Overall rate 18/99 (18%) 20/100 (20%) 

Adjusted rate 27.5% 28.0% 

Terminal rate 9/51 (18%) 13/61 (21%) 

First incidence (days) 548 507 

Life table test P ̆0.533N

Logistic regression test P ̆0.452 

Fisher exact test P ̆0.442 

Liver: Hepatocellular Adenoma or Carcinoma

Overall rate 61/99 (62%) 62/100 (62%) 

Adjusted rate 82.9% 73.4% 

Terminal rate 39/51 (76%) 39/61 (64%) 

First incidence (days) 548 507 

Life table test P ̆0.213N

Logistic regression test P ̆0.535N

Fisher exact test P ̆0.536 

Lung: Alveolar/bronchiolar Adenoma

Overall rate 7/98 (7%) 8/100 (8%) 

Adjusted rate 11.8% 11.7% 

Terminal rate 3/51 (6%) 6/61 (10%) 

First incidence (days) 611 313 

Life table test P ̆0.603 

Logistic regression test P ̆0.516 

Fisher exact test P ̆0.516 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 87 

TABLE A3c
 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control vs. 25%
#

Vehicle Control 25% 

Lung: Alveolar/bronchiolar Carcinoma

Overall rate 3/98 (3%) 5/100 (5%) 

Adjusted rate 5.0% 7.8% 

Terminal rate 2/51 (4%) 4/61 (7%) 

First incidence (days) 548 675 

Life table test P ̆0.437 

Logistic regression test P ̆0.377 

Fisher exact test P ̆0.372 

Lung: Alveolar/bronchiolar Adenoma or Carcinoma

Overall rate 10/98 (10%) 13/100 (13%) 

Adjusted rate 16.4% 19.3% 

Terminal rate 5/51 (10%) 10/61 (16%) 

First incidence (days) 548 313 

Life table test P ̆0.461 

Logistic regression test P ̆0.349 

Fisher exact test P ̆0.348 

Ovary: Cystadenoma

Overall rate 5/97 (5%) 3/97 (3%) 

Adjusted rate 9.4% 4.8% 

Terminal rate 4/51 (8%) 2/59 (3%) 

First incidence (days) 711 690 

Life table test P ̆0.290N

Logistic regression test P ̆0.320N

Fisher exact test P ̆0.360N

Pituitary Gland (Pars Distalis): Adenoma

Overall rate 9/86 (10%) 10/84 (12%) 

Adjusted rate 14.9% 16.5% 

Terminal rate 4/47 (9%) 6/50 (12%) 

First incidence (days) 620 634 

Life table test P ̆0.559 

Logistic regression test P ̆0.478 

Fisher exact test P ̆0.478 

Thyroid Gland (Follicular Cell): Adenoma

Overall rate 9/96 (9%) 11/100 (11%) 

Adjusted rate 15.8% 16.7% 

Terminal rate 6/51 (12%) 8/61 (13%) 

First incidence (days) 634 637 

Life table test P ̆0.549 

Logistic regression test P ̆0.472 

Fisher exact test P ̆0.445 

Thyroid Gland (Follicular Cell): Adenoma or Carcinoma

Overall rate 10/96 (10%) 11/100 (11%) 

Adjusted rate 17.6% 16.7% 

Terminal rate 7/51 (14%) 8/61 (13%) 

First incidence (days) 634 637 

Life table test P ̆0.535N

Logistic regression test P ̆0.571 

Fisher exact test P ̆0.540 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

88 

c

Polyvinyl Alcohol, NTP TR 474 

TABLE A3c
 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Intravaginal Study of Polyvinyl Alcohol: 

Vehicle Control vs. 25%
#

Vehicle Control	 25% 

All Organs: Malignant Lymphoma

Overall rate 14/100 (14%) 18/100 (18%) 

Adjusted rate 23.0% 25.8% 

Terminal rate 8/51 (16%) 12/61 (20%) 

First incidence (days) 627 624 

Life table test P ̆0.447 

Logistic regression test P ̆0.316 

Fisher exact test P ̆0.282 

All Organs: Benign Neoplasms

Overall rate 72/100 (72%) 69/100 (69%) 

Adjusted rate 92.1% 81.9% 

Terminal rate 45/51 (88%) 46/61 (75%) 

First incidence (days) 588 313 

Life table test P ̆0.070N

Logistic regression test P ̆0.292N

Fisher exact test P ̆0.378N

All Organs: Malignant Neoplasms

Overall rate 42/100 (42%) 51/100 (51%) 

Adjusted rate 55.9% 60.9% 

Terminal rate 21/51 (41%) 30/61 (49%) 

First incidence (days) 548 324 

Life table test P ̆0.397 

Logistic regression test P ̆0.089 

Fisher exact test P ̆0.128 

All Organs: Benign or Malignant Neoplasms

Overall rate 82/100 (82%) 88/100 (88%) 

Adjusted rate 96.4% 91.6% 

Terminal rate 48/51 (94%) 53/61 (87%) 

First incidence (days) 548 313 

Life table test P ̆0.314N

Logistic regression test P ̆0.141 

Fisher exact test P ̆0.161 

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for liver, lung, ovary, 

pituitary gland, and thyroid gland; for other tissues, denominator is number of animals necropsied. b	 Kaplan-Meier estimated neoplasm incidence at the end of the study after adjustment for intercurrent mortality

Observed incidence at terminal kill

d	 Beneath the dosed group incidence are the P values corresponding to pairwise comparisons between the vehicle control group and the dosed group. The life

table test regards neoplasms in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. The logistic regression test regards these

lesions as nonfatal. The Fisher exact test compares directly the overall incidence rates. For all tests, a lower incidence in the dosed group is indicated by N. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 89 

TABLE A4 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Intravaginal Study

of Polyvinyl Alcohola

Untreated Control Vehicle Control 25% 

Disposition Summary

Animals initially in study 100 100 100 

Early deaths

Accidental deaths 10 4 5 

Moribund 19 25 13 

Natural deaths 24 20 21 

Survivors

Terminal sacrifice 47 51 61 

Animals examined microscopically 100 100 100 

Alimentary System

Esophagus (100) (100) (99) 

Periesophageal tissue, inflammation, chronic 1 (1%) 

Gallbladder (76) (87) (79) 

Hyperplasia 1 (1%) 

Intestine large, colon (92) (93) (97) 

Inflammation, chronic 1 (1%) 1 (1%) 

Lymphoid tissue, hyperplasia 1 (1%) 

Serosa, inflammation, chronic 1 (1%) 

Intestine large, rectum (89) (91) (96) 

Inflammation, chronic 1 (1%) 1 (1%) 

Serosa, inflammation, chronic 1 (1%) 

Intestine large, cecum (88) (92) (96) 

Inflammation, chronic 1 (1%) 

Serosa, inflammation, chronic 1 (1%) 

Intestine small, duodenum (88) (90) (92) 

Inflammation, chronic 1 (1%) 

Epithelium, hyperplasia 2 (2%) 1 (1%) 

Serosa, inflammation, chronic 1 (1%) 

Intestine small, jejunum (89) (90) (91) 

Inflammation, chronic 1 (1%) 

Epithelium, hyperplasia 1 (1%) 

Peyer's patch, hyperplasia 2 (2%) 

Serosa, inflammation, chronic 1 (1%) 

Intestine small, ileum (88) (90) (92) 

Inflammation, chronic 1 (1%) 

Epithelium, hyperplasia 1 (1%) 

Peyer’s patch, hyperplasia, lymphoid 1 (1%) 

Serosa, inflammation, chronic 1 (1%) 

Liver (99) (99) (100) 

Atrophy 1 (1%) 10 (10%) 2 (2%) 

Basophilic focus 2 (2%) 1 (1%) 

Clear cell focus 1 (1%) 10 (10%) 6 (6%) 

Depletion glycogen 20 (20%) 37 (37%) 30 (30%) 

Eosinophilic focus 2 (2%) 3 (3%) 2 (2%) 

Fibrosis 1 (1%) 2 (2%) 

Hematopoietic cell proliferation 23 (23%) 35 (35%) 25 (25%) 

Infarct 1 (1%) 1 (1%) 

Inflammation 3 (3%) 2 (2%) 1 (1%) 

Necrosis 3 (3%) 5 (5%) 4 (4%) 

Pigmentation, hemosiderin 1 (1%) 2 (2%) 

Vacuolization cytoplasmic 38 (38%) 43 (43%) 39 (39%) 

Centrilobular, dilatation 1 (1%) 

Centrilobular, inflammation, chronic 1 (1%) 

Serosa, inflammation, chronic 1 (1%) 

a Number of animals examined microscopically at the site and the number of animals with lesion
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

90 Polyvinyl Alcohol, NTP TR 474 

TABLE A4 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Intravaginal Study

of Polyvinyl Alcohol

Untreated Control Vehicle Control 25% 

Alimentary System (continued) 

Mesentery (33) (25) (36) 

Inflammation, chronic 3 (9%) 1 (4%) 

Necrosis 27 (82%) 23 (92%) 31 (86%) 

Pancreas (97) (95) (98) 

Atrophy 11 (11%) 8 (8%) 6 (6%) 

Hyperplasia 1 (1%) 

Hyperplasia, lymphoid 1 (1%) 

Inflammation, chronic 18 (19%) 40 (42%) 36 (37%) 

Necrosis 1 (1%) 

Vacuolization cytoplasmic 1 (1%) 

Acinus, atrophy 1 (1%) 

Duct, cyst 1 (1%) 

Duct, dilatation 1 (1%) 

Salivary glands (99) (97) (100) 

Atrophy 6 (6%) 6 (6%) 5 (5%) 

Inflammation, chronic 52 (53%) 61 (63%) 58 (58%) 

Stomach, forestomach (94) (93) (97) 

Inflammation 1 (1%) 

Epithelium, hyperplasia 1 (1%) 3 (3%) 

Serosa, inflammation, chronic 1 (1%) 

Stomach, glandular (93) (93) (96) 

Ectopic liver 1 (1%) 

Hemorrhage 1 (1%) 

Inflammation, chronic 1 (1%) 1 (1%) 

Epithelium, atrophy 1 (1%) 

Epithelium, hyperplasia 1 (1%) 1 (1%) 

Epithelium, metaplasia, squamous 1 (1%) 

Epithelium, mineralization 1 (1%) 

Serosa, inflammation, chronic 1 (1%) 

Cardiovascular System

Blood vessel (1) (2) 

Aorta, degeneration 1 (100%) 

Aorta, metaplasia, osseous 1 (50%) 

Heart (100) (99) (100) 

Cardiomyopathy 2 (2%) 4 (4%) 6 (6%) 

Degeneration 83 (83%) 92 (93%) 90 (90%) 

Inflammation, chronic 1 (1%) 1 (1%) 1 (1%) 

Mineralization 1 (1%) 

Thrombosis 1 (1%) 

Epicardium, hyperplasia, lymphoid 1 (1%) 

Epicardium, mineralization 1 (1%) 

Valve, thrombosis 1 (1%) 3 (3%) 

Endocrine System

Adrenal cortex (100) (94) (97) 

Accessory adrenal cortical nodule 1 (1%) 4 (4%) 1 (1%) 

Angiectasis 2 (2%) 

Atrophy 1 (1%) 

Hematopoietic cell proliferation 1 (1%) 

Hemorrhage 1 (1%) 

Vacuolization cytoplasmic 1 (1%) 

Capsule, hyperplasia 4 (4%) 5 (5%) 7 (7%) 

Capsule, inflammation, chronic 2 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 91 

TABLE A4 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Intravaginal Study

of Polyvinyl Alcohol

Untreated Control Vehicle Control 25% 

Endocrine System (continued) 

Adrenal cortex (continued) (100) (94) (97) 

Zona glomerulosa, atrophy 1 (1%) 

Zona glomerulosa, hyperplasia 11 (11%) 9 (10%) 17 (18%) 

Zona reticularis, hematopoietic cell proliferation 1 (1%) 

Zona reticularis, hyperplasia 6 (6%) 4 (4%) 3 (3%) 

Adrenal medulla (99) (94) (92) 

Hemorrhage 1 (1%) 

Islets, pancreatic (97) (94) (97) 

Atrophy 2 (2%) 2 (2%) 

Hyperplasia 70 (72%) 80 (85%) 78 (80%) 

Infiltration cellular, lymphocyte 1 (1%) 

Necrosis 1 (1%) 

Parathyroid gland (59) (59) (69) 

Cyst 1 (2%) 

Hyperplasia 2 (3%) 1 (1%) 

Infiltration cellular, lymphocyte 1 (2%) 

Inflammation, chronic 1 (1%) 

Pituitary gland (88) (86) (84) 

Atrophy 1 (1%) 

Hemorrhage 2 (2%) 1 (1%) 

Pigmentation, hemosiderin 1 (1%) 

Pars distalis, angiectasis 1 (1%) 

Pars distalis, hyperplasia 27 (31%) 28 (33%) 29 (35%) 

Pars intermedia, angiectasis 1 (1%) 

Pars intermedia, hyperplasia 1 (1%) 

Thyroid gland (100) (96) (100) 

Inflammation, chronic 1 (1%) 

Follicular cell, cyst 1 (1%) 

Follicular cell, hyperplasia 57 (57%) 57 (59%) 58 (58%) 

General Body System

None

Genital System

Clitoral gland (89) (81) (83) 

Atrophy 29 (33%) 26 (32%) 18 (22%) 

Hyperplasia 4 (4%) 8 (10%) 10 (12%) 

Inflammation, chronic 2 (2%) 1 (1%) 

Ovary (95) (97) (97) 

Angiectasis 1 (1%) 1 (1%) 

Atrophy 1 (1%) 

Cyst 13 (14%) 13 (13%) 15 (15%) 

Hemorrhage 2 (2%) 1 (1%) 2 (2%) 

Hyperplasia, lymphoid 1 (1%) 

Hyperplasia, tubulostromal 1 (1%) 

Inflammation, acute 1 (1%) 

Inflammation, chronic 2 (2%) 2 (2%) 

Necrosis 1 (1%) 2 (2%) 4 (4%) 

Thrombosis 2 (2%) 2 (2%) 1 (1%) 

Periovarian tissue, inflammation, chronic 2 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

92 Polyvinyl Alcohol, NTP TR 474 

TABLE A4 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Intravaginal Study

of Polyvinyl Alcohol

Untreated Control Vehicle Control 25% 

Genital System (continued) 

Uterus (100) (100) (100) 

Amyloid deposition 1 (1%) 

Diestrus 1 (1%) 

Hemorrhage 2 (2%) 1 (1%) 

Hydrometra 7 (7%) 2 (2%) 2 (2%) 

Inflammation 2 (2%) 

Inflammation, chronic active 1 (1%) 1 (1%) 

Endometrium, angiectasis 1 (1%) 1 (1%) 

Endometrium, hemorrhage 1 (1%) 

Endometrium, hyperplasia, cystic 90 (90%) 97 (97%) 98 (98%) 

Serosa, inflammation, chronic 2 (2%) 

Vagina (97) (99) (99) 

Diestrus 1 (1%) 

Inflammation, acute 2 (2%) 

Inflammation, chronic 2 (2%) 1 (1%) 

Epithelium, hyperplasia 1 (1%) 

Epithelium, inflammation, chronic 1 (1%) 

Hematopoietic System

Bone marrow (100) (98) (100) 

Amyloid deposition 1 (1%) 

Depletion cellular 1 (1%) 

Hyperplasia 12 (12%) 16 (16%) 11 (11%) 

Infiltration cellular, histiocyte 1 (1%) 

Myelofibrosis 19 (19%) 19 (19%) 26 (26%) 

Pigmentation, hemosiderin 1 (1%) 

Lymph node (15) (21) (21) 

Ectasia 1 (5%) 

Hyperplasia 2 (13%) 3 (14%) 

Infiltration cellular, plasma cell 1 (5%) 

Bronchial, hemorrhage 1 (7%) 

Iliac, hemorrhage, chronic 1 (5%) 

Iliac, hyperplasia 1 (5%) 3 (14%) 

Iliac, inflammation, acute 1 (5%) 

Mediastinal, hemorrhage 1 (7%) 

Mediastinal, hyperplasia 1 (7%) 3 (14%) 4 (19%) 

Renal, hemorrhage 1 (7%) 

Renal, hyperplasia 1 (5%) 

Renal, inflammation, acute 1 (5%) 

Lymph node, mandibular (92) (94) (93) 

Atrophy 12 (13%) 6 (6%) 12 (13%) 

Hemorrhage 1 (1%) 

Hyperplasia 16 (17%) 18 (19%) 10 (11%) 

Hyperplasia, lymphoid 1 (1%) 

Infiltration cellular, histiocyte 1 (1%) 

Necrosis 2 (2%) 

Pigmentation, hemosiderin 2 (2%) 2 (2%) 3 (3%) 

Lymph node, mesenteric (90) (93) (93) 

Atrophy 12 (13%) 14 (15%) 10 (11%) 

Hemorrhage 1 (1%) 

Hyperplasia 7 (8%) 6 (6%) 6 (6%) 

Inflammation, chronic 2 (2%) 2 (2%) 2 (2%) 

Necrosis 1 (1%) 1 (1%) 

Pigmentation, hemosiderin 1 (1%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 93 

TABLE A4 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Intravaginal Study

of Polyvinyl Alcohol

Untreated Control Vehicle Control 25% 

Hematopoietic System (continued) 

Spleen (98) (96) (98) 

Fibrosis 1 (1%) 

Hematopoietic cell proliferation 52 (53%) 56 (58%) 59 (60%) 

Inflammation, chronic 1 (1%) 

Necrosis 2 (2%) 

Pigmentation, hemosiderin 41 (42%) 49 (51%) 46 (47%) 

Thrombosis 1 (1%) 

Capsule, inflammation, chronic 1 (1%) 

Lymphoid follicle, atrophy 8 (8%) 1 (1%) 4 (4%) 

Lymphoid follicle, hyperplasia 52 (53%) 65 (68%) 64 (65%) 

Red pulp, atrophy 7 (7%) 1 (1%) 3 (3%) 

Thymus (98) (93) (99) 

Atrophy 66 (67%) 82 (88%) 79 (80%) 

Hemorrhage 2 (2%) 

Hyperplasia, lymphoid 1 (1%) 

Inflammation, chronic 1 (1%) 1 (1%) 

Necrosis 1 (1%) 

Integumentary System

Mammary gland (93) (92) (91) 

Atrophy 1 (1%) 

Hyperplasia 8 (9%) 5 (5%) 7 (8%) 

Inflammation, chronic 1 (1%) 

Skin (98) (98) (100) 

Edema 1 (1%) 2 (2%) 

Inflammation, chronic 1 (1%) 4 (4%) 

Epidermis, hyperplasia 1 (1%) 

Hair follicle, atrophy 2 (2%) 2 (2%) 1 (1%) 

Subcutaneous tissue, inflammation, chronic 1 (1%) 

Vulva, inflammation, chronic 1 (1%) 

Vulva, ulcer 1 (1%) 

Musculoskeletal System

Bone (100) (100) (100) 

Hyperostosis 1 (1%) 2 (2%) 

Osteoporosis 1 (1%) 1 (1%) 

Skeletal muscle (9) (10) (8) 

Degeneration 1 (10%) 

Inflammation, chronic 3 (33%) 

Metaplasia, osseous 1 (10%) 

Nervous System

Brain (100) (99) (100) 

Hydrocephalus 2 (2%) 3 (3%) 2 (2%) 

Infiltration cellular, lymphocyte 1 (1%) 

Inflammation, chronic 1 (1%) 1 (1%) 

Choroid plexus, hyperplasia 1 (1%) 

Meninges, infiltration cellular, lymphocyte 1 (1%) 

Thalamus, mineralization 46 (46%) 53 (54%) 33 (33%) 

Peripheral nerve (3) (4) (4) 

Inflammation, chronic 1 (33%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

94 Polyvinyl Alcohol, NTP TR 474 

TABLE A4 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Intravaginal Study

of Polyvinyl Alcohol

Untreated Control Vehicle Control 25% 

Respiratory System

Lung (100) (98) (100) 

Edema 9 (9%) 9 (9%) 3 (3%) 

Hemorrhage 8 (8%) 3 (3%) 2 (2%) 

Infiltration cellular 1 (1%) 

Inflammation, acute 7 (7%) 1 (1%) 

Inflammation, chronic 9 (9%) 17 (17%) 16 (16%) 

Pigmentation, hemosiderin 1 (1%) 

Thrombosis 1 (1%) 1 (1%) 

Alveolar epithelium, hyperplasia 1 (1%) 1 (1%) 

Bronchus, inflammation, chronic 1 (1%) 

Nose (100) (100) (100) 

Hemorrhage 1 (1%) 1 (1%) 

Respiratory epithelium, inflammation 22 (22%) 15 (15%) 22 (22%) 

Trachea (100) (100) (100) 

Peritracheal tissue, inflammation, chronic 1 (1%) 

Special Senses System

Eye (4) (6) (3) 

Atrophy 1 (25%) 

Cataract 2 (33%) 

Cornea, inflammation, chronic 3 (75%) 4 (67%) 3 (100%) 

Urinary System

Kidney (100) (98) (100) 

Congestion 1 (1%) 

Hydronephrosis 1 (1%) 3 (3%) 2 (2%) 

Inflammation 1 (1%) 1 (1%) 2 (2%) 

Metaplasia, osseous 1 (1%) 

Mineralization 1 (1%) 

Nephropathy 88 (88%) 90 (92%) 93 (93%) 

Glomerulus, amyloid deposition 1 (1%) 1 (1%) 

Urinary bladder (96) (96) (98) 

Atrophy 1 (1%) 

Degeneration 1 (1%) 

Inflammation, chronic 2 (2%) 3 (3%) 

Serosa, inflammation, chronic 1 (1%) 
 

 

 

 

 

 

 

 

 

95 

APPENDIX B
 

CHEMICAL CHARACTERIZATION
 

AND DOSE FORMULATION STUDIES
 

PROCUREMENT AND CHARACTERIZATION OF POLYVINYL ALCOHOL ........................ 96 
 #

PREPARATION AND ANALYSIS OF DOSE FORMULATIONS ................................ 96 
 #

FIGURE B1 Infrared Absorption Spectrum of Polyvinyl Alcohol ......................... 98 
 #

FIGURE B2 Nuclear Magnetic Resonance Spectrum of Polyvinyl Alcohol ................... 99 
 #

TABLE B1 Preparation and Storage of Dose Formulations in the Intravaginal Studies
 

of Polyvinyl Alcohol .............................................. 100 
 #

TABLE B2 Results of Analyses of Dose Formulations Administered to Female Mice
 

in the 2-Year Intravaginal Study of Polyvinyl Alcohol ....................... 101 
 #
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

96 Polyvinyl Alcohol, NTP TR 474 

CHEMICAL CHARACTERIZATION

AND DOSE FORMULATION STUDIES

PROCUREMENT AND CHARACTERIZATION OF POLYVINYL ALCOHOL

Polyvinyl alcohol was obtained from Marubeni America Corporation (New York, NY) in one lot

(N082889), which was used during the 30-day and 2-year studies. Identity, purity, and stability analyses

were conducted by the analytical chemistry laboratory, Midwest Research Institute (Kansas City, MO). 

Reports on analyses performed in support of the polyvinyl alcohol studies are on file at the National Institute

of Environmental Health Sciences. 

The chemical, an off-white crystalline solid, was identified as polyvinyl alcohol by infrared, ultraviolet/ 

visible, and nuclear magnetic resonance spectroscopy. The infrared spectrum was consistent with the

literature spectrum (Cobler et al., 1968), and the infrared, ultraviolet/visible, and nuclear magnetic

resonance spectra were consistent with the structure of polyvinyl alcohol. The infrared and nuclear

magnetic resonance spectra are presented in Figures B1 and B2. The melting point of 193.7E C, at which

decomposition also occurred, was consistent with a literature reference (Merck Index, 1989). A density of

1.0064 ± 0.0011 g/mL was determined for lot N082889. The molecular weight was determined with highperformance liquid chromatography (HPLC) with the following system: TSK-GEL® G3000 PWXL column

with refractive index detection and a solvent system of 0.1 M sodium nitrate. The flow rate was

0.8 mL/minute. Polyvinyl alcohol internal standards of molecular weights 15,000, 22,000, and 49,000 

were also analyzed. The molecular weight of lot N082889 was determined to be approximately 24,000. 

The purity of lot N082889 was determined by elemental analyses, United States Pharmacopeia (USP) 

Method XXII analyses (weight loss on drying, degree of hydrolysis, pH, viscosity, residue on ignition, 

water-insoluble substances), and HPLC. HPLC was performed with the system described for the molecular

weight determination. 

Results of elemental analyses were slightly high for carbon and slightly low for hydrogen when compared

with the theoretical values for polyvinyl alcohol. The USP analyses for polyvinyl alcohol indicated the

following results: weight loss on drying, 4.2% ± 0.1%; degree of hydrolysis, 88.3% ± 0.1%; pH, 

5.9 ± 0.1; viscosity, 4.82 cps; residue on ignition, 0.75% ± 0.04%; water-insoluble substances, 0.09%. 

These results indicate that lot N082889 met the USP XXII specifications for polyvinyl alcohol. HPLC

indicated one major peak and three impurities with a combined area of 1.1% relative to the major peak area. 

The overall purity was determined to be approximately 99%. 

Accelerated stability studies of the bulk chemical were performed by the analytical chemistry laboratory. 

HPLC was performed using the system described above. These studies indicated that polyvinyl alcohol was

stable as a bulk chemical for 2 weeks when stored protected from light at temperatures up to 60E C. To

ensure stability, the bulk chemical was stored at room temperature, protected from light, in sealed

containers in a vented cabinet. Stability was monitored during the 30-day and 2-year studies with HPLC. 

No degradation of the bulk chemical was detected. 

PREPARATION AND ANALYSIS OF DOSE FORMULATIONS

The dose formulations were prepared by mixing polyvinyl alcohol with heated, charcoal-filtered, deionized

water (Millipore Corporation, Bedford, MA) to give the required concentration (Table B1). The dose

formulations were stored at room temperature, protected from light, in sealed containers for up to 5 weeks

(30-day study) or 4 weeks (2-year study). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 97 

The analytical chemistry laboratory determined density, viscosity, and syringeability values of 5%, 10%, 

15%, and 20% polyvinyl alcohol formulations. Viscosity was determined with Ubbelohde and Routine

Opaque viscometers. Syringeability was tested with different sizes of gavage needles and catheters. 

Density ranged from 1.011 g/mL for the 5% solution to 1.066 g/mL for the 20% solution; viscosity ranged

from 6.16 cP for the 5% solution to 540.8 cP for the 20% solution. The syringeability of up to a

15% solution through a 5.5-inch catheter was verified. 

Stability studies of a 15% (150 mg/mL) polyvinyl alcohol dose formulation were also performed by the

analytical chemistry laboratory using HPLC with the same system as for the bulk stability analyses but with

a solvent system of Milli-Q water. The stability of the dose formulation was confirmed for 4 weeks when

stored at room temperature protected from light and for 3 weeks when stored open to air and light. 

Additional stability analyses of the dose formulation were performed by the study laboratory with HPLC. 

The 25% dose formulation was determined to be stable for at least 97 days when stored at room

temperature, sealed and protected from light, and for 3 hours under simulated dosing conditions (open to air

and light). 

For the 30-day study, doses were prepared once and analyzed by HPLC. The dose formulation (25.46%) 

was within 2% of the target concentration of 25%. An animal room sample from the 30-day study was also

analyzed and was determined to be 26.59% (6.4% greater than the target concentration). 

Periodic analyses of the dose formulations in the 2-year study of polyvinyl alcohol were conducted at the

study laboratory using HPLC. The formulations were analyzed every 4 to 8 weeks (Table B2). All dose

formulations analyzed and used during the 2-year studies were within 10% of the target concentration, with

no value greater than 105% of the target concentration; all animal room samples were also within 10% of

the target concentration, with no value greater than 104% of the target concentration. 
 

98 Polyvinyl Alcohol, NTP TR 474
 

FIGURE B1 

Infrared Absorption Spectrum of Polyvinyl Alcohol 
 

Polyvinyl Alcohol , NTP TR 474
 99 

FIGURE B2 

Nuclear Magnetic Resonance Spectrum of Polyvinyl Alcohol 
 

 

 

 

 

 

 

 

100 Polyvinyl Alcohol, NTP TR 474 

TABLE B1 

Preparation and Storage of Dose Formulations in the Intravaginal Studies of Polyvinyl Alcohol

30-Day Study 2-Year Study

Preparation

Polyvinyl alcohol was stirred for 60 to 90 minutes with a magnetic Same as 30-day study; water bath at 85E C. 

stir bar in deionized water in a sealed bottle in a heated water bath

(75E-85E C). 

Chemical Lot Number

N082889 N082889 

Maximum Storage Time

5 weeks 4 weeks

Storage Conditions

Stored in sealed containers at room temperature protected from Same as 30-day study

light

Study Laboratory

Arthur D. Little, Inc. (Cambridge, MA) Arthur D. Little, Inc. (Cambridge, MA) 

Analytical Chemistry Laboratory

Midwest Research Institute (Kansas City, MO) Midwest Research Institute (Kansas City, MO) 
 

 

 

 

Polyvinyl Alcohol, NTP TR 474 101 

TABLE B2 

Results of Analyses of Dose Formulations Administered to Female Mice in the 2-Year Intravaginal Study

of Polyvinyl Alcohol

Target Determined Difference

Date Prepared Date Analyzed Concentration Concentrationa from Target

(%) (%) (%) 

13 February 1992 13 February 1992 25 25.36 +1 

16 March 1992b 25 25.06 0 

7 April 1992 8 April 1992 25 24.98 0 

7 May 1992 7 May 1992 25 25.72 +3 

3 June 1992 3 June 1992 25 26.23 +5 

28 July 1992 28 July 1992 25 25.67 +3 

29 September 1992b 25 25.01 0 

23 September 1992 29 September 1992 25 24.59 !2 

18 November 1992 19 November 1992 25 25.10 0 

14 January 1993 14 January 1993 25 24.48 !2 

1 March 1993b 25 25.51 +2 

9 March 1993 10 March 1993 25 24.09 !4 

5 May 1993 5 May 1993 25 26.14 +5 

29 June 1993 30 June 1993 25 26.00 +4 

27 August 1993b 25 26.06 +4 

26 August 1993 27 August 1993 25 25.76 +3 

20 October 1993 22 October 1993 25 24.25 !3 

14 December 1993 15 December 1993 25 25.02 0 

23 January 1994b 25 25.50 +2 

a

b

Results of duplicate analyses

Animal room sample
102 Polyvinyl Alcohol, NTP TR 474 
 

 

 

 

 

103 

APPENDIX C

INGREDIENTS, NUTRIENT COMPOSITION, 

AND CONTAMINANT LEVELS

IN NIH-07 RAT AND MOUSE RATION

TABLE C1 

TABLE C2 

TABLE C3 

TABLE C4 

Ingredients of NIH-07 Rat and Mouse Ration ............................. 

Vitamins and Minerals in NIH-07 Rat and Mouse Ration ..................... 

Nutrient Composition of NIH-07 Rat and Mouse Ration ...................... 

Contaminant Levels in NIH-07 Rat and Mouse Ration ....................... 

104 

104 

105 

106 
 

 

 

 

 

 

 

 

 

 

 

 

 

104 Polyvinyl Alcohol, NTP TR 474 

TABLE C1 

Ingredients of NIH-07 Rat and Mouse Rationa

Ingredientsb Percent by Weight

Ground #2 yellow shelled corn 24.50 

Ground hard winter wheat 23.00 

Soybean meal (49% protein) 12.00 

Fish meal (60% protein) 10.00 

Wheat middlings 10.00 

Dried skim milk 5.00 

Alfalfa meal (dehydrated, 17% protein) 4.00 

Corn gluten meal (60% protein) 3.00 

Soy oil 2.50 

Dried brewer’s yeast 2.00 

Dry molasses 1.50 

Dicalcium phosphate 1.25 

Ground limestone 0.50 

Salt 0.50 

Premixes (vitamin and mineral) 0.25 

a NCI, 1976; NIH, 1978 b Ingredients were ground to pass through a U.S. Standard Screen No. 16 before being mixed. 

TABLE C2 

Vitamins and Minerals in NIH-07 Rat and Mouse Rationa

Amount Source

Vitamins

A 5,500,000 IU Stabilized vitamin A palmitate or acetate

D3 4,600,000 IU D-activated animal sterol

K3 2.8 g Menadione

d-"-Tocopheryl acetate 20,000 IU

Choline 560.0 g Choline chloride

Folic acid 2.2 g

Niacin 30.0 g

d-Pantothenic acid 18.0 g d-Calcium pantothenate

Riboflavin 3.4 g

Thiamine 10.0 g Thiamine mononitrate

B12 4,000 μg

Pyridoxine 1.7 g Pyridoxine hydrochloride

Biotin 140.0 mg d-Biotin

Minerals

Iron 120.0 g Iron sulfate

Manganese 60.0 g Manganous oxide

Zinc 16.0 g Zinc oxide

Copper 4.0 g Copper sulfate

Iodine 1.4 g Calcium iodate

Cobalt 0.4 g Cobalt carbonate

a Per ton (2,000 lb) of finished product
 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 105 

TABLE C3 

Nutrient Composition of NIH-07 Rat and Mouse Ration

Mean ± Standard

Nutrient Deviation Range Number of Samples

Protein (% by weight) 23.33 ± 0.47 22.2 – 24.2 26 

Crude fat (% by weight) 5.38 ± 0.17 5.10 – 5.90 26 

Crude fiber (% by weight) 3.20 ± 0.33 2.60 – 4.30 26 

Ash (% by weight) 6.36 ± 0.22 5.94 – 6.81 26 

Amino Acids (% of total diet) 

Arginine 1.280 ± 0.083 1.110 – 1.390 11 

Cystine 0.308 ± 0.071 0.181 – 0.400 11 

Glycine 1.158 ± 0.048 1.060 – 1.220 11 

Histidine 0.584 ± 0.027 0.531 – 0.630 11 

Isoleucine 0.917 ± 0.033 0.867 – 0.965 11 

Leucine 1.975 ± 0.051 1.850 – 2.040 11 

Lysine 1.274 ± 0.049 1.200 – 1.370 11 

Methionine 0.437 ± 0.109 0.306 – 0.699 11 

Phenylalanine 0.999 ± 0.120 0.665 – 1.110 11 

Threonine 0.904 ± 0.058 0.824 – 0.985 11 

Tryptophan 0.218 ± 0.153 0.107 – 0.671 11 

Tyrosine 0.685 ± 0.094 0.564 – 0.794 11 

Valine 1.086 ± 0.055 0.962 – 1.170 11 

Essential Fatty Acids (% of total diet) 

Linoleic 2.407 ± 0.227 1.830 – 2.570 10 

Linolenic 0.259 ± 0.065 0.100 – 0.320 10 

Vitamins

Vitamin A (IU/kg) 6,635 ± 544 5,940 – 8,800 26 

Vitamin D (IU/kg) 4,450 ± 1382 3,000 – 6,300 4 

"-Tocopherol (ppm) 35.43 ± 8.98 22.5 – 48.9 11 

Thiamine (ppm) 16.52 ± 2.26 13.0 – 22.0 25 

Riboflavin (ppm) 7.83 ± 0.923 6.10 – 9.00 11 

Niacin (ppm) 99.22 ± 24.27 65.0 – 150.0 11 

Pantothenic acid (ppm) 30.55 ± 3.52 23.0 – 34.6 11 

Pyridoxine (ppm) 9.11 ± 2.53 5.60 – 14.0 11 

Folic acid (ppm) 2.46 ± 0.63 1.80 – 3.70 11 

Biotin (ppm) 0.268 ± 0.047 0.190 – 0.354 11 

Vitamin B12 (ppb) 40.5 ± 19.1 10.6 – 65.0 11 

Choline (ppm) 2,991 ± 382 2,300 – 3,430 10 

Minerals

Calcium (%) 1.13 ± 0.04 1.06 – 1.20 26 

Phosphorus (%) 0.90 ± 0.05 0.760 – 1.00 26 

Potassium (%) 0.886 ± 0.063 0.772 – 0.971 9 

Chloride (%) 0.529 ± 0.087 0.380 – 0.635 9 

Sodium (%) 0.316 ± 0.033 0.258 – 0.371 11 

Magnesium (%) 0.166 ± 0.010 0.148 – 0.181 11 

Sulfur (%) 0.272 ± 0.059 0.208 – 0.420 10 

Iron (ppm) 350.5 ± 87.3 255.0 – 523.0 11 

Manganese (ppm) 92.48 ± 5.14 81.7 – 99.4 11 

Zinc (ppm) 59.33 ± 10.2 46.1 – 81.6 11 

Copper (ppm) 11.81 ± 2.50 8.09 – 15.4 11 

Iodine (ppm) 3.54 ± 1.19 1.52 – 5.83 10 

Chromium (ppm) 1.66 ± 0.46 0.85 – 2.09 11 

Cobalt (ppm) 0.76 ± 0.23 0.49 – 1.15 7 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

106 Polyvinyl Alcohol, NTP TR 474 

TABLE C4 

Contaminant Levels in NIH-07 Rat and Mouse Rationa

Mean ± Standard

Deviationb Range Number of Samples

Contaminants

Arsenic (ppm) 0.54 ± 0.14 0.10 – 0.70 26 

Cadmium (ppm) 0.09 ± 0.07 0.04 – 0.20 26 

Lead (ppm) 0.31 ± 0.12 0.20 – 0.70 26 

Mercury (ppm) 0.02 0.02 – 0.03 26 

Selenium (ppm) 0.36 ± 0.08 0.10 – 0.50 26 

Aflatoxins (ppb) <5.0 26 c Nitrate nitrogen (ppm) 7.00 ± 2.79 2.90 – 14.0 26 c Nitrite nitrogen (ppm) 0.70 ± 0.93 0.10 – 3.50 26 

BHA (ppm)

d 2.19 ± 4.04 1.00 – 20.0 26 

BHT (ppm)

d 1.58 ± 0.99 1.0 – 5.00 26 

Aerobic plate count (CFU/g) 101,400 ± 157,227 7,200 – 710,000 26 

Coliform (MPN/g) 4 ± 3.9 3 – 23 26 

Escherichia coli (MPN/g) <3 26 

Salmonella (MPN/g) Negative 26 e Total nitrosoamines (ppb) 10.97 ± 4.39 4.70 – 23.00 26 e N-Nitrosodimethylamine (ppb) 8.72 ± 4.44 2.90 – 21.0 26 e N-Nitrosopyrrolidine (ppb) 2.26 ± 1.14 1.00 – 6.00 26 

Pesticides (ppm) 

"-BHC <0.01 26 

$-BHC <0.02 26 

(-BHC <0.01 26 

*-BHC <0.01 26 

Heptachlor <0.01 26 

Aldrin <0.01 26 

Heptachlor epoxide <0.01 26 

DDE <0.01 26 

DDD <0.01 26 

DDT <0.01 26 

HCB <0.01 26 

Mirex <0.01 26 

Methoxychlor <0.05 26 

Dieldrin <0.01 26 

Endrin <0.01 26 

Telodrin <0.01 26 

Chlordane <0.05 26 

Toxaphene <0.10 26 

Estimated PCBs <0.20 26 

Ronnel <0.01 26 

Ethion <0.02 26 

Trithion <0.05 26 

Diazinon <0.10 26 

Methyl parathion <0.02 26 

Ethyl parathion <0.02 26 

Malathion 0.13 ± 0.13 0.05 – 0.53 26 

Endosulfan I <0.01 26 

Endosulfan II <0.01 26 

Endosulfan sulfate <0.03 26 

a CFU ̆colony forming units; MPN ̆most probable number; BHC ̆hexachlorocyclohexane or benzene hexachloride

b For values less than the limit of detection, the detection limit is given as the mean. 

Sources of contamination: alfalfa, grains, and fish meal

d Sources of contamination: soy oil and fish meal e All values were corrected for percent recovery. 

c
 

107 

APPENDIX D

SENTINEL ANIMAL PROGRAM

METHODS .............................................................. 

RESULTS ............................................................... 

108 

109 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

108 Polyvinyl Alcohol, NTP TR 474 

SENTINEL ANIMAL PROGRAM
 

METHODS

Rodents used in the Carcinogenesis Program of the National Toxicology Program are produced in optimally

clean facilities to eliminate potential pathogens that may affect study results. The Sentinel Animal Program

is part of the periodic monitoring of animal health that occurs during the toxicologic evaluation of chemical

compounds. Under this program, the disease state of the rodents is monitored via serology on sera from

extra (sentinel) animals in the study rooms. These animals and the study animals are subject to identical

environmental conditions. The sentinel animals come from the same production source and weanling

groups as the animals used for the studies of chemical compounds. 

Serum samples were collected from randomly selected mice during the 2-year study. Blood from each

animal was collected and allowed to clot, and the serum was separated. The samples were processed

appropriately and sent to Microbiological Associates, Inc. (Bethesda, MD), for determination of antibody

titers. The laboratory serology methods and viral agents for which testing was performed are tabulated

below; the times at which blood was collected during the studies are also listed. 

Method and Test Time of Analysis

ELISA

Ectromelia virus

EDIM (epizootic diarrhea of infant mice) 

GDVII (mouse encephalomyelitis virus) 

LCM (lymphocytic choriomeningitis virus) 

Mouse adenoma virus-FL

MHV (mouse hepatitis virus) 

Mycoplasma arthritidis

Mycoplasma pulmonis

PVM (pneumonia virus of mice) 

Reovirus 3 

Sendai

6, 12, 18, and 24 months

6, 12, and 24 months

6, 12, 18, and 24 months

6, 12, 18, and 24 months

6, 12, 18, and 24 months

6, 12, 18, and 24 months

24 months

24 months

6, 12, 18, and 24 months

6, 12, 18, and 24 months

6, 12, 18, and 24 months

Immunofluorescence Assay

Ectromelia virus 18 months

EDIM 18 and 24 months

GDVII 18 months

LCM 24 months

Hemagglutination Inhibition

K (papovavirus) 

MVM (minute virus of mice) 

Polyoma virus

6, 12, 18, and 24 months

6, 12, 18, and 24 months

6, 12, 18, and 24 months
 

 

 

 

 

 

 

Polyvinyl Alcohol, NTP TR 474 109 

RESULTS
 

One sample was positive for M. arthritidis at 24 months. Further evaluation of the sample positive for

M. arthritidis by immunoblot and Western blot procedures indicated that the positive titer may have been

due to cross reaction with antibodies of nonpathogenic Mycoplasma or other agents. Only one sample was

positive, and there were no clinical findings or histopathologic changes of M. arthritidis infection in the

animal with the positive titer. Accordingly, the M. arthritidis-positive titer was considered to be false

positive. One sample was positive for EDIM antibodies by ELISA, but this result could not be confirmed

by immunofluorescence assay due to insufficient serum. 
110 Polyvinyl Alcohol, NTP TR 474