NTP TECHNICAL REPORT
 

ON THE 

TOXICOLOGY AND CARCINOGENESIS
 

STUDIES OF
 

FURFURYL ALCOHOL
 

(CAS NO. 98-00-0) 

IN F344/N RATS AND B6C3F1 MICE

(INHALATION STUDIES) 

February 1999 

NATIONAL TOXICOLOGY PROGRAM
 

P.O. Box 12233
 

Research Triangle Park, NC 27709
 

NTP TR 482
 

NIH Publication No. 99-3972
 

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 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
 

FURFURYL ALCOHOL
 

(CAS NO. 98-00-0) 

IN F344/N RATS AND B6C3F1 MICE

(INHALATION STUDIES) 

February 1999 

NATIONAL TOXICOLOGY PROGRAM
 

P.O. Box 12233
 

Research Triangle Park, NC 27709
 

NTP TR 482
 

NIH Publication No. 99-3972
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

National Institutes of Health
 
2 Furfuryl Alcohol, NTP TR 482 

CONTRIBUTORS
 

National Toxicology Program 

Evaluated and interpreted results and reported findings 

R.D. Irwin, 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. 

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

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., Integrated Laboratory Systems 

Battelle Pacific Northwest Laboratories 

Conducted studies, evaluated pathology findings 

B.J. Chou, D.V.M., Ph.D., Principal Investigator 

S.L. Grumbein, D.V.M., Ph.D. (2-year rats) 

P.W. Mellick, D.V.M., Ph.D. (16-day studies and 14-week 

rats) 

R.A. Miller, D.V.M., Ph.D. (14-week and 2-year mice) 

S.E. Rowe, D.V.M., M.S. (16-day and 14-week studies) 

R.B. Westerberg, 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 

Analytical Sciences, Inc. 

Provided statistical analyses 

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

S.R. Lloyd, M.S. 

N.G. Mintz, B.S. 

NTP Pathology Working Group 

Evaluated slides, prepared pathology report on rats 

(26 September 1996) 

M.P. Jokinen, D.V.M., Chairperson 

Pathology Associates International 

J. Everitt, D.V.M. 

Chemical Industry Institute of Toxicology 

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

National Toxicology Program 

J.R. Leininger, 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. 

M.G. Evans, D.V.M., Ph.D., Observer 

Pathology Associates International 

Evaluated slides, prepared pathology report on mice 

(14 November 1996) 

M.P. Jokinen, D.V.M., Chairperson 

Pathology Associates International 

J. Everitt, D.V.M. 

Chemical Industry Institute of Toxicology 

R.A. Herbert, D.V.M., Ph.D. 

National Toxicology Program 

J.R. Leininger, 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. 

H. White, M.D., Observer 

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 ................... 10
 

TECHNICAL REPORTS REVIEW SUBCOMMITTEE .......................................... 11
 

SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS ............... 12
 

INTRODUCTION ............................................................................ 13
 

MATERIALS AND METHODS ............................................................... 19
 

RESULTS ................................................................................... 31
 

DISCUSSION AND CONCLUSIONS ........................................................... 59
 

REFERENCES .............................................................................. 63
 

APPENDIX A Summary of Lesions in Male Rats in the 2-Year Inhalation Study
 

of Furfuryl Alcohol ............................................................ 67
 

APPENDIX B Summary of Lesions in Female Rats in the 2-Year Inhalation Study
 

of Furfuryl Alcohol ............................................................ 101
 

APPENDIX C Summary of Lesions in Male Mice in the 2-Year Inhalation Study
 

of Furfuryl Alcohol ............................................................ 131
 

APPENDIX D Summary of Lesions in Female Mice in the 2-Year Inhalation Study
 

of Furfuryl Alcohol ............................................................ 161
 

APPENDIX E Genetic Toxicology ............................................................ 197
 

APPENDIX F Hematology and Clinical Chemistry Results ....................................... 211
 

APPENDIX G Organ Weights and Organ-Weight-to-Body-Weight Ratios ......................... 217
 

APPENDIX H Reproductive Tissue Evaluations and Estrous Cycle Characterization ................ 223
 

APPENDIX I Urinary Metabolite Study ...................................................... 227
 

APPENDIX J Chemical Characterization and Generation of Chamber Concentrations .............. 229
 

APPENDIX K Ingredients, Nutrient Composition, and Contaminant Levels 

in NIH-07 Rat and Mouse Ration ............................................... 241
 

APPENDIX L Sentinel Animal Program ....................................................... 245
 
4 Furfuryl Alcohol, NTP TR 482 
O CH2OH 

5 

ABSTRACT
 

FURFURYL ALCOHOL 

CAS No. 98-00-0 

Chemical Formula: C 5 6 2 H O Molecular Weight: 98.10

Synonyms: 2-Furancarbinol; 2-furanmethanol; furfuralcohol; "-furylcarbinol; 2-furylcarbinol; 2-hydroxymethylfuran 

Furfuryl alcohol-based resins are used as binding agents female rats exposed to 125 ppm gained less weight than 

in foundry sand and as corrosion inhibitors in mortar, the chamber control groups. Clinical findings included 

grout, and cement. Because of their heat resistance, furan dyspnea, hypoactivity, and nasal and ocular discharge in 

resins are used in the manufacture of fiberglass-reinforced males and females exposed to 63, 125, or 250 ppm. All 

plastic equipment. Furfuryl alcohol was selected for exposed animals developed lesions in the nasal 

evaluation because of the absence of data on its respiratory epithelium and olfactory epithelium, and the 

carcinogenic potential and its large production volume, severities of these lesions generally increased with 

widespread use in manufacturing, and ubiquitous increasing exposure concentration. 

presence in consumer goods. Male and female F344/N 

rats and B6C3F mice were exposed to furfuryl alcohol 1 

(greater than 98% pure) by inhalation for 16 days, 14 

weeks, or 2 years. Genetic toxicology studies were 

conducted in Salmonella typhimurium, cultured Chinese 16-DAY STUDY IN MICE 

hamster ovary cells, and mouse bone marrow cells. Groups of five male and five female mice were exposed 

to concentrations of 0, 16, 31, 63, 125, or 250 ppm 

furfuryl alcohol by inhalation, 6 hours per day, 5 days per 

16-DAY STUDY IN RATS week for 16 days. All male and female mice exposed to 

Groups of five male and five female rats were exposed to 250 ppm died by day 4 of the study, and one female 

concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl mouse exposed to 125 ppm died on day 14. Mean body 

alcohol by inhalation, 6 hours per day, 5 days per week weights of male and female mice exposed to 63 or 

for 16 days. All male and female rats exposed to 125 ppm were significantly less than those of the 

250 ppm died by day 2 of the study, and one male rat chamber control groups. All exposed animals except one 

exposed to 125 ppm died on day 5. Final mean body 16 ppm male developed lesions in the nasal respiratory 

weights of male and female rats exposed to 125 ppm epithelium and/or olfactory epithelium, and the severities 

were significantly less than those of the chamber control of these lesions generally increased with increasing 

groups. Male rats exposed to 31, 63, or 125 ppm and exposure concentration. 
6 Furfuryl Alcohol, NTP TR 482 

14-WEEK STUDY IN RATS 

Groups of 10 male and 10 female rats were exposed to 

furfuryl alcohol at concentrations of 0, 2, 4, 8, 16, or 

32 ppm, 6 hours per day, 5 days per week for 14 weeks. 

All rats survived to the end of the study. The mean body 

weight gain of females exposed to 32 ppm was less than 

that of the chamber control group. Exposure-related 

increases in the incidences of squamous metaplasia of the 

respiratory and transitional epithelium, goblet cell 

hyperplasia of the respiratory epithelium, and 

hypertrophy of the respiratory epithelium lining the 

nasopharyngeal duct were observed in the nose of male 

and female rats. The incidences of degeneration, 

hyperplasia, metaplasia, and surface exudate of the 

olfactory epithelium generally increased with increasing 

exposure concentration in males and females. 

14-WEEK STUDY IN MICE 

Groups of 10 male and 10 female mice were exposed to 

furfuryl alcohol at concentrations of 0, 2, 4, 8, 16, or 

32 ppm, 6 hours per day, 5 days per week for 14 weeks. 

All mice survived to the end of the study. Heart weights 

of 32 ppm males were significantly less than those of the 

chamber controls. Exposure-related histologic changes 

included degeneration, metaplasia, and chronic 

inflammation of the olfactory epithelium; hyaline droplets 

of the respiratory epithelium; and squamous metaplasia 

of the submucosal gland of the cuboidal epithelium in 

males and females. 

2-YEAR STUDY IN RATS 

Groups of 50 male and 50 female rats were exposed to 

furfuryl alcohol by inhalation, 6 hours per day, 5 days per 

week for 105 weeks, at concentrations of 0, 2, 8, or 

32 ppm. 

Survival and Body Weights 

All male rats exposed to 32 ppm died by week 99; 

survival of all other exposed groups of male and female 

rats was similar to that of the chamber control groups. 

Mean body weights of 32 ppm males were less than those 

of the chamber control group beginning at week 19. 

Pathology Findings 

All groups of exposed male and female rats had 

significantly increased incidences of nonneoplastic 

histologic changes of the nose compared to the chamber 

control groups. An adenoma of the lateral wall of the 

nose was observed in one 2 ppm male and one 8 ppm 

female, an adenoma of the respiratory epithelium was 

observed in one 8 ppm male and one 32 ppm female, one 

carcinoma of the respiratory epithelium was observed in 

a 32 ppm male, and squamous cell carcinomas of the 

nose were observed in three 32 ppm males. Renal tubule 

adenomas were present in one chamber control male, one 

2 ppm male, two 8 ppm males, and two 32 ppm females. 

One 2 ppm female had a renal tubule carcinoma. 

Additional histologic sections from the kidney revealed 

the presence of additional hyperplasias in all groups of 

males and females; one additional renal tubule adenoma 

was observed in each of the chamber control, 2 ppm, and 

8 ppm male groups, and four additional adenomas were 

observed in 32 ppm males. In females, two additional 

adenomas were found in the 8 ppm group, one adenoma 

in the 32 ppm group, and one carcinoma in the 2 ppm 

group. The severities of nephropathy relative to the 

chamber controls were increased in 32 ppm males and 

females. Males exposed to 32 ppm had extrarenal signs 

indicative of marked nephropathy including parathyroid 

gland hyperplasia and fibrous osteodystrophy. 

2-YEAR STUDY IN MICE 

Groups of 50 male and 50 female mice were exposed to 

furfuryl alcohol by inhalation, 6 hours per day, 5 days per 

week for 105 weeks, at concentrations of 0, 2, 8, or 

32 ppm. 

Survival, Body Weights, and Clinical Findings 

Survival of exposed males and females was similar to 

that of the chamber control groups. Mean body weights 

of exposed males were generally similar to those of the 

chamber control group throughout the study. Mean body 

weights of exposed females were less than those of the 

chamber control group during year 2 of the study. 

Female mice exposed to 32 ppm developed focal corneal 

opacities. 
 

__________ 

Furfuryl Alcohol, NTP TR 482 7 

Pathology Findings 

The incidences of renal tubule neoplasms were increased 

in 32 ppm male mice compared to the chamber control 

group and exceeded the historical control range for 

inhalation studies. Step sectioning revealed the presence 

of additional hyperplasias in the chamber control and 

exposed groups and one adenoma in 32 ppm males. The 

severity of nephropathy increased with increasing 

exposure concentration in male mice. The incidence of 

renal tubule degeneration in male mice exposed to 

32 ppm was significantly greater than in the chamber 

control group. Incidences of a variety of nonneoplastic 

lesions of the nose were significantly greater in all 

exposed groups of male and female mice than in the 

chamber control groups. The incidence of degeneration 

of the cornea was significantly greater in 32 ppm female 

mice compared to the chamber control group. 

GENETIC TOXICOLOGY 

Furfuryl alcohol was not mutagenic in Salmonella 

typhimurium strain TA98, TA100, TA1535, or TA1537, 

with or without S9. It did induce sister chromatid 

exchanges in cultured Chinese hamster ovary cells in the 

absence of S9, but not in the presence of S9. No 

induction of chromosomal aberrations was noted in 

cultured Chinese hamster ovary cells treated with furfuryl 

alcohol in the absence 

of S9, but in the presence of S9 an equivocal result was 

obtained. In vivo, no induction of sister chromatid 

exchanges, chromosomal aberrations, or micronuclei was 

noted in bone marrow cells of male mice after treatment 

with furfuryl alcohol. 

CONCLUSIONS 

Under the conditions of these 2-year inhalation studies, 

there was some evidence of carcinogenic activity* of 

furfuryl alcohol in male F344/N rats based on increased 

incidences of combined neoplasms of the nose. There 

was equivocal evidence of carcinogenic activity of 

furfuryl alcohol in female F344/N rats based on 

marginally increased incidences of neoplasms of the nose 

and renal tubule neoplasms. There was some evidence of 

carcinogenic activity of furfuryl alcohol in male B6C3F1 

mice based on increased incidences of renal tubule 

neoplasms. There was no evidence of carcinogenic 

activity of furfuryl alcohol in female B6C3F1 mice 

exposed to 2, 8, or 32 ppm. 

Exposure of male and female rats and male mice to 

furfuryl alcohol was associated with increased incidences 

of nonneoplastic lesions of the nose and increased 

severities of nephropathy. Exposure of female mice to 

furfuryl alcohol was associated with increased incidences 

of nonneoplastic lesions of the nose and corneal 

degeneration. 

* Explanation of Levels of Evidence of Carcinogenic Activity is on page 10. A summary of the Technical Reports Review Subcommittee comments 

and the public discussion on this Technical Report appears on page 12. 
8 Furfuryl Alcohol, NTP TR 482 

Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies of Furfuryl Alcohol 

Male Female Male Female 

F344/N Rats F344/N Rats B6C3F Mice 1 B6C3F Mice 1 

Concentrations 0, 2, 8, or 32 ppm 0, 2, 8, or 32 ppm 0, 2, 8, or 32 ppm 0, 2, 8, or 32 ppm 

in air 

Body weights 32 ppm group less than 

chamber control group 

Exposed groups similar to 

chamber control group 

Exposed groups similar to 

chamber control group 

Exposed groups less than 

chamber control group 

Survival rates 8/50, 5/50, 9/50, 0/50 26/50, 26/50, 22/49, 16/50 34/50, 36/50, 30/50, 38/50 34/50, 33/49, 32/50, 40/50 

Nonneoplastic 

effects 

Nose (all sites): suppurative 

inflammation (3/50, 6/50, 

Nose (all sites): suppurative 

inflammation (4/49, 1/50, 

Nose (all sites): suppurative 

inflammation (7/50, 11/49, 

Nose (all sites): suppurative 

inflammation (5/50, 12/48, 

17/50, 44/50); glands, 5/48, 23/49); glands, 27/49, 28/50); glands, 25/49, 42/50); glands, 

hyperplasia (0/50, 0/50, hyperplasia (0/49, 0/50, hyperplasia (0/50, 10/49, hyperplasia (0/50, 33/48, 

22/50, 49/50); lateral wall 24/48, 46/49); lateral wall 48/49, 46/50); glands, 46/49, 47/50); glands, 

hyperplasia (1/50, 49/50, hyperplasia (0/49, 39/50, squamous metaplasia (0/50, squamous metaplasia (1/50, 

50/50, 50/50); lateral wall, 48/48, 49/49); lateral wall, 6/49, 35/49, 47/50); lateral 1/48, 34/49, 46/50); lateral 

squamous metaplasia (1/50, squamous metaplasia (0/49, wall, squamous metaplasia wall, squamous metaplasia 

1/50, 8/50, 33/50) 1/50, 0/48, 24/49) (0/50, 9/49, 10/49, 20/50) (3/50, 14/48, 16/49, 36/50) 

Nose (olfactory epithelium): Nose (olfactory epithelium): Nose (olfactory epithelium): Nose (olfactory epithelium): 

atrophy (1/50, 12/50, 47/50, atrophy (0/49, 6/50, 44/48, atrophy (3/50, 15/49, 49/49, atrophy (2/50, 35/48, 49/49, 

50/50); hyaline degeneration 49/49); hyaline degeneration 50/50); hyaline degeneration 50/50); hyaline degeneration 

(42/50, 48/50, 50/50, (43/49, 50/50, 47/48, (2/50, 3/49, 21/49, 39/50); (7/50, 14/48, 28/49, 45/50); 

47/50); fibrosis (0/50, 1/50, 48/49); fibrosis (0/49, 0/50, metaplasia (0/50, 12/49, metaplasia (0/50, 31/48, 

26/50, 40/50); hyperplasia 16/48, 31/49); hyperplasia 49/49, 50/50) 49/49, 49/50) 

(0/50, 1/50, 42/50, 40/50); (0/49, 0/50, 31/48, 41/49); 

metaplasia (1/50, 8/50, metaplasia (0/49, 5/50, Nose (respiratory Nose (respiratory 

37/50, 49/50) 37/48, 48/49) epithelium): hyaline epithelium): hyaline 

degeneration (5/50, 18/49, degeneration (19/50, 44/48, 

Nose (respiratory Nose (respiratory 42/49, 45/50); squamous 49/49, 48/50); squamous 

epithelium): hyaline epithelium): hyaline metaplasia (0/50, 2/49, metaplasia (1/50, 9/48, 

degeneration (12/50, 14/50, degeneration (23/49, 39/50, 10/49, 20/50); regeneration 21/49, 39/50); regeneration 

45/50, 3/50); hyperplasia 45/48, 6/49); hyperplasia (0/50, 1/49, 13/49, 21/50) (0/50, 0/48, 9/49, 13/50) 

(0/50, 26/50, 50/50, 50/50); (0/49, 18/50, 40/48, 49/49); 

squamous metaplasia (0/50, squamous metaplasia (0/49, Kidney (all sites): severity Eye: cornea, degeneration 

0/50, 3/50, 26/50) 0/50, 2/48, 10/49) of nephropathy (1.2, 1.4, (3/49, 1/49, 4/49, 26/50) 

1.5, 1.8) 

Kidney (all sites): severity Kidney (all sites): severity 

of nephropathy (2.9, 2.9, of nephropathy (1.9, 1.9, 

3.1, 3.7) 1.9, 2.4) 

Neoplastic effects Nose (all sites): adenoma, 

carcinoma, or squamous cell 

None Kidney (renal tubule): 

adenoma (standard 

None 

carcinoma (0/50, 1/50, 1/50, evaluation - 0/50, 0/49, 

4/50) 0/49, 2/50; standard and 

extended evaluations 

combined - 0/50, 0/49, 0/49, 

3/50); carcinoma (standard 

evaluation - 0/50, 0/49, 

0/49, 2/50; standard and 

extended evaluations 

combined - 0/50, 0/49, 0/49, 

2/50); adenoma or 

carcinoma (standard 

evaluation - 0/50, 0/49, 

0/49, 4/50; standard and 

extended evaluations 

combined - 0/50, 0/49, 0/49, 

5/50) 
Furfuryl Alcohol, NTP TR 482 9 

Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies of Furfuryl Alcohol 

Male Female Male Female 

F344/N Rats F344/N Rats B6C3F Mice 1 B6C3F Mice 1 

Uncertain None Nose (all sites): lateral wall, None None 

findings adenoma (0/49, 0/50, 1/48, 

0/49) 

Nose (respiratory 

epithelium): adenoma 

(0/49, 0/50, 0/48, 1/49); 

lateral wall, adenoma (0/49, 

0/50, 1/48, 0/49) 

Kidney (renal tubule): 

adenoma (standard 

evaluation - 0/50, 0/49, 

0/49, 2/50; standard and 

extended evaluations 

combined - 0/50, 0/49, 2/49, 

2/50); carcinoma (standard 

evaluation - 0/50, 1/49, 

0/49, 0/50; standard and 

extended evaluations 

combined - 0/50, 1/49, 0/49, 

0/50); adenoma or 

carcinoma (standard 

evaluation - 0/50, 1/49, 

0/49, 2/50; standard and 

extended evaluations 

combined - 0/50, 1/49, 2/49, 

2/50) 

Level of evidence Some evidence Equivocal evidence Some evidence No evidence 

of carcinogenic 

activity 

Genetic toxicology 

Salmonella typhimurium gene mutations: Negative in strains TA98, TA100, TA1535, and TA1537 with and without S9 

Sister chromatid exchanges 

Cultured Chinese hamster ovary cells in vitro: Positive without S9; negative with S9 

Mouse bone marrow in vivo: Negative 

Chromosomal aberrations 

Cultured Chinese hamster ovary cells in vitro: Negative without S9; equivocal with S9 

Mouse bone marrow in vivo: Negative 

Micronucleated erythrocytes 

Mouse bone marrow in vivo: Negative 
10 Furfuryl Alcohol, NTP TR 482 

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 longterm 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. 
Furfuryl Alcohol, NTP TR 482 11 

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 furfuryl alcohol on 

10 December 1997 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 the 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 John M. Cullen, Ph.D., V.M.D., Principal Reviewer 

School of Health Sciences Department of Microbiology, Parasitology, and Pathology 

Purdue University College of Veterinary Medicine 

West Lafayette, IN North Carolina State University 

Raleigh, NC 

A. John Bailer, Ph.D. 

Department of Mathematics and Statistics Susan M. Fischer, Ph.D. 

Miami University M.D. Anderson Cancer Center 

Oxford, OH University of Texas 

Smithville, TX 

Steven A. Belinsky, Ph.D. 

Inhalation Toxicology Research Institute Thomas L. Goldsworthy, Ph.D. 

Kirkland Air Force Base Integrated Laboratory Systems 

Albuquerque, NM Research Triangle Park, NC 

James S. Bus, Ph.D., Principal Reviewer Irma Russo, M.D. 

Health and Environmental Sciences Fox Chase Cancer Center 

Dow Chemical Company Philadelphia, PA 

Midland, MI 

Linda A. Chatman, D.V.M. 

Pfizer, Inc. 

Groton, CT 

Special Reviewers 

Stephen S. Hecht, Ph.D. Jose Russo, M.D., Principal Reviewer

University of Minnesota Cancer Centers Fox Chase Cancer Center

Minneapolis, MN Philadelphia, PA

Michele Medinsky, Ph.D. 

Chemical Industry Institute of Toxicology 

Research Triangle Park, NC 
 

12 Furfuryl Alcohol, NTP TR 482 

SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS
 

On 10 December 1997 the draft Technical Report on the 

toxicity and carcinogenicity studies of furfuryl alcohol 

received public review by the National Toxicology 

Programs’s Board of Scientific Counselor’s Technical 

Reports Review Subcommittee. The review meeting was 

held at the National Institute of Environmental Health 

Sciences, Research Triangle Park, NC. 

Dr. R.D. Irwin, NIEHS, introduced the toxicity and 

carcinogenesis studies of furfuryl alcohol by discussing 

the uses of the chemical and the rationale for study, 

describing the experimental design, reporting on survival 

and body weight effects, and commenting on compoundrelated neoplastic and nonneoplastic lesions in rats and 

mice. The proposed conclusions for the 2-year studies 

were some evidence of carcinogenic activity in male 

F344/N rats and male B6C3F1 mice, equivocal evidence

of carcinogenic activity in female F344/N rats, and no 

evidence of carcinogenic activity in female B6C3F1 

mice. 

Drs. Cullen and J. Russo, principal reviewers, agreed 

with the proposed conclusions. 

Dr. Bus, a principal reviewer, agreed with the proposed 

conclusions. He noted that the proposed conclusion for 

female rats was partly based on the observation of renal 

tubule neoplasms, particularly when they are observed in 

extended evaluation step sections. Dr. Bus also noted 

that the proposed conclusion for male mice was based 

entirely on the same observation. He stated that it is 

unclear whether the neoplasms observed in the step 

sections were new or the same neoplasms observed in the 

standard evaluation (see p. 43). Dr. Bus commented that 

more attention should have been paid to the 14-week rat 

study results in setting exposure concentrations for the 

2-year study, in that 32 ppm appeared to exceed the maximum tolerated dose and 2 ppm was above the no-effect 

level. Dr. Irwin said that in setting exposure 

concentrations for the 2-year study, mean body weights at 

32 ppm were within 10% of the controls and the shape of 

the growth curve indicating this would probably not 

change much or that these animals might recover. In the 

2-year study, mean body weights of 32 ppm female rats 

were observed to be approximately the same as those of 

the chamber controls. 

Dr. Carlson commented on the rationale for studying 

furfuryl alcohol as part of a class study with furan and 

furfural, noting that cholangiocarcinomas and other 

hepatocellular neoplasms were significant neoplastic 

findings with furan and furfural. He noted that no liver 

response was seen with furfuryl alcohol in contrast with 

the other two analogues. Dr. Bailer said he thought the 

proposed level of evidence in male rats should have been 

clear evidence of carcinogenic activity based on an 

exposure-related response and four malignant neoplasms 

in the high exposure group. Dr. J.K. Haseman, NIEHS, 

said that although there were no squamous cell 

carcinomas of the nose in the chamber control groups for 

inhalation studies, there have been one or two in some 

control groups in other concurrent studies. Dr. Irwin said 

that the lack of supporting data in females also entered 

into the decision to go with the proposed conclusion of 

some evidence of carcinogenic activity for male rats. 

Dr. Bus moved that the Technical Report on furfuryl 

alcohol be accepted with the revisions discussed and the 

conclusions as written for male rats and mice, some 

evidence of carcinogenic activity; for female rats, 

equivocal evidence of carcinogenic activity; and for 

female mice, no evidence of carcinogenic activity. 

Dr. Cullen seconded the motion, which was accepted by 

six yes votes to two no votes (Drs. Bailer and 

Goldsworthy). 
 

O CH2OH 

 

13 

INTRODUCTION
 

FURFURYL ALCOHOL 

CAS No. 98-00-0 

Chemical Formula: C 5 6 2 H O Molecular Weight: 98.10

Synonyms: 2-Furancarbinol; 2-furanmethanol; furfuralcohol; "-furylcarbinol; 2-furylcarbinol; 2-hydroxymethylfuran 

CHEMICAL AND PHYSICAL PROPERTIES 

Furfuryl alcohol is a member of an industrially important 

class of compounds containing the furan ring. It is a 

clear liquid under standard conditions, with a vapor 

pressure of 0.4 mm Hg at 20E C and a boiling point of 

170E C. Furfuryl alcohol is soluble in water, alcohol, 

benzene, and chloroform but insoluble in paraffinic 

hydrocarbons (Kirk-Othmer, 1985). 

PRODUCTION, USE, 

AND HUMAN EXPOSURE 

Furfuryl alcohol is produced by high-pressure reduction 

(hydrogenation) of furfural in the liquid or vapor phase 

over a copper catalyst (Kirk-Othmer, 1985). The current 

production volume is not listed by the United States 

International Trade Commission (USITC, 1994). 

The major industrial uses of furfuryl alcohol are based on 

its ability to undergo acid-catalyzed polymerization into 

linear, branched, and cross-linked polymers or resins 

often called furan resins. The resins are heat stable and 

resistant to acid, alkali, and solvents. Furfuryl alcohol 

also forms copolymers with furfural, formaldehyde, urea, 

and phenolic derivatives. A major application involves 

the use of these resins as binders of foundry sand. The 

resin is mixed with foundry sand (sufficient resin is added 

to equal approximately 1% of the weight of the sand) and 

exposed to catalyst (heat, acid) to initiate “curing” 

(polymerization). As the curing proceeds, it causes the 

sand to become dimensionally stable. Because 

polymerization is a highly exothermic reaction, some 

furfuryl alcohol is vaporized as the resin cures. Furan 

resins are also added to mortars, grouts, and cements as 

corrosion inhibitors. Because of their heat resistance, 

furan resins are used in the manufacture of fiberglassreinforced plastic equipment (Kirk-Othmer, 1980; 

Quaker Oats, 1985). 

Furfuryl alcohol is also used as a viscosity reducer in 

epoxy resins, as an accelerator or liquefier for amine 

curatives of epoxy resins, as a solvent in textile printing 

and in alkaline paint strippers, and as an intermediate in 

the synthesis of numerous other organic chemicals (KirkOthmer, 1980; Quaker Oats, 1985). 

The numerous uses of furfuryl alcohol and furfuryl 

alcohol-based resins provide considerable potential for 

occupational exposure. Furfuryl alcohol is regulated as 

an air contaminant by the National Institute for 

Occupational Safety and Health; recommended exposure 

limits for airborne concentrations were lowered in 1993 3 from a maximum of 50 ppm (200 mg/m ) to 10 ppm 3 (40 mg/m ) determined as a time-weighted average for up

to a 10-hour work shift or 40-hour work week 

(NIOSH, 1997). The American Conference of 

Governmental Industrial Hygienists suggests an 8-hour, 

time-weighted average threshold limit value (TLV) of 

10 ppm and a 15-minute, time-weighted exposure limit 

of 15 ppm (ACGIH, 1997). The National Occupational 

Hazard Survey conducted by NIOSH from 1972 to 1974 
 

14 Furfuryl Alcohol, NTP TR 482 

estimated that 11,577 workers in 2,939 plants were 

potentially exposed to furfuryl alcohol (NIOSH, 1976). 

Occupations with the largest number of exposed workers 

were carpentry, tile setting, metal molding, packaging 

and filling machine operation, and casting. A second 

workplace survey conducted from 1981 to 1983 

estimated that 5,358 workers in 74 plants were 

potentially exposed (NIOSH, 1990). The stone, clay, 

glass, primary metal, and chemical and allied industries 

employ the largest number of exposed workers. 

A NIOSH health hazard survey conducted at a foundry in 

Salt Lake City, Utah, examined 10 workers potentially 

exposed to furfuryl alcohol (Burton and Rivera, 1972). 

Five of the ten were core makers with measured 

exposures of 11, 25, 30, 32, and 66 mg/m . 

3 In another 

health hazard survey at a foundry in Tigard, Oregon, 

furfuryl alcohol concentrations ranging from 2.2 to 

15.8 ppm were recorded during a casting cycle with the 

furfuryl alcohol concentration dependent on the 

temperature of the sand used in core production (Apol, 

1973). Virtamo and Tossavainen (1976) examined the 

furfuryl alcohol and formaldehyde concentrations in the 

air around core-making facilities at 10 iron and steel 

foundries in Finland. The mean concentration of furfuryl 

alcohol was 4.3 ppm, but the actual measured concentration exceeded the TLV of 5 ppm in 22% of the 

determinations. 

More recently, Ahman et al. (1991) conducted lung 

function evaluations of molders and core makers exposed 

to furan resin sand as well as unexposed controls before 

and after a work shift. The time-weighted average 3 concentration of furfuryl alcohol was 7 mg/m with peak

values exceeding the short-term exposure limit of 

40 mg/m . 

3 During the work shift, exposed workers 

exhibited an average decrease in forced vital capacity and 

had more complaints of airway symptoms than unexposed 

workers; however, no decrease in any other lung function 

variable was detected. Exposed workers evaluated after 

work exhibited a post-shift decrease in total lung 

capacity. In spite of these acute responses, no evidence 

of chronic lung impairment was detected. 

Furfuryl alcohol and furfural are present in thermally 

processed foods because of the dehydration of pentoses in 

reactions similar to those that occur during the 

commercial preparation of furfural from agricultural 

waste. Consumer products that contain furfuryl alcohol 

include cocoa, tea, coffee, dehydrated orange products, 

cooked beef and pork, milk products, nuts, bread, 

popcorn, and vegetables. Furfuryl alcohol is a 

component of cigarette smoke (Maga, 1979). 

ABSORPTION, DISTRIBUTION, 

METABOLISM, AND EXCRETION 

Experimental Animals 

The metabolites present in the urine of male F344/N rats 

14 14 administered [ C]-furfural or [ C]-furfuryl alcohol by

gavage in corn oil have been examined by Irwin et al. 

(1985). A diagram of the urinary metabolites of furfuryl 

alcohol is presented in Figure 1. Greater than 70% of the 

administered dose was recovered as urinary metabolites. 

Furoylglycine was identified as the major metabolite 

present in urine after administration of either compound; 

the minor urinary metabolites, furoic acid and 

furanacrylic acid, were also the same for either furfural or 

furfuryl alcohol. These results were interpreted as 

indicating that the major route of metabolic 

transformation of furfuryl alcohol is oxidation to furfural, 

which is then further oxidized to furoic acid and 

conjugated with glycine to form furoylglycine. A 

secondary route involves the formation of furanacrylic 

acid. 

Nomeir et al. (1992) examined the metabolism and 

disposition of furfural and furfuryl alcohol in F344 rats 14 following oral administration of [ C]-furfuryl alcohol

(corn oil gavage) at doses of 0.275, 2.75, or 27.5 mg/kg 14 or [ C]-furfural at doses of 0.127, 1.15, or 12.5 mg/kg.

Both compounds were well absorbed from the 

gastrointestinal tract and metabolized extensively prior to 

excretion. Of the administered doses, 83% to 88% was 

eliminated in the urine and 2% to 4% was eliminated in 

the feces. Furoylglycine was the major metabolite present 

in the urine (73%-80%); furoic acid (1%-6%) and furanacrylic acid (3%-8%) were identified as minor 

metabolites. Approximately 7% of the label from the 

12.5 mg/kg dose of furfural was eliminated as CO ; none

was detected after administration of furfuryl alcohol. At 

72 hours after administration, the pattern of tissue 

distribution was very similar for both compounds with 

2 
CH2OH 

O 

Furfuryl alcohol 

CHO 

O 

Furfural 

CH3COOH 

(?) 

CH=CHCOOH COOH 

O O 

Furanacrylic acid Furoic acid 

H2NCH2COOH H2NCH2COOH 

CH=CHCONHCH2COOH CONHCH2COOH 

O O 

Furanacryloylglycine 2-Furoylglycine 

Furfuryl Alcohol, NTP TR 482 15 

FIGURE 1 

Metabolic Pathway of Furfuryl Alcohol 

the highest concentration being present in the liver and species, the major urinary metabolite was furoylglycine, 

kidney and the lowest in the brain. In general, the which accounted for approximately 80% of the dose in 

amount of radioactivity present in a given tissue was male rats and 85% to 89% of the total dose in male mice. 

proportional to the dose. Based on these results, the However, the second most abundant metabolite 

authors concluded that furfuryl alcohol is oxidized to was furanacryloylglycine, the glycine conjugate of 

furfural, which is then oxidized to furoic acid and furanacrylic acid. Free furoic acid was detected only at 

conjugated with glycine or is converted to furanacrylic the highest doses as a minor metabolite (approximately 

acid. 2% in rats and male mice and 4%-10% in female mice). 

These authors suggested that furanacryloyl-CoA is 

Parkash and Caldwell (1994) examined the metabolism formed from furanacrylic acid and then conjugated with 

of furfural in F344 rats administered single oral doses of glycine to form furanacryloylglycine. 

1, 10, or 60 mg/kg and CD-1 mice administered 1, 20, or 

200 mg/kg. They also confirmed that the major route of Humans 

elimination was in urine for both rats and mice, with only A similar metabolic profile has been determined for 

small amounts eliminated in the feces or as CO . 2 In both humans exposed to furfural. In a series of experiments, 
16 Furfuryl Alcohol, NTP TR 482 

human volunteers were exposed to furfural vapors for drinking water for 20 days; the only effect observed was 

periods of up to 8 hours. The mean pulmonary retention weight loss. Unfortunately, no details were included in 

was determined to be 77.9% and was not dependent on the report (Gajewski and Alsdorf, 1949). 

the exposure concentrations over the range of exposure; 

analysis of the metabolites present in urine revealed that In 14-day and 13-week studies furfuryl alcohol was 

furoylglycine was the major metabolite and furan acrylic administered in corn oil by gavage (NTP, unpublished 

acid a minor metabolite. No furoic acid was detected in data). During the 14-day studies, compound-related 

freshly expressed urine (Sedivec and Flek, 1978). mortality and clinical findings were observed among both 

F344/N rats and B6C3F1 mice but there were no 

Dermal absorption was also found to be significant in significant gross observations at necropsy. During the 

human volunteers exposed to furfural vapor or liquid. In 13-week studies, rats received doses of 0, 38, 75, 150, or 

this series of experiments, subjects were placed in a room 300 mg furfuryl alcohol per kg body weight in corn oil, 

and exposed to an atmosphere containing 30 mg/m 3 and mice received doses of 0, 38, 75, 150, 300, or 

furfural vapor while breathing pure air through a 600 mg/kg in corn oil. All male and female rats 

breathing tube attached to a mask. An 8-hour exposure receiving 150 or 300 mg/kg died prior to the end of the 

under these conditions resulted in percutaneous study, and significant mortality was also observed in 

absorption of 20% to 30% of the dose retained by the male and female mice receiving 300 or 600 mg/kg. Mean 

lungs under the same exposure conditions, based on the body weights of rats receiving 38, 75, or 150 mg/kg were 

quantity of metabolites recovered in urine. Moreover, similar to those of the controls; because of the significant 

increasing the temperature or humidity of the air early mortality, mean body weights of rats receiving 150 

substantially increased the percutaneous absorption of or 300 mg/kg were not calculated. Mean body weights of 

furfural. In another experiment, three subjects immersed male and female mice receiving 600 mg/kg were 15% 

their left hands, up to the wrist, in a vessel of pure liquid lower than those of the controls while other dose groups 

furfural for 15 minutes; the amount absorbed was were within 10% of the controls. Mean absolute liver 

determined based on the quantity of urinary metabolites and kidney weights of male and female rats receiving 

excreted. The results indicated that the 15-minute 75 mg/kg were significantly greater than those of the 

immersion in liquid furfural resulted in percutaneous controls (P<0.05); no significant organ weight differences 

absorption of the same amount of furfural as would be were observed among dosed and control mice. 

absorbed during an 8-hour inhalation exposure to 3 atmospheres containing 10 mg/m (Sedivec and Flek, Histopathologic lesions of the liver and kidney were 

1978). observed in rats receiving 75, 150, or 300 mg furfuryl 

alcohol/kg body weight and in mice receiving 300 or 

Total urinary furoic acid concentration has been 600 mg/kg. The renal and liver lesions in rats were mild 

suggested as a measure of furfuryl alcohol exposure and consisted of degeneration of individual hepatocytes 

in foundry workers. Furfuryl alcohol exposure was and tubular epithelial cells in the renal cortex, 

determined by collecting urine samples from six foundry accompanied by some cytoplasmic vacuolization. In 

workers; their excretion of urinary furoic acid was then mice, the lesions were more severe and included necrosis 

determined after alkaline hydrolysis of the glycine and cytoplasmic vacuolization. In a prechronic 

conjugates. The product of the sampling time and vapor inhalation study, 15 rats and eight mice (sex and strain 

concentration of furfuryl alcohol correctly predicted total not specified) were exposed to 19 ppm furfuryl alcohol 

urinary furoic acid concentration (Pfaffli et al., 1985). 6 hours per day, 5 days per week for 3 weeks. One rat 

died after the third exposure and one mouse died after the 

ninth exposure; exposed and control animals exhibited 

TOXICITY IN EXPERIMENTAL ANIMALS similar mean body weight gains. At necropsy, diffuse 

The acute toxicity of furfuryl alcohol has been evaluated congestion was noted in the entire respiratory tract but no 

in several studies, and the results of these studies indicate other organs or tissues were grossly affected (Comstock 

that in experimental animals furfuryl alcohol is absorbed and Oberst, 1952). 

and is toxic when administered dermally, orally, or by 

inhalation. In a prechronic inhalation study, 3-month-old Wistar rats 

(20 per group) were exposed to 25, 50, or 100 ppm 

The oral toxicity of furfuryl alcohol has been examined in furfuryl alcohol 6 hours per day, 5 days per week for 

two prechronic studies. In one study, reported only in an 16 weeks (Savolainen and Pfaffli, 1983). Mean body 

abstract, furfuryl alcohol was administered to rats in weights of all groups of exposed animals were less than 
Furfuryl Alcohol, NTP TR 482 17 

those of the controls throughout the study, and animals 2-year period without additional chemical exposure. 

exposed to 100 ppm exhibited muscle hypotonia Groups of 10 animals were evaluated for the presence of 

(unspecified) after 13 weeks of exposure. After 4, 9, 13, neoplasms at the end of the 13-week exposure period and 

or 16 weeks of exposure, five animals per group were at 9 and 15 months. Cholangiocarcinoma was present in 

sacrificed and their brains removed. The specific activity all 10 animals examined at the 9- and 15-month interim 

of creatinine kinase (a marker for astroglial cells) in evaluations and occurred with an overall incidence of 

homogenates of the cerebellum was elevated in all 100% in the stop-exposure group of rats. Among mice, 

exposed groups and was significantly greater (P<0.01) the incidence of hepatocellular carcinoma was 7/50, 

than control activity for animals exposed to 50 or 32/50, and 34/50 for vehicle control, 8 mg/kg, and 

100 ppm. In the same homogenates, however, the 15 mg/kg males, and 2/50, 7/50, and 27/50 for vehicle 

specific activity of succinate dehydrogenase, a general control, 8 mg/kg, and 15 mg/kg females. No stopglial cell marker, was reduced in a dose-dependent exposure study was conducted with mice. 

manner and was also found to be lower in glial cell 

preparations. These results were interpreted as an In the 2-year study of furfural, F344/N rats received 

indication that exposure to furfuryl alcohol may be doses of 30 or 60 mg/kg and mice received doses of 50, 

cytotoxic for glial cells, resulting in increased 100, or 150 mg/kg (NTP, 1990). Cholangiocarcinomas 

proliferation of astroglial cells. were present in two 60 mg/kg male rats, and two 

additional 60 mg/kg males had bile duct dysplasia with 

Analysis of cerebral extracts by electrophoresis in fibrosis, a precursor lesion for cholangiocarcinoma. The 

polyacrylamide gels containing sodium dodecyl sulfate incidences of hepatocellular adenoma and carcinoma were 

revealed an apparent reduction in the relative amount of increased in dosed male mice, and the incidences of 

myelin basic protein. Moreover, the specific activity of hepatocellular adenoma were increased in dosed female 

an acid protease was significantly elevated (P<0.05) in mice. 

the glial cell fraction. Because degradation of myelin 

basic protein by an acid protease is an early step in the 

process of demyelination, the observed changes may be GENETIC TOXICITY an indication of demyelination caused by chemical 

There is little published mutagenicity data for furfuryl exposure, which is consistent with primary effects on 

alcohol, and the available data show little evidence glial cells (Savolainen and Pfaffli, 1983). for genotoxic activity. Florin et al. (1980) and 

Mortelmans et al. (1986) reported no increase in gene 

reversion after treatment with furfuryl alcohol, with or CARCINOGENICITY without liver metabolic activation enzymes (S9), in 

IN EXPERIMENTAL ANIMALS various strains of Salmonella typhimurium. There was 

There are no published studies that have examined the one report of chromosomal aberration induction in 

carcinogenicity of furfuryl alcohol in experimental cultured Chinese hamster ovary cells treated with furfuryl 

animals; however, the NTP has completed 2-year alcohol with and without S9 (Stich et al., 1981); 

carcinogenicity studies of two related compounds, furan however, these data were presented in a way that made 

and furfural. The vehicle in both of these gavage studies independent assessment difficult, and the results require 

was corn oil. In the furan study (NTP, 1993), F344/N confirmation. No increases in sister chromatid exchanges 

rats received doses of 2, 4, or 8 mg/kg, and B6C3F mice were noted in cultured human lymphocytes after exposure 1 

received doses of 8 or 15 mg/kg. The liver was the major to furfuryl alcohol (Gomez-Arroyo and Souza S., 1985; 

target organ in rats and mice. Among groups of rats, the Jansson et al., 1986). And finally, no evidence for 

incidences of cholangiocarcinoma were 0/50 for vehicle mutagenic activity of furfuryl alcohol was seen in a 

controls, 43/50, 48/50, and 49/50 for 2, 4, and 8 mg/kg Drosophila melanogaster sex-linked recessive lethal 

males, and 49/50, 50/50, and 48/50 for 2, 4, and 8 mg/kg assay or a sex-chromosome loss test; both these germ cell 

females, respectively. Incidences of hepatocellular tests employed adult injection and larval feeding as routes 

adenoma and carcinoma were also significantly increased of administration (Rodriguez-Arnaiz et al., 1989). 

in dosed male rats, and the incidences of hepatocellular 

adenoma were significantly increased in dosed female 

rats. A separate stop-exposure group of 50 male rats was STUDY RATIONALE 

administered a single dose of 30 mg/kg furan for Furfuryl alcohol, furfural, and furan were selected for 

13 weeks and then maintained for the remainder of the evaluation as a class study because of the absence of data 
18 Furfuryl Alcohol, NTP TR 482 

on carcinogenic potential and because their large 

production volume, widespread use in manufacturing, 

and ubiquitous presence in consumer goods and 

foodstuffs suggested the potential for widespread human 

exposure. 

Furfuryl alcohol was evaluated in 14-day and 13-week 

corn oil gavage studies (NTP, unpublished data) as part 

of the comparative class study with furan and furfural. 

However, human exposure to furfuryl alcohol occurs 

predominantly in occupational settings where inhalation 

is the major route of exposure. Therefore, it was 

considered most appropriate to evaluate the carcinogenic 

potential of furfuryl alcohol by inhalation. 
19 

MATERIALS AND METHODS
 

PROCUREMENT 

AND CHARACTERIZATION 

OF FURFURYL ALCOHOL 

Furfuryl alcohol was obtained from QO Chemicals, Inc. 

(Memphis, TN), in one lot (7B19M-2), which was used 

during the 16-day, 14-week, 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 furfuryl alcohol studies are on 

file at the National Institute of Environmental Health 

Sciences. 

The chemical, a clear yellow liquid, was identified as 

furfuryl alcohol by infrared, ultraviolet/visible, and 

nuclear magnetic resonance spectroscopy. The purity of 

lot 7B19M-2 was determined by elemental analyses, Karl 

Fischer water analysis, and gas chromatography. 

Elemental analyses for carbon and hydrogen were in 

agreement with the theoretical values for furfuryl alcohol. 

Karl Fischer water analysis indicated 0.098% ± 0.008% 

water. Gas chromatography by two systems indicated 

one major peak and five impurities with areas greater 

than 0.1% relative to the major peak area; the combined 

impurity peak areas were 1.36% by one system and 

1.17% by the second system. Major peak comparison 

between lot 7B19M-2 and lot Q0112979, a previously 

analyzed lot not used in the current studies, indicated a 

purity of 100.9% ± 0.6% for lot 7B19M-2 relative to lot 

Q0112979. The overall purity was determined to be 

greater than 98%. 

During the studies, the bulk chemical was stored under a 

nitrogen blanket in its original shipping containers at 

approximately !20E C. Stability was monitored by the 

study laboratory throughout the studies with gas 

chromatography; no degradation of the bulk chemical was 

detected. 

VAPOR GENERATION 

AND EXPOSURE SYSTEM 

Furfuryl alcohol was pumped into the top of a glass 

evaporation column filled with glass beads. A heated 

nitrogen stream entered the column from below, 

vaporized the furfuryl alcohol, and carried it to a heated 

condenser column. During the 2-year studies, the 

evaporation column was heated by wrapping with heat 

tape; additional heated nitrogen was added to the furfuryl 

alcohol vapor leaving the evaporation column to dilute 

the vapor. Detailed descriptions of the inhalation 

chamber and vapor generation system are provided in 

Appendix J. 

During the 16-day and 14-week studies, the vapor was 

drawn through a heated line and injected into the inlet air 

stream of a mixing chamber and then pumped through a 

pneumatic valve into the distribution line. The charcoaland HEPA-filtered air was conditioned to room 

temperature and maintained at minimum relative 

humidity to prevent the vapor from condensing. During 

the 16-day studies, condensation particles were filtered 

from the vapor with Teflon-membrane filters before 

entering the distribution line. In the 2-year studies, no 

mixing chamber was used; the vapor was drawn through 

a heated line and then mixed with heated air at the 

entrance of a short vapor distribution manifold. An 

automatic controller maintained constant flow in the 

distribution manifold. 

From the distribution manifold, individual temperaturecontrolled delivery lines carried the vapor to each 

exposure chamber. The study laboratory designed the 

inhalation exposure chamber so that uniform vapor 

concentrations could be maintained throughout the 

chamber with the catch pans in place. A small particle 

detector (Type CN, Gardner Associates, Schenectady, 

NY) was used with and without animals in the exposure 
20 Furfuryl Alcohol, NTP TR 482 

chambers to ensure that furfuryl alcohol vapor, and not 

aerosol, was produced. The minimum resolvable level of 

the detector is approximately 200 particles per cubic 

centimeter. During the 16-day studies, without animals 

in the chambers, particle concentrations were below the 

limit of detection in the 16 and 31 ppm chambers but 3 ranged up to 600 particles/cm in the 63 ppm chambers

and 8,400 particles/cm3 in the 125 ppm chambers; 

concentrations in the 250 ppm chambers ranged from 

8,400 to 36,000 particles/cm . 

3 With animals in the 

chambers, concentrations were below the limit of 

detection in all but the 125 and 250 ppm chambers, 

which had concentrations of 1,470 and 3 11,200 particles/cm , respectively. During the 14-week 

studies, particle concentrations in the 32 ppm chamber 

were 200 particles/cm3 without animals present and 

245 particles/cm3 with animals; concentrations in all 

other chambers were below the limit of detection, with 

and without animals present. During the 2-year studies, 

the 32 ppm mouse chamber had a concentration of 3 370 particles/cm with no animals present; all other rat

and mouse chambers, with and without animals present, 

had concentrations below the limit of detection. 

VAPOR CONCENTRATION MONITORING 

The chamber concentrations of furfuryl alcohol were 

monitored by a Hewlett-Packard Model 5890 on-line gas 

chromatograph. Samples were drawn through a 12-port 

stream select valve. The monitoring system was 

calibrated against a gravimetrically prepared standard of 

furfuryl alcohol in nitrogen. Additionally, the on-line 

monitor was calibrated by a comparison of chamber 

concentration data to grab samples analyzed by an offline gas chromatograph. The operation of the chamber 

monitor was checked throughout the day against an online standard. The grab samples were collected in 

bubblers containing dimethylformamide and analyzed by 

an off-line gas chromatograph. The off-line gas 

chromatograph was calibrated with gravimetrically 

prepared furfuryl alcohol standards in 

dimethylformamide. Chamber concentration uniformity 

was maintained throughout the studies. Summaries of the 

chamber concentrations during the studies are presented 

in Tables J1 through J3. 

CHAMBER ATMOSPHERE 

CHARACTERIZATION 

The buildup of vapor concentration in the chamber to 

90% of its final stable concentration (T 90 ) at the

beginning of exposure and the decay of concentration at 

the end of exposure to 10% (T 10 ) were measured with and

without animals in the chambers. A T90 of 12 minutes 

was initially used for all studies. However, because the 

actual T90 values for the 14-week studies were 

considerably longer than 12 minutes (16 to 20 minutes), 

the T90 was increased to 20 minutes on the seventeenth 

exposure day; this value was used until the end of the 

studies. To compensate for the slow buildup, additional 

vapor was delivered to the exposure chambers during the 

first 30 to 60 minutes. 

Throughout the studies, stability was monitored by 

testing furfuryl alcohol samples (collected with bubblers 

or gas sampling tubes) with gas chromatography. No 

degradation of furfuryl alcohol was detected. 

16-DAY STUDIES 

Male and female F344/N rats and B6C3F1 mice were 

obtained from Simonsen Laboratories (Gilroy, CA). On 

receipt, the rats and mice were approximately 4 weeks 

old. Animals were quarantined for 12 days and were 

6 weeks old on the first day of the studies. Before the 

studies began, five male and five female rats and mice 

were randomly selected for parasite evaluation and gross 

observation for evidence of disease. 

Groups of five male and five female rats and mice were 

exposed to concentrations of 0, 16, 31, 63, 125, or 250 

ppm furfuryl alcohol by inhalation, 6 hours plus T 90 

(12 minutes) per day, 5 days per week, for 16 days. Rats 

and mice received a total of 12 exposures, including at 

least two consecutive exposures before necropsy. Feed 

was available ad libitum except during exposure periods; 

water was available ad libitum. Rats and mice were 

housed individually. Clinical findings were recorded 

twice daily for rats and mice. The animals were weighed 

initially, on day 8, and at the end of the studies. Details 

of the study design and animal maintenance are 

summarized in Table 1. 
 

Furfuryl Alcohol, NTP TR 482 21 

At the end of the 16-day studies, a necropsy was 

performed on all rats and mice. The heart, right kidney, 

liver, lung, right testis, and thymus were weighed. 

Histopathologic examinations were performed on all rats 

and mice. Table 1 lists the tissues and organs examined. 

14-WEEK STUDIES 

The 14-week studies were conducted to evaluate the 

cumulative toxic effects of repeated exposure to furfuryl 

alcohol and to determine the appropriate exposure 

concentrations to be used in the 2-year studies. 

Male and female F344/N rats and B6C3F1 mice were 

obtained from Simonsen Laboratories (Gilroy, CA). On 

receipt, the rats and mice were approximately 4 weeks 

old. Animals were quarantined for 12 or 13 days and 

were 6 weeks old on the first day of the studies. Before 

the studies began, five male and five female rats and mice 

were randomly selected for parasite evaluation and gross 

observation for evidence of disease. At the end of the 

studies, serologic analyses were performed on five male 

and five female sentinel rats and control mice using the 

protocols of the NTP Sentinel Animal Program 

(Appendix L). 

Groups of 10 male and 10 female rats and mice were 

exposed to furfuryl alcohol at concentrations of 0, 2, 4, 8, 

16, or 32 ppm for 6 hours plus T90 (12 minutes through 

day 16, 20 minutes thereafter) per day, 5 days per week 

for 14 weeks. Additional groups of 10 male and 

10 female rats designated for special clinical pathology 

evaluations were exposed to the same concentrations of 

furfuryl alcohol as the core study rats. Feed was 

available ad libitum except during exposure periods; 

water was available ad libitum. Rats and mice were 

housed individually. Clinical findings were recorded 

weekly. The core study animals were weighed initially, 

weekly, and at the end of the studies. Details of the study 

design and animal maintenance are summarized in 

Table 1. 

Blood was collected from the special clinical pathology 

groups of rats on days 3 and 23 and from core study rats 

at the end of the 14-week study. After the day 23 blood 

collection, the special clinical pathology rats were killed 

and discarded without a necropsy being performed. The 

rats were anesthetized with 70% CO2 and blood was 

collected from the retroorbital plexus. Blood for 

hematology determinations was placed in tubes 

containing potassium EDTA as an anticoagulant. 

Erythrocyte, total leukocyte, and platelet counts, 

hematocrit, hemoglobin concentration, mean cell volume, 

mean cell hemoglobin, and mean cell hemoglobin 

concentration were measured on an Ortho ELT-8/ds 

hematology analyzer (Ortho Instruments, Westwood, 

MA). Differential leukocyte counts were based on 

classifying a minimum of 100 leukocytes in blood smears 

stained with a Gam-Rad automatic stainer (Gam-Rad, 

Inc., Chilhowie, VA), and these values were calculated in 

absolute numbers. Reticulocytes were stained with new 

methylene blue and counted as a reticulocyte/erythrocyte 

ratio using the Miller disc method. Blood for serum 

clinical chemistry analyses was collected in containers 

without anticoagulant but containing a separator gel, 

allowed to clot, and centrifuged to separate the serum. 

For the day 3 and day 23 clinical chemistry evaluations, 

the following were assayed using an Abbott VP chemistry 

analyzer (Abbott Laboratories, Abbott Park, IL): urea 

nitrogen, creatinine, total protein, albumin, globulin, 

alanine aminotransferase, alkaline phosphatase, creatine 

kinase, and sorbitol dehydrogenase. For the core study 

samples at the end of the study, only sorbitol 

dehydrogenase was measured using the Abbott VP 

analyzer; all other analyses were performed by a Roche 

Cobas Fara analyzer (Roche Diagnostic Systems, Inc., 

Montclair, NJ). Total bile acids were determined using 

a commercially obtained kit (Enzabile®) with the optical 

density of the colored end-product read on a recording 

spectrophotometer. The parameters measured are listed 

in Table 1. 

At the end of the 14-week studies, samples were collected 

for sperm motility and vaginal cytology evaluations on 

rats and mice exposed to 0, 2, 8, and 32 ppm. The 

parameters evaluated are listed in Table 1. Methods used 

were those described in the NTP’s sperm morphology 

and vaginal cytology evaluations protocol (NTP, 1987). 

For 12 consecutive days prior to scheduled terminal 

sacrifice, the vaginal vaults of the females were 

moistened with saline, if necessary, and samples of 

vaginal fluid and cells were stained. Relative numbers of 

leukocytes, nucleated epithelial cells, and large squamous 

epithelial cells were determined and used to ascertain 

estrous cycle stage (i.e., diestrus, proestrus, estrus, and 

metestrus). Male animals were evaluated for sperm count 

and motility. The left testis and left epididymis were 

isolated and weighed. The tail of the epididymis (cauda 

epididymis) was then removed from the epididymal body 

(corpus epididymis) and weighed. Test yolk (rats) or 

modified Tyrode’s buffer (mice) was applied to slides, 

and a small incision was made at the distal border of the 

cauda epididymis. The sperm effluxing from the incision 

were dispersed in the buffer on the slides, and the 

numbers of motile and nonmotile spermatozoa were 

counted for five fields per slide by two observers. 
 

22 Furfuryl Alcohol, NTP TR 482 

Following completion of sperm motility estimates, each 

left cauda epididymis was placed in buffered saline 

solution. Caudae were finely minced, and the tissue was 

incubated in the saline solution and then heat fixed at 

65E C. Sperm density was then determined microscopically with the aid of a hemacytometer. To quantify 

spermatogenesis, the testicular spermatid head count was 

determined by removing the tunica albuginea and 

homogenizing the left testis in phosphate-buffered saline 

containing 10% dimethyl sulfoxide. Homogenizationresistant spermatid nuclei were counted with a 

hemacytometer. 

A necropsy was performed on all core study animals. 

The heart, right kidney, liver, lung, right testis, and 

thymus were weighed. Tissues for microscopic 

examination 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. A complete 

histopathologic examination was performed on core study 

rats and mice in the 0 and 32 ppm groups. Additionally, 

the nose and gross lesions of male and female rats and 

mice in the 2, 4, 8, and 16 ppm groups were examined. 

Table 1 lists the tissues and organs routinely examined. 

2-YEAR STUDIES 

Study Design 

Groups of 50 male and 50 female rats and mice were 

exposed to furfuryl alcohol by inhalation, 6 hours plus T90 

(12 minutes) per day, 5 days per week for 105 weeks, at 

concentrations of 0, 2, 8, or 32 ppm. 

Postexposure 16-hour urine samples were collected at 

study termination from rats from each exposure group. 

Water was available ad libitum during the 16-hour 

collection periods, and all urine samples were analyzed 

for volume, creatinine, furoylglycine, and 

furanacryloylglycine. Analyses were accomplished using 

solvent extraction followed by derivitization and gas 

chromatography/mass spectrometry using a HewlettPackard Model 5890 gas chromatograph with an 

HP-5971 mass selective detector and an HP-7673 autosampler (Hewlett-Packard, Palo Alto, CA). 

Source and Specification of Animals 

Male and female F344/N rats and B6C3F1 mice were 

obtained from Taconic Farms (Germantown, NY) for use 

in the 2-year studies. Rats and mice were quarantined for 

12 to 14 days before the beginning of the studies. Five 

male and five female rats and mice were randomly 

selected for parasite evaluation and gross observation of 

disease. Rats and mice were approximately 6 weeks old 

at the beginning of the studies. The health of the animals 

was monitored during the studies according to the 

protocols of the NTP Sentinel Animal Program 

(Appendix L). 

Animal Maintenance 

Rats and mice were housed individually. Feed was 

available ad libitum except during exposure and urine 

collection periods; water was available ad libitum. 

Chambers were rotated weekly. Further details of animal 

maintenance are given in Table 1. Information on feed 

composition and contaminants is provided in 

Appendix K. 

Clinical Examinations and Pathology 

All animals were observed twice daily. Animals were 

weighed initially, weekly for 12 weeks, monthly until 

week 91, then every 2 weeks until the end of the studies. 

Clinical findings were recorded initially, approximately 

monthly until week 91, then every 2 weeks until the end 

of the studies. 

A complete necropsy and microscopic examination were 

performed on all rats and 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 (e.g., adrenal gland, 

kidney, ovary), samples from each organ were examined. 

For extended evaluation of renal proliferative lesions, 

kidneys were step sectioned at 1-mm (rats) or 0.5-mm 

(mice) intervals, and four additional sections were 

obtained from each kidney. 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 studies, 

a quality assessment pathologist evaluated slides from all 

tumors and all potential target organs, which included the 

adrenal gland, kidney, lung, nose, pituitary gland, and 

skin of male rats; adrenal gland, bone, lung, nose, and 
Furfuryl Alcohol, NTP TR 482 23 

skin of female rats; adrenal gland, kidney, lung, nose, and consisted of the quality assessment pathologist and other 

pancreatic islets of male mice; and eye, lung, nose, pathologists experienced in rodent toxicologic pathology. 

pituitary gland, and thyroid gland of female mice. This group examined the tissues without any knowledge 

of dose groups or previously rendered diagnoses. When 

The quality assessment report and the reviewed slides the PWG consensus differed from the opinion of the 

were submitted to the NTP Pathology Working Group laboratory pathologist, the diagnosis was changed. Final 

(PWG) chairperson, who reviewed the selected tissues diagnoses for reviewed lesions represent a consensus 

and addressed any inconsistencies in the diagnoses between the laboratory pathologist, reviewing 

made by the laboratory and quality assessment pathologist(s), and the PWG. Details of these review 

pathologists. Representative histopathology slides procedures have been described, in part, by Maronpot 

containing examples of lesions related to chemical and Boorman (1982) and Boorman et al. (1985). For 

administration, examples of disagreements in diagnoses subsequent analyses of the pathology data, the decision of 

between the laboratory and quality assessment whether to evaluate the diagnosed lesions for each tissue 

pathologists, or lesions of general interest were presented type separately or combined was generally based on the 

by the chairperson to the PWG for review. The PWG guidelines of McConnell et al. (1986). 
24 Furfuryl Alcohol, NTP TR 482 

TABLE 1 

Experimental Design and Materials and Methods in the Inhalation Studies of Furfuryl Alcohol 

16-Day Studies 14-Week Studies 2-Year Studies 

Study Laboratory 

Battelle Pacific Northwest Laboratories 

(Richland, WA) 

Strain and Species 

Rats: F344/N 

Mice: B6C3F1 

Animal Source 

Simonsen Laboratories (Gilroy, CA) 

Time Held Before Studies 

12 days 

Average Age When Studies Began 

6 weeks 

Date of First Exposure 

Rats: 18 July 1988 

Mice: 19 July 1988 

Duration of Exposure 

6 hours plus T90 (12 minutes) per day, 5 days 

per week, for 16 days 

Date of Last Exposure 

Rats: 2 August 1988 

Mice: 3 August 1988 

Necropsy Dates 

Rats: 3 August 1988 

Mice: 4 August 1988 

Average Age at Necropsy 

9 weeks 

Size of Study Groups 

5 males and 5 females 

Method of Distribution 

Animals were distributed randomly into 

groups of approximately equal initial mean 

body weights. 

Animals per Cage 

Method of Animal Identification 

Tail tattoo 

Battelle Pacific Northwest Laboratories 

(Richland, WA) 

Rats: F344/N 

Mice: B6C3F1 

Simonsen Laboratories (Gilroy, CA) 

Rats: 12 days (males) or 13 days (females) 

Mice: 13 days 

6 weeks 

Rats: 19 (males) or 

20 (females) December 1988 

Mice: 20 December 1988 

6 hours plus T90 (12 minutes initially, 

increased to 20 minutes on seventeenth 

exposure day) per day, 5 days per week, for 

14 weeks 

Rats: 20 (males) or 

21 (females) March 1989 

Mice: 22 (males) or 

23 (females) March 1989 

Rats: 21 (males) or 

22 (females) March 1989 

Mice: 23 (males) or 

24 (females) March 1989 

19 weeks 

10 males and 10 females 

Same as 16-day studies 

1 

Tail tattoo 

Battelle Pacific Northwest Laboratories 

(Richland, WA) 

Rats: F344/N 

Mice: B6C3F1 

Taconic Farms (Germantown, NY) 

Rats: 12 days 

Mice: 14 days 

6 weeks 

Rats: 26 November 1991 

Mice: 21 November 1991 

6 hours plus T90 (12 minutes) per day, 5 days per 

week, for 105 weeks 

Rats: 24 November 1993 

Mice: 19 November 1993 

Rats: 29-30 November 1993 

Mice: 22-24 November 1993 

111 weeks 

50 males and 50 females 

Same as 16-day studies 

1 

Tail tattoo 

1 
Furfuryl Alcohol, NTP TR 482 25 

TABLE 1 

Experimental Design and Materials and Methods in the Inhalation Studies of Furfuryl Alcohol 

16-Day Studies 14-Week Studies 2-Year Studies 

Diet 

NIH-07 open formula pelleted diet (Zeigler 

Brothers, Inc., Gardners, PA), available 

ad libitum except during exposure periods, 

changed weekly 

Same as 16-day studies NIH-07 open formula pelleted diet (Zeigler 

Brothers, Inc., Gardners, PA), available 

ad libitum except during exposure and urine 

collection periods, changed weekly 

Water Distribution 

Tap water (Richland municipal supply) via 

automatic watering system (Edstrom 

Industries, Waterford, WI), available 

ad libitum 

Same as 16-day studies Same as 16-day studies 

Cages 

Stainless steel (Harford Systems, Aberdeen, 

MD), changed once per week 

Same as 16-day studies Same as 16-day studies 

Bedding 

Techsorb® untreated cageboard (Shepherd 

Specialty Papers, Inc., Kalamazoo, MI), 

changed daily 

Same as 16-day studies Untreated cageboard (Bunzl Cincinnati Paper 

Co., Cincinnati, OH), changed daily 

Chamber Air Supply Filters 

Single HEPA filter (Flanders Filters, Inc., San 

Rafael, CA); charcoal filter (RSE, Inc., New 

Baltimore, MI) 

Same as 16-day studies Same as 16-day studies 

Chambers 

Stainless steel (Harford Systems, Aberdeen, 

MD), changed once per week 

Same as 16-day studies Same as 16-day studies 

Chamber Environment 

Mean temperature: 22.8E-23.7E C 

Mean relative humidity: 45%-61% 

Room fluorescent light: 12 hours/day 

Chamber air changes: 15/hour 

Mean temperature: 23.6E-24.1E C 

Mean relative humidity: 55%-56% 

Room fluorescent light: 12 hours/day 

Chamber air changes: 15/hour 

Mean temperature: 23.9E-24.3E C (rats); 

23.8E-24.1E C (mice) 

Mean relative humidity: 55%-57% (rats); 51%­

55% (mice) 

Room fluorescent light: 12 hours/day 

Chamber air changes: 15/hour 

Exposure Concentrations 

0, 16, 31, 63, 125, or 250 ppm 0, 2, 4, 8, 16, or 32 ppm 0, 2, 8, or 32 ppm 

Type and Frequency of Observation 

Observed twice daily; animals were weighed 

initially, on day 8, and at the end of the 

studies; clinical findings were recorded 

twice daily. 

Observed twice daily; animals were weighed 

initially, weekly, and at the end of the 

studies; clinical findings were recorded 

weekly. 

Observed twice daily; animals were weighed 

initially, weekly for 12 weeks, monthly until 

week 91, then every 2 weeks until the end of the 

studies. Clinical findings were recorded initially, 

approximately monthly until week 91, then every 

2 weeks until the end of the studies. 

Method of Sacrifice 

70% CO2 Same as 16-day studies Same as 16-day studies 

Necropsy 

Necropsy was performed on all animals. 

Organs weighed were heart, right kidney, 

liver, lung, right testis, and thymus. 

Necropsy was performed on all core study 

animals. Organs weighed were heart, right 

kidney, liver, lung, right testis, and thymus. 

Necropsy was performed on all animals. 
26 Furfuryl Alcohol, NTP TR 482 

TABLE 1 

Experimental Design and Materials and Methods in the Inhalation Studies of Furfuryl Alcohol 

16-Day Studies 14-Week Studies 2-Year Studies 

Clinical Pathology 

None Blood was collected from special clinical None 

pathology groups on days 3 and 23, and from 

all core study rats at the end of the study for 

hematology and clinical chemistry analyses. 

Blood was collected from the retroorbital 

plexus of animals anesthetized with 70% 

CO 2 /30% room air after at least two

consecutive days of exposure. 

Hematology: hematocrit; hemoglobin 

concentration; erythrocyte, reticulocyte, and 

platelet counts; mean cell volume; mean cell 

hemoglobin; mean cell hemoglobin 

concentration; and total leukocyte count and 

differentials 

Clinical chemistry: urea nitrogen, 

creatinine, total protein, albumin, globulin, 

albumin/globulin ratio, alanine 

aminotransferase, alkaline phosphatase, 

creatine kinase, sorbitol dehydrogenase, and 

total bile acids 

Histopathology 

Histopathology was performed on all rats and Complete histopathology was performed on Complete histopathology was performed on all 

mice. In addition to gross lesions and tissue core study rats and mice in the 0 and 32 ppm rats and mice. In addition to gross lesions and 

masses, the following tissues were examined: groups. In addition to gross lesions and tissue masses, the following tissues were 

larynx, lung, nose, and trachea. tissue masses, the following tissues were examined: adrenal gland, bone and marrow, 

examined: adrenal gland, bone and marrow, brain, clitoral gland, esophagus, gallbladder 

brain, clitoral gland, esophagus, gallbladder (mice), heart, large intestine (cecum, colon, 

(mice), heart and aorta, large intestine rectum), small intestine (duodenum, jejunum, 

(cecum, colon, rectum), small intestine ileum), kidney, larynx, liver, lung, lymph nodes 

(duodenum, jejunum, ileum), kidney, larynx, (mandibular, mesenteric, bronchial, mediastinal), 

liver, lung, lymph nodes (mandibular, mammary gland (with skin), nose, ovary, 

mesenteric, bronchial, mediastinal), pancreas, parathyroid gland, pituitary gland, 

mammary gland, thigh muscle, nose, ovary, preputial gland, prostate gland, salivary gland, 

pancreas, parathyroid gland, pharynx, spleen, stomach (forestomach and glandular), 

pituitary gland, preputial gland, prostate testis (with epididymis and seminal vesicle), 

gland, salivary gland, skin, spleen, stomach thymus, thyroid gland, trachea, urinary bladder, 

(forestomach and glandular), testis (with and uterus. 

epididymis and seminal vesicle), thymus, 

thyroid gland, trachea, urinary bladder, 

uterus, and vagina. Additionally, the nose 

and gross lesions of rats and mice in the 2, 4, 

8, and 16 ppm groups were examined. 

Sperm Motility and Vaginal Cytology 

None Sperm samples were collected from rats and None 

mice in the 0, 2, 8, and 32 ppm groups at the 

end of the studies and evaluated for sperm 

count and motility. The left cauda 

epididymis, left epididymis, and left testis 

were weighed. Vaginal samples were 

collected for up to 12 consecutive days prior 

to the end of the studies and evaluated for the 

relative frequency of estrous stages and for 

estrous cycle length. 
Furfuryl Alcohol, NTP TR 482 27 

TABLE 1 

Experimental Design and Materials and Methods in the Inhalation Studies of Furfuryl Alcohol 

16-Day Studies 14-Week Studies 2-Year Studies 

Urinary Metabolite Study 

None None Urine samples were obtained from rats from each 

exposure group at study termination. Samples 

from fasted animals were collected over ice for 

16 hours and stored at !70E C. Parameters 

measured included volume, creatinine, 

furoylglycine, and furanacryloylglycine. 

STATISTICAL METHODS 

Survival Analyses 

The probability of survival was estimated by the productlimit procedure of Kaplan and Meier (1958) and is 

presented in the form of graphs. Animals found dead of 

other than natural causes or pregnant were censored from 

the survival analyses; animals dying from natural causes 

were not censored. Statistical analyses for possible doserelated effects on survival used Cox’s (1972) method for 

testing two groups for equality and Tarone’s (1975) life 

table test to identify dose-related trends. All reported 

P values for the survival analyses are two sided. 

Calculation of Incidence 

The incidences of neoplasms or nonneoplastic lesions are 

presented in Tables A1, A5, B1, B5, C1, C5, D1, and D4 

as the numbers of animals bearing such lesions at a 

specific anatomic site and the numbers of animals with 

that site examined microscopically. For calculation of 

statistical significance, the incidences of most neoplasms 

(Tables A3, B3, C3, and D3) 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. 

Kidney step sections provide approximately eight 

additional sections per animal that may have additional 

proliferative lesions. In the incidence tables and standard 

statistical analyses given in the appendixes, only the 

proliferative lesions in the original (typically two) kidney 

sections are considered. However, separate analyses of 

the additional lesions found in the step sections and of the 

combined lesions in original and step section often 

provided significant additional information and are given 

in this report. Since the same large proliferative lesions 

may be present both on an original section and on 

subsequent step sections, such a lesion is only counted 

once in the combination analysis. Animals with 

proliferative lesions identified in the step-section review 

are listed in a separate document for the specific study, 

Report of the Special Pathology Working Group for 

Kidney Step Sections, and is available on request. 

Tables A3, B3, C3, and D3 also give the survivaladjusted neoplasm rate for each group and each sitespecific neoplasm. This survival-adjusted rate (based on 

the Poly-3 method described below) accounts for 

differential mortality by assigning a reduced risk of 

neoplasm, proportional to the third power of the fraction 

of time on study, to animals that do not reach terminal 

sacrifice. 

Analysis of Neoplasm 

and Nonneoplastic Lesion Incidences 

The Poly-k test (Bailer and Portier, 1988; Portier and 

Bailer, 1989; Piegorsch and Bailer, 1997) was used to 

assess neoplasm and nonneoplastic lesion prevalence. 

This test is a survival-adjusted quantal-response 

procedure that modifies the Cochran-Armitage linear 

trend test to take survival differences into account. More 

specifically, this method modifies the denominator in the 

quantal estimate of lesion incidence to approximate more 

closely the total number of animal years at risk. For 

analysis of a given site, each animal is assigned a risk 

weight. This value is one if the animal had a lesion at 

that site or if it survived until terminal sacrifice; if the 

animal died prior to terminal sacrifice and did not have a 

lesion at that site, its risk weight is the fraction of the 

entire study time that it survived, raised to the kth power. 

This method yields a lesion prevalence rate that depends 

only upon the choice of a shape parameter for a Weibull 

hazard function describing cumulative lesion incidence 
28 Furfuryl Alcohol, NTP TR 482 

over time (Bailer and Portier, 1988). Unless otherwise 

specified, a value of k=3 was used in the analysis of sitespecific lesions. This value was recommended by Bailer 

and Portier (1988) following an evaluation of neoplasm 

onset time distributions for a variety of site-specific 

neoplasms in control F344 rats and B6C3F mice (Portier 1 

et al., 1986). Bailer and Portier (1988) showed that the 

Poly-3 test gave valid results if the true value of k was 

anywhere in the range from 1 to 5. A further advantage 

of the Poly-3 method is that it does not require lesion 

lethality assumptions. Variation introduced by the use of 

risk weights, which reflect differential mortality, was 

accommodated by adjusting the variance of the Poly-3 

statistic as recommended by Bieler and Williams (1993). 

Tests of significance included pairwise comparisons of 

each exposed group with chamber controls and a test for 

an overall exposure-related trend. Continuity-corrected 

tests were used in the analysis of lesion incidence, and 

reported P values are one sided. Values of P greater than 

0.5 are presented as 1-P with the letter N added to 

indicate a lower incidence or negative trend in neoplasm 

occurrence relative to the control group (e.g., P=0.99 is 

presented as P=0.01N). 

Analysis of Continuous Variables 

Two approaches were employed to assess the significance 

of pairwise comparisons between exposed and chamber 

control groups in the analysis of continuous variables. 

Organ and body weight data, which have approximately 

normal distributions, were analyzed with the parametric 

multiple comparison procedures of Dunnett (1955) and 

Williams (1971, 1972). Hematology, clinical chemistry, 

spermatid, and epididymal spermatozoal data, which 

have typically skewed distributions, were analyzed using 

the nonparametric multiple comparison methods of 

Shirley (1977) and Dunn (1964). Jonckheere’s test 

(Jonckheere, 1954) was used to assess the significance of 

the dose-related trends and to determine whether a trendsensitive test (Williams’ or Shirley’s test) was more 

appropriate for pairwise comparisons than a test that does 

not assume a monotonic dose-related trend (Dunnett’s or 

Dunn’s test). Prior to statistical analysis, extreme values 

identified by the outlier test of Dixon and Massey (1951) 

were examined by NTP personnel, and implausible 

values were eliminated from the analysis. Average 

severity values were analyzed for significance with the 

Mann-Whitney U test (Hollander and Wolfe, 1973). 

Because vaginal cytology data are proportions (the 

proportion of the observation period that an animal was 

in a given estrous stage), an arcsine transformation was 

used to bring the data into closer conformance with a 

normality assumption. Treatment effects were investigated by applying a multivariate analysis of variance 

(Morrison, 1976) to the transformed data to test for 

simultaneous equality of measurements across exposure 

concentrations. 

Historical Control Data 

Although the concurrent control group is always the first 

and most appropriate control group used for evaluation, 

historical control data can be helpful in the overall 

assessment of neoplasm incidence in certain instances. 

Consequently, neoplasm incidences from the NTP 

historical control database, which is updated yearly, are 

included in the NTP reports for neoplasms appearing to 

show compound-related effects. 

QUALITY ASSURANCE METHODS 

The 14-week and 2-year studies were conducted in 

compliance with Food and Drug Administration Good 

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

addition, as records from the 2-year studies were 

submitted to the NTP Archives, these studies were 

audited retrospectively by an independent quality 

assurance contractor. Separate audits covered completeness and accuracy of the pathology data, pathology 

specimens, final pathology tables, and a draft of this NTP 

Technical Report. 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, 

and all comments were resolved or otherwise addressed 

during the preparation of this Technical Report. 

GENETIC TOXICOLOGY 

The genetic toxicity of furfuryl alcohol was assessed by 

testing the ability of the chemical to induce mutations in 

various strains of Salmonella typhimurium, sister 

chromatid exchanges and chromosomal aberrations in 

cultured Chinese hamster ovary cells and mouse bone 

marrow cells, and micronucleated erythrocytes in bone 

marrow of mice. The protocols for these studies and the 

results are given in Appendix E. 

The genetic toxicity studies of furfuryl alcohol are part of 

a larger effort by the NTP to develop a database that 

would permit the evaluation of carcinogenicity in 

experimental animals from the molecular structure and 

the effects of the chemical in short-term in vitro and 

in vivo genetic toxicity tests. These genetic toxicity tests 

were originally developed to study mechanisms of 

chemically induced DNA damage and to predict 

carcinogenicity in animals, based on the electrophilicity 
Furfuryl Alcohol, NTP TR 482 29 

theory of chemical mutagenesis and the somatic mutation Salmonella mutagens are rodent carcinogens), and that 

theory of cancer (Miller and Miller, 1977; Straus, 1981; there is no complementarity among the in vitro genetic 

Crawford, 1985). toxicity tests. That is, no battery of tests that included the 

Salmonella test improved the predictivity of the 

There is a strong correlation between a chemical’s Salmonella test alone. 

potential electrophilicity (structural alert to DNA 

reactivity), mutagenicity in Salmonella, and carcinogenicity in rodents. The combination of electrophil- The predictivity for carcinogenicity of a positive response 

icity and Salmonella mutagenicity is highly correlated in bone marrow chromosome aberration or micronucleus 

with the induction of carcinogenicity in rats and mice tests appears to be less than the Salmonella test (Shelby 

and/or at multiple tissue sites (Ashby and Tennant, et al., 1993; Shelby and Witt, 1995). Positive responses 

1991). Other in vitro genetic toxicity tests correlate in long-term peripheral blood micronucleus tests have not 

less well with rodent carcinogenicity (Tennant et al., been formally evaluated for their predictivity for rodent 

1987; Zeiger et al., 1990), although these other tests can carcinogenicity. But, because of the theoretical and 

provide information on the types of DNA and observed associations between induced genetic damage 

chromosome effects that can be induced by the chemical and adverse effects in somatic and germ cells, the 

being investigated. Data from NTP studies show that a determination of in vivo genetic effects is important to the 

positive response in Salmonella is the most predictive overall understanding of the risks associated with 

in vitro test for rodent carcinogenicity (89% of the exposure to a particular chemical. 
30 Furfuryl Alcohol, NTP TR 482 
31 

RESULTS
 

RATS 

16-DAY STUDY 

All male and female rats exposed to 250 ppm died by day exposed to 31, 63, or 125 ppm and female rats exposed 

2 of the study, and one male rat exposed to 125 ppm died to 125 ppm gained less weight than the chamber control 

on day 5 (Table 2). Final mean body weights of male and groups. Clinical findings included dyspnea, hypoactivity, 

female rats exposed to 125 ppm were significantly less and nasal and ocular discharge in males and females 

than those of the chamber control groups. Male rats exposed to 63, 125, or 250 ppm. 

TABLE 2 

Survival and Body Weights of Rats in the 16-Day Inhalation Study of Furfuryl Alcohol 

b	 Final Weight Concentration	 Mean Body Weight (g) a Survival	 Relative to (ppm)	 Initial Final Change Controls (%) 

Male 

0 5/5 111 ± 3 186 ± 5 76 ± 4 

16 5/5 119 ± 5 194 ± 4 75 ± 2 104 

31 5/5 111 ± 2 172 ± 3 61 ± 3* 92 

63 5/5 116 ± 4 174 ± 6 58 ± 3** 93 

125 

250 

4/5c 

0/5d 

116 ± 3 

118 ± 4 

159 ± 7** 

— 

43 ± 7** 

— 

85 

— 

Female 

0 5/5 94 ± 3 130 ± 4 36 ± 3 

16 5/5 98 ± 2 131 ± 4 33 ± 2 101 

31 5/5 94 ± 3 125 ± 3 31 ± 1 96 

63 5/5 97 ± 3 126 ± 2 30 ± 2 97 

125 5/5 94 ± 3 113 ± 4** 20 ± 2** 87 

250 0/5e 97 ± 4 — — — 

* Significantly different (P#0.05) from the chamber control group by Williams’ or Dunnett’s test 

** P#0.01 a Number of animals surviving at 16 days/number initially in group b	 Weights and weight changes are given as mean ± standard error. No final mean body weights were calculated for groups with 100% mortality. 

Subsequent calculations are based on animals surviving to the end of the study. 

Day of death: 5 d	 Day of death: 2 e Day of death: 1, 1, 2, 2, 2 

c 
32 Furfuryl Alcohol, NTP TR 482 

Absolute heart and thymus weights of 125 ppm males acute and/or suppurative inflammation; necrosis, 

and females were significantly less than those of the regeneration, and squamous metaplasia of the respiratory 

chamber control groups; absolute lung weights were epithelium; and necrosis and degeneration of the olfactory 

significantly less in 63 and 125 ppm males and 125 ppm epithelium (Table 3). The severity of exposure-induced 

females than in the chamber controls (Table G1). These nasal lesions generally increased with increasing 

differences were attributed to the lower mean body exposure concentration. A no-observable-effect level for 

weights of these groups. All exposed animals exhibited furfuryl alcohol was not determined in this study. 

TABLE 3 

Incidences of Nonneoplastic Lesions of the Nose in Rats in the 16-Day Inhalation Study 

of Furfuryl Alcohol 

Chamber 

Control 16 ppm 31 ppm 63 ppm 125 ppm 250 ppm 

Male 

Number Examined Microscopically 

Acute and/or Suppurative Inflammationa 

Respiratory Epithelium, Necrosis 

Respiratory Epithelium, Regeneration 

Respiratory Epithelium, 

Squamous Metaplasia 

Olfactory Epithelium, Necrosis 

Olfactory Epithelium, Degeneration 

5 

0 

0 

0 

0 

0 

0 

5 

1 

5** 

4* 

5** 

4* 

5** 

(1.2)b 

(1.5) 

(1.2) 

(1.3) 

(2.0) 

5 

3 

5** 

5** 

5** 

5** 

5** 

(1.8) 

(2.4) 

(1.2) 

(1.4) 

(2.6) 

5 

4* 

5** 

5** 

5** 

5** 

5** 

(2.2) 

(2.4) 

(1.4) 

(2.8) 

(2.8) 

5 

5** 

5** 

5** 

4* 

5** 

4* 

(2.2) 

(1.8) 

(2.8) 

(2.8) 

(2.8) 

5 

5** 

0 

0 

0 

0 

0 

Female 

Number Examined Microscopically 

Acute and/or Suppurative Inflammation 

Respiratory Epithelium, Necrosis 

Respiratory Epithelium, Regeneration 

Respiratory Epithelium, 

Squamous Metaplasia 

Olfactory Epithelium, Necrosis 

Olfactory Epithelium, Degeneration 

5 

0 

0 

0 

0 

0 

0 

5 

0 

2 

5** 

5** 

0 

5** 

(1.0) 

(1.2) 

(1.0) 

(1.2) 

5 

0 

4* 

5** 

5** 

0 

5** 

(1.3) 

(1.4) 

(1.2) 

(2.8) 

5 

2 

5** 

5** 

5** 

5** 

5** 

(1.8) 

(2.2) 

(1.0) 

(1.6) 

(3.4) 

5 

1 

4* 

5** 

5** 

4* 

5** 

(1.8) 

(1.4) 

(1.4) 

(1.8) 

(2.6) 

5 

5** 

0 

0 

0 

0 

0 

* Significantly different (P#0.05) from the chamber control group by the Fisher exact test 

** P#0.01 a Number of animals with lesion 

b Average severity grade of lesions in affected animals: 1=minimal, 2=mild, 3=moderate, 4=marked 
Furfuryl Alcohol, NTP TR 482 33 

14-WEEK STUDY 

All rats survived to the end of the study (Table 4). The exposure-related clinical findings. Swelling was 

final mean body weight and body weight gain of females observed around the face and eyes of exposed rats, and 

exposed to 32 ppm were significantly less than those of urine stains were present in all groups of exposed 

the chamber control group. There were no serious females. 

TABLE 4 

Survival and Body Weights of Rats in the 14-Week Inhalation Study of Furfuryl Alcohol 

Concentration 

(ppm) Survivala 

Initial 

Mean Body Weight (g) 

Final 

b 

Change Relative to 

Final Weight 

Controls (%) 

Male 

0 

2 

4 

8 

16 

32 

10/10 

10/10 

10/10 

10/10 

10/10 

10/10 

102 ± 3 

98 ± 3 

98 ± 2 

99 ± 3 

98 ± 3 

100 ± 2 

316 ± 7 

315 ± 7 

325 ± 5 

316 ± 5 

302 ± 4 

304 ± 6 

213 ± 6 

218 ± 6 

227 ± 5 

217 ± 4 

203 ± 5 

204 ± 5 

100 

103 

100 

96 

96 

Female 

0 

2 

4 

8 

16 

32 

10/10 

10/10 

10/10 

10/10 

10/10 

10/10 

96 ± 2 

96 ± 2 

92 ± 2 

93 ± 3 

91 ± 2 

92 ± 2 

195 ± 4 

194 ± 2 

194 ± 4 

186 ± 4 

187 ± 2 

176 ± 3** 

99 ± 3 

98 ± 2 

102 ± 3 

93 ± 4 

96 ± 2 

84 ± 3** 

100 

100 

96 

96 

90 

** Significantly different (P#0.01) from the chamber control group by Williams’ or Dunnett’s test a Number of animals surviving at 14 weeks/number initially in group b Weights and weight changes are given as mean ± standard error. 

Absolute liver and lung weights of 32 ppm females were activity of 16 and 32 ppm males and females. Jenkins 

significantly less than those of the chamber control group and Robinson (1975) reported that decreased feed 

(Table G2). However, these differences were small in consumption can result in decreased serum alkaline 

magnitude and considered to be associated with the lower phosphatase activity. The clinical pathology data suggest 

body weight of this group. The hematology and clinical that by day 3 of the study, exposed rats had decreased 

chemistry data for rats are presented in Table F1. On water and feed consumption, but that this effect was 

day 3, a minimal exposure-related erythrocytosis, transient. Changes in other hematology and clinical 

evidenced by increases in hematocrit values, hemoglobin chemistry variables were minimal, inconsistent between 

concentrations, and erythrocyte counts, occurred in males males and females, and within physiological values; they 

and females exposed to 4 ppm or greater. The increased were not considered toxicologically relevant. 

circulating red cell mass would be consistent with 

erythrocytosis of dehydration and would be related to 

hemoconcentration. Hemoconcentration of dehydration 

was supported by the increases in albumin and total The spermatid count and number of spermatid heads per 

protein concentrations observed in males exposed to testis were significantly increased in 32 ppm males 

4 ppm or greater. The erythrocytosis was transient, and (Table H1). Spermatid heads per gram of testis were 

by day 23, hematocrit values, hemoglobin concentrations, significantly increased in 16 and 32 ppm males. There 

and erythrocyte counts of exposed groups were similar to were no significant differences in vaginal cytology 

the chamber control values. On day 3, there was a parameters between exposed and chamber control females 

minimal decrease in the serum alkaline phosphatase (Table H2). 
34 Furfuryl Alcohol, NTP TR 482 

Exposure-related increases in the incidences of squamous exudate of the olfactory epithelium generally increased 

metaplasia of the respiratory and transitional epithelium, with increasing exposure concentration in males and 

goblet cell hyperplasia of the respiratory epithelium, and females. The incidences of cellular infiltrate of the 

hypertrophy of the respiratory epithelium lining the lamina propria of the nose in males and females in the 16 

nasopharyngeal duct were observed in the nose of male and 32 ppm groups were significantly increased 

and female rats (Table 5). The incidences of compared to the chamber control groups. 

degeneration, hyperplasia, metaplasia, and surface 

TABLE 5 

Incidences of Nonneoplastic Lesions of the Nose in Rats in the 14-Week Inhalation Study 

of Furfuryl Alcohol 

Chamber 

Control 2 ppm 4 ppm 8 ppm 16 ppm 32 ppm 

Male 

Number Examined Microscopically 10 10 10 10 10 10 

Respiratory Epithelium, 

Squamous Metaplasiaa 0 0 0 5* (1.4)b 10** (2.0) 10** (2.3) 

Respiratory Epithelium, Goblet Cell, 

Hyperplasia 0 0 0 7** (1.0) 6** (1.3) 10** (1.1) 

Transitional (Cuboidal) Epithelium, 

Squamous Metaplasia 0 9** (1.0) 10** (1.1) 10** (2.1) 10** (2.0) 10** (2.7) 

Nasopharyngeal Duct, Epithelium, 

Hypertrophy 0 0 0 2 (1.0) 6** (1.0) 10** (1.0) 

Olfactory Epithelium, Degeneration 0 1 (1.0) 4* (1.0) 9** (1.3) 10** (2.2) 10** (3.0) 

Olfactory Epithelium, Hyperplasia 0 0 1 (1.0) 2 (1.0) 9** (1.2) 9** (1.9) 

Olfactory Epithelium, Metaplasia 0 0 0 0 0 2 (1.0) 

Olfactory Epithelium, Surface Exudate 0 0 0 0 6** (1.0) 7** (1.0) 

Lamina Propria, Mixed Cell, 

Cellular Infiltrate 0 0 0 1 (1.0) 7** (1.0) 10** (1.0) 

Female 

Number Examined Microscopically 10 10 10 10 10 10 

Respiratory Epithelium, 

Squamous Metaplasia 0 0 0 6** (1.0) 10** (1.2) 10** (1.6) 

Respiratory Epithelium, Goblet Cell, 

Hyperplasia 0 0 0 2 (1.0) 8** (1.0) 9** (1.0) 

Transitional (Cuboidal) Epithelium, 

Squamous Metaplasia 0 9** (1.0) 10** (1.0) 10** (1.9) 10** (2.2) 10** (2.2) 

Nasopharyngeal Duct, Epithelium, 

Hypertrophy 0 0 0 0 3 (1.0) 9** (1.0) 

Olfactory Epithelium, Degeneration 0 3 (1.3) 7** (1.1) 10** (1.4) 10** (2.3) 10** (2.8) 

Olfactory Epithelium, Hyperplasia 0 0 0 2 (1.0) 5* (1.4) 10** (1.2) 

Olfactory Epithelium, Metaplasia 0 0 0 0 1 (1.0) 5* (1.2) 

Olfactory Epithelium, Surface Exudate 0 0 0 2 (1.0) 6** (1.0) 10** (1.0) 

Lamina Propria, Mixed Cell, 

Cellular Infiltrate 0 2 (1.0) 0 3 (1.3) 8** (1.0) 6** (1.0) 

* Significantly different (P#0.05) from the chamber control group by the Fisher exact test 

** P#0.01 a Number of animals with lesion 

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

Furfuryl Alcohol, NTP TR 482 35 

Exposure Concentration Selection Rationale: The 

selection of exposure concentrations for the 2-year rat 

study was based on the incidences and severities of 

cytological alterations in the nasal mucosa associated 

with exposure to furfuryl alcohol. In the 14-week study, 

squamous metaplasia of the transitional epithelium and 

degeneration of the olfactory epithelium were present in 

all exposed groups; however, other chemical-related 

changes in the nasal mucosa occurred only at 

concentrations of 8 ppm or greater. Although the 

incidences of several lesions increased between 8 and 32 

ppm, the severity of these lesions generally ranged from 

minimal to mild and were similar in severity to those 

observed at 16 or 31 ppm during the 16-day study. The 

longer exposure time in the 14-week study did not result 

in a significant increase in the severity of changes in the 

nasal mucosa, and it was considered unlikely that the 

lesions would become life-threatening during a 2-year 

study. Therefore, 32 ppm was selected as the high 

exposure concentration for the 2-year rat study. A noobservable-effect level was not achieved in either the 

16-day or 14-week studies. Since the three lowest 

concentrations in the 14-week study were below the 

currently recommended TLVs (TLV time-weighted 

average=10 ppm; TLV short-term exposure 

limit=15 ppm) for occupational exposure, lower 

concentrations of 2 and 8 ppm were selected for 

the 2-year study. This provided three concentrations 

over a range that covered documented occupational 

exposures. 
36 Furfuryl Alcohol, NTP TR 482 

2-YEAR STUDY 

Survival 

Estimates of 2-year survival probabilities for male and 

female rats are shown in Table 6 and in the Kaplan-Meier 

survival curves (Figure 2). All male rats exposed to 

32 ppm died by week 99. Survival of all other exposed 

groups of male and female rats was similar to that of the 

chamber control groups. 

Body Weights and Clinical Findings 

Mean body weights of 32 ppm males were less than those 

of the chamber controls beginning week 19; 

mean body weights of 2 and 8 ppm male groups and 

TABLE 6 

all exposed female groups were similar to those of the 

chamber control groups throughout the study (Tables 7 

and 8; Figure 3). There were no exposure-related clinical 

findings. 

Urinary Metabolites 

The concentrations of furoylglycine and furanacryloylglycine, the two major metabolites of furfuryl 

alcohol, were increased in the urine of exposed rats. For 

both metabolites, the increase was approximately 

proportional to exposure concentration. 

Survival of Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Male 

Animals initially in study	 50 50 50 50 

Moribund 34 43 31 43 

Natural deaths 8 2 10 7 

Animals surviving to study termination 8d 5 9 0 a Percent probability of survival at end of study 16 10 18 0 

Mean survival (days)b 8 620 630 593 

c Survival analysis	 P<0.001 P=0.597 P=0.915N P<0.001 

Female 

Animals initially in study	 50 50 50 50 

e Pregnant 0 0 1 0 

Moribund 23 21 24 32 

Natural deaths 1 3 3 2 

Animals surviving to study termination 26 26d 22 16 

Percent probability of survival at end of study 52 52 45 32 

Mean survival (days) 667 683 678 651 

Survival analysis	 P=0.028 P=0.982N P=0.681 P=0.094 

a Kaplan-Meier determinations b	 Mean of all deaths (uncensored, censored, and terminal sacrifice) 

The result of the life table trend test (Tarone, 1975) is in the chamber control column, and the results of the life table pairwise comparisons (Cox, 

1972) with the chamber controls are in the exposed group columns. A lower mortality in an exposure group is indicated by N. d	 Includes one animal that died during the last week of the study e Censored from survival analyses 

c 
 

 

 

Furfuryl Alcohol, NTP TR 482 37 

FIGURE 2
 

Kaplan-Meier Survival Curves for Male and Female Rats
 

Administered Furfuryl Alcohol by Inhalation for 2 Years
 
38 Furfuryl Alcohol, NTP TR 482 

TABLE 7 

Mean Body Weights and Survival of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Weeks Chamber Control 2 ppm 8 ppm 32 ppm 

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

Study (g) Survivors (g) controls) Survivors (g) controls) Survivors (g) controls) Survivors 

1 151 50 149 99 50 148 98 50 144 96 50 

2 206 50 202 98 50 201 98 50 193 94 50 

3 237 50 234 99 50 233 98 50 225 95 50 

4 262 50 260 99 50 256 98 50 248 95 50 

5 283 50 282 100 50 279 99 50 267 94 50 

6 299 50 298 100 50 297 100 50 285 95 50 

7 315 50 313 99 50 313 100 50 300 95 50 

8 329 50 326 99 50 327 99 50 316 96 50 

9 342 50 338 99 50 340 99 50 330 97 50 

10 352 50 349 99 50 350 100 50 336 95 50 

12 368 50 365 99 50 366 99 50 352 96 50 

15 398 50 395 99 50 396 100 50 380 95 50 

19 425 50 418 98 50 416 98 50 399 94 50 

23 449 50 441 98 50 441 98 50 423 94 50 

27 466 50 457 98 50 457 98 50 435 93 50 

31 479 50 468 98 50 469 98 50 446 93 50 

35 491 50 482 98 50 482 98 50 459 93 50 

39 503 50 491 98 50 493 98 50 468 93 50 

44 507 50 499 98 50 497 98 50 469 92 50 

47 515 49 506 98 50 510 99 50 482 94 50 

51 525 47 513 98 50 516 98 50 491 94 49 

55 529 46 516 98 50 519 98 50 491 93 49 

59 536 46 523 98 49 525 98 50 497 93 49 

63 545 46 531 98 49 533 98 49 503 92 48 

67 546 46 525 96 48 537 98 49 501 92 48 

71 547 44 534 98 42 536 98 45 503 92 45 

75 544 42 532 98 42 529 97 43 499 92 42 

80 545 39 528 97 40 535 98 38 489 90 40 

83 534 35 510 96 35 529 99 34 472 88 36 

87 535 29 492 92 31 520 97 30 444 83 27 

91 535 26 484 90 23 515 96 28 409 76 16 

93 525 25 493 94 20 509 97 25 

95 511 23 498 97 18 494 97 24 

97 504 22 487 97 17 492 98 19 

99 492 15 471 96 12 504 102 16 

101 501 11 479 96 9 494 99 14 

103 485 9 466 96 8 491 101 10 

Mean for weeks 

1-13 286 283 99 283 99 272 95 

14-52 476 467 98 468 98 445 93 

53-103 526 504 96 516 98 481 91 
Furfuryl Alcohol, NTP TR 482 39 

TABLE 8 

Mean Body Weights and Survival of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Weeks Chamber Control 2 ppm 8 ppm 32 ppm 

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

Study (g) Survivors (g) controls) Survivors (g) controls) Survivors (g) controls) Survivors 

1 122 50 118 97 50 118 97 49 117 96 50 

2 145 50 144 99 50 143 98 49 138 95 50 

3 158 50 154 98 50 156 99 49 149 95 50 

4 167 50 166 100 50 163 98 49 159 96 50 

5 176 50 175 99 50 175 99 49 168 95 50 

6 182 50 180 99 50 181 99 49 175 96 50 

7 188 50 186 99 50 186 99 49 179 95 50 

8 193 50 191 99 50 191 99 49 185 96 50 

9 198 50 195 99 50 196 99 49 191 97 50 

10 202 50 200 99 50 200 99 49 191 95 50 

12 208 50 205 98 50 206 99 49 201 97 50 

15 219 49 216 99 50 219 100 49 211 97 50 

19 228 49 224 98 50 223 98 49 221 97 50 

23 241 49 237 99 50 235 98 49 234 97 50 

27 249 49 244 98 50 243 98 49 241 97 50 

31 256 49 253 99 50 252 98 49 252 98 50 

35 265 49 262 99 50 259 98 49 258 97 50 

39 278 49 272 98 50 272 98 49 269 97 50 

44 290 49 284 98 50 282 97 49 280 96 50 

47 303 49 296 98 50 297 98 49 296 98 49 

51 312 49 308 99 50 311 100 49 308 99 49 

55 323 49 317 98 50 317 98 49 318 99 49 

59 332 49 325 98 50 327 99 49 328 99 49 

63 340 49 333 98 49 336 99 49 337 99 47 

67 347 48 339 98 49 343 99 49 346 100 47 

71 356 45 347 98 48 351 99 49 353 99 46 

75 359 45 348 97 46 353 98 47 358 100 43 

80 365 45 357 98 44 360 98 44 364 100 41 

83 360 44 358 100 43 359 100 43 363 101 40 

87 361 40 360 100 41 359 99 40 356 99 37 

91 381 35 363 95 40 369 97 35 364 96 34 

93 381 35 361 95 39 362 95 34 361 95 31 

95 382 33 365 96 37 365 95 32 356 93 30 

97 378 32 367 97 35 358 95 31 356 94 27 

99 372 32 363 98 33 361 97 29 352 95 25 

101 364 31 359 99 32 373 103 25 348 96 23 

103 374 26 364 97 29 368 99 24 361 97 18 

Mean for weeks 

1-13 176 174 99 174 99 168 95 

14-52 264 260 98 259 98 257 97 

53-103 361 352 98 354 98 351 97 
 

 

40 Furfuryl Alcohol, NTP TR 482 

FIGURE 3
 

Growth Curves for Male and Female Rats
 

Administered Furfuryl Alcohol by Inhalation for 2 Years
 
 

Furfuryl Alcohol, NTP TR 482 41 

Pathology and Statistical Analyses 

This section describes the statistically significant or 

biologically noteworthy changes in the incidences of 

neoplasms and nonneoplastic lesions of the nose and 

kidney. Summaries of the incidences of neoplasms and 

nonneoplastic lesions, individual animal tumor 

diagnoses, statistical analyses of primary neoplasms that 

occurred with an incidence of at least 5% in at least one 

animal group, and historical incidences for the neoplasms 

mentioned in this section are presented in Appendix A for 

male rats and Appendix B for female rats. 

Nose: One lateral wall adenoma was observed in a 

2 ppm male and one in an 8 ppm female, one respiratory 

epithelium adenoma was observed in an 8 ppm male and 

one in a 32 ppm female, and one carcinoma of the 

respiratory epithelium and three squamous cell 

carcinomas were observed in 32 ppm males (Tables 9, 

A1, and B1). These incidences were not significantly 

greater than those in the chamber control groups, but 

squamous cell carcinoma has not been observed in male 

historical controls (Tables 9 and A4a). All of the 

neoplasms in the nose were of epithelial origin. The 

squamous cell carcinomas were masses of pleomorphic 

stratified squamous epithelium that became protrusions 

into the nasal cavity and also invaded the underlying 

lamina propria (Plate 1). The adenomas of the 

respiratory epithelium and the epithelium of the lateral 

wall consisted of proliferations of multiple glandular 

structures (Plate 2). 

Furfuryl alcohol was irritating and toxic to the nose. All 

groups of exposed male and female rats had significantly 

increased incidences of nonneoplastic lesions in the nose 

(Tables 9, A5, and B5). In general, the severity increased 

with increasing exposure concentration, but the overall 

architecture of the nasal turbinates was not distorted and 

the mucosal lining remained intact. Suppurative 

inflammation consisted of aggregates of neutrophils 

beneath the epithelial lining or within the nasal lumens. 

Hyperplastic Bowman’s glands had multiple layers of 

polyhedral epithelium instead of the normal single layer. 

Hyperplasia of both the respiratory epithelium (Plate 3) 

and transitional epithelium of the lateral wall consisted of 

replacement of the normal single layer with multiple 

layers of polyhedral epithelium. Squamous metaplasia of 

the transitional epithelium of the lateral wall or of the 

respiratory epithelium generally occurred within 

hyperplastic areas and consisted of areas of keratinizing 

stratified squamous epithelium. Hyperplasia and 

squamous metaplasia represent conversion of highly 

specialized nasal epithelium to more resistant types of 

epithelium and represent adaptive responses to chronic 

irritation. Hyaline degeneration of both respiratory and 

olfactory epithelium is a common degenerative change 

consisting of cytoplasmic accumulations of eosinophilic 

refractile material. Atrophy of the olfactory epithelium 

was an attenuation of the normally tall pseudostratified 

columnar cells. Metaplasia of the olfactory epithelium 

often accompanied atrophy and consisted of replacement 

of neurosensory cells by ciliated respiratory-type 

epithelial cells. Hyperplasia of the olfactory epithelium 

consisted of replacement of the normally tall 

pseudostratified columnar cells by densely packed, 

somewhat disorganized neurosensory cells. Fibrosis of 

the olfactory epithelium sometimes accompanied 

hyperplasia. Fibrosis affected the connective tissue 

underlying olfactory epithelium and consisted of thin 

bundles of dense collagen. 
42 Furfuryl Alcohol, NTP TR 482 

TABLE 9 

Incidences of Neoplasms and Nonneoplastic Lesions of the Nose in Rats in the 2-Year Inhalation Study 

of Furfuryl Alcohol 

Chamber 

Control 2 ppm 8 ppm 32 ppm 

Male 

Number Examined Microscopically 

Suppurative Inflammationa 

Glands, Hyperplasia 

Lateral Wall, Hyperplasia 

Lateral Wall, Squamous Metaplasia 

Olfactory Epithelium, Atrophy 

Olfactory Epithelium, Hyaline Degeneration 

Olfactory Epithelium, Fibrosis 

Olfactory Epithelium, Hyperplasia 

Olfactory Epithelium, Metaplasia 

Respiratory Epithelium, Hyaline Degeneration 

Respiratory Epithelium, Hyperplasia 

Respiratory Epithelium, Squamous Metaplasia 

50 

3 

0 

1 

1 

1 

42 

0 

0 

1 

12 

0 

0 

(1.0)b 

(1.0) 

(1.0) 

(1.0) 

(1.3) 

(1.0) 

(1.0) 

50 

6 

0 

49** 

1 

12** 

48 

1 

1 

8* 

14 

26** 

0 

(1.5) 

(1.5) 

(1.0) 

(1.1) 

(1.5) 

(1.0) 

(1.0) 

(1.3) 

(1.0) 

(1.8) 

50 

17** 

22** 

50** 

8* 

47** 

50** 

26** 

42** 

37** 

45** 

50** 

3 

(1.7) 

(1.0) 

(2.4) 

(1.1) 

(1.8) 

(2.6) 

(1.0) 

(1.0) 

(1.5) 

(1.6) 

(2.5) 

(1.0) 

50 

44** 

49** 

50** 

33** 

50** 

47 

40** 

40** 

49** 

3* 

50** 

26** 

(2.1) 

(2.3) 

(3.5) 

(1.3) 

(2.4) 

(2.7) 

(2.0) 

(1.8) 

(2.2) 

(1.7) 

(3.5) 

(1.4) 

Lateral Wall, Adenoma 

Respiratory Epithelium, Adenomac 

Respiratory Epithelium, Carcinomad 

Respiratory Epithelium, Squamous Cell Carcinomad 

Adenoma, Carcinoma, 

or Squamous Cell Carcinoma (Combined) 

0 

0 

0 

0 

0 

1 

0 

0 

0 

1 

0 

1 

0 

0 

1 

0 

0 

1 

3 

4* 

Female 

Number Examined Microscopically 

Suppurative Inflammation 

Glands, Hyperplasia 

Lateral Wall, Hyperplasia 

Lateral Wall, Squamous Metaplasia 

Olfactory Epithelium, Atrophy 

Olfactory Epithelium, Hyaline Degeneration 

Olfactory Epithelium, Fibrosis 

Olfactory Epithelium, Hyperplasia 

Olfactory Epithelium, Metaplasia 

Respiratory Epithelium, Hyaline Degeneration 

Respiratory Epithelium, Hyperplasia 

Respiratory Epithelium, Squamous Metaplasia 

49 

4 

0 

0 

0 

0 

43 

0 

0 

0 

23 

0 

0 

(2.3) 

(1.2) 

(1.0) 

50 

1 

0 

39** 

1 

6* 

50* 

0 

0 

5* 

39** 

18** 

0 

(2.0) 

(1.3) 

(1.0) 

(1.3) 

(1.6) 

(1.2) 

(1.2) 

(1.4) 

48 

5 

24** 

48** 

0 

44** 

47 

16** 

31** 

37** 

45** 

40** 

2 

(1.4) 

(1.0) 

(2.1) 

(1.7) 

(2.7) 

(1.3) 

(1.2) 

(1.5) 

(1.9) 

(2.1) 

(1.0) 

49 

23** 

46** 

49** 

24** 

49** 

48 

31** 

41** 

48** 

6** 

49** 

10** 

(1.7) 

(2.2) 

(3.3) 

(1.0) 

(2.3) 

(3.3) 

(1.7) 

(1.5) 

(2.2) 

(2.0) 

(3.2) 

(1.2) 

Lateral Wall, Adenoma 

Respiratory Epithelium, Adenomae 

Adenoma (Combined) 

0 

0 

0 

0 

0 

0 

1 

0 

1 

0 

1 

1 

* Significantly different (P#0.05) from the chamber control group by the Poly-3 test 

** P#0.01 a Number of animals with lesion 

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

Historical incidence for 2-year NTP inhalation studies with untreated chamber controls (mean ± standard deviation): 1/897 (0.1% ± 0.5%); range, 

0%-2% 

d Historical incidence: 0/897 e Historical incidence: 1/892 (0.1% ± 0.5%); range, 0%-2% 

c 
 

Furfuryl Alcohol, NTP TR 482 43 

Kidney: One atypical nephroblastoma and one stromal 

nephroma occurred in male rats exposed to 8 ppm 

(Tables 10 and A1). Renal tubule adenomas were 

observed in one chamber control male, one 2 ppm male, 

two 8 ppm males, and two 32 ppm females, and one 

2 ppm female had a renal tubule carcinoma. These 

incidences were within the historical control range for 

male rats but exceeded the historical control range for 

female rats (Tables 10, A4b, and B4b). Incidences of 

renal tubule hyperplasia in exposed rats were not 

significantly different from those in the chamber control 

groups (Tables 10, A5, and B5). 

Kidney step sections provided approximately eight additional sections per animal to examine for additional 

proliferative lesions. Separate analyses of the additional 

lesions found in the step sections and of the combined 

lesions in original and step sections often provided 

significant additional information. Since the same large 

proliferative lesions may be present both on an original 

section and on subsequent step sections, such a lesion is 

only counted once in the combination analysis. Animals 

with proliferative lesions identified in the step-section 

review are listed in a separate document for the specific 

study, Report of the Special Pathology Working Group 

for Kidney Step Sections, which is available on request. 

Step sections revealed the presence of one additional 

renal tubule adenoma in each of the chamber control, 

2 ppm, and 8 ppm groups of males and four additional 

adenomas in 32 ppm males. Two adenomas were 

observed in 8 ppm females and one in a 32 ppm female, 

and a carcinoma was observed in a 2 ppm female. 

Additional hyperplasias were observed in all groups of 

males and females. 

Renal tubule adenomas were small, discrete proliferations 

of epithelial cells that typically compressed the adjacent 

parenchyma. Adenomas were five or more renal tubule 

diameters in size and had no orientation to the tubule 

basement membrane. Hyperplasia of the renal tubule 

epithelium was a stratification of the normally singlelayered epithelium with the maintenance of cellular 

orientation to the tubule basement membrane. 

Nephropathy was present in virtually all of the animals in 

this study. Nephropathy is a common spontaneous renal 

disease of F344/N rats characterized by renal tubule 

epithelial necrosis and regeneration, interstitial fibrosis, 

inflammation, and renal tubule dysfunction. The 

severities of nephropathy relative to chamber controls 

were increased in 32 ppm males and females. Males 

exposed to 32 ppm had extrarenal signs of kidney failure 

including parathyroid gland hyperplasia and fibrous 

osteodystrophy (Tables 10 and A5). 

TABLE 10 

Incidences of Selected Neoplasms and Nonneoplastic Lesions in Rats in the 2-Year Inhalation Study 

of Furfuryl Alcohol 

Chamber 

Control 2 ppm 8 ppm 32 ppm 

Male 

Kidney 50 50 50 50 

Single Sections (Standard Evaluation) 

Mineralizationa 2 (3.0)b 2 (3.0) 2 (4.0) 28** (3.3) 

Nephropathy 50 (2.9) 49 (2.9) 50 (3.1) 50 (3.7)** 

Renal Tubule, Hyperplasia 5 (2.8) 5 (2.0) 2 (1.5) 6 (2.5) 

Nephroblastoma 0 0 1 0 

Stromal Nephroma 0 0 1 0 

Renal Tubule, Adenomac 1 1 2 0 
44 Furfuryl Alcohol, NTP TR 482 

TABLE 10 

Incidences of Selected Neoplasms and Nonneoplastic Lesions in Rats in the 2-Year Inhalation Study 

of Furfuryl Alcohol 

Chamber 

Control 2 ppm 8 ppm 32 ppm 

Male (continued) 

Kidney (continued) 50 50 50 50 

Step Sections (Extended Evaluation) 

Renal Tubule, Hyperplasia 7 (1.7) 5 (2.0) 7 (2.3) 23** (2.7) 

Renal Tubule, Adenoma 1 1 1 4 

Single Sections and Step Sections (Combined) 

Renal Tubule, Hyperplasia 10 (2.4) 7 (2.3) 7 (2.3) 25** (2.8) 

Renal Tubule, Adenoma 2 2 3 4 

Parathyroid Gland 49 45 50 49 

Hyperplasia 9 (2.1) 5 (3.0) 12 (2.4) 39** (3.6) 

Bone 50 50 50 50 

Fibrous Osteodystrophy 2 (2.0) 5 (2.2) 6 (2.5) 34** (3.2) 

Female 

Kidney 50 49 49 50 

Single Sections (Standard Evaluation) 

Mineralization 0 1 (2.0) 0 0 

Nephropathy 47 (1.9) 45 (1.9) 47 (1.9) 47 (2.4)** 

Renal Tubule, Hyperplasia 0 0 0 2 (2.5) 

Renal Tubule, Adenomad 0 0 0 2 

Renal Tubule, Carcinomae 

Renal Tubule, Adenoma or Carcinomaf 

0 

0 

1 

1 

0 

0 

0 

2 

Step Sections (Extended Evaluation) 

Renal Tubule, Hyperplasia 2 (1.0) 1 (2.0) 3 (2.0) 9 (1.9) 

Renal Tubule, Adenoma 0 0 2 1 

Renal Tubule, Carcinoma 0 1 0 0 

Renal Tubule, Adenoma or Carcinoma 0 1 2 1 

Single Sections and Step Sections (Combined) 

Renal Tubule, Hyperplasia 2 (1.0) 1 (2.0) 3 (2.0) 11* (2.0) 

Renal Tubule, Adenoma 0 0 2 2 

Renal Tubule, Carcinoma 0 1 0 0 

Renal Tubule, Adenoma or Carcinoma 0 1 2 2 

* Significantly different (P#0.05) from the chamber control group by the Poly-3 test 

** Significantly different (P#0.01) from the chamber control group by the Poly-3 test (incidences) or Mann-Whitney U test (severities) a Number of animals with lesion 

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

Historical incidence for 2-year NTP inhalation studies with untreated chamber controls (mean ± standard deviation): 9/902 (1.0% ± 1.2%); range, 

0%-4% 

d Historical incidence: 1/898 (0.1% ± 0.5%); range, 0%-2% e Historical incidence: 4/898 (0.5% ± 0.9%); range, 0%-2% f Historical incidence: 5/898 (0.6% ± 0.9%); range, 0%-2% 

c 
c 

Furfuryl Alcohol, NTP TR 482 45 

MICE 

16-DAY STUDY 

All male and female mice exposed to 250 ppm died by weights and body weight gains of male and female mice 

day 4 of the study, and one female mouse exposed to exposed to 63 or 125 ppm were significantly less than 

125 ppm died on day 14 (Table 11). Final mean body those of the chamber control groups. 

TABLE 11 

Survival and Body Weights of Mice in the 16-Day Inhalation Study of Furfuryl Alcohol 

b	 Final Weight Concentration	 Mean Body Weight (g) a Survival	 Relative to (ppm)	 Initial Final Change Controls (%) 

Male 

0 5/5 24.0 ± 0.4 27.8 ± 0.5 3.8 ± 0.4 

16 5/5 24.2 ± 0.4 28.5 ± 0.3 4.3 ± 0.5 102 

31 5/5 23.9 ± 0.3 27.8 ± 0.7 4.0 ± 0.6 100 

63 5/5 24.2 ± 0.4 25.8 ± 0.3* 1.6 ± 0.3** 93 

125 5/5 24.1 ± 0.4 24.5 ± 0.7** 0.4 ± 0.3** 88 

250 0/5c 23.9 ± 0.4 — — — 

Female 

0 5/5 19.5 ± 0.4 22.6 ± 0.3 3.1 ± 0.3 

16 5/5 20.2 ± 0.3 23.2 ± 0.3 3.0 ± 0.1 103 

31 5/5 19.3 ± 0.3 22.6 ± 0.4 3.3 ± 0.3 100 

63 

125 

5/5 

4/5d 

19.9 ± 0.4 

19.5 ± 0.3 

21.1 ± 0.3** 

19.9 ± 0.2** 

1.3 ± 0.2** 

0.5 ± 0.3** 

93 

88 

250 0/5e 19.4 ± 0.4 — — — 

* Significantly different (P#0.05) from the chamber control group by Williams’ or Dunnett’s test 

** P#0.01 a Number of animals surviving at 16 days/number initially in group b	 Weights and weight changes are given as mean ± standard error. No final mean body weights were calculated for groups with 100% mortality. 

Subsequent calculations are based on animals surviving to the end of the study. 

Day of death: 3, 4, 4, 4, 4 d	 Day of death: 14 e Day of death: 2 
46 Furfuryl Alcohol, NTP TR 482 

Absolute heart and kidney weights of 63 and 125 ppm epithelium and/or olfactory epithelium (Table 12). The 

males and females and absolute thymus weights of severities of exposure-related changes increased with 

125 ppm males and females were significantly less than increasing exposure concentration. Although a 

those of the chamber controls (Table G3). These no-observable-effect level for furfuryl alcohol-induced 

differences were attributed to the lower body weights of nasal alterations was not achieved in this study, most 

these groups. All exposed animals except one 16 ppm changes that occurred in mice exposed to 16 ppm were 

male had histologic changes in the nasal respiratory minimal. 

TABLE 12 

Incidences of Nonneoplastic Lesions of the Nose in Mice in the 16-Day Inhalation Study 

of Furfuryl Alcohol 

Chamber 

Control 16 ppm 31 ppm 63 ppm 125 ppm 250 ppm 

Male 

Number Examined Microscopically 

Acute and/or Suppurative Inflammationa 

Respiratory Epithelium, Necrosis 

Respiratory Epithelium, 

Squamous Metaplasia 

Olfactory Epithelium, Necrosis 

Olfactory Epithelium, Degeneration 

5 

0 

0 

0 

0 

0 

5 

0 

0 

3 

0 

3 

(1.0) 

(1.0) 

5 

0 

2 

5** 

1 

5** 

(1.0) 

(1.0) 

(1.0) 

(2.8) 

5 

2 

2 

5** 

4* 

5** 

(1.0)b 

(1.0) 

(1.0) 

(1.0) 

(3.4) 

5 

4* 

0 

5** 

4* 

5** 

(1.5) 

(1.6) 

(1.8) 

(3.4) 

5 

5** 

5** 

0 

2 

0 

(4.0) 

(4.0) 

(2.5) 

Female 

Number Examined Microscopically 

Acute and/or Suppurative Inflammation 

Respiratory Epithelium, Necrosis 

Respiratory Epithelium, 

Squamous Metaplasia 

Olfactory Epithelium, Necrosis 

Olfactory Epithelium, Degeneration 

5 

0 

0 

0 

0 

0 

5 

0 

0 

3 

0 

5** 

(1.0) 

(1.6) 

5 

0 

1 

5** 

2 

5** 

(1.0) 

(1.0) 

(1.0) 

(3.2) 

5 

3 

2 

5** 

5** 

5** 

(1.0) 

(1.0) 

(1.2) 

(1.4) 

(3.4) 

5 

5** 

4* 

5** 

5** 

5** 

(1.8) 

(1.0) 

(1.8) 

(1.2) 

(3.2) 

5 

5** 

5** 

0 

1 

1 

(2.2) 

(3.4) 

(2.0) 

(2.0) 

* Significantly different (P#0.05) from the chamber control group by the Fisher exact test 

** P#0.01 a Number of animals with lesion 

b Average severity grade of lesions in affected animals: 1=minimal, 2=mild, 3=moderate, 4=marked 
Furfuryl Alcohol, NTP TR 482 47 

14-WEEK STUDY 

All mice survived to the end of the study (Table 13). The than those of the chamber control group. There were no 

final mean body weight and body weight gain of male exposure-related clinical findings. 

mice exposed to 2 ppm were significantly greater 

TABLE 13 

Survival and Body Weights of Mice in the 14-Week Inhalation Study of Furfuryl Alcohol 

Concentration 

(ppm) Survivala 

Initial 

Mean Body Weight (g) 

Final 

b 

Change Relative to 

Final Weight 

Controls (%) 

Male 

0 

2 

4 

8 

16 

32 

10/10 

10/10 

10/10 

10/10 

10/10 

10/10 

24.1 ± 0.4 

24.4 ± 0.2 

24.1 ± 0.3 

24.4 ± 0.4 

24.6 ± 0.4 

23.9 ± 0.2 

33.1 ± 0.6 

36.0 ± 0.7* 

35.2 ± 0.8 

35.5 ± 0.8 

35.5 ± 0.5 

32.7 ± 0.7 

9.0 ± 0.6 

11.7 ± 0.6* 

11.1 ± 0.6 

11.2 ± 0.7 

10.9 ± 0.5 

8.9 ± 0.7 

109 

106 

107 

107 

99 

Female 

0 

2 

4 

8 

16 

32 

10/10 

10/10 

10/10 

10/10 

10/10 

10/10 

19.2 ± 0.4 

19.4 ± 0.4 

19.1 ± 0.3 

19.2 ± 0.3 

19.2 ± 0.3 

19.3 ± 0.4 

30.1 ± 0.8 

30.7 ± 0.9 

30.6 ± 0.9 

30.4 ± 0.9 

30.6 ± 0.8 

28.9 ± 0.7 

10.9 ± 0.6 

11.3 ± 0.7 

11.5 ± 0.8 

11.3 ± 0.7 

11.5 ± 0.7 

9.6 ± 0.6 

102 

102 

101 

102 

96 

* Significantly different (P#0.05) from the chamber control group by Williams’ or Dunnett’s test a Number of animals surviving at 14 weeks/number initially in group b Weights and weight changes are given as mean ± standard error. 

Absolute and relative heart weights of 32 ppm males and Exposure-related histologic changes included 

the absolute heart weight of 32 ppm females degeneration, metaplasia, and chronic inflammation of 

were significantly less than those of the chamber controls the olfactory epithelium; hyaline droplets of the 

(Table G4). There were no significant differences respiratory epithelium; and squamous metaplasia of the 

in sperm motility or vaginal cytology parameters between submucosal gland of the cuboidal epithelium (Table 14). 

chamber control and exposed mice (Tables H3 and H4). 
48 Furfuryl Alcohol, NTP TR 482 

TABLE 14 

Incidences of Nonneoplastic Lesions of the Nose in Mice in the 14-Week Inhalation Study 

of Furfuryl Alcohol 

Chamber 

Control 2 ppm 4 ppm 8 ppm 16 ppm 32 ppm 

Male 

Number Examined Microscopically 

Olfactory Epithelium, Degenerationa 

Olfactory Epithelium, Metaplasia 

Olfactory Epithelium, 

Chronic Inflammation 

Respiratory Epithelium, Hyaline Droplets 

Cuboidal Epithelium, Submucosal Gland, 

Squamous Metaplasia 

10 

0 

0 

0 

0 

0 

10 

4* 

4* 

0 

2 

0 

(1.0)b 

(1.0) 

(1.0) 

10 

5* 

2 

4* 

3 

0 

(1.0) 

(1.0) 

(1.0) 

(1.0) 

10 

9** 

4* 

8** 

3 

4* 

(1.4) 

(1.5) 

(1.1) 

(1.0) 

(1.0) 

10 

10** 

10** 

10** 

9** 

9** 

(2.3) 

(2.3) 

(1.4) 

(1.2) 

(1.0) 

10 

10** 

10** 

10** 

10** 

10** 

(2.7) 

(2.7) 

(1.6) 

(1.5) 

(1.0) 

Female 

Number Examined Microscopically 

Olfactory Epithelium, Degeneration 

Olfactory Epithelium, Metaplasia 

Olfactory Epithelium, 

Chronic Inflammation 

Respiratory Epithelium, Hyaline Droplets 

Cuboidal Epithelium, Submucosal Gland, 

Squamous Metaplasia 

10 

0 

0 

0 

0 

0 

10 

3 

2 

0 

8** 

0 

(1.0) 

(1.0) 

(1.3) 

10 

8** 

2 

1 

9** 

0 

(1.1) 

(1.0) 

(1.0) 

(1.1) 

10 

10** 

8** 

10** 

10** 

1 

(1.7) 

(1.4) 

(1.0) 

(1.5) 

(1.0) 

10 

10** 

10** 

10** 

10** 

5* 

(2.9) 

(2.8) 

(1.0) 

(3.0) 

(1.0) 

10 

10** 

10** 

10** 

10** 

10** 

(3.1) 

(3.0) 

(2.0) 

(2.9) 

(1.0) 

* Significantly different (P#0.05) from the chamber control group by the Fisher exact test 

** P#0.01 a Number of animals with lesion 

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

Exposure Concentration Selection Rationale: The trations, they were within the mild to moderate range of 

selection of exposure concentrations for the 2-year mouse severities and it was considered unlikely that they would 

study was based on the incidences and severities of progress to become life-threatening during a 2-year study. 

alterations in the nasal mucosa associated with exposure Therefore, 32 ppm was selected as the high exposure 

to furfuryl alcohol. In mice, exposure-related changes in concentration for the 2-year mouse study. A nothe olfactory and respiratory epithelium were observed in observable-effect level was not achieved in either the 

all exposed groups. During the 14-week study, the 16-day or 14-week studies. Since the three lowest 

incidences and severities of changes in the nasal mucosa concentrations in the 14-week study were below the 

increased with increasing exposure concentration up to currently recommended TLVs for occupational exposure, 

8 ppm but changed very little between 16 and 32 ppm. lower concentrations of 2 and 8 ppm were selected for the 

Although the lesions were somewhat more severe at the 2-year study. This provided three concentrations over a 

end of the 14-week study than those observed in range that covered documented occupational exposures. 

the 16-day study at comparable exposure concen­
49 

c 

Furfuryl Alcohol, NTP TR 482 

2-YEAR STUDY 

Survival	 Body Weights and Clinical Findings 

Estimates of 2-year survival probabilities for male and Mean body weights of exposed males were generally 

female mice are shown in Table 15 and in the similar to those of the chamber control group throughout 

Kaplan-Meier survival curves (Figure 4). Survival of the study. Mean body weights of females exposed to 2, 

exposed males and females was similar to that of the 8, or 32 ppm were less than those of the chamber control 

chamber control groups. group beginning at weeks 59, 59, or 39, respectively 

(Figure 5; Tables 16 and 17). Female mice exposed to 

32 ppm developed focal corneal opacities. 

TABLE 15 

Survival of Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Male 

Animals initially in study	 50 50 50 50 

Moribund 11 10 14 8 

Natural deaths 5 4 6 4 

Animals surviving to study termination 34 36 30 38 a Percent probability of survival at end of study 68 72 60 76 

Mean survival (days)b 688 682 656 705 

c Survival analysis	 P=0.351N P=0.838N P=0.410 P=0.431N 

Female 

Animals initially in study	 50 50 50 50 

d Accidental deaths 0 1 1 0 

Pregnantd 0 1 0 0 

Moribund 11 12 15 8 

Natural deaths 5 3 2 2 

Animals surviving to study termination 34 33 32 40 

Percent probability of survival at end of study 68 69 66 80 

Mean survival (days) 690 685 690 715 

Survival analysis	 P=0.145N P=1.000N P=1.000 P=0.212N 

a Kaplan-Meier determinations b	 Mean of all deaths (uncensored, censored, and terminal sacrifice) 

The result of the life table trend test (Tarone, 1975) is in the chamber control column, and the results of the life table pairwise comparisons (Cox, 

1972) with the chamber controls are in the exposed group columns. A negative trend or lower mortality in an exposure group is indicated by N. d	 Censored from survival analyses 
50 Furfuryl Alcoho., NTP TR 482 

FIGURE 4
 

Kaplan-Meier Survival Curves for Male and Female Mice
 

Administered Furfuryl Alcohol by Inhalation for 2 Years
 
 

 

Furfuryl Alcohol, NTP TR 482 51 

FIGURE 5
 

Growth Curves for Male and Female Mice
 

Administered Furfuryl Alcohol by Inhalation for 2 Years
 
52 Furfuryl Alcohol, NTP TR 482 

TABLE 16 

Mean Body Weights and Survival of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Weeks Chamber Control 2 ppm 8 ppm 32 ppm 

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

Study (g) Survivors (g) controls) Survivors (g) controls) Survivors (g) controls) Survivors 

1 26.3 50 26.7 102 50 26.5 101 50 25.0 95 50 

2 27.9 50 28.2 101 50 28.1 101 50 26.6 95 50 

3 28.5 50 29.1 102 50 28.7 101 50 28.0 98 50 

4 29.2 50 29.9 102 50 29.7 102 50 28.6 98 50 

5 30.5 50 30.9 101 50 30.7 101 50 29.7 97 50 

6 31.1 50 31.7 102 50 31.3 101 50 30.5 98 50 

7 31.6 50 32.6 103 50 32.2 102 50 31.2 99 50 

8 32.6 50 33.0 101 50 33.0 101 50 31.6 97 50 

9 33.3 50 33.7 101 50 33.5 101 50 32.3 97 50 

10 33.6 50 34.4 102 50 34.2 102 50 33.0 98 50 

11 34.6 50 35.0 101 50 34.5 100 50 33.3 96 50 

12 34.5 50 36.3 105 50 35.4 103 50 34.6 100 50 

15 36.8 50 38.0 103 50 37.1 101 50 35.4 96 50 

19 40.2 50 41.5 103 50 40.6 101 50 38.1 95 50 

23 43.0 50 43.9 102 50 43.3 101 50 40.1 93 50 

27 44.0 50 45.4 103 50 44.3 101 50 42.4 96 50 

31 45.7 50 47.0 103 50 46.0 101 50 43.8 96 50 

35 47.7 50 48.3 101 50 47.8 100 50 44.6 94 50 

39 47.9 50 49.0 102 48 48.1 100 50 45.4 95 50 

43 48.6 50 49.7 102 47 48.7 100 49 46.1 95 50 

47 49.4 50 50.4 102 48 49.2 100 48 46.7 95 50 

51 49.8 50 50.7 102 48 50.6 102 48 48.0 96 50 

55 49.5 50 51.1 103 48 50.2 101 48 47.7 96 49 

59 50.4 49 51.2 102 48 50.4 100 47 47.9 95 49 

63 51.1 49 52.5 103 47 51.0 100 47 49.2 96 48 

67 51.3 48 52.3 102 47 51.7 101 46 49.4 96 48 

71 51.5 47 53.0 103 47 52.3 102 43 49.9 97 48 

75 51.4 46 52.8 103 46 52.3 102 41 49.2 96 48 

79 51.6 44 52.6 102 46 52.2 101 39 49.0 95 48 

84 50.6 42 51.6 102 44 51.5 102 38 48.7 96 48 

87 51.4 41 53.5 104 40 51.9 101 37 49.2 96 45 

91 50.9 41 52.5 103 39 51.3 101 36 48.6 96 45 

93 50.7 41 52.4 103 39 51.0 101 36 48.6 96 43 

95 51.4 39 52.3 102 39 51.0 99 35 48.8 95 43 

97 50.2 39 51.2 102 38 51.0 102 31 48.4 96 43 

99 50.6 37 51.0 101 38 50.9 101 31 48.4 96 43 

101 50.7 36 51.1 101 37 50.4 99 31 48.6 96 43 

103 50.3 35 50.7 101 36 49.8 99 30 49.2 98 39 

Mean for weeks 

1-13 31.1 31.8 102 31.5 101 30.4 98 

14-52 45.3 46.4 102 45.6 101 43.1 95 

53-103 50.9 52.0 102 51.2 101 48.8 96 
Furfuryl Alcohol, NTP TR 482 53 

TABLE 17 

Mean Body Weights and Survival of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Weeks Chamber Control 2 ppm 8 ppm 32 ppm 

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

Study (g) Survivors (g) controls) Survivors (g) controls) Survivors (g) controls) Survivors 

1 21.1 50 21.2 101 49 21.4 101 50 20.6 98 50 

2 22.7 50 22.8 100 49 22.5 99 50 22.2 98 50 

3 23.1 50 23.5 102 49 23.7 103 50 23.2 100 50 

4 23.7 50 24.2 102 49 24.3 103 50 23.9 101 50 

5 24.6 50 24.5 100 49 24.8 101 50 24.9 101 50 

6 25.7 50 25.8 100 49 25.5 99 50 26.0 101 50 

7 26.2 50 26.9 103 49 27.3 104 50 26.8 102 50 

8 26.6 50 26.9 101 49 27.8 105 50 27.4 103 50 

9 26.7 50 26.8 100 49 27.8 104 50 27.9 105 50 

10 27.0 50 27.8 103 49 28.3 105 50 28.3 105 50 

11 28.4 50 28.6 101 49 29.2 103 50 28.7 101 50 

12 28.4 50 29.1 103 49 30.0 106 50 29.8 105 50 

15 30.4 50 30.9 102 49 31.3 103 50 30.9 102 50 

19 33.1 50 34.7 105 49 34.8 105 50 33.6 102 50 

23 37.1 50 38.2 103 49 38.3 103 50 36.2 98 50 

27 37.9 50 39.4 104 49 39.2 103 50 38.3 101 50 

31 40.4 50 42.1 104 49 40.8 101 50 39.6 98 50 

35 42.9 50 43.8 102 49 42.9 100 50 41.6 97 50 

39 44.2 50 43.7 99 48 43.6 99 50 41.2 93 50 

43 45.6 50 44.3 97 48 44.8 98 50 42.5 93 50 

47 47.0 50 45.9 98 48 46.8 100 50 43.1 92 50 

51 49.5 49 48.1 97 48 48.8 99 50 44.9 91 50 

55 50.2 49 47.9 95 48 48.7 97 50 45.0 90 50 

59 52.1 49 48.5 93 48 48.6 93 49 45.9 88 50 

63 54.9 49 51.4 94 48 51.0 93 48 48.3 88 50 

67 56.9 48 53.1 93 45 53.0 93 47 49.3 87 50 

71 57.7 48 54.8 95 45 54.6 95 47 51.3 89 50 

75 57.4 48 54.7 95 44 54.5 95 47 50.0 87 50 

79 58.5 46 55.2 94 43 54.0 92 47 50.0 86 50 

84 58.0 44 55.3 95 43 53.1 92 47 49.6 86 48 

87 58.8 41 55.7 95 41 53.2 91 45 49.9 85 46 

91 58.9 40 54.9 93 41 52.1 89 42 49.3 84 45 

93 58.4 40 54.1 93 39 53.2 91 39 48.8 84 45 

95 59.1 38 54.4 92 39 53.6 91 39 49.1 83 44 

97 57.3 38 52.9 92 39 51.9 91 36 48.2 84 43 

99 56.8 37 52.5 92 36 51.4 91 35 48.2 85 42 

101 57.2 36 52.2 91 36 52.5 92 32 49.0 86 41 

103 56.7 34 51.3 91 36 52.6 93 32 48.6 86 40 

Mean for weeks 

1-13 25.4 25.7 101 26.1 103 25.8 102 

14-52 40.8 41.1 101 41.1 101 39.2 96 

53-103 56.8 53.1 93 52.4 92 48.8 86 
 

54 Furfuryl Alcohol, NTP TR 482 

Pathology and Statistical Analyses 

This section describes the statistically significant or mentioned in this section are presented in Appendix C for
 

biologically noteworthy changes in the incidences of male mice and Appendix D for female mice.
 

neoplasms and/or nonneoplastic lesions of the kidney,
 

nose, and eye. Summaries of the incidences of neoplasms Kidney: Male mice exposed to 32 ppm had increased
 

and nonneoplastic lesions, individual animal tumor numbers of renal tubule neoplasms (Tables 18 and C1).
 

diagnoses, statistical analyses of primary neoplasms that The incidences of renal tubule adenoma, carcinoma, and
 

occurred with an incidence of at least 5% in at least one adenoma or carcinoma (combined) in males were not
 

animal group, and historical incidences for the neoplasms significantly greater than in the chamber control group
 

TABLE 18 

Incidences of Neoplasms and Nonneoplastic Lesions of the Kidney in Mice in the 2-Year Inhalation Study 

of Furfuryl Alcohol 

Chamber 

Control 2 ppm 8 ppm 32 ppm 

Male 

Number Examined Microscopically 

Single Sections (Standard Evaluation) 

Nephropathya 

Renal Tubule, Degeneration 

Renal Tubule, Hyperplasia 

50 

49 

0 

1 

(1.2)b 

(1.0) 

49 

48 

0 

3 

(1.4) 

(1.0) 

49 

43 

1 

0 

(1.5) 

(1.0) 

50 

47 

48** 

3 

(1.8) 

(1.0) 

(1.7) 

Renal Tubule, Adenomac 

Renal Tubule, Carcinomad 

Renal Tubule, Adenoma or Carcinomae 

0 

0 

0 

0 

0 

0 

0 

0 

0 

2 

2 

4 

Step Sections (Extended Evaluation) 

Renal Tubule, Hyperplasia 3 (1.7) 5 (1.0) 3 (1.0) 2 (2.5) 

Renal Tubule, Adenoma 

Renal Tubule, Carcinoma 

Renal Tubule, Adenoma or Carcinoma 

0 

0 

0 

0 

0 

0 

0 

0 

0 

1 

0 

0 

Single Sections and Step Sections (Combined) 

Renal Tubule, Hyperplasia 4 (1.5) 8 (1.0) 3 (1.0) 5 (2.0) 

Renal Tubule, Adenoma 

Renal Tubule, Carcinoma 

Renal Tubule, Adenoma or Carcinoma 

0 

0 

0 

0 

0 

0 

0 

0 

0 

3 

2 

5* 

Female 

Number Examined Microscopically 

Nephropathy 

50 

41 (1.0) 

48 

35 (1.1) 

49 

40 (1.2) 

49 

39 (1.0) 

* Significantly different (P#0.05) from the chamber control group by the Poly-3 test 

** P#0.01 a Number of animals with lesion 

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

Historical incidence for 2-year NTP inhalation studies with untreated chamber controls (mean ± standard deviation): 3/1,093 (0.3% ± 0.6%); 

range, 0%-2% d Historical incidence: 1/1,093 (0.1% ± 0.4%); range, 0%-2% e Historical incidence: 4/1,093 (0.4% ± 1.0%); range, 0%-4% 

c 
Furfuryl Alcohol, NTP TR 482 55 

but exceeded historical control ranges for inhalation chamber control groups (Tables 19, C5, and D4). 

studies (Tables 18 and C4), and the incidence of renal Furfuryl alcohol was irritating and toxic to the nose. 

tubule adenoma or carcinoma (combined) occurred with Suppurative inflammation consisted of aggregates of 

a positive trend (Table C3). Step sectioning revealed the neutrophils beneath the epithelial lining or within 

presence of additional hyperplasias in chamber control the nasal lumens. Hyperplastic Bowman’s glands had 

and exposed groups and one adenoma in 32 ppm male multiple layers of polyhedral epithelium instead of the 

mice. Renal tubule adenomas were small, discrete normal single layer. Metaplasia of Bowman’s glands 

(approximately 1 mm in diameter) proliferations of generally affected the ducts, which had replacement of the 

epithelial cells in clusters and tubular structures (Plate 4). normally cuboidal epithelium by squamous epithelium. 

Renal tubule carcinomas were 1- to 2-cm-diameter Metaplasia of both the respiratory epithelium and the 

masses that replaced much of the kidney. Carcinomas transitional epithelium of the lateral wall consisted of 

had solid, highly pleomorphic clusters of cells. replacement of the normal single layer of cuboidal or 

columnar cells by areas of stratified squamous 

Nephropathy was observed in all groups of male and epithelium. Squamous metaplasia represents conversion 

female mice (Tables 18, C5, and D4). The severity of of highly specialized nasal epithelium to a more resistant 

nephropathy increased with increasing exposure type of epithelium and represents adaptive responses to 

concentration in male mice. Nephropathy consisted of chronic irritation. Hyaline degeneration of both 

necrosis and regeneration of renal tubule epithelium and respiratory and olfactory epithelium was increased in all 

inflammation and fibrosis in the interstitium. The exposed groups. Atrophy of the olfactory epithelium was 

incidence of renal tubule degeneration in male mice an attenuation of the normally tall pseudostratified 

exposed to 32 ppm was significantly greater than in the columnar cells. Metaplasia of the olfactory epithelium 

chamber control group. Renal tubule degeneration was often accompanied atrophy and consisted of replacement 

separately diagnosed and consisted of slightly distended of neurosensory cells by ciliated respiratory-type 

tubules with lumens containing eosinophilic, finely epithelial cells. Necrosis of respiratory epithelium was 

granular material. Some degenerate tubules had one to a observed in only a very few mice, but regeneration of the 

few enlarged epithelial cells with large, sometimes respiratory epithelium was increased in 8 and 32 ppm 

pleomorphic, nuclei. male and female mice. Despite the numerous 

nonneoplastic alterations in the nasal epithelium of 

Nose: There were no exposure-related neoplasms in the exposed mice, the overall architecture of the nasal 

nose of males or females. Incidences of a variety of turbinates was not distorted. Except for the very few 

nonneoplastic histologic changes in the nose were mice with focal necrosis of the respiratory epithelium, the 

significantly greater in all exposed groups than in the mucosa lining remained intact. 
 

56 Furfuryl Alcohol, NTP TR 482 

TABLE 19 

Incidences of Nonneoplastic Lesions of the Nose in Mice in the 2-Year Inhalation Study 

of Furfuryl Alcohol 

Chamber 

Control 2 ppm 8 ppm 32 ppm 

Male 

Number Examined Microscopically 

Suppurative Inflammationa 50 7 (1.4)b 

49 

11 (1.2) 

49 

27** (1.3) 

50 

28** (1.7) 

Glands, Hyperplasia 0 10** (1.0) 48** (1.8) 46** (3.3) 

Glands, Squamous Metaplasia 0 6* (1.0) 35** (1.1) 47** (1.5) 

Lateral Wall, Squamous Metaplasia 0 9** (1.0) 10** (1.7) 20** (1.5) 

Olfactory Epithelium, Atrophy 3 (1.0) 15** (1.2) 49** (2.2) 50** (3.6) 

Olfactory Epithelium, Hyaline Degeneration 2 (1.5) 3 (1.7) 21** (1.3) 39** (2.0) 

Olfactory Epithelium, Metaplasia 0 12** (1.1) 49** (2.1) 50** (3.5) 

Respiratory Epithelium, Hyaline Degeneration 5 (1.0) 18** (1.1) 42** (1.3) 45** (1.2) 

Respiratory Epithelium, Squamous Metaplasia 0 2 (1.0) 10** (1.1) 20** (1.4) 

Respiratory Epithelium, Necrosis 1 (2.0) 0 0 1 (1.0) 

Respiratory Epithelium, Regeneration 0 1 (1.0) 13** (1.0) 21** (1.0) 

Female 

Number Examined Microscopically 50 48 49 50 

Suppurative Inflammation 5 (1.2) 12* (1.1) 25** (1.5) 42** (2.0) 

Glands, Hyperplasia 0 33** (1.1) 46** (2.8) 47** (3.1) 

Glands, Squamous Metaplasia 1 (1.0) 1 (1.0) 34** (1.1) 46** (1.5) 

Lateral Wall, Squamous Metaplasia 3 (1.0) 14** (1.4) 16** (1.4) 36** (1.9) 

Olfactory Epithelium, Atrophy 2 (1.0) 35** (1.2) 49** (3.0) 50** (3.6) 

Olfactory Epithelium, Hyaline Degeneration 7 (1.3) 14 (1.4) 28** (1.8) 45** (2.2) 

Olfactory Epithelium, Metaplasia 0 31** (1.2) 49** (3.0) 49** (3.6) 

Respiratory Epithelium, Hyaline Degeneration 19 (1.4) 44** (1.5) 49** (1.3) 48** (1.4) 

Respiratory Epithelium, Squamous Metaplasia 1 (1.0) 9** (1.8) 21** (1.7) 39** (1.9) 

Respiratory Epithelium, Necrosis 0 0 2 (2.5) 3 (1.3) 

Respiratory Epithelium, Regeneration 0 0 9** (1.0) 13** (1.2) 

* Significantly different (P#0.05) from the chamber control group by the Poly-3 test 

** P#0.01 a Number of animals with lesion 

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

Eye: There was a high incidence of degeneration of the analysis which showed peaks for both calcium and 

cornea in 32 ppm female mice (3/49, 1/49, 4/49, 26/50; phosphorus. In more severe cases, there was thickening 

Table D4). Corneal degeneration consisted (hyperplasia) and/or ulceration of the overlying 

of mineralization of the stroma immediately beneath the epithelium and/or a slight infiltrate of inflammatory cells 

corneal epithelium (Plate 5). Mineralization was positive at the site of mineralization. 

in a von Kossa stain for minerals and an X-ray elemental 
Furfuryl Alcohol, NTP TR 482 57 

GENETIC TOXICOLOGY 

Furfuryl alcohol (33-10,000 μg/plate) was not mutagenic 

in Salmonella typhimurium strain TA98, TA100, 

TA1535, or TA1537, with or without S9 metabolic 

activation enzymes (Mortelmans et al., 1986; Table E1). 

It did induce sister chromatid exchanges in cultured 

Chinese hamster ovary cells in each of two trials 

conducted in the absence of S9 (Table E2). In the second 

trial without S9, significant cell cycle delay occurred at 

the highest dose (500 μg/mL) requiring harvest of 

additional cells at a later time (31 hours culture time) to 

provide sufficient cells for analysis. No induction of 

sister chromatid exchanges was noted following treatment 

with furfuryl alcohol in the presence of S9. Furfuryl 

alcohol did not induce chromosomal aberrations in 

cultured Chinese hamster ovary cells treated with furfuryl 

alcohol in the absence of S9, but in the presence of S9, an 

equivocal result was obtained (Table E3). In the 

chromosomal aberrations test with S9, the first trial 

showed a clear dose-related increase in aberrations, with 

significant elevations seen at 500 and 1,000 μg/mL. 

Results of the second trial were negative, and the assay 

overall was determined to be equivocal. In vivo, no 

induction of sister chromatid exchanges (Table E4), 

chromosomal aberrations (Table E5), or micronuclei 

(Table E6) was noted in bone marrow cells of male 

B6C3F1 mice after administration of furfuryl alcohol by

intraperitoneal injection. In the chromosomal aberrations 

test, results of the initial 36-hour trial were positive 

(P=0.003). However, results of two additional 36-hour 

trials were negative and the assay was concluded to be 

negative overall. 

In conclusion, with the exception of the positive response 

observed in the sister chromatid exchange test in cultured 

Chinese hamster ovary cells in vitro, no indication of 

genetic activity was seen with furfuryl alcohol. 
58 Furfuryl Alcohol, NTP TR 482 
PLATE 1 

Nose from a male F344 rat exposed to 32 ppm furfuryl alcohol 

via inhalation for 2 years. There is a squamous cell carcinoma of 

the respiratory epithelium along the nasal septum. This solid 

proliferation of keratinizing squamous epithelium shows limited 

invasion of the underlying tissue but the cells are strikingly 

disorganized. H&E; 25 × 

PLATE 3 

Nose from a male F344 rat exposed to 32ppm furfuryl alcohol 

via inhalation for 2 years. Compare the hyperplasia of the 

respiratory epithelium to the more normal single layer of 

columnar epithelium on the septum (top). The hyperplastic 

epithelium has additional cell layers and forms cyst-like spaces. 

H&E; 33 × 

PLATE 2 

Nose from a male F344 rat exposed to 8 ppm furfuryl alcohol via 

inhalation for 2 years. Adenoma of the respiratory epithelium 

consists of a single neoplastic proliferation protruding from the 

nasal turbinate (the separation is an artefact). H&E; 20 × 
PLATE 4 PLATE 5 

Kidney from a male B6C3F1 mouse exposed to 32 ppm furfuryl Eye from a female B6C3F1 mouse exposed to 8 ppm furfuryl 

alcohol via inhalation for 2 years. A renal tubule adenoma alcohol via inhalation for 2 years. The cornea has focal 

compresses (arrows) the surrounding parenchyma. H&E; 25 × degeneration and mineralization. H&E; 10 × 
59 

DISCUSSION AND CONCLUSIONS
 

Furan, furfural, and furfuryl alcohol are commercially Exposure to concentrations of furfuryl alcohol up to 

important compounds which are produced in large 32 ppm for 14 weeks produced few overt signs 

quantities and have many industrial applications. of toxicity. The mean body weight of female rats exposed 

Furfuryl alcohol is used in numerous industrial and to 32 ppm was less than that of the chamber controls, but 

manufacturing processes with considerable potential for body weights of other groups of rats and of male and 

occupational exposure. Occupations with the greatest female mice were unaffected. The most significant 

number of exposed workers include carpentry, tile setting, response occurred in the nose, where exposure to furfuryl 

and metal molding and casting, in which workers are alcohol vapor produced a spectrum of inflammatory, 

exposed through the use of grouts, mortars, and furan degenerative, and proliferative lesions of the respiratory, 

resin sand containing furfuryl alcohol-based resins, and transitional, and olfactory epithelium of rats and of the 

packaging and filling machine operation, in which respiratory and olfactory epithelium of mice. In general, 

workers are exposed to furfuryl alcohol in solvents. The the changes were more severe in the anterior portion than 

stone, clay, glass, primary metal, and chemical and allied in the posterior portion of the nose; however, at no point 

industries employ the largest number of exposed workers was the integrity of the nasal mucosa or nasal passages 

(NIOSH, 1976, 1990). Furfuryl alcohol is regulated as disrupted. Squamous metaplasia of the transitional 

an air contaminant by the Occupational Safety and Health epithelium and degeneration of the olfactory epithelium 

Administration with exposure limits for airborne were observed in all exposed groups of rats and increased 

concentrations currently recommended not to exceed in severity with increasing exposure concentration. 3 50 ppm (200 mg/m ) determined as a time-weighted Squamous metaplasia and goblet cell hyperplasia of the 

average for up to a 10-hour work shift or 40-hour work respiratory epithelium, as well as hyperplasia and 

week. The American Conference of Governmental metaplasia of the olfactory epithelium, were observed 

Industrial Hygienists suggests an 8-hour, time-weighted primarily at an exposure concentration of 8 ppm or 

average threshold limit value (TLV) of 10 ppm and a greater. In mice, nasal lesions of the olfactory and 

15-minute, time-weighted exposure limit of 15 ppm respiratory epithelium were observed in all exposed 

(ACGIH, 1997). Therefore, the exposure concentrations groups. In rats and mice, the lesions were mostly of 

used in the present studies are well within the range minimal to mild severity at 2, 4, and 8 ppm, and even at 

allowable for occupational exposure. 16 and 32 ppm the mean severities were minimal to 

moderate. Moreover, the nasal lesions were considered 

In the 16-day studies, exposure to 125 or 250 ppm unlikely to progress and become life-threatening during 

furfuryl alcohol was associated with lower survival rates a 2-year study. Based on this response, exposure 

and decreased mean body weights and body weight gains concentrations of 2, 8, and 32 ppm were selected for the 

in male and female rats and mice compared to the 2-year studies. 

chamber control groups. Histologic lesions associated 

with furfuryl alcohol exposure occurred only in the nose Chronic exposure to furfuryl alcohol vapor 6 hours per 

in both rats and mice, and the incidences and severities of day, 5 days per week for up to 105 weeks resulted in 

these lesions increased with increasing exposure concentration-related increases in the incidences and 

concentration. Exposure to 63 ppm did not reduce severities of inflammatory, degenerative, and proliferative 

survival or decrease mean body weights in rats; however, lesions of the nasal epithelium, including degeneration, 

the severities of nasal lesions in rats at this concentration hyperplasia, and metaplasia of the respiratory and 

were nearly the same as those observed at 125 ppm. olfactory epithelium in exposed groups of rats and 

Moreover, a no-observable-effect level was not achieved. degeneration and metaplasia of the respiratory and 

Based on these results, 32 ppm was selected as the olfactory epithelium in exposed groups of mice. There 

highest exposure concentration for the 14-week studies. was no evidence of a response in the lung during the 
60 Furfuryl Alcohol, NTP TR 482 

14-week or 2-year studies, suggesting that the majority of 

furfuryl alcohol vapors were removed by the upper 

respiratory tract. 

Neoplasms of the respiratory epithelium occurred only in 

rats and were present in one male exposed to 2 ppm, one 

male and one female exposed to 8 ppm, and four males 

and one female exposed to 32 ppm. Neoplasms of the 

epithelium lining the nasal cavity are uncommon in 

control F344/N rats. Their presence in exposed groups 

of males and females and the increase of combined 

incidences of neoplasms in 32 ppm males relative to 

controls was associated with furfuryl alcohol exposure. 

However, the low incidence and lack of an increase in 

females against the significant background of 

nonneoplastic proliferative lesions was a weak response 

even for an uncommon neoplasm. 

Nephropathy was observed in all groups of rats but was 

most severe in males, especially in the 32 ppm group, in 

which the associated parathyroid gland hyperplasia and 

fibrous osteodystrophy were markedly increased in 

incidence and severity. In the standard evaluation of 

kidney sections, renal tubule adenomas were observed in 

one chamber control male, one 2 ppm male, two 8 ppm 

males, and two 32 ppm females. In addition, a renal 

tubule carcinoma was observed in one 2 ppm female. No 

renal tubule neoplasms were observed in 32 ppm males, 

although nephropathy was marked in this group and the 

kidneys were fibrotic with diffuse loss of most of the 

renal tubules. In order to confirm this response, the 

kidneys of male and female rats were step sectioned and 

examined for the presence of previously undetected 

lesions. In males, analysis of the extended evaluation 

revealed one additional adenoma in each of the chamber 

control, 2 ppm, and 8 ppm groups, and four previously 

undetected adenomas in the 32 ppm group. Additional 

hyperplasias were also observed. The initial review of 

single sections combined with the analysis of step 

sections indicates a significant increase in renal tubule 

hyperplasia in 32 ppm males, but only a marginal, 

nonsignificant increase in the incidence of renal tubule 

adenomas. The presence of two adenomas in chamber 

control animals and the marginal increase in 32 ppm 

males over a 16-fold increase in exposure concentration 

do not support an association between renal tubule 

adenomas and exposure to furfuryl alcohol. 

The extended analysis of step sections from female rats 

identified two previously unidentified animals with 

adenomas in the 8 ppm group and one in the 32 ppm 

group as well as additional hyperplasias in all groups. 

The combination of single section and step section 

analyses indicates a slight increase in the incidence of 

combined renal tubule neoplasms in exposed groups. 

Renal tubule neoplasms are uncommon in female F344/N 

rats and the slight exposure and treatment-related 

increase is suggestive of an association with furfuryl 

alcohol exposure. However, the relationship of these 

neoplasms to furfuryl alcohol exposure is considered 

uncertain for several reasons. Both the 8 and 32 ppm 

groups had two adenomas, but renal tubule hyperplasias 

were increased only in the 32 ppm group relative to 

chamber controls. In addition, the step section analysis 

identified additional adenomas in the 8 ppm group but 

only one new renal tubule neoplasm in the 32 ppm group. 

Therefore, over a 16-fold increase in exposure 

concentration (from 2 to 32 ppm) the incidence of renal 

tubule adenomas increased only marginally, and over a 

fourfold increase in exposure concentration (8 to 32 ppm) 

and against a background of increasing renal tubule 

hyperplasia, the incidence of adenomas did not increase. 

Nephropathy was also observed in male and female mice, 

and the severity was slightly increased in the 32 ppm 

male group. Renal tubule degeneration was observed in 

48 of 50 male mice in the 32 ppm group but did not 

involve the loss or destruction of tubules. In the standard 

microscopic evaluation of kidney sections, incidences of 

renal tubule hyperplasia did not increase with increasing 

exposure concentration; however, two renal tubule 

adenomas and two renal tubule carcinomas were 

observed in 32 ppm males. Renal tubule neoplasms are 

uncommon in male B6C3F mice, and their presence in 1 

four 32 ppm males is consistent with an exposure-related 

carcinogenic response. Therefore, to determine whether 

additional hyperplasias or neoplasms were present, the 

kidneys of male mice were step sectioned. The extended 

evaluation revealed one additional adenoma in a 32 ppm 

male. Additional hyperplasias were also observed in 

chamber control and exposed groups. 

Exposure to furfuryl alcohol clearly exacerbated 

age-related nephropathy in both rats and mice. As 

illustrated in Figure 1, the major biotransformation 

pathway for furfuryl alcohol in rodents and humans is 

oxidation to furfural, which is further oxidized to furoic 

acid. Furoic acid is then conjugated with glycine to form 

furoylglycine and eliminated in urine. Furfuryl alcohol is 

also converted to furanacrylic acid and conjugated with 

glycine to form furanacryloylglycine, which is also 

eliminated in urine. The data in Appendix I indicate that 

elevated concentrations of these two major metabolites 

were present in the urine of rats at the end of the 2-year 

studies. Although the liver is the primary site of these 

biotransformations, the kidney also contains the 
Furfuryl Alcohol, NTP TR 482 61 

necessary enzymes. Therefore, the increased severity of major metabolite of furfuryl alcohol. In the only 

nephropathy in rats may be associated with the renal inhalation study of furfural in which the nose was 

metabolism and/or urinary elimination of furfuryl alcohol examined histologically, Syrian golden hamsters were 

and its metabolites. exposed to 0, 20, 115, or 552 ppm furfural, 6 hours per 

day, 5 days per week for 13 weeks (Feron et al., 1979). 

Corneal degeneration involving mineralization of the In this study, the nose was the only target organ; 20 ppm 

stroma immediately beneath the corneal epithelium was was the no-observable-effect level, while 115 and 

observed in all groups of female mice and was 552 ppm caused atrophy and hyperplasia of the olfactory 

significantly increased relative to chamber controls in the epithelium but were without effect on the respiratory 

32 ppm group. Corneal degeneration is a typical epithelium. These results indicate that furfural is 

response to irritation, and the increase in the 32 ppm considerably less toxic to the nose than furfuryl alcohol. 

group is associated with furfuryl alcohol exposure. 

However, it is unclear why this lesion was observed only At concentrations well below the currently recommended 

in female mice. Other clinical observations in female TLVs, exposure to furfuryl alcohol is associated with 

mice were similar to those in males. Moreover, cages significant toxicity to the nasal mucosa in rodents. 

were rotated within the inhalation chambers weekly and, Moreover, because the concentration of metabolites was 

therefore, it was unlikely to be associated with cage proportional to dose throughout the range of doses used, 

position. Mean body weights of exposed female mice the metabolic capacity did not appear to be exceeded. 

were less than those of chamber controls throughout Toxicity was evident in both the olfactory and respiratory 

much of the study. This was especially true for the epithelium even at the 2 ppm exposure concentration. 

32 ppm female group, which had body weights that were Therefore, the no-observable-effect level for chronic 

considerably less than other groups. By contrast, the exposure is probably significantly less than 2 ppm. 

mean body weight of 32 ppm males was only slightly less Studies of other nasal irritants such as formaldehyde or 

than the other groups. This indicates that furfuryl alcohol chlorine gas suggest that rodent nasal passages are more 

was more toxic to female mice than to males. As a result, sensitive and exhibit an irritant response at exposure 

32 ppm females, the group with the lowest body weights, concentrations somewhat lower than observed in 

may have been less inclined to close their eyes to avoid nonhuman primates such as monkeys or as recorded in 

the irritating effects of furfuryl alcohol vapor than less documented human exposures (Swenberg et al., 1980; 

severely affected groups. Monticello et al., 1996). However, the present studies 

clearly indicate that furfuryl alcohol has the potential to 

The results of the present studies demonstrate that be a nasal irritant at exposure concentrations less than 

furfuryl alcohol is an obvious nasal irritant in both rats those normally encountered in occupational settings. 

and mice. However, it is unknown if the primary irritant 

is the parent alcohol or a metabolite. At vapor 

concentrations similar to those used in the present 

study, simple aliphatic alcohols such as methanol and CONCLUSIONS 

ethanol are essentially nontoxic to the nose (Andrews et Under the conditions of these 2-year inhalation studies, 

al., 1987; Poon et al., 1994). By contrast, their there was some evidence of carcinogenic activity* of 

respective aldehydes, formaldehyde and acetaldehyde, are furfuryl alcohol in male F344/N rats based on increased 

nasal toxicants and nasal carcinogens (Swenberg et al., incidences of combined neoplasms of the nose. There 

1980; Appelman et al., 1982; Woutersen et al., 1984; was equivocal evidence of carcinogenic activity of 

Monticello et al., 1996). Furfural, an aldehyde, is the furfuryl alcohol in female F344/N rats based on 
__________ 

62 Furfuryl Alcohol, NTP TR 482 

marginally increased incidences of neoplasms of the nose 

and renal tubule neoplasms. There was some evidence of 

carcinogenic activity of furfuryl alcohol in male B6C3F 1 

mice based on increased incidences of renal tubule 

neoplasms. There was no evidence of carcinogenic 

activity of furfuryl alcohol in female B6C3F1 mice 

exposed to 2, 8, or 32 ppm. 

Exposure of male and female rats and male mice to 

furfuryl alcohol was associated with increased incidences 

of nonneoplastic lesions of the nose and increased 

severities of nephropathy. Exposure of female mice to 

furfuryl alcohol was associated with increased incidences 

of nonneoplastic lesions of the nose and corneal 

degeneration. 

* Explanation of Levels of Evidence of Carcinogenic Activity is on page 10. A summary of the Technical Reports Review Subcommittee comments 

and the public discussion on this Technical Report appears on page 12. 
63 

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67 

APPENDIX A 

SUMMARY OF LESIONS IN MALE RATS 

IN THE 2-YEAR INHALATION STUDY 

OF FURFURYL ALCOHOL 

TABLE A1 

TABLE A2 

TABLE A3 

TABLE A4a 

TABLE A4b 

TABLE A5 

Summary of the Incidence of Neoplasms in Male Rats 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 

Individual Animal Tumor Pathology of Male Rats 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 

Statistical Analysis of Primary Neoplasms in Male Rats 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 

Historical Incidence of Nasal Neoplasms 

in Chamber Control Male F344/N Rats .............................................. 

Historical Incidence of Renal Tubule Neoplasms 

in Chamber Control Male F344/N Rats .............................................. 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 

68 

72 

90 

95 

95 

96 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

68 Furfuryl Alcohol, NTP TR 482 

TABLE A1 

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohola 

Chamber Control 2 ppm 8 ppm 32 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 34 43 31 43 

Natural deaths 8 2 10 7 

Survivors 

Died last week of study 1 

Terminal sacrifice 7 5 9 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Intestine large, colon (49) (50) (48) (47) 

Intestine large, cecum (46) (49) (44) (45) 

Intestine small, duodenum (50) (50) (50) (49) 

Intestine small, jejunum (46) (50) (43) (44) 

Carcinoma 1 (2%) 

Intestine small, ileum (47) (49) (43) (45) 

Liver (50) (50) (50) (50) 

Hepatocellular adenoma 1 (2%) 1 (2%) 

Histiocytic sarcoma 2 (4%) 

Mesentery (11) (13) (9) (26) 

Oral mucosa (1) (1) (1) (1) 

Pharyngeal, squamous cell papilloma 1 (100%) 

Pancreas (50) (50) (50) (49) 

Adenoma 1 (2%) 1 (2%) 

Carcinoma, metastatic, kidney 1 (2%) 

Salivary glands (47) (50) (49) (49) 

Histiocytic sarcoma 1 (2%) 

Stomach, forestomach (50) (50) (50) (50) 

Squamous cell papilloma 1 (2%) 

Stomach, glandular (50) (50) (50) (49) 

Cardiovascular System 

Heart (50) (50) (50) (50) 

Carcinoma, metastatic, kidney 1 (2%) 

Endocrine System 

Adrenal cortex (50) (50) (50) (50) 

Adenoma 1 (2%) 

Carcinoma, metastatic, kidney 1 (2%) 

Bilateral, adenoma 1 (2%) 

Adrenal medulla (50) (50) (50) (50) 

Carcinoma, metastatic, kidney 1 (2%) 

Pheochromocytoma malignant 1 (2%) 2 (4%) 1 (2%) 

Pheochromocytoma complex 1 (2%) 

Pheochromocytoma benign 11 (22%) 13 (26%) 12 (24%) 6 (12%) 

Bilateral, pheochromocytoma benign 8 (16%) 14 (28%) 10 (20%) 20 (40%) 

Islets, pancreatic (50) (50) (50) (49) 

Adenoma 3 (6%) 2 (4%) 

Carcinoma 1 (2%) 1 (2%) 1 (2%) 

Parathyroid gland (49) (45) (50) (49) 

Adenoma 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 69 

TABLE A1 

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Endocrine System (continued) 

Pituitary gland (50) (50) (48) (50) 

Pars distalis, adenoma 36 (72%) 37 (74%) 39 (81%) 31 (62%) 

Thyroid gland (49) (49) (49) (47) 

C-cell, adenoma 5 (10%) 6 (12%) 5 (10%) 

C-cell, carcinoma 1 (2%) 1 (2%) 

Follicular cell, adenoma 2 (4%) 

Follicular cell, carcinoma 1 (2%) 

General Body System 

Peritoneum (1) (1) (1) 

Genital System 

Epididymis (50) (50) (50) (50) 

Preputial gland (49) (50) (49) (50) 

Adenoma 2 (4%) 3 (6%) 2 (4%) 2 (4%) 

Carcinoma 3 (6%) 2 (4%) 5 (10%) 2 (4%) 

Schwannoma malignant 1 (2%) 

Bilateral, carcinoma 1 (2%) 

Prostate (50) (50) (50) (50) 

Adenoma 1 (2%) 1 (2%) 1 (2%) 

Seminal vesicle (49) (49) (46) (47) 

Adenoma 1 (2%) 

Testes (50) (50) (50) (50) 

Bilateral, interstitial cell, adenoma 28 (56%) 27 (54%) 27 (54%) 18 (36%) 

Interstitial cell, adenoma 7 (14%) 8 (16%) 10 (20%) 14 (28%) 

Hematopoietic System 

Bone marrow (50) (50) (50) (49) 

Lymph node (10) (8) (10) (12) 

Lymph node, bronchial (39) (28) (33) (22) 

Carcinoma, metastatic, kidney 1 (3%) 

Lymph node, mandibular (44) (42) (48) (46) 

Lymph node, mesenteric (48) (50) (50) (45) 

Carcinoma, metastatic, kidney 1 (2%) 

Lymph node, mediastinal (45) (47) (46) (44) 

Carcinoma, metastatic, kidney 1 (2%) 

Spleen (50) (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Thymus (43) (40) (41) (38) 

Thymoma benign 1 (3%) 

Integumentary System 

Mammary gland (30) (25) (29) (27) 

Carcinoma 2 (7%) 

Carcinoma, multiple 1 (3%) 

Fibroadenoma 2 (7%) 1 (4%) 5 (17%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

70 Furfuryl Alcohol, NTP TR 482 

TABLE A1 

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Integumentary System (continued) 

Skin (50) (50) (50) (50) 

Basal cell adenoma 1 (2%) 3 (6%) 

Basal cell carcinoma 2 (4%) 1 (2%) 

Keratoacanthoma 5 (10%) 1 (2%) 7 (14%) 4 (8%) 

Squamous cell carcinoma 1 (2%) 

Squamous cell papilloma 2 (4%) 

Sebaceous gland, carcinoma 2 (4%) 

Subcutaneous tissue, fibroma 4 (8%) 2 (4%) 5 (10%) 1 (2%) 

Subcutaneous tissue, fibroma, multiple 1 (2%) 

Subcutaneous tissue, histiocytic sarcoma 1 (2%) 

Subcutaneous tissue, schwannoma malignant 2 (4%) 1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) (50) 

Osteoma 1 (2%) 

Turbinate, osteosarcoma 1 (2%) 

Nervous System 

Brain (50) (50) (50) (50) 

Meningioma malignant 1 (2%) 

Respiratory System 

Lung (50) (50) (50) (50) 

Alveolar/bronchiolar adenoma 2 (4%) 1 (2%) 

Alveolar/bronchiolar carcinoma 1 (2%) 

Alveolar/bronchiolar carcinoma, metastatic,

 lung 1 (2%) 

Carcinoma, metastatic, kidney 1 (2%) 

Carcinoma, metastatic, preputial gland 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Pheochromocytoma malignant, metastatic,

 adrenal medulla 1 (2%) 

Nose (50) (50) (50) (50) 

Lateral wall, adenoma 1 (2%) 

Respiratory epithelium, adenoma 1 (2%) 

Respiratory epithelium, carcinoma 1 (2%) 

Respiratory epithelium, squamous cell

 carcinoma 3 (6%) 

Special Senses System 

Zymbal’s gland (1) (1) (3) 

Adenoma 1 (100%) 

Carcinoma 1 (100%) 3 (100%) 
 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 71 

TABLE A1 

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Urinary System 

Kidney 

Histiocytic sarcoma

Lipoma

Nephroblastoma 

Stromal nephroma

Renal tubule, adenoma

Transitional epithelium, carcinoma

Urinary bladder 

(50) 

 1 (2%) 

(50) 

(50) 

 1 (2%) 

 1 (2%) 

(50) 

(50) 

 1 (2%) 

1 (2%) 

 1 (2%) 

 2 (4%) 

 1 (2%) 

(50) 

(50) 

(50) 

Systemic Lesions 

Multiple organsb 

Histiocytic sarcoma

Leukemia mononuclear

Mesothelioma malignant

(50) 

 29 (58%) 

 3 (6%) 

(50) 

 31 (62%) 

 2 (4%) 

(50) 

 2 (4%) 

 28 (56%) 

 1 (2%) 

(50) 

 15 (30%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 

Total primary neoplasms 

Total animals with benign neoplasms 

Total benign neoplasms 

Total animals with malignant neoplasms 

Total malignant neoplasms 

Total animals with metastatic neoplasms 

Total metastatic neoplasms 

50 

161 

47 

115 

35 

46 

50 

166 

50 

126 

35 

40 

50 

189 

49 

139 

34 

50 

4 

11 

50 

125 

47 

98 

26 

27 

a 

b 

c 

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

Number of animals with any tissue examined microscopically 

Primary neoplasms: all neoplasms except metastatic neoplasms 
 

 

 

 

 

 

 

 

 

 

 

72 Furfuryl Alcohol, NTP TR 482 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

3 3 3 3 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 

Number of Days on Study	 0 3 5 8 6 9 0 2 2 3 3 6 7 7 7 8 9 9 9 9 0 0 1 2 4 

2 3 1 2 9 0 7 2 5 2 6 1 2 4 8 1 1 5 9 9 6 9 7 4 8 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

Carcass ID Number 3 1 1 0 2 2 0 4 2 0 4 1 4 0 0 3 4 3 0 4 1 5 2 1 0 

8 6 1 9 1 6 3 2 4 7 6 4 8 4 8 5 7 9 5 9 0 0 2 9 6 

Alimentary System 

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

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

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

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

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

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

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

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

Hepatocellular adenoma 

Mesentery + + + 

Oral mucosa 

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

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

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

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

Cardiovascular System 

Blood vessel 

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

Endocrine System 

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

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

Pheochromocytoma malignant 

Pheochromocytoma benign X X X X 

Bilateral, pheochromocytoma benign X 

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

Adenoma X 

Carcinoma 

Parathyroid gland + + + + + + M + + + + + + + + + + + + + + + + + + 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

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

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

C-cell, adenoma X 

General Body System 

Peritoneum + 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma X X 

Carcinoma X 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 

Bilateral, interstitial cell, adenoma X X X X X X X 

Interstitial cell, adenoma X X X X X 

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

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

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 73 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

6 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 5 6 6 7 8 8 8 8 8 9 9 9 9 0 1 1 2 3 3 3 3 3 3 3 3 

7 4 5 9 1 4 5 5 6 0 3 6 6 2 5 7 7 5 5 5 5 5 5 5 5 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Total 

Carcass ID Number 4 1 1 1 4 0 2 3 4 2 3 2 2 3 1 1 3 0 2 2 3 3 3 4 4 Tissues/ 

3 7 2 5 5 1 7 6 0 5 1 0 3 0 8 3 2 2 8 9 3 4 7 1 4 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, rectum + I + + + + + + + + + + + + + A + + + + + + + + + 47 

Intestine large, cecum + A + + + + + + + + + + + A + A + + + + + + + + + 46 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine small, jejunum + + + + A + + + + + + + + A + + A + + + + + + + + 46 

Intestine small, ileum + A + + + + + + + + + + + + + + A + + + + + + + + 47 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocellular adenoma X 1 

Mesentery + + + + + + + + 11 

Oral mucosa + 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Salivary glands + + M + + + + M + + + + M + + + + + + + + + + + + 47 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cardiovascular System 

Blood vessel + + 2 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma malignant X 1 

Pheochromocytoma benign X X X X X X X 11 

Bilateral, pheochromocytoma benign X X X X X X X 8 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X X 3 

Carcinoma X 1 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X X X 36 

Thyroid gland + + + + + + + + + + + + + + + A + + + + + + + + + 49 

C-cell, adenoma X X X X 5 

General Body System 

Peritoneum 1 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Preputial gland + M + + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma 2 

Carcinoma X X 3 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Seminal vesicle + + + + + + + + + + + + + + + A + + + + + + + + + 49 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Bilateral, interstitial cell, adenoma X X X X X X X X X X X X X X X X X X X X X 28 

Interstitial cell, adenoma X X 7 
 

 

 

 

 

 

 

 

 

 

 

74 Furfuryl Alcohol, NTP TR 482 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

3 3 3 3 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 

Number of Days on Study 0 3 5 8 6 9 0 2 2 3 3 6 7 7 7 8 9 9 9 9 0 0 1 2 4 

2 3 1 2 9 0 7 2 5 2 6 1 2 4 8 1 1 5 9 9 6 9 7 4 8 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

Carcass ID Number 3 1 1 0 2 2 0 4 2 0 4 1 4 0 0 3 4 3 0 4 1 5 2 1 0 

8 6 1 9 1 6 3 2 4 7 6 4 8 4 8 5 7 9 5 9 0 0 2 9 6 

Hematopoietic System 

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

Lymph node + + + + + + +
 

Lymph node, bronchial + + M M + + + + + + + + + M M + + + + + + + + + +
 

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

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

Lymph node, mediastinal + + M + + M + + + + + M + + + + + + + + + + + + +
 

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

Thymus + + + + + + + + M + + + + + + + + M + + + + + + +
 

Integumentary System 

Mammary gland + M M M M + + M + M + M M + M + + M M M + + M + + 

Carcinoma, multiple 

Fibroadenoma X 

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

Basal cell carcinoma 

Keratoacanthoma X 

Sebaceous gland, carcinoma X 

Subcutaneous tissue, fibroma X 

Subcutaneous tissue, schwannoma malignant X 

Musculoskeletal System 

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

Osteoma X 

Nervous System 

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

Meningioma malignant X 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 

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

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

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

Special Senses System 

Zymbal’s gland + 

Carcinoma X 

Urinary System 

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

Renal tubule, adenoma 

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

Systemic Lesions 

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

Leukemia mononuclear X X X X X X X X X X X X X X X X 

Mesothelioma malignant X 
 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 75 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

6 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 5 6 6 7 8 8 8 8 8 9 9 9 9 0 1 1 2 3 3 3 3 3 3 3 3 

7 4 5 9 1 4 5 5 6 0 3 6 6 2 5 7 7 5 5 5 5 5 5 5 5 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Total 

Carcass ID Number 4 1 1 1 4 0 2 3 4 2 3 2 2 3 1 1 3 0 2 2 3 3 3 4 4 Tissues/ 

3 7 2 5 5 1 7 6 0 5 1 0 3 0 8 3 2 2 8 9 3 4 7 1 4 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node + + + 10 

Lymph node, bronchial + M M M + + + M M M + + + + + + M + + + + + + + + 39 

Lymph node, mandibular + + M M + + + M + + + + M + + + + + + + + + + + + 44 

Lymph node, mesenteric + + + + + + + + + + M + + + + + + + + + + M + + + 48 

Lymph node, mediastinal + + M + + + + + + + M + + + + + + + + + + + + + + 45 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Thymus + + M M + + M + + + + + + + + + + M + + M + + + + 43 

Integumentary System 

Mammary gland + + M M + + + + + M + + M M + + M + + + + M + + + 30 

Carcinoma, multiple X 1 

Fibroadenoma X 2 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Basal cell carcinoma X X 2 

Keratoacanthoma X X X X 5 

Sebaceous gland, carcinoma X 2 

Subcutaneous tissue, fibroma X X X 4 

Subcutaneous tissue, schwannoma malignant X 2 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Osteoma 1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Meningioma malignant 1 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Trachea + + + + + + + + + + + + + + + A + + + + + + + + + 49 

Special Senses System 

Zymbal’s gland 1 

Carcinoma 1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Renal tubule, adenoma X 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Leukemia mononuclear X X X X X X X X X X X X X 29 

Mesothelioma malignant X X 3 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

76 Furfuryl Alcohol, NTP TR 482 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

3 4 4 4 4 4 4 4 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 

Number of Days on Study 9 6 7 7 9 9 9 9 2 4 5 6 7 7 7 8 0 0 0 0 0 0 1 1 2 

9 2 7 7 0 0 0 1 5 3 5 0 1 8 8 1 1 4 6 9 9 9 6 6 2 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

Carcass ID Number 2 0 1 3 1 1 2 2 3 2 0 3 1 3 4 3 3 1 0 1 3 3 4 4 1 

7 6 2 4 4 6 2 5 5 8 7 1 0 0 0 9 2 8 4 3 3 7 6 8 5 

Alimentary System 

Esophagus + + + + + + + + + + + + M + + + + + + + + + + + + 

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

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

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

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

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

Carcinoma X 

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

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

Hepatocellular adenoma X 

Mesentery + + + + + 

Oral mucosa + 

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

Adenoma 

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

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

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

Tongue + 

Cardiovascular System 

Blood vessel 

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

Endocrine System 

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

Adenoma X 

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

Pheochromocytoma benign X X X X X X X X 

Bilateral, pheochromocytoma benign X X X 

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

Carcinoma 

Parathyroid gland + + + + + + + + M + + + M + + + + + + + + + M + + 

Adenoma 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

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

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

C-cell, adenoma X 

C-cell, carcinoma 

General Body System 

Peritoneum 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Penis 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma X 

Carcinoma X 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma X 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma X 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 

Bilateral, interstitial cell, adenoma X X X X X X X X X X 

Interstitial cell, adenoma X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 77 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 2 2 3 3 4 5 6 7 8 8 8 8 9 9 9 0 1 2 2 2 3 3 3 3 3 

3 7 7 7 4 2 0 8 6 6 9 9 1 3 4 5 6 1 6 8 5 5 5 5 5 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Total 

Carcass ID Number 3 0 2 4 4 1 4 4 0 3 1 4 4 0 2 2 0 4 0 0 1 2 2 2 5 Tissues/ 

6 1 1 3 7 9 9 5 3 8 7 1 4 5 6 0 2 2 8 9 1 3 4 9 0 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + M + + + + + + + + + + + + + + 48 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, cecum + + + + + + + + + + A + + + + + + + + + + + + + + 49 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma 1 

Intestine small, ileum + + + + + + + + + + A + + + + + + + + + + + + + + 49 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocellular adenoma 1 

Mesentery + + + + + + + + 13 

Oral mucosa 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Tongue 1 

Cardiovascular System 

Blood vessel + + 2 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma benign X X X X X 13 

Bilateral, pheochromocytoma benign X X X X X X X X X X X 14 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma X 1 

Parathyroid gland + + + M + + + M + + + + + + + + + + + + + + + + + 45 

Adenoma X 1 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X X X 37 

Thyroid gland + + + I + + + + + + + + + + + + + + + + + + + + + 49 

C-cell, adenoma X X X X X 6 

C-cell, carcinoma X 1 

General Body System 

Peritoneum + 1 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Penis + 1 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X X 3 

Carcinoma X 2 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma 1 

Seminal vesicle + + + + + + + + + + A + + + + + + + + + + + + + + 49 

Adenoma 1 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Bilateral, interstitial cell, adenoma X X X X X X X X X X X X X X X X X 27 

Interstitial cell, adenoma X X X X X X X 8 
 

 

 

 

 

 

 

 

 

78 Furfuryl Alcohol, NTP TR 482 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

Number of Days on Study 

3 

9 

9 

4 

6 

2 

4 

7 

7 

4 

7 

7 

4 

9 

0 

4 

9 

0 

4 

9 

0 

4 

9 

1 

5 

2 

5 

5 

4 

3 

5 

5 

5 

5 

6 

0 

5 

7 

1 

5 

7 

8 

5 

7 

8 

5 

8 

1 

6 

0 

1 

6 

0 

4 

6 

0 

6 

6 

0 

9 

6 

0 

9 

6 

0 

9 

6 

1 

6 

6 

1 

6 

6 

2 

2 

Carcass ID Number 

2 

2 

7 

2 

0 

6 

2 

1 

2 

2 

3 

4 

2 

1 

4 

2 

1 

6 

2 

2 

2 

2 

2 

5 

2 

3 

5 

2 

2 

8 

2 

0 

7 

2 

3 

1 

2 

1 

0 

2 

3 

0 

2 

4 

0 

2 

3 

9 

2 

3 

2 

2 

1 

8 

2 

0 

4 

2 

1 

3 

2 

3 

3 

2 

3 

7 

2 

4 

6 

2 

4 

8 

2 

1 

5 

Hematopoietic System 

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

Lymph node + + +
 

Lymph node, bronchial + M + + + + + M + + M + + + + M M M + M M M + + +
 

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

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

Lymph node, mediastinal + + + + + + M + + + + + + + + + + + + + + + + + +
 

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

Thymus + + + + + M M + + + + + + M + + + M + + M + + + +
 

Integumentary System 

Mammary gland M M + M M M M M M M + + M + M M + + M M M M + + M 

Fibroadenoma X 

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

Basal cell adenoma 

Keratoacanthoma 

Squamous cell papilloma 

Subcutaneous tissue, fibroma 

Subcutaneous tissue, schwannoma malignant X 

Musculoskeletal System 

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

Turbinate, osteosarcoma X 

Nervous System 

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

Spinal cord + 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 

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

Alveolar/bronchiolar adenoma X 

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

Lateral wall, adenoma 

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

Special Senses System 

Eye + + + 

Harderian gland + 

Urinary System 

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

Lipoma 

Renal tubule, adenoma 

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

Systemic Lesions 

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

Leukemia mononuclear X X X X X X X X X X X X X 

Mesothelioma malignant 
 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 79 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

Number of Days on Study 

6 

2 

3 

6 

2 

7 

6 

3 

7 

6 

3 

7 

6 

4 

4 

6 

5 

2 

6 

6 

0 

6 

7 

8 

6 

8 

6 

6 

8 

6 

6 

8 

9 

6 

8 

9 

6 

9 

1 

6 

9 

3 

6 

9 

4 

7 

0 

5 

7 

1 

6 

7 

2 

1 

7 

2 

6 

7 

2 

8 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

Carcass ID Number 

2 

3 

6 

2 

0 

1 

2 

2 

1 

2 

4 

3 

2 

4 

7 

2 

1 

9 

2 

4 

9 

2 

4 

5 

2 

0 

3 

2 

3 

8 

2 

1 

7 

2 

4 

1 

2 

4 

4 

2 

0 

5 

2 

2 

6 

2 

2 

0 

2 

0 

2 

2 

4 

2 

2 

0 

8 

2 

0 

9 

2 

1 

1 

2 

2 

3 

2 

2 

4 

2 

2 

9 

2 

5 

0 

Total 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node + + + + + 8 

Lymph node, bronchial M + M M + + M M + + + + + M + + M M + M + M M M M 28 

Lymph node, mandibular M + + + + + M + + + + + + + + + M + + + + + + + + 42 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node, mediastinal + + + + + + + + + + + + + + + + + + + + M + + + M 47 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Thymus + + M + M + + + + M M + + + + + + + + + M + + + + 40 

Integumentary System 

Mammary gland + M M + + + + M M + + + + M + + + + + + M + M + M 25 

Fibroadenoma 1 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Basal cell adenoma X 1 

Keratoacanthoma X 1 

Squamous cell papilloma X X 2 

Subcutaneous tissue, fibroma X X 2 

Subcutaneous tissue, schwannoma malignant 1 

Musculoskeletal System 

Bone 

Turbinate, osteosarcoma

+ + + + + + + + + + + + + + + + + + + + + + + + + 50 

1 

Nervous System 

Brain 

Spinal cord

+ + + + + + + + + + + + + + + + + + + + + + + + + 50 

1 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar adenoma X 2 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lateral wall, adenoma X 1 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Eye 3 

Harderian gland 1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lipoma X 1 

Renal tubule, adenoma X 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Leukemia mononuclear X X X X X X X X X X X X X X X X X X 31 

Mesothelioma malignant X X 2 
 

 

 

 

 

 

 

 

 

80 Furfuryl Alcohol, NTP TR 482 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 

Number of Days on Study 2 7 7 8 9 0 1 2 3 4 4 5 5 7 7 8 8 8 9 9 1 2 3 3 4 

8 3 8 3 2 5 9 5 6 6 7 4 9 1 2 0 5 8 2 7 6 1 5 9 6 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 

Carcass ID Number 1 3 3 4 2 0 4 2 2 3 3 0 3 3 3 2 3 1 2 4 4 3 1 1 1 

1 2 0 4 6 4 1 1 7 9 6 3 3 5 8 5 1 5 0 5 3 7 7 6 4 

Alimentary System 

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

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

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

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

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

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

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

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

Histiocytic sarcoma 

Mesentery + + 

Oral mucosa + 

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

Adenoma 

Carcinoma, metastatic, kidney 

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

Histiocytic sarcoma 

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

Squamous cell papilloma X 

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

Cardiovascular System 

Blood vessel + 

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

Carcinoma, metastatic, kidney 

Endocrine System 

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

Carcinoma, metastatic, kidney 

Bilateral, adenoma 

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

Carcinoma, metastatic, kidney 

Pheochromocytoma malignant X 

Pheochromocytoma complex X 

Pheochromocytoma benign X X X X 

Bilateral, pheochromocytoma benign X X X X X 

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

Adenoma 

Carcinoma 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 

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

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

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

C-cell, adenoma X 

C-cell, carcinoma X 

Follicular cell, adenoma 

Follicular cell, carcinoma 

General Body System 

Peritoneum 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 81 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 5 6 6 6 7 7 7 8 9 9 0 0 0 0 1 3 3 3 3 3 3 3 3 3 3 

2 5 6 6 0 1 9 8 2 3 0 8 8 8 6 0 5 5 5 5 5 5 5 5 5 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 Total 

Carcass ID Number 4 4 2 4 2 2 2 0 1 4 0 0 1 3 1 4 0 0 0 0 1 1 2 4 5 Tissues/ 

9 7 2 0 8 4 9 5 0 2 8 6 8 4 3 8 1 2 7 9 2 9 3 6 0 Tumors 

Alimentary System 

Esophagus + + + + + + M + + + + + + + + + + + + + + + + + + 49 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, cecum + + + + A + + + A + + + + + + A + + + + + + + + + 44 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine small, jejunum + + + + A + + + A + + + + + + A + + + + + + + + + 43 

Intestine small, ileum + + + + A + + + A + + + + + + A + + + + + + + + + 43 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma X X 2 

Mesentery + + + + + + + 9 

Oral mucosa 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Carcinoma, metastatic, kidney X 1 

Salivary glands + + + + + + + + M + + + + + + + + + + + + + + + + 49 

Histiocytic sarcoma X 1 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Squamous cell papilloma 1 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cardiovascular System 

Blood vessel + + 3 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, kidney X 1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, kidney X 1 

Bilateral, adenoma X 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, kidney X 1 

Pheochromocytoma malignant X 2 

Pheochromocytoma complex 1 

Pheochromocytoma benign X X X X X X X X 12 

Bilateral, pheochromocytoma benign X X X X X 10 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X X 2 

Carcinoma X 1 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pituitary gland + + + + + + + + + + + + + + + M + + + + + + + + + 48 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X X X X X X 39 

Thyroid gland + + + + A + + + + + + + + + + + + + + + + + + + + 49 

C-cell, adenoma X X X X 5 

C-cell, carcinoma 1 

Follicular cell, adenoma X X 2 

Follicular cell, carcinoma X 1 

General Body System 

Peritoneum + 1 
 

 

 

 

 

 

 

 

82 Furfuryl Alcohol, NTP TR 482 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 

Number of Days on Study 2 7 7 8 9 0 1 2 3 4 4 5 5 7 7 8 8 8 9 9 1 2 3 3 4 

8 3 8 3 2 5 9 5 6 6 7 4 9 1 2 0 5 8 2 7 6 1 5 9 6 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 

Carcass ID Number 1 3 3 4 2 0 4 2 2 3 3 0 3 3 3 2 3 1 2 4 4 3 1 1 1 

1 2 0 4 6 4 1 1 7 9 6 3 3 5 8 5 1 5 0 5 3 7 7 6 4 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma 

Carcinoma X X X 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma 

Seminal vesicle + + A + + + + + + + + + + + + + + + + A + + + + + 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 

Bilateral, interstitial cell, adenoma X X X X X X X 

Interstitial cell, adenoma X X X X X X X 

Hematopoietic System 

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

Lymph node + + + + + 

Lymph node, bronchial + + + + + + + + + + + + M + + + + M M + + M + M + 

Carcinoma, metastatic, kidney 

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

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

Carcinoma, metastatic, kidney 

Lymph node, mediastinal + + + + + + M + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, kidney 

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

Histiocytic sarcoma 

Thymus + + + + + + + M + M M + + + + + + + + + + M + + + 

Integumentary System 

Mammary gland M M + M M + M + M M M + M M M + + + + M + + + + + 

Carcinoma X 

Fibroadenoma X 

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

Basal cell adenoma 

Basal cell carcinoma 

Keratoacanthoma X X X 

Squamous cell carcinoma 

Subcutaneous tissue, fibroma X X 

Subcutaneous tissue, fibroma, multiple 

Subcutaneous tissue, histiocytic sarcoma 

Musculoskeletal System 

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

Nervous System 

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

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 83 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 5 6 6 6 7 7 7 8 9 9 0 0 0 0 1 3 3 3 3 3 3 3 3 3 3 

2 5 6 6 0 1 9 8 2 3 0 8 8 8 6 0 5 5 5 5 5 5 5 5 5 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 Total 

Carcass ID Number 4 4 2 4 2 2 2 0 1 4 0 0 1 3 1 4 0 0 0 0 1 1 2 4 5 Tissues/ 

9 7 2 0 8 4 9 5 0 2 8 6 8 4 3 8 1 2 7 9 2 9 3 6 0 Tumors 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Preputial gland + + + + + + + + M + + + + + + + + + + + + + + + + 49 

Adenoma X X 2 

Carcinoma X X 5 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Seminal vesicle + + + + A + + + + + + + + + + M + + + + + + + + + 46 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Bilateral, interstitial cell, adenoma X X X X X X X X X X X X X X X X X X X X 27 

Interstitial cell, adenoma X X X 10 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node + + + + + 10 

Lymph node, bronchial M + + + + + M + + + + + M + M M M M + M M + M M M 33 

Carcinoma, metastatic, kidney X 1 

Lymph node, mandibular + + + + + + + + M + + + + + + M + + + + + + + + + 48 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, kidney X 1 

Lymph node, mediastinal + + + + + + + + + + + + + M + + + + + + + + + M M 46 

Carcinoma, metastatic, kidney X 1 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma X 1 

Thymus + + + + + + M + + M + + + + + M + + + + + + + M M 41 

Integumentary System 

Mammary gland + M + M M M M + M + + M M + + + M + + + + + + + + 29 

Carcinoma X 2 

Fibroadenoma X X X X 5 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Basal cell adenoma X X X 3 

Basal cell carcinoma X 1 

Keratoacanthoma X X X X 7 

Squamous cell carcinoma X 1 

Subcutaneous tissue, fibroma X X X 5 

Subcutaneous tissue, fibroma, multiple X 1 

Subcutaneous tissue, histiocytic sarcoma X 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 
 

 

 

 

84 Furfuryl Alcohol, NTP TR 482 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 

Number of Days on Study 2 7 7 8 9 0 1 2 3 4 4 5 5 7 7 8 8 8 9 9 1 2 3 3 4 

8 3 8 3 2 5 9 5 6 6 7 4 9 1 2 0 5 8 2 7 6 1 5 9 6 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 

Carcass ID Number 1 3 3 4 2 0 4 2 2 3 3 0 3 3 3 2 3 1 2 4 4 3 1 1 1 

1 2 0 4 6 4 1 1 7 9 6 3 3 5 8 5 1 5 0 5 3 7 7 6 4 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 

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

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar carcinoma 

Alveolar/bronchiolar carcinoma, metastatic, lung 

Carcinoma, metastatic, kidney 

Carcinoma, metastatic, preputial gland 

Histiocytic sarcoma 

Pheochromocytoma malignant, metastatic,

 adrenal medulla X 

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

Respiratory epithelium, adenoma X 

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

Special Senses System 

Eye + 

Zymbal’s gland 

Adenoma 

Urinary System 

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

Histiocytic sarcoma 

Nephroblastoma X 

Stromal nephroma 

Renal tubule, adenoma 

Transitional epithelium, carcinoma 

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

Systemic Lesions 

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

Histiocytic sarcoma 

Leukemia mononuclear X X X X X X X X X X X X X X 

Mesothelioma malignant 
 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 85 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 5 6 6 6 7 7 7 8 9 9 0 0 0 0 1 3 3 3 3 3 3 3 3 3 3 

2 5 6 6 0 1 9 8 2 3 0 8 8 8 6 0 5 5 5 5 5 5 5 5 5 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 Total 

Carcass ID Number 4 4 2 4 2 2 2 0 1 4 0 0 1 3 1 4 0 0 0 0 1 1 2 4 5 Tissues/ 

9 7 2 0 8 4 9 5 0 2 8 6 8 4 3 8 1 2 7 9 2 9 3 6 0 Tumors 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar adenoma X 1 

Alveolar/bronchiolar carcinoma X 1 

Alveolar/bronchiolar carcinoma, metastatic, lung X 1 

Carcinoma, metastatic, kidney X 1 

Carcinoma, metastatic, preputial gland X 1 

Histiocytic sarcoma X 1 

Pheochromocytoma malignant, metastatic, 

adrenal medulla 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Respiratory epithelium, adenoma 1 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Eye 1 

Zymbal’s gland + 1 

Adenoma X 1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma X 1 

Nephroblastoma 1 

Stromal nephroma X 1 

Renal tubule, adenoma X X 2 

Transitional epithelium, carcinoma X 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma X X 2 

Leukemia mononuclear X X X X X X X X X X X X X X 28 

Mesothelioma malignant X 1 
 

 

 

 

 

 

 

 

 

 

 

86 Furfuryl Alcohol, NTP TR 482 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

3 4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 

Number of Days on Study 4 2 6 7 7 9 2 2 2 3 5 6 8 8 8 8 8 8 9 9 0 0 0 0 0 

7 1 9 2 6 7 1 2 6 2 5 8 0 0 1 1 3 5 4 9 1 4 6 9 9 

6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 

Carcass ID Number 3 4 0 2 1 4 2 3 1 1 1 0 2 4 0 2 3 3 0 4 1 2 0 0 2 

8 5 5 0 2 8 9 3 4 5 6 4 7 6 8 4 4 0 2 3 7 6 3 9 5 

Alimentary System 

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

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

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

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

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

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

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

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

Mesentery + + + + + + + + + 

Oral mucosa + 

Pharyngeal, squamous cell papilloma X 

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

Salivary glands + + + + + + + + + + + + + + + + + + + + + M + + + 

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

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

Cardiovascular System 

Blood vessel + + + + + + + + 

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

Endocrine System 

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

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

Pheochromocytoma malignant 

Pheochromocytoma benign X 

Bilateral, pheochromocytoma benign X X X X X X X 

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

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

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

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

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

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Penis 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Adenoma X 

Carcinoma X X 

Schwannoma malignant 

Bilateral, carcinoma X 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 

Seminal vesicle + + + + A + + + + + + + + + + + + A + + + + + + + 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 

Bilateral, interstitial cell, adenoma X X X X X X 

Interstitial cell, adenoma X X X X X X X 
 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 87 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 

Number of Days on Study 1 1 1 1 1 2 2 2 3 3 3 3 3 3 3 4 5 5 5 6 6 7 8 8 9 

0 0 2 3 5 2 2 3 1 7 7 7 8 8 8 9 0 1 1 4 8 4 1 2 3 

6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 Total 

Carcass ID Number 1 3 2 0 3 1 1 5 0 4 4 4 1 4 4 3 3 2 4 3 0 3 2 1 2 Tissues/ 

0 2 1 6 5 8 9 0 7 2 4 7 3 1 9 1 7 8 0 9 1 6 3 1 2 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, colon + + + + + + + + + + + + A + + + + + + + + + + + + 47 

Intestine large, rectum + + + + + + + + + + + + + + + A + + + + + + + + + 47 

Intestine large, cecum + + + A + + + + + + + + A + + A + + + + + + + + + 45 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, jejunum + + + A + + + + + + + + + + + A A + A + + + + + + 44 

Intestine small, ileum + + + A + + + + + + + + A + + A + + + + + + + + + 45 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Mesentery + + + + + + + + + + + + + + + + + 26 

Oral mucosa 1 

Pharyngeal, squamous cell papilloma 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + 31 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma malignant X 1 

Pheochromocytoma benign X X X X X 6 

Bilateral, pheochromocytoma benign X X X X X X X X X X X X X 20 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pars distalis, adenoma X X X X X X X X X X X X X X X 31 

Thyroid gland + + + A + + + + + + + + + + + + + + A + + + + + + 47 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Penis + 1 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 2 

Carcinoma 2 

Schwannoma malignant X 1 

Bilateral, carcinoma 1 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Seminal vesicle + + + + + + + + + + + + + + + A + + + + + + + + + 47 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Bilateral, interstitial cell, adenoma X X X X X X X X X X X X 18 

Interstitial cell, adenoma X X X X X X X 14 
 

 

 

 

 

 

 

88 Furfuryl Alcohol, NTP TR 482 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

3 4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 

Number of Days on Study 4 2 6 7 7 9 2 2 2 3 5 6 8 8 8 8 8 8 9 9 0 0 0 0 0 

7 1 9 2 6 7 1 2 6 2 5 8 0 0 1 1 3 5 4 9 1 4 6 9 9 

6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 

Carcass ID Number 3 4 0 2 1 4 2 3 1 1 1 0 2 4 0 2 3 3 0 4 1 2 0 0 2 

8 5 5 0 2 8 9 3 4 5 6 4 7 6 8 4 4 0 2 3 7 6 3 9 5 

Hematopoietic System 

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

Lymph node + + + + + + 

Lymph node, bronchial + M + + + + + + + M + M + M + M + M M + M + M M + 

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

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

Lymph node, mediastinal + + + + + M + + + + + + + + + + + M + + + + + + M 

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

Thymus + M + M + + + + M M M M + M + + + + + + + + + + M 

Thymoma benign X 

Integumentary System 

Mammary gland + + M + + M M M + M M + M M M M M M M M + M + + M 

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

Keratoacanthoma X 

Subcutaneous tissue, fibroma 

Musculoskeletal System 

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

Nervous System 

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

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 

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

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

Respiratory epithelium, carcinoma 

Respiratory epithelium, squamous cell carcinoma X 

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

Special Senses System 

Eye + + 

Harderian gland 

Zymbal’s gland + + 

Carcinoma X X 

Urinary System 

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

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

Systemic Lesions 

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

Leukemia mononuclear X X X X X X X X X X X X 
 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 89 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 

Number of Days on Study 1 1 1 1 1 2 2 2 3 3 3 3 3 3 3 4 5 5 5 6 6 7 8 8 9 

0 0 2 3 5 2 2 3 1 7 7 7 8 8 8 9 0 1 1 4 8 4 1 2 3 

6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 Total 

Carcass ID Number 1 3 2 0 3 1 1 5 0 4 4 4 1 4 4 3 3 2 4 3 0 3 2 1 2 Tissues/ 

0 2 1 6 5 8 9 0 7 2 4 7 3 1 9 1 7 8 0 9 1 6 3 1 2 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lymph node + + + + + + 12 

Lymph node, bronchial M + + M M M M + + M M M + M M M M + M M M + M M M 22 

Lymph node, mandibular + + + + + M + + + + + + + + + + + + M + + + + + + 46 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + M + M + + + 45 

Lymph node, mediastinal + + + + M + M + + + + + + + + M + + + + + + + + + 44 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Thymus + + + + + + + + + + + + M + + + + M + M M + + + + 38 

Thymoma benign 1 

Integumentary System 

Mammary gland + + + + M + + + + M M + + + M + + + + M + M + M + 27 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Keratoacanthoma X X X 4 

Subcutaneous tissue, fibroma X 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Respiratory epithelium, carcinoma X 1 

Respiratory epithelium, squamous cell carcinoma X X 3 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Eye + 3 

Harderian gland + 1 

Zymbal’s gland + 3 

Carcinoma X 3 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Leukemia mononuclear X X X 15 
90 Furfuryl Alcohol, NTP TR 482 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Adrenal Medulla: Benign Pheochromocytoma a Overall rate 19/50 (38%) 27/50 (54%) 22/50 (44%) 26/50 (52%) 

Adjusted rateb 52.3% 68.0% 55.9% 69.7% c Terminal rate 5/8 (63%) 4/5 (80%) 4/9 (44%) 0/0 

First incidence (days) 532 490 492 555 

Poly-3 testd P=0.150 P=0.097 P=0.462 P=0.069 

Adrenal Medulla: Benign, Complex, or Malignant Pheochromocytoma 

Overall rate 19/50 (38%) 27/50 (54%) 24/50 (48%) 26/50 (52%) 

Adjusted rate 52.3% 68.0% 59.8% 69.7% 

Terminal rate 5/8 (63%) 4/5 (80%) 4/9 (44%) 0/0 

First incidence (days) 532 490 492 555 

Poly-3 test P=0.162 P=0.097 P=0.319 P=0.069 

Kidney (Renal Tubule): Adenoma (Single and Step Sections) 

Overall rate 2/50 (4%) 2/50 (4%) 3/50 (6%) 4/50 (8%) 

Adjusted rate 6.1% 6.3% 8.9% 13.9% 

Terminal rate 0/8 (0%) 1/5 (20%) 0/9 (0%) 0/0 

First incidence (days) 681 726 700 609 

Poly-3 test P=0.186 P=0.687 P=0.514 P=0.273 

Mammary Gland: Fibroadenoma 

Overall rate 2/50 (4%) 1/50 (2%) 5/50 (10%) 0/50 (0%) 

Adjusted rate 6.1% 3.1% 14.8% 0.0% 

Terminal rate 1/8 (13%) 0/5 (0%) 4/9 (44%) 0/0 e First incidence (days) 648 578 592 —

Poly-3 test P=0.273N P=0.505N P=0.223 P=0.278N
 

Mammary Gland: Fibroadenoma or Carcinoma 

Overall rate 3/50 (6%) 1/50 (2%) 6/50 (12%) 0/50 (0%)
 

Adjusted rate 9.1% 3.1% 17.5% 0.0%
 

Terminal rate 1/8 (13%) 0/5 (0%) 4/9 (44%) 0/0
 

First incidence (days) 648 578 554 —
 

Poly-3 test P=0.203N P=0.309N P=0.257 P=0.152N
 

Nose: Squamous Cell Carcinoma 

Overall rate 0/50 (0%) 0/50 (0%) 0/50 (0%) 3/50 (6%) 

Adjusted rate 0.0% 0.0% 0.0% 10.5% 

Terminal rate 0/8 (0%) 0/5 (0%) 0/9 (0%) 0/0 

First incidence (days) — — — 606 

Poly-3 test P=0.006 —f — P=0.094 

Nose: Adenoma, Carcinoma, or Squamous Cell Carcinoma 

Overall rate 0/50 (0%) 1/50 (2%) 1/50 (2%) 4/50 (8%) 

Adjusted rate 0.0% 3.1% 3.0% 13.8% 

Terminal rate 0/8 (0%) 0/5 (0%) 0/9 (0%) 0/0 

First incidence (days) — 721 585 606 

Poly-3 test P=0.013 P=0.496 P=0.509 P=0.044 

Pancreatic Islets: Adenoma 

Overall rate 3/50 (6%) 0/50 (0%) 2/50 (4%) 0/49 (0%)
 

Adjusted rate 9.1% 0.0% 6.0% 0.0%
 

Terminal rate 1/8 (13%) 0/5 (0%) 2/9 (22%) 0/0
 

First incidence (days) 624 — 735 (T) —
 

Poly-3 test P=0.229N P=0.122N P=0.495N P=0.154N
 
Furfuryl Alcohol, NTP TR 482 91 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Pancreatic Islets: Adenoma or Carcinoma 

Overall rate 4/50 (8%) 1/50 (2%) 3/50 (6%) 0/49 (0%) 

Adjusted rate 12.1% 3.1% 8.9% 0.0% 

Terminal rate 2/8 (25%) 1/5 (20%) 2/9 (22%) 0/0 

First incidence (days) 624 735 (T) 666 — 

Poly-3 test P=0.128N P=0.185N P=0.489N P=0.085N 

Pituitary Gland (Pars Distalis): Adenoma 

Overall rate 36/50 (72%) 37/50 (74%) 39/48 (81%) 31/50 (62%) 

Adjusted rate 82.8% 82.3% 89.9% 75.5% 

Terminal rate 7/8 (88%) 4/5 (80%) 9/9 (100%) 0/0 

First incidence (days) 333 399 478 472 

Poly-3 test P=0.146N P=0.598N P=0.220 P=0.260N 

Preputial Gland: Adenoma 

Overall rate 2/49 (4%) 3/50 (6%) 2/49 (4%) 2/50 (4%) 

Adjusted rate 6.1% 9.2% 6.2% 7.2% 

Terminal rate 0/8 (0%) 0/5 (0%) 1/9 (11%) 0/0 

First incidence (days) 572 616 730 609 

Poly-3 test P=0.608N P=0.501 P=0.695 P=0.640 

Preputial Gland: Carcinoma 

Overall rate 3/49 (6%) 2/50 (4%) 5/49 (10%) 3/50 (6%) 

Adjusted rate 9.2% 6.1% 14.7% 10.3% 

Terminal rate 0/8 (0%) 0/5 (0%) 2/9 (22%) 0/0 

First incidence (days) 572 399 554 522 

Poly-3 test P=0.495 P=0.495N P=0.379 P=0.614 

Preputial Gland: Adenoma or Carcinoma 

Overall rate 4/49 (8%) 5/50 (10%) 7/49 (14%) 5/50 (10%) 

Adjusted rate 12.2% 14.9% 20.6% 16.8% 

Terminal rate 0/8 (0%) 0/5 (0%) 3/9 (33%) 0/0 

First incidence (days) 572 399 554 522 

Poly-3 test P=0.445 P=0.515 P=0.272 P=0.434 

Skin: Keratoacanthoma 

Overall rate 5/50 (10%) 1/50 (2%) 7/50 (14%) 4/50 (8%) 

Adjusted rate 15.1% 3.1% 19.8% 13.8% 

Terminal rate 1/8 (13%) 1/5 (20%) 1/9 (11%) 0/0 

First incidence (days) 591 735 (T) 492 555 

Poly-3 test P=0.441 P=0.105N P=0.424 P=0.589N 

Skin: Squamous Cell Papilloma or Keratoacanthoma 

Overall rate 5/50 (10%) 3/50 (6%) 7/50 (14%) 4/50 (8%) 

Adjusted rate 15.1% 9.3% 19.8% 13.8% 

Terminal rate 1/8 (13%) 1/5 (20%) 1/9 (11%) 0/0 

First incidence (days) 591 644 492 555 

Poly-3 test P=0.561 P=0.369N P=0.424 P=0.589N 

Skin: Basal Cell Adenoma 

Overall rate 0/50 (0%) 1/50 (2%) 3/50 (6%) 0/50 (0%) 

Adjusted rate 0.0% 3.1% 8.9% 0.0% 

Terminal rate 0/8 (0%) 0/5 (0%) 0/9 (0%) 0/0 

First incidence (days) — 705 666 — 

Poly-3 test P=0.513N P=0.497 P=0.124 — 
92 Furfuryl Alcohol, NTP TR 482 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Skin: Basal Cell Adenoma or Basal Cell Carcinoma 

Overall rate 2/50 (4%) 1/50 (2%) 4/50 (8%) 0/50 (0%)
 

Adjusted rate 6.1% 3.1% 11.8% 0.0%
 

Terminal rate 1/8 (13%) 0/5 (0%) 1/9 (11%) 0/0
 

First incidence (days) 690 705 666 —
 

Poly-3 test P=0.267N P=0.507N P=0.351 P=0.276N
 

Skin: Squamous Cell Papilloma, Keratoacanthoma, or Squamous Cell Carcinoma 

Overall rate 5/50 (10%) 3/50 (6%) 8/50 (16%) 4/50 (8%) 

Adjusted rate 15.1% 9.3% 22.5% 13.8% 

Terminal rate 1/8 (13%) 1/5 (20%) 1/9 (11%) 0/0 

First incidence (days) 591 644 492 555 

Poly-3 test P=0.570 P=0.369N P=0.314 P=0.589N 

Skin: Squamous Cell Papilloma, Keratoacanthoma, Basal Cell Adenoma, Basal Cell Carcinoma, or Squamous Cell Carcinoma 

Overall rate 7/50 (14%) 4/50 (8%) 11/50 (22%) 4/50 (8%) 

Adjusted rate 21.0% 12.4% 30.8% 13.8% 

Terminal rate 2/8 (25%) 1/5 (20%) 2/9 (22%) 0/0 

First incidence (days) 591 644 492 555 

Poly-3 test P=0.379N P=0.270N P=0.253 P=0.340N 

Skin (Subcutaneous Tissue): Fibroma 

Overall rate 4/50 (8%) 2/50 (4%) 6/50 (12%) 1/50 (2%) 

Adjusted rate 12.0% 6.2% 17.2% 3.6% 

Terminal rate 1/8 (13%) 0/5 (0%) 1/9 (11%) 0/0 

First incidence (days) 525 652 547 638 

Poly-3 test P=0.261N P=0.349N P=0.396 P=0.235N 

Testes: Adenoma 

Overall rate 35/50 (70%) 35/50 (70%) 37/50 (74%) 32/50 (64%) 

Adjusted rate 84.9% 85.1% 85.9% 79.2% 

Terminal rate 7/8 (88%) 5/5 (100%) 9/9 (100%) 0/0 

First incidence (days) 469 477 428 469 

Poly-3 test P=0.202N P=0.644 P=0.594 P=0.316N 

Thyroid Gland (C-cell): Adenoma 

Overall rate 5/49 (10%) 6/49 (12%) 5/49 (10%) 0/47 (0%)
 

Adjusted rate 15.2% 18.7% 14.8% 0.0%
 

Terminal rate 0/8 (0%) 3/5 (60%) 0/9 (0%) 0/0
 

First incidence (days) 522 571 554 —
 

Poly-3 test P=0.034N P=0.482 P=0.620N P=0.053N
 

Thyroid Gland (C-cell): Adenoma or Carcinoma 

Overall rate 5/49 (10%) 7/49 (14%) 5/49 (10%) 0/47 (0%)
 

Adjusted rate 15.2% 21.6% 14.8% 0.0%
 

Terminal rate 0/8 (0%) 3/5 (60%) 0/9 (0%) 0/0
 

First incidence (days) 522 571 554 —
 

Poly-3 test P=0.027N P=0.362 P=0.620N P=0.053N
 

Thyroid Gland (Follicular Cell): Adenoma or Carcinoma 

Overall rate 0/49 (0%) 0/49 (0%) 3/49 (6%) 0/47 (0%)
 

Adjusted rate 0.0% 0.0% 9.2% 0.0%
 

Terminal rate 0/8 (0%) 0/5 (0%) 1/9 (11%) 0/0
 

First incidence (days) — — 692 —
 

Poly-3 test P=0.662N — P=0.123 —
 
Furfuryl Alcohol, NTP TR 482 93 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Zymbal’s Gland: Carcinoma 

Overall rate 1/50 (2%) 0/50 (0%) 0/50 (0%) 3/50 (6%) 

Adjusted rate 3.0% 0.0% 0.0% 10.3% 

Terminal rate 0/8 (0%) 0/5 (0%) 0/9 (0%) 0/0 

First incidence (days) 609 — — 347 

Poly-3 test P=0.039 P=0.507N P=0.497N P=0.259 

Zymbal’s Gland: Adenoma or Carcinoma 

Overall rate 1/50 (2%) 0/50 (0%) 1/50 (2%) 3/50 (6%) 

Adjusted rate 3.0% 0.0% 3.0% 10.3% 

Terminal rate 0/8 (0%) 0/5 (0%) 1/9 (11%) 0/0 

First incidence (days) 609 — 735 (T) 347 

Poly-3 test P=0.064 P=0.507N P=0.759N P=0.259 

All Organs: Mononuclear Cell Leukemia 

Overall rate 29/50 (58%) 31/50 (62%) 28/50 (56%) 15/50 (30%) 

Adjusted rate 67.9% 75.3% 65.9% 42.2% 

Terminal rate 6/8 (75%) 4/5 (80%) 6/9 (67%) 0/0 

First incidence (days) 302 490 428 421 

Poly-3 test P<0.001N P=0.285 P=0.515N P=0.011N 

All Organs: Malignant Mesothelioma 

Overall rate 3/50 (6%) 2/50 (4%) 1/50 (2%) 0/50 (0%) 

Adjusted rate 9.1% 6.2% 3.0% 0.0% 

Terminal rate 1/8 (13%) 1/5 (20%) 1/9 (11%) 0/0 

First incidence (days) 561 627 735 (T) — 

Poly-3 test P=0.126N P=0.514N P=0.300N P=0.154N 

All Organs: Benign Neoplasms 

Overall rate 47/50 (94%) 50/50 (100%) 49/50 (98%) 47/50 (94%) 

Adjusted rate 99.3% 100.0% 99.4% 98.6% 

Terminal rate 8/8 (100%) 5/5 (100%) 9/9 (100%) 0/0 

First incidence (days) 333 399 428 469 

Poly-3 test P=0.606N P=1.000 P=0.997 P=0.925N 

All Organs: Malignant Neoplasms 

Overall rate 35/50 (70%) 35/50 (70%) 34/50 (68%) 26/50 (52%) 

Adjusted rate 77.7% 81.5% 76.8% 63.5% 

Terminal rate 6/8 (75%) 5/5 (100%) 7/9 (78%) 0/0 

First incidence (days) 302 399 428 347 

Poly-3 test P=0.023N P=0.419 P=0.565N P=0.086N 
94 

c 

Furfuryl Alcohol, NTP TR 482 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

All Organs: Benign or Malignant Neoplasms 

Overall rate 50/50 (100%) 50/50 (100%) 50/50 (100%) 50/50 (100%) 

Adjusted rate 100.0% 100.0% 100.0% 100.0% 

Terminal rate 8/8 (100%) 5/5 (100%) 9/9 (100%) 0/0 

First incidence (days) 302 399 428 347 

Poly-3 test — — — — 

(T)Terminal sacrifice 

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for adrenal gland, kidney, nose, 

pancreatic islets, pituitary gland, preputial gland, testis, and thyroid gland; for other tissues, denominator is number of animals necropsied. b Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality 

Observed incidence at terminal kill 

d	 Beneath the chamber control incidence are the P values associated with the trend test. Beneath the exposed group incidence are the P values corresponding to 

pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for differential mortality in animals that do not reach terminal 

sacrifice. A negative trend or a lower incidence in an exposure group is indicated by N. e Not applicable; no neoplasms in animal group f Value of statistic cannot be computed. 
Furfuryl Alcohol, NTP TR 482 95 

TABLE A4a 

Historical Incidence of Nasal Neoplasms in Chamber Control Male F344/N Ratsa 

Incidence in Controls 

Study Adenoma Carcinoma Squamous Cell 

Carcinoma 

Historical Incidence at Battelle Pacific Northwest Laboratories 

Acetonitrile 0/48 0/48 0/48 

"-Chloroacetophenone 0/46 0/46 0/46 

Cobalt Sulfate Heptahydrate 0/50 0/50 0/50 

Epinephrine Hydrochloride 1/50 0/50 0/50 

Hexachlorocyclopentadiene 0/48 0/48 0/48 

Isobutyraldehyde 0/50 0/50 0/50 

Molybdenum Trioxide 0/50 0/50 0/50 

Nitromethane 0/50 0/50 0/50 

o-Chlorobenzalmalononitrile 0/50 0/50 0/50 

Ozone 0/50 0/50 0/50 

Tetrafluoroethylene 0/50 0/50 0/50 

Tetrahydrofuran 0/50 0/50 0/50 

Overall Historical Incidence 

Total 1/897 (0.1%) 0/897 0/897
 

Standard deviation 0.5%
 

Range 0%-2%
 

a Data as of 15 October 1996 

TABLE A4b 

Historical Incidence of Renal Tubule Neoplasms in Chamber Control Male F344/N Ratsa 

Incidence in Controls 

Study Adenoma Carcinoma Adenoma 

or Carcinoma 

Historical Incidence at Battelle Pacific Northwest Laboratories 

Acetonitrile 1/48 0/48 1/48 

"-Chloroacetophenone 1/49 0/49 1/49 

Cobalt Sulfate Heptahydrate 1/50 0/50 1/50 

Epinephrine Hydrochloride 0/50 0/50 0/50 

Hexachlorocyclopentadiene 0/50 0/50 0/50 

Isobutyraldehyde 0/50 0/50 0/50 

Molybdenum Trioxide 1/50 0/50 1/50 

Nitromethane 0/50 0/50 0/50 

o-Chlorobenzalmalononitrile 1/50 0/50 1/50 

Ozone 2/50 0/50 2/50 

Tetrafluoroethylene 0/50 1/50 1/50 

Tetrahydrofuran 1/50 0/50 1/50 

Overall Historical Incidence 

Total 9/902 (1.0%) 1/902 (0.1%) 10/902 (1.1%) 

Standard deviation 1.2% 0.5% 1.2% 

Range 0%-4% 0%-2% 0%-4% 

a Data as of 15 October 1996 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

96 Furfuryl Alcohol, NTP TR 482 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohola 

Chamber Control 2 ppm 8 ppm 32 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 34 43 31 43 

Natural deaths 8 2 10 7 

Survivors 

Died last week of study 1 

Terminal sacrifice 7 5 9 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Esophagus (50) (48) (49) (50) 

Inflammation, suppurative 1 (2%) 

Intestine large, colon (49) (50) (48) (47) 

Mineralization 1 (2%) 9 (19%) 

Parasite metazoan 3 (6%) 4 (8%) 6 (13%) 5 (11%) 

Intestine large, rectum (47) (50) (48) (47) 

Mineralization 2 (4%) 

Parasite metazoan 1 (2%) 3 (6%) 4 (8%) 1 (2%) 

Intestine large, cecum (46) (49) (44) (45) 

Parasite metazoan 2 (4%) 2 (4%) 8 (18%) 4 (9%) 

Intestine small, duodenum (50) (50) (50) (49) 

Inflammation, suppurative 1 (2%) 1 (2%) 

Intestine small, ileum (47) (49) (43) (45) 

Inflammation, suppurative 1 (2%) 

Mineralization 1 (2%) 

Parasite metazoan 1 (2%) 1 (2%) 

Liver (50) (50) (50) (50) 

Angiectasis 6 (12%) 2 (4%) 3 (6%) 4 (8%) 

Basophilic focus 9 (18%) 12 (24%) 27 (54%) 31 (62%) 

Clear cell focus 5 (10%) 1 (2%) 4 (8%) 

Cyst 2 (4%) 

Degeneration, cystic 12 (24%) 18 (36%) 12 (24%) 9 (18%) 

Degeneration, fatty 5 (10%) 9 (18%) 3 (6%) 7 (14%) 

Eosinophilic focus 4 (8%) 2 (4%) 3 (6%) 4 (8%) 

Hepatodiaphragmatic nodule 1 (2%) 4 (8%) 6 (12%) 

Mixed cell focus 1 (2%) 2 (4%) 2 (4%) 

Necrosis 2 (4%) 2 (4%) 

Regeneration 1 (2%) 3 (6%) 2 (4%) 

Tension lipidosis 1 (2%) 

Vacuolization cytoplasmic, focal 1 (2%) 

Bile duct, hyperplasia 28 (56%) 31 (62%) 30 (60%) 13 (26%) 

Centrilobular, necrosis 12 (24%) 17 (34%) 15 (30%) 8 (16%) 

Mesentery (11) (13) (9) (26) 

Pigmentation 1 (11%) 

Thrombosis 1 (4%) 

Artery, inflammation, chronic active 3 (12%) 

Artery, mineralization 2 (15%) 22 (85%) 

Fat, hemorrhage 2 (15%) 1 (11%) 2 (8%) 

Fat, necrosis 10 (91%) 6 (46%) 7 (78%) 4 (15%) 

Oral mucosa (1) (1) (1) (1) 

Gingival, inflammation, chronic active 1 (100%) 

Pharyngeal, hyperplasia 1 (100%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 97 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Alimentary System (continued) 

Pancreas (50) (50) (50) (49) 

Atrophy 22 (44%) 22 (44%) 23 (46%) 17 (35%) 

Basophilic focus 3 (6%) 1 (2%) 2 (4%) 1 (2%) 

Hyperplasia 5 (10%) 2 (4%) 2 (4%) 

Artery, inflammation 1 (2%) 5 (10%) 

Artery, mineralization 1 (2%) 3 (6%) 

Salivary glands (47) (50) (49) (49) 

Atrophy 1 (2%) 1 (2%) 

Inflammation, chronic active 1 (2%) 

Stomach, forestomach (50) (50) (50) (50) 

Hyperplasia, squamous 1 (2%) 

Inflammation, acute 1 (2%) 1 (2%) 

Mineralization 1 (2%) 2 (4%) 2 (4%) 12 (24%) 

Necrosis 9 (18%) 6 (12%) 10 (20%) 6 (12%) 

Stomach, glandular (50) (50) (50) (49) 

Mineralization 2 (4%) 2 (4%) 3 (6%) 32 (65%) 

Necrosis 7 (14%) 3 (6%) 4 (8%) 4 (8%) 

Cardiovascular System 

Blood vessel (2) (2) (3) (31) 

Aorta, mineralization 2 (100%) 2 (100%) 2 (67%) 31 (100%) 

Heart (50) (50) (50) (50) 

Cardiomyopathy 38 (76%) 32 (64%) 40 (80%) 42 (84%) 

Inflammation, suppurative 1 (2%) 

Artery, mineralization 2 (4%) 2 (4%) 2 (4%) 29 (58%) 

Atrium, thrombosis 3 (6%) 6 (12%) 1 (2%) 3 (6%) 

Endocrine System 

Adrenal cortex (50) (50) (50) (50) 

Hyperplasia 15 (30%) 19 (38%) 20 (40%) 24 (48%) 

Hypertrophy 3 (6%) 3 (6%) 1 (2%) 4 (8%) 

Necrosis 2 (4%) 1 (2%) 

Vacuolization cytoplasmic 4 (8%) 3 (6%) 4 (8%) 8 (16%) 

Adrenal medulla (50) (50) (50) (50) 

Hyperplasia 30 (60%) 17 (34%) 24 (48%) 19 (38%) 

Islets, pancreatic (50) (50) (50) (49) 

Hyperplasia 1 (2%) 

Parathyroid gland (49) (45) (50) (49) 

Hyperplasia 9 (18%) 5 (11%) 12 (24%) 39 (80%) 

Necrosis 1 (2%) 

Pituitary gland (50) (50) (48) (50) 

Mineralization 1 (2%) 

Pars distalis, angiectasis 1 (2%) 

Pars distalis, hemorrhage 1 (2%) 

Pars distalis, hyperplasia 4 (8%) 8 (16%) 3 (6%) 11 (22%) 

Pars intermedia, hyperplasia 1 (2%) 

Thyroid gland (49) (49) (49) (47) 

C-cell, hyperplasia 27 (55%) 33 (67%) 30 (61%) 21 (45%) 

Follicular cell, hyperplasia 1 (2%) 1 (2%) 2 (4%) 2 (4%) 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

98 Furfuryl Alcohol, NTP TR 482 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Genital System 

Preputial gland (49) (50) (49) (50) 

Hyperplasia 1 (2%) 1 (2%) 

Inflammation, chronic active 1 (2%) 2 (4%) 4 (8%) 

Prostate (50) (50) (50) (50) 

Hyperplasia 7 (14%) 3 (6%) 5 (10%) 

Inflammation, chronic active 9 (18%) 8 (16%) 3 (6%) 5 (10%) 

Seminal vesicle (49) (49) (46) (47) 

Inflammation, suppurative 1 (2%) 

Mineralization 1 (2%) 3 (6%) 

Testes (50) (50) (50) (50) 

Atrophy 1 (2%) 1 (2%) 3 (6%) 5 (10%) 

Artery, inflammation, chronic active 3 (6%) 1 (2%) 4 (8%) 8 (16%) 

Interstitial cell, hyperplasia 4 (8%) 6 (12%) 4 (8%) 7 (14%) 

Hematopoietic System 

Bone marrow (50) (50) (50) (49) 

Necrosis 2 (4%) 

Lymph node (10) (8) (10) (12) 

Ectasia 1 (8%) 

Iliac, ectasia 1 (8%) 

Renal, ectasia 4 (33%) 

Renal, hemorrhage 1 (10%) 1 (10%) 3 (25%) 

Lymph node, mandibular (44) (42) (48) (46) 

Infiltration cellular, plasma cell 1 (2%) 1 (2%) 

Lymph node, mediastinal (45) (47) (46) (44) 

Hemorrhage 2 (5%) 

Spleen (50) (50) (50) (50) 

Accessory spleen 3 (6%) 1 (2%) 

Angiectasis 1 (2%) 

Fibrosis 14 (28%) 13 (26%) 10 (20%) 12 (24%) 

Hematopoietic cell proliferation 1 (2%) 2 (4%) 2 (4%) 4 (8%) 

Hemorrhage 3 (6%) 

Hyperplasia, focal 1 (2%) 1 (2%) 

Necrosis 2 (4%) 2 (4%) 3 (6%) 2 (4%) 

Thymus (43) (40) (41) (38) 

Cyst 1 (3%) 

Integumentary System 

Mammary gland (30) (25) (29) (27) 

Degeneration 1 (3%) 1 (3%) 

Galactocele 6 (20%) 2 (8%) 6 (21%) 7 (26%) 

Skin (50) (50) (50) (50) 

Cyst epithelial inclusion 2 (4%) 

Fibrosis, focal 1 (2%) 

Inflammation, acute 2 (4%) 

Inflammation, chronic active 1 (2%) 2 (4%) 2 (4%) 2 (4%) 

Inflammation, granulomatous 1 (2%) 

Mineralization 1 (2%) 

Necrosis 1 (2%) 

Subcutaneous tissue, edema 1 (2%) 

Tail, hyperkeratosis 1 (2%) 

Tail, inflammation, chronic active 1 (2%) 2 (4%) 6 (12%) 18 (36%) 

Tail, subcutaneous tissue, thrombosis 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 99 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Musculoskeletal System 

Bone (50) (50) (50) (50) 

Fibrous osteodystrophy 2 (4%) 5 (10%) 6 (12%) 34 (68%) 

Fracture 1 (2%) 

Hyperostosis 5 (10%) 1 (2%) 

Nervous System 

Brain (50) (50) (50) (50) 

Necrosis 2 (4%) 

Respiratory System 

Lung (50) (50) (50) (50) 

Foreign body 1 (2%) 

Hemorrhage 1 (2%) 1 (2%) 

Inflammation, granulomatous 1 (2%) 

Inflammation, suppurative 1 (2%) 

Metaplasia, osseous 1 (2%) 1 (2%) 

Metaplasia, squamous 1 (2%) 

Mineralization 1 (2%) 2 (4%) 2 (4%) 24 (48%) 

Thrombosis 1 (2%) 1 (2%) 

Alveolar epithelium, hyperplasia 12 (24%) 7 (14%) 5 (10%) 8 (16%) 

Artery, mediastinum, mineralization 1 (2%) 2 (4%) 2 (4%) 26 (52%) 

Mediastinum, inflammation, suppurative 1 (2%) 

Perivascular, infiltration cellular,

 mononuclear cell 1 (2%) 

Nose (50) (50) (50) (50) 

Inflammation, suppurative 3 (6%) 6 (12%) 17 (34%) 44 (88%) 

Thrombosis 10 (20%) 15 (30%) 11 (22%) 2 (4%) 

Glands, hyperplasia 22 (44%) 49 (98%) 

Lateral wall, hyperplasia 1 (2%) 49 (98%) 50 (100%) 50 (100%) 

Lateral wall, metaplasia, squamous 1 (2%) 1 (2%) 8 (16%) 33 (66%) 

Lateral wall, necrosis 1 (2%) 

Nasopharyngeal duct, inflammation, acute 1 (2%) 

Olfactory epithelium, atrophy 1 (2%) 12 (24%) 47 (94%) 50 (100%) 

Olfactory epithelium, degeneration, hyaline 42 (84%) 48 (96%) 50 (100%) 47 (94%) 

Olfactory epithelium, fibrosis 1 (2%) 26 (52%) 40 (80%) 

Olfactory epithelium, hyperplasia 1 (2%) 42 (84%) 40 (80%) 

Olfactory epithelium, metaplasia 1 (2%) 8 (16%) 37 (74%) 49 (98%) 

Respiratory epithelium, degeneration, hyaline 12 (24%) 14 (28%) 45 (90%) 3 (6%) 

Respiratory epithelium, hyperplasia 26 (52%) 50 (100%) 50 (100%) 

Respiratory epithelium, metaplasia, squamous 3 (6%) 26 (52%) 

Trachea (49) (50) (50) (50) 

Inflammation, suppurative 1 (2%) 

Special Senses System 

Eye (3) (1) (3) 

Cataract 1 (33%) 1 (100%) 1 (33%) 

Inflammation, chronic active 2 (67%) 1 (33%) 

Retina, atrophy 1 (33%) 1 (33%) 

Harderian gland (1) (1) 

Hyperplasia 1 (100%) 

Inflammation, chronic active 1 (100%) 
 

 

 

 

 

 

100 Furfuryl Alcohol, NTP TR 482 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Urinary System 

Kidney (50) (50) (50) (50) 

Cyst 1 (2%) 3 (6%) 4 (8%) 

Hydronephrosis 2 (4%) 

Hyperplasia, oncocytic 1 (2%) 

Infarct 1 (2%) 2 (4%) 1 (2%) 

Mineralization 2 (4%) 2 (4%) 2 (4%) 28 (56%) 

Nephropathy 50 (100%) 49 (98%) 50 (100%) 50 (100%) 

Stromal hyperplasia 1 (2%) 

Papilla, necrosis 1 (2%) 

Renal tubule, hyperplasia 5 (10%) 5 (10%) 2 (4%) 6 (12%) 

Urinary bladder (50) (50) (50) (50) 

Inflammation, chronic active 1 (2%) 1 (2%) 1 (2%) 

Necrosis 1 (2%) 

Transitional epithelium, hyperplasia 1 (2%) 
101 

APPENDIX B 

SUMMARY OF LESIONS IN FEMALE RATS 

IN THE 2-YEAR INHALATION STUDY 

OF FURFURYL ALCOHOL 

TABLE B1 

TABLE B2 

TABLE B3 

TABLE B4a 

TABLE B4b 

TABLE B5 

Summary of the Incidence of Neoplasms in Female Rats 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 

Individual Animal Tumor Pathology of Female Rats 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 

Statistical Analysis of Primary Neoplasms in Female Rats 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 

Historical Incidence of Nasal Adenoma 

in Chamber Control Female F344/N Rats ............................................ 

Historical Incidence of Renal Tubule Neoplasms 

in Chamber Control Female F344/N Rats ............................................ 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 

102 

106 

122 

126 

126 

127 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

102 Furfuryl Alcohol, NTP TR 482 

TABLE B1 

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohola 

Chamber Control 2 ppm 8 ppm 32 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 23 21 24 32 

Natural deaths 1 3 3 2 

Survivors 

Died last week of study 1 

Terminal sacrifice 26 25 22 16 

Pregnant 1 

Animals examined microscopically 50 50 49 50 

Alimentary System 

Intestine large, colon (50) (47) (48) (48) 

Intestine large, rectum (50) (47) (47) (49) 

Fibroma 1 (2%) 

Leiomyosarcoma 1 (2%) 

Intestine large, cecum (49) (47) (46) (48) 

Intestine small, duodenum (50) (49) (47) (49) 

Intestine small, jejunum (49) (47) (47) (48) 

Adenocarcinoma 1 (2%) 

Intestine small, ileum (49) (47) (46) (48) 

Liver (50) (49) (49) (50) 

Hepatocellular adenoma 1 (2%) 

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

Osteosarcoma, metastatic, bone 2 (4%) 

Mesentery (15) (8) (11) (7) 

Carcinoma, metastatic, kidney 1 (13%) 

Sarcoma stromal, metastatic, uterus 1 (14%) 

Oral mucosa (1) (1) (1) 

Pharyngeal, squamous cell papilloma 1 (100%) 

Pancreas (49) (49) (48) (50) 

Carcinoma, metastatic, kidney 1 (2%) 

Salivary glands (49) (50) (49) (50) 

Stomach, forestomach (50) (50) (49) (50) 

Leiomyosarcoma 1 (2%) 

Stomach, glandular (50) (49) (49) (50) 

Tongue (1) (4) (1) (3) 

Squamous cell carcinoma 1 (25%) 1 (33%) 

Squamous cell papilloma 2 (50%) 1 (33%) 

Cardiovascular System 

Heart (50) (50) (49) (50) 

Endocrine System 

Adrenal cortex (50) (50) (48) (50) 

Adenoma 2 (4%) 2 (4%) 

Histiocytic sarcoma 1 (2%) 

Osteosarcoma, metastatic, bone 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 103 

TABLE B1 

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Endocrine System (continued) 

Adrenal medulla (50) (50) (48) (50) 

Histiocytic sarcoma 1 (2%) 

Pheochromocytoma malignant 1 (2%) 

Pheochromocytoma complex 1 (2%) 

Pheochromocytoma benign 4 (8%) 5 (10%) 2 (4%) 5 (10%) 

Bilateral, pheochromocytoma benign 2 (4%) 2 (4%) 2 (4%) 

Islets, pancreatic (49) (48) (48) (50) 

Adenoma 1 (2%) 3 (6%) 

Carcinoma 1 (2%) 1 (2%) 

Parathyroid gland (46) (43) (44) (46) 

Adenoma 1 (2%) 

Pituitary gland (50) (49) (48) (50) 

Pars distalis, adenoma 38 (76%) 35 (71%) 34 (71%) 35 (70%) 

Thyroid gland (49) (49) (47) (48) 

C-cell, adenoma 7 (14%) 5 (10%) 6 (13%) 5 (10%) 

C-cell, carcinoma 1 (2%) 1 (2%) 2 (4%) 

Follicular cell, adenoma 1 (2%) 

Follicular cell, carcinoma 2 (4%) 1 (2%) 

General Body System 

None 

Genital System 

Clitoral gland (44) (45) (46) (45) 

Adenoma 3 (7%) 2 (4%) 2 (4%) 7 (16%) 

Carcinoma 3 (7%) 2 (4%) 1 (2%) 

Bilateral, adenoma 1 (2%) 

Bilateral, carcinoma 1 (2%) 

Ovary (50) (50) (49) (50) 

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

Sertoli cell tumor benign 1 (2%) 

Uterus (50) (50) (49) (50) 

Adenoma 1 (2%) 

Leiomyosarcoma, metastatic, intestine large,

 rectum 1 (2%) 

Polyp stromal 5 (10%) 9 (18%) 6 (12%) 2 (4%) 

Polyp stromal, multiple 1 (2%) 

Sarcoma stromal 2 (4%) 

Schwannoma malignant 2 (4%) 1 (2%) 

Vagina (1) (3) 

Leiomyosarcoma, metastatic, intestine large,

 rectum 1 (33%) 

Polyp 1 (33%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

104 Furfuryl Alcohol, NTP TR 482 

TABLE B1 

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Hematopoietic System 

Bone marrow (49) (48) (48) (50) 

Lymph node (4) (5) (8) (11) 

Lymph node, bronchial (37) (30) (40) (25) 

Carcinoma, metastatic, thyroid gland 1 (3%) 

Histiocytic sarcoma 1 (4%) 

Lymph node, mandibular (46) (46) (46) (42) 

Lymph node, mesenteric (50) (50) (49) (50) 

Carcinoma, metastatic, kidney 1 (2%) 

Lymph node, mediastinal (43) (37) (45) (40) 

Carcinoma, metastatic, kidney 1 (3%) 

Spleen (49) (49) (49) (50) 

Hemangiosarcoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Osteosarcoma, metastatic, bone 1 (2%) 

Sarcoma 1 (2%) 

Thymus (47) (44) (44) (43) 

Integumentary System 

Mammary gland (50) (49) (49) (50) 

Adenoma 1 (2%) 

Carcinoma 7 (14%) 2 (4%) 2 (4%) 5 (10%) 

Carcinoma, multiple 2 (4%) 1 (2%) 

Fibroadenoma 17 (34%) 17 (35%) 19 (39%) 14 (28%) 

Fibroadenoma, multiple 2 (4%) 7 (14%) 6 (12%) 6 (12%) 

Skin (50) (50) (48) (50) 

Keratoacanthoma 1 (2%) 2 (4%) 

Squamous cell papilloma 1 (2%) 

Subcutaneous tissue, fibroma 3 (6%) 2 (4%) 

Musculoskeletal System 

Bone (50) (50) (49) (50) 

Fibroma 1 (2%) 

Osteosarcoma 2 (4%) 1 (2%) 

Nervous System 

Brain (50) (50) (49) (50) 

Astrocytoma malignant 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Respiratory System 

Larynx (50) (49) (49) (49) 

Carcinoma, metastatic, thyroid gland 1 (2%) 

Lung (50) (50) (49) (50) 

Alveolar/bronchiolar adenoma 1 (2%) 

Alveolar/bronchiolar carcinoma 1 (2%) 

Carcinoma, metastatic, mammary gland 1 (2%) 

Carcinoma, metastatic, thyroid gland 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Osteosarcoma, metastatic, bone 2 (4%) 

Mediastinum, osteosarcoma, metastatic, bone 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 105 

TABLE B1 

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Respiratory System (continued) 

Nose 

Lateral wall, adenoma

Respiratory epithelium, adenoma

(49) (50) (48) 

 1 (2%) 

(49) 

 1 (2%) 

Special Senses System 

None 

Urinary System 

Kidney (50) (49) (49) (50) 

Histiocytic sarcoma 1 (2%) 

Renal tubule, adenoma 2 (4%) 

Renal tubule, carcinoma 1 (2%) 

Transitional epithelium, carcinoma 1 (2%) 

Urinary bladder (49) (49) (49) (50) 

Leiomyosarcoma, metastatic, intestine large,

 rectum 1 (2%) 

Transitional epithelium, carcinoma 1 (2%) 

Systemic Lesions 

Multiple organsb (50) (50) (49) (50) 

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

Leukemia mononuclear 21 (42%) 19 (38%) 18 (37%) 29 (58%) 

Lymphoma malignant 1 (2%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 49 49 49 49 

Total primary neoplasms 127 119 120 131 

Total animals with benign neoplasms 48 47 46 43 

Total benign neoplasms 88 87 87 88 

Total animals with malignant neoplasms 31 28 32 36 

Total malignant neoplasms 39 32 33 43 

Total animals with metastatic neoplasms 1 2 3 1 

Total metastatic neoplasms 3 5 10 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 
 

 

 

 

 

 

 

 

 

 

 

106 Furfuryl Alcohol, NTP TR 482 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

0 4 4 4 4 5 5 5 5 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 

Number of Days on Study 9 5 7 7 7 7 8 8 9 0 0 0 1 2 3 5 6 7 9 0 0 0 0 2 3 

8 6 0 7 8 3 1 1 9 4 9 9 6 7 1 2 1 3 3 7 7 7 7 1 5 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

Carcass ID Number 3 3 0 2 2 0 0 1 3 4 2 3 0 1 0 3 2 3 0 1 2 3 4 1 0 

4 3 6 1 0 7 3 6 8 3 8 2 9 8 2 1 9 7 4 2 5 6 2 0 1 

Alimentary System 

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

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

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

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

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

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

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

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

Hepatocellular adenoma 

Mesentery + + + + + 

Oral mucosa + 

Pharyngeal, squamous cell papilloma X 

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

Salivary glands + + + + + + + + + + + + + + + + M + + + + + + + + 

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

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

Tongue + 

Tooth + 

Cardiovascular System 

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

Endocrine System 

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

Adenoma X 

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

Pheochromocytoma malignant 

Pheochromocytoma benign X X X 

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

Adenoma 

Parathyroid gland + + + + + + M + + + M + + + + + + + + + + + + + + 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

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

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

C-cell, adenoma X X X X 

C-cell, carcinoma X 

General Body System 

None 

Genital System 

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

Adenoma 

Carcinoma X 

Bilateral, adenoma X 

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

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

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

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 107 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 0 0 1 1 1 1 1 1 2 2 2 2 2 3 3 3 4 4 4 4 4 4 4 4 5 Tissues/ 

5 8 1 3 4 5 7 9 2 3 4 6 7 0 5 9 0 1 4 5 6 7 8 9 0 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + M + + + + + + + + + + + + + + 49 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocellular adenoma X 1 

Mesentery + + + + + + + + + + 15 

Oral mucosa 1 

Pharyngeal, squamous cell papilloma 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Tongue 1 

Tooth 1 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 2 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma malignant X 1 

Pheochromocytoma benign X 4 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma X 1 

Parathyroid gland + + + + + + + + + M + + + + + + + + + + + + M + + 46 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X X X X 38 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

C-cell, adenoma X X X 7 

C-cell, carcinoma 1 

General Body System 

None 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + M 44 

Adenoma X X X 3 

Carcinoma X X 3 

Bilateral, adenoma 1 

Ovary	 + + + + + + + + + + + + + + + + + + + + + + + + + 50 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

108 Furfuryl Alcohol, NTP TR 482 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

0 4 4 4 4 5 5 5 5 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 

Number of Days on Study 9 5 7 7 7 7 8 8 9 0 0 0 1 2 3 5 6 7 9 0 0 0 0 2 3 

8 6 0 7 8 3 1 1 9 4 9 9 6 7 1 2 1 3 3 7 7 7 7 1 5 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

Carcass ID Number 3 3 0 2 2 0 0 1 3 4 2 3 0 1 0 3 2 3 0 1 2 3 4 1 0 

4 3 6 1 0 7 3 6 8 3 8 2 9 8 2 1 9 7 4 2 5 6 2 0 1 

Genital System (continued) 

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

Adenoma 

Polyp stromal X X 

Polyp stromal, multiple 

Schwannoma malignant X 

Hematopoietic System 

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

Lymph node + + + 

Lymph node, bronchial + + + M M M M + M + + M + M + + + + M + + + M + + 

Carcinoma, metastatic, thyroid gland X 

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

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

Lymph node, mediastinal + M + + + + + M + + + + + + + + M + + + M + M + + 

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

Hemangiosarcoma 

Sarcoma X 

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

Integumentary System 

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

Adenoma 

Carcinoma X X 

Carcinoma, multiple X X 

Fibroadenoma X X X X X X X 

Fibroadenoma, multiple X X 

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

Keratoacanthoma 

Musculoskeletal System 

Bone 

Fibroma 

+ + + 

X 

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

Nervous System 

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

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 

Carcinoma, metastatic, thyroid gland X 

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

Alveolar/bronchiolar adenoma 

Carcinoma, metastatic, thyroid gland X 

Nose + + + + + + + + + + + + + + + + + + + + + + + A + 

Trachea + + + + + + + + + + + + + + + + + + + + + + + A + 

Special Senses System 

Eye 

Urinary System 

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

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + I + 

Systemic Lesions 

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

Leukemia mononuclear X X X X X X X X X X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 109 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 0 0 1 1 1 1 1 1 2 2 2 2 2 3 3 3 4 4 4 4 4 4 4 4 5 Tissues/ 

5 8 1 3 4 5 7 9 2 3 4 6 7 0 5 9 0 1 4 5 6 7 8 9 0 Tumors 

Genital System (continued) 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Polyp stromal X X X 5 

Polyp stromal, multiple X 1 

Schwannoma malignant X 2 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lymph node + 4 

Lymph node, bronchial + + + + + + + + + + + + M + + + M + M + + + + M + 37 

Carcinoma, metastatic, thyroid gland 1 

Lymph node, mandibular + + + + + + + + + + + + + + M + + + + + + + + M + 46 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node, mediastinal + + + + + + + + + + M + + + + + + + + + M + + + + 43 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hemangiosarcoma X 1 

Sarcoma 1 

Thymus + + + + + M + + + + + + + + + M + + + + + + + M + 47 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 1 

Carcinoma X X X X X 7 

Carcinoma, multiple 2 

Fibroadenoma X X X X X X X X X X 17 

Fibroadenoma, multiple 2 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Keratoacanthoma X 1 

Musculoskeletal System 

Bone 

Fibroma

+ + + + + + + + + + + + + + + + + + + + + + + + + 50 

1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, thyroid gland 1 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar adenoma X 1 

Carcinoma, metastatic, thyroid gland 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Special Senses System 

Eye	 +

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Leukemia mononuclear X X X X X X X 21 

 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

110 Furfuryl Alcohol, NTP TR 482 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

4 4 4 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 

Number of Days on Study 2 6 9 0 3 4 7 8 0 2 3 5 5 7 7 7 9 9 0 0 1 2 2 3 3 

8 9 7 6 5 7 1 1 3 8 7 1 1 6 7 9 0 3 7 8 6 1 7 2 5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

Carcass ID Number 3 0 1 4 4 3 0 1 2 4 1 0 4 3 0 0 3 2 4 1 3 4 0 1 0 

6 7 1 0 7 4 4 2 7 1 9 9 5 5 8 6 1 0 9 7 3 8 1 5 2 

Alimentary System 

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

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

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

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

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

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

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

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

Histiocytic sarcoma X 

Mesentery + + + + 

Carcinoma, metastatic, kidney X 

Oral mucosa 

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

Carcinoma, metastatic, kidney X 

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

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

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

Tongue + + 

Squamous cell carcinoma X 

Squamous cell papilloma 

Cardiovascular System 

Blood vessel + 

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

Endocrine System 

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

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

Pheochromocytoma complex X 

Pheochromocytoma benign X 

Bilateral, pheochromocytoma benign X 

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

Carcinoma X 

Parathyroid gland + + + M + + M + + + + + + + + + + + + M + + + + + 

Pituitary gland + + + + + + A + + + + + + + + + + + + + + + + + + 

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

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

C-cell, adenoma X X X 

C-cell, carcinoma X 

Follicular cell, carcinoma 

General Body System 

None 

Genital System 

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

Adenoma X 

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

Granulosa cell tumor benign X 

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

Polyp stromal X X X X 

Schwannoma malignant X 

Vagina + 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 111 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 0 0 1 1 1 1 1 2 2 2 2 2 2 2 2 3 3 3 3 3 4 4 4 4 5 Tissues/ 

3 5 0 3 4 6 8 1 2 3 4 5 6 8 9 0 2 7 8 9 2 3 4 6 0 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, colon + + + + + + + + + + + + + + + + + + M + + + + + + 47 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Histiocytic sarcoma 1 

Mesentery + + + + 8 

Carcinoma, metastatic, kidney 1 

Oral mucosa + 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Carcinoma, metastatic, kidney 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Tongue + + 4 

Squamous cell carcinoma 1 

Squamous cell papilloma X X 2 

Cardiovascular System 

Blood vessel 1 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma complex 1 

Pheochromocytoma benign X X X X 5 

Bilateral, pheochromocytoma benign X 2 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Carcinoma 1 

Parathyroid gland + + + + + + M + + + + + + + + M + + + M + + M + + 43 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X X X 35 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

C-cell, adenoma X X 5 

C-cell, carcinoma 1 

Follicular cell, carcinoma X X 2 

General Body System 

None 

Genital System 

Clitoral gland + + + + + + + M + + + + + + + + + M + + + + + + M 45 

Adenoma X 2 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Granulosa cell tumor benign 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Polyp stromal X X X X X 9 

Schwannoma malignant 1 

Vagina 1 
 

 

 

 

 

 

 

 

 

112 Furfuryl Alcohol, NTP TR 482 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

4 4 4 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 

Number of Days on Study 2 6 9 0 3 4 7 8 0 2 3 5 5 7 7 7 9 9 0 0 1 2 2 3 3 

8 9 7 6 5 7 1 1 3 8 7 1 1 6 7 9 0 3 7 8 6 1 7 2 5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

Carcass ID Number 3 0 1 4 4 3 0 1 2 4 1 0 4 3 0 0 3 2 4 1 3 4 0 1 0 

6 7 1 0 7 4 4 2 7 1 9 9 5 5 8 6 1 0 9 7 3 8 1 5 2 

Hematopoietic System 

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

Lymph node + + + + 

Lymph node, bronchial M + + + + + + M + + M + + + + M M M + + + + M + M 

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

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

Carcinoma, metastatic, kidney X 

Lymph node, mediastinal M + + + M + M + M + + + + + + M + + + + + + M + + 

Carcinoma, metastatic, kidney X 

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

Thymus + + + + + + + + + + + + + M + + + M M M + + + + + 

Integumentary System 

Mammary gland + + + M + + + + + + + + + + + + + + + + + + + + + 

Carcinoma X X 

Fibroadenoma X X X X X 

Fibroadenoma, multiple X X 

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

Keratoacanthoma 

Musculoskeletal System 

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

Nervous System 

Brain 

Astrocytoma malignant 

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

Respiratory System 

Larynx + + + + + + A + + + + + + + + + + + + + + + + + + 

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

Carcinoma, metastatic, mammary gland X 

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

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

Special Senses System 

Zymbal’s gland 

Urinary System 

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

Renal tubule, carcinoma X 

Urinary bladder + + + + + + + + + + + + + + I + + + + + + + + + + 

Transitional epithelium, carcinoma X 

Systemic Lesions 

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

Histiocytic sarcoma X 

Leukemia mononuclear X X X X X X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 113 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 0 0 1 1 1 1 1 2 2 2 2 2 2 2 2 3 3 3 3 3 4 4 4 4 5 Tissues/ 

3 5 0 3 4 6 8 1 2 3 4 5 6 8 9 0 2 7 8 9 2 3 4 6 0 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Lymph node + 5 

Lymph node, bronchial + M M M + M + + + M + + + M M M + + + + M M M M + 30 

Lymph node, mandibular + + M + + + + + + + + + + + + + + + + + + + + + + 46 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, kidney 1 

Lymph node, mediastinal + M + M + M + + + + + M + + M + + M + + M + + + + 37 

Carcinoma, metastatic, kidney 1 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Thymus + + + + + M + + + + + + + M + + + + + + + + + + + 44 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Carcinoma 2 

Fibroadenoma X X X X X X X X X X X X 17 

Fibroadenoma, multiple X X X X X 7 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Keratoacanthoma X X 2 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Nervous System 

Brain 

Astrocytoma malignant 

+ + + + + + + + + 

X

+ + + + + + + + + + + + + + + + 50 

1 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, mammary gland 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Zymbal’s gland +

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Renal tubule, carcinoma 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Transitional epithelium, carcinoma 1 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Leukemia mononuclear X X X X X X X X X 19 

 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

114 Furfuryl Alcohol, NTP TR 482 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 7 

Number of Days on Study 1 2 4 4 4 6 8 9 0 0 1 2 2 2 3 5 5 7 7 7 9 9 9 0 

8 2 6 7 7 3 9 5 6 9 6 3 7 8 9 2 8 0 9 9 3 4 4 0 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

Carcass ID Number 1 2 3 2 2 0 3 5 2 0 4 1 0 1 0 1 1 2 3 4 2 2 3 1 

8 4 0 1 2 7 6 0 7 6 2 0 9 3 2 4 9 3 9 0 8 6 3 5 

Alimentary System 

Esophagus + + + + + + + + + + + + + M + + + + + + + + + + 

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

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

Fibroma 

Leiomyosarcoma X 

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

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

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

Adenocarcinoma 

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

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

Osteosarcoma, metastatic, bone X X 

Mesentery + + + 

Oral mucosa 

Pancreas + + + + + + + + + M + + + + + + + + + + + + + + 

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

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

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

Tongue + 

Cardiovascular System 

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

Endocrine System 

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

Osteosarcoma, metastatic, bone X 

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

Pheochromocytoma benign X 

Bilateral, pheochromocytoma benign X 

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

Adenoma 

Carcinoma 

Parathyroid gland + + + + + M + + + + + M + + + + + + + + + + + + 

Pituitary gland + + + + + + + + + + + + + + + + + A + + + + + + 

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

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

C-cell, adenoma X X X 

C-cell, carcinoma X 

Follicular cell, carcinoma 

General Body System 

None 

Genital System 

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

Adenoma X 

Carcinoma X 

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

Granulosa cell tumor benign X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 115 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 1 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 9 2 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 Total 

Carcass ID Number 1 4 3 0 0 0 0 0 1 1 1 2 2 2 3 3 3 3 3 4 4 4 4 4 4 Tissues/ 

7 1 4 1 3 4 5 8 1 2 6 0 5 9 1 2 5 7 8 3 4 5 7 8 9 Tumors 

Alimentary System 

Esophagus + + + + + + + + + M + + + + + + M + + + M + + + + 45 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Fibroma X 1 

Leiomyosarcoma 1 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Adenocarcinoma X 1 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Osteosarcoma, metastatic, bone 2 

Mesentery + + + + + + + + 11 

Oral mucosa + 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Tongue 1 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Osteosarcoma, metastatic, bone 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Pheochromocytoma benign X 2 

Bilateral, pheochromocytoma benign X 2 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Adenoma X X X 3 

Carcinoma X 1 

Parathyroid gland + + + + + + + + + M + + M + + + + + + + M + + + + 44 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X X X X 34 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 47 

C-cell, adenoma X X X 6 

C-cell, carcinoma X 2 

Follicular cell, carcinoma X 1 

General Body System 

None 

Genital System 

Clitoral gland + + M + + + + + + M + + + + + + + + + + + + + + + 46 

Adenoma X 2 

Carcinoma X 2 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Granulosa cell tumor benign 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

116 Furfuryl Alcohol, NTP TR 482 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

Number of Days on Study 

5 

1 

8 

5 

2 

2 

5 

4 

6 

5 

4 

7 

5 

4 

7 

5 

6 

3 

5 

8 

9 

5 

9 

5 

6 

0 

6 

6 

0 

9 

6 

1 

6 

6 

2 

3 

6 

2 

7 

6 

2 

8 

6 

3 

9 

6 

5 

2 

6 

5 

8 

6 

7 

0 

6 

7 

9 

6 

7 

9 

6 

9 

3 

6 

9 

4 

6 

9 

4 

7 

0 

0 

Carcass ID Number 

5 

1 

8 

5 

2 

4 

5 

3 

0 

5 

2 

1 

5 

2 

2 

5 

0 

7 

5 

3 

6 

5 

5 

0 

5 

2 

7 

5 

0 

6 

5 

4 

2 

5 

1 

0 

5 

0 

9 

5 

1 

3 

5 

0 

2 

5 

1 

4 

5 

1 

9 

5 

2 

3 

5 

3 

9 

5 

4 

0 

5 

2 

8 

5 

2 

6 

5 

3 

3 

5 

1 

5 

Genital System (continued) 

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

Leiomyosarcoma, metastatic, intestine large, rectum X 

Polyp stromal X 

Vagina + + 

Leiomyosarcoma, metastatic, intestine large, rectum X 

Polyp X 

Hematopoietic System 

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

Lymph node + + + + + 

Lymph node, bronchial + + + + + + + M M + + + + + + M + + + + + + + M 

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

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

Lymph node, mediastinal + + + + + M + + + + + + M + + + + + + + + + + + 

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

Osteosarcoma, metastatic, bone X 

Thymus + + + + + + + + M + + + + + + M M + + + + + + + 

Integumentary System 

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

Carcinoma X 

Fibroadenoma X X X X X X X X X 

Fibroadenoma, multiple X 

Skin + I + + + + + + + + + + + + + + + + + + + + + + 

Subcutaneous tissue, fibroma X 

Musculoskeletal System 

Bone 

Osteosarcoma 

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

X 

+ 

X 

+ + + + + + + + + 

Nervous System 

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

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + 

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

Alveolar/bronchiolar carcinoma 

Osteosarcoma, metastatic, bone X X 

Mediastinum, osteosarcoma, metastatic, bone X 

Nose + + + + + A + + + + + + + + + + + + + + + + + + 

Lateral wall, adenoma X 

Trachea + + + + + A + + + + + + + + + + + + + + + + + + 

Special Senses System 

Eye + 

Urinary System 

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

Transitional epithelium, carcinoma 

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

Leiomyosarcoma, metastatic, intestine large, rectum X 

Systemic Lesions 

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

Leukemia mononuclear X X X X X X X X X X X X 

Lymphoma malignant X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 117 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 1 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 9 2 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 Total 

Carcass ID Number 1 4 3 0 0 0 0 0 1 1 1 2 2 2 3 3 3 3 3 4 4 4 4 4 4 Tissues/ 

7 1 4 1 3 4 5 8 1 2 6 0 5 9 1 2 5 7 8 3 4 5 7 8 9 Tumors 

Genital System (continued) 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Leiomyosarcoma, metastatic, intestine large, rectum 1 

Polyp stromal X X X X X 6 

Vagina + 3 

Leiomyosarcoma, metastatic, intestine large, rectum 1 

Polyp 1 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Lymph node + + + 8 

Lymph node, bronchial + M + + + + + M + + + + M + M + + + + + + M + + + 40 

Lymph node, mandibular M + + + + + + + + + + + + + + + + + + + + M + + + 46 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lymph node, mediastinal + + + + + + + + + + + + + + M + + + + M + + + + + 45 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Osteosarcoma, metastatic, bone 1 

Thymus + + + + + + + + + + + + + + + + M + + + + + + M + 44 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Carcinoma X 2 

Fibroadenoma X X X X X X X X X X 19 

Fibroadenoma, multiple X X X X X 6 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Subcutaneous tissue, fibroma X X 3 

Musculoskeletal System 

Bone 

Osteosarcoma

+ + + + + + + + + + + + + + + + + + + + + + + + + 49 

2 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Alveolar/bronchiolar carcinoma X 1 

Osteosarcoma, metastatic, bone 2 

Mediastinum, osteosarcoma, metastatic, bone 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Lateral wall, adenoma 1 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Special Senses System 

Eye 1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Transitional epithelium, carcinoma X 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Leiomyosarcoma, metastatic, intestine large, rectum 1 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Leukemia mononuclear X X X X X X 18 

Lymphoma malignant 1 
 

 

 

 

 

 

 

 

 

 

 

 

118 Furfuryl Alcohol, NTP TR 482 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

3 4 4 4 4 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 

Number of Days on Study 0 2 3 7 9 1 1 2 2 6 8 9 9 1 2 3 3 3 4 5 6 7 7 8 8 

2 9 8 8 7 8 8 5 6 0 1 7 9 6 1 2 8 9 2 8 5 0 1 6 9 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Carcass ID Number 3 3 0 4 2 1 1 1 4 4 2 2 2 3 3 4 3 3 2 5 2 0 4 1 3 

4 2 8 2 8 1 4 9 7 4 9 6 7 1 8 6 9 7 1 0 0 5 3 5 6 

Alimentary System 

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

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

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

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

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

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

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

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

Histiocytic sarcoma X 

Mesentery + + + + 

Sarcoma stromal, metastatic, uterus X 

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

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

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

Leiomyosarcoma 

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

Tongue + + 

Squamous cell carcinoma X 

Squamous cell papilloma 

Tooth + 

Cardiovascular System 

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

Endocrine System 

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

Adenoma X 

Histiocytic sarcoma X 

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

Histiocytic sarcoma X 

Pheochromocytoma benign X X 

Bilateral, pheochromocytoma benign 

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

Parathyroid gland + + + M + + + + + + + + + M + + + M + + M + + + + 

Adenoma 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

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

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

C-cell, adenoma X X 

Follicular cell, adenoma 

General Body System 

None 

Genital System 

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

Adenoma X X X X 

Carcinoma 

Bilateral, carcinoma 

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

Sertoli cell tumor benign 

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

Polyp stromal X 

Sarcoma stromal X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 119 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 9 0 0 1 1 1 1 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

3 6 7 1 2 2 5 1 3 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 Total 

Carcass ID Number 3 4 0 1 1 1 0 4 0 0 0 0 0 1 1 1 2 2 2 2 3 3 4 4 4 Tissues/ 

5 8 6 8 2 3 2 5 3 1 4 7 9 0 6 7 2 3 4 5 0 3 0 1 9 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Mesentery + + + 7 

Sarcoma stromal, metastatic, uterus 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Leiomyosarcoma X 1 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Tongue + 3 

Squamous cell carcinoma 1 

Squamous cell papilloma X 1 

Tooth 1 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 2 

Histiocytic sarcoma 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Pheochromocytoma benign X X X 5 

Bilateral, pheochromocytoma benign X X 2 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Adenoma X 1 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X X X X 35 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 48 

C-cell, adenoma X X X 5 

Follicular cell, adenoma X 1 

General Body System 

None 

Genital System 

Clitoral gland + + + + + + + M + + + + + + + + M + + + + + + + M 45 

Adenoma X X X 7 

Carcinoma X 1 

Bilateral, carcinoma X 1 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Sertoli cell tumor benign X 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Polyp stromal X 2 

Sarcoma stromal 2 
 

 

 

 

 

 

 

 

 

 

 

 

120 Furfuryl Alcohol, NTP TR 482 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

3 4 4 4 4 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 

Number of Days on Study 0 2 3 7 9 1 1 2 2 6 8 9 9 1 2 3 3 3 4 5 6 7 7 8 8 

2 9 8 8 7 8 8 5 6 0 1 7 9 6 1 2 8 9 2 8 5 0 1 6 9 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Carcass ID Number 3 3 0 4 2 1 1 1 4 4 2 2 2 3 3 4 3 3 2 5 2 0 4 1 3 

4 2 8 2 8 1 4 9 7 4 9 6 7 1 8 6 9 7 1 0 0 5 3 5 6 

Hematopoietic System 

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

Lymph node + + + + 

Lymph node, bronchial + M + + + + M M + + + M + + + M M + M + + M M M M 

Histiocytic sarcoma X 

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

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

Lymph node, mediastinal M M + M + + M M + + + + + + + M + + + + + + + + + 

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

Histiocytic sarcoma X 

Thymus + + + + + + M M + M + + + + + + + + + M + + + + + 

Integumentary System 

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

Carcinoma X X 

Carcinoma, multiple 

Fibroadenoma X X X X X 

Fibroadenoma, multiple 

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

Squamous cell papilloma 

Subcutaneous tissue, fibroma 

Musculoskeletal System 

Bone 

Osteosarcoma 

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

Nervous System 

Brain 

Histiocytic sarcoma 

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

X 

+ + + + 

Respiratory System 

Larynx + + + + + A + + + + + + + + + + + + + + + + + + + 

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

Histiocytic sarcoma X 

Nose + + + + + A + + + + + + + + + + + + + + + + + + + 

Respiratory epithelium, adenoma 

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

Special Senses System 

Eye + 

Urinary System 

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

Histiocytic sarcoma X 

Renal tubule, adenoma X 

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

Systemic Lesions 

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

Histiocytic sarcoma X 

Leukemia mononuclear X X X X X X X X X X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 121 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 9 0 0 1 1 1 1 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

3 6 7 1 2 2 5 1 3 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 Total 

Carcass ID Number 3 4 0 1 1 1 0 4 0 0 0 0 0 1 1 1 2 2 2 2 3 3 4 4 4 Tissues/ 

5 8 6 8 2 3 2 5 3 1 4 7 9 0 6 7 2 3 4 5 0 3 0 1 9 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node + + + + + + + 11 

Lymph node, bronchial M M + M + M M M M M + + + + M + M M + + M + M + M 25 

Histiocytic sarcoma 1 

Lymph node, mandibular + M M + + + + + M + M + + + + + + M + + + + + + + 42 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node, mediastinal + + + + + + + + M + M + + + + + + + + M + + M + + 40 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Thymus + M + + + + + + M + + + + + + + + + + M + + + + + 43 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma X X X 5 

Carcinoma, multiple X 1 

Fibroadenoma X X X X X X X X X 14 

Fibroadenoma, multiple X X X X X X 6 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Squamous cell papilloma X 1 

Subcutaneous tissue, fibroma X X 2 

Musculoskeletal System 

Bone 

Osteosarcoma 

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

X

+ + + + + 50 

1 

Nervous System 

Brain 

Histiocytic sarcoma

+ + + + + + + + + + + + + + + + + + + + + + + + + 50 

1 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Respiratory epithelium, adenoma X 1 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Eye 1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Renal tubule, adenoma X 2 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Leukemia mononuclear X X X X X X X X X X X X X X X 29 
122 Furfuryl Alcohol, NTP TR 482 

TABLE B3 

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Adrenal Medulla: Benign Pheochromocytoma a Overall rate 4/50 (8%) 7/50 (14%) 4/48 (8%) 7/50 (14%) 

Adjusted rateb 9.9% 16.7% 10.2% 18.6% c Terminal rate 1/26 (4%) 5/26 (19%) 1/22 (5%) 3/16 (19%) 

First incidence (days) 707 693 679 670 

Poly-3 testd P=0.260 P=0.278 P=0.629 P=0.217 

Adrenal Medulla: Benign, Complex, or Malignant Pheochromocytoma 

Overall rate 5/50 (10%) 8/50 (16%) 4/48 (8%) 7/50 (14%)
 

Adjusted rate 12.4% 18.9% 10.2% 18.6%
 

Terminal rate 2/26 (8%) 5/26 (19%) 1/22 (5%) 3/16 (19%)
 

First incidence (days) 707 571 679 670
 

Poly-3 test P=0.378 P=0.304 P=0.518N P=0.327 

Clitoral Gland: Adenoma 

Overall rate 4/44 (9%) 2/45 (4%) 2/46 (4%) 7/45 (16%)
 

Adjusted rate 11.3% 5.3% 5.3% 20.1%
 

Terminal rate 3/24 (13%) 1/23 (4%) 1/21 (5%) 2/14 (14%)
 

First incidence (days) 693 679 627 518
 

Poly-3 test P=0.044 P=0.302N P=0.307N P=0.246 

Clitoral Gland: Carcinoma 

Overall rate 3/44 (7%) 0/45 (0%) 2/46 (4%) 2/45 (4%) 

Adjusted rate 8.5% 0.0% 5.3% 6.0% 

Terminal rate 2/24 (8%) 0/23 (0%) 1/21 (5%) 2/14 (14%) e First incidence (days) 707 — 522 735 (T) 

Poly-3 test P=0.514 P=0.105N P=0.468N P=0.529N 

Clitoral Gland: Adenoma or Carcinoma 

Overall rate 7/44 (16%) 2/45 (4%) 4/46 (9%) 9/45 (20%)
 

Adjusted rate 19.8% 5.3% 10.5% 25.9%
 

Terminal rate 5/24 (21%) 1/23 (4%) 2/21 (10%) 4/14 (29%)
 

First incidence (days) 693 679 522 518
 

Poly-3 test P=0.052 P=0.059N P=0.214N P=0.372 

Mammary Gland: Fibroadenoma 

Overall rate 19/50 (38%) 24/50 (48%) 25/49 (51%) 20/50 (40%)
 

Adjusted rate 45.5% 54.7% 57.5% 50.4%
 

Terminal rate 11/26 (42%) 17/26 (65%) 13/22 (59%) 10/16 (63%)
 

First incidence (days) 627 497 546 497
 

Poly-3 test P=0.556N P=0.254 P=0.176 P=0.407 

Mammary Gland: Fibroadenoma or Adenoma 

Overall rate 20/50 (40%) 24/50 (48%) 25/49 (51%) 20/50 (40%)
 

Adjusted rate 47.9% 54.7% 57.5% 50.4%
 

Terminal rate 12/26 (46%) 17/26 (65%) 13/22 (59%) 10/16 (63%)
 

First incidence (days) 627 497 546 497
 

Poly-3 test P=0.506N P=0.333 P=0.242 P=0.496 

Mammary Gland: Carcinoma 

Overall rate 9/50 (18%) 2/50 (4%) 2/49 (4%) 6/50 (12%)
 

Adjusted rate 22.1% 4.7% 5.0% 15.7%
 

Terminal rate 5/26 (19%) 0/26 (0%) 1/22 (5%) 2/16 (13%)
 

First incidence (days) 661 497 679 518
 

Poly-3 test P=0.433 P=0.019N P=0.025N P=0.332N
 
Furfuryl Alcohol, NTP TR 482 123 

TABLE B3 

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Mammary Gland: Adenoma or Carcinoma 

Overall rate 10/50 (20%) 2/50 (4%) 2/49 (4%) 6/50 (12%)
 

Adjusted rate 24.6% 4.7% 5.0% 15.7%
 

Terminal rate 6/26 (23%) 0/26 (0%) 1/22 (5%) 2/16 (13%)
 

First incidence (days) 661 497 679 518
 

Poly-3 test P=0.510 P=0.010N P=0.013N P=0.243N
 

Mammary Gland: Fibroadenoma, Adenoma, or Carcinoma 

Overall rate 25/50 (50%) 25/50 (50%) 26/49 (53%) 23/50 (46%)
 

Adjusted rate 59.2% 56.7% 59.5% 56.8%
 

Terminal rate 15/26 (58%) 17/26 (65%) 13/22 (59%) 11/16 (69%)
 

First incidence (days) 627 497 546 497
 

Poly-3 test P=0.498N P=0.494N P=0.578 P=0.500N
 

Oral Cavity (Oral Mucosa or Tongue): Squamous Cell Papilloma or Squamous Cell Carcinoma 

Overall rate 1/50 (2%) 3/50 (6%) 0/49 (0%) 2/50 (4%) 

Adjusted rate 2.4% 7.1% 0.0% 5.3% 

Terminal rate 0/26 (0%) 2/26 (8%) 0/22 (0%) 0/16 (0%) 

First incidence (days) 478 469 — 639 

Poly-3 test P=0.535 P=0.318 P=0.506N P=0.471 

Pancreatic Islets: Adenoma 

Overall rate 1/49 (2%) 0/48 (0%) 3/48 (6%) 0/50 (0%)
 

Adjusted rate 2.6% 0.0% 7.7% 0.0%
 

Terminal rate 1/26 (4%) 0/26 (0%) 3/22 (14%) 0/16 (0%)
 

First incidence (days) 735 (T) — 735 (T) —
 

Poly-3 test P=0.442N P=0.494N P=0.304 P=0.511N
 

Pancreatic Islets: Adenoma or Carcinoma 

Overall rate 1/49 (2%) 1/48 (2%) 4/48 (8%) 0/50 (0%)
 

Adjusted rate 2.6% 2.5% 10.2% 0.0%
 

Terminal rate 1/26 (4%) 0/26 (0%) 4/22 (18%) 0/16 (0%)
 

First incidence (days) 735 (T) 732 735 (T) —
 

Poly-3 test P=0.325N P=0.754N P=0.176 P=0.511N
 

Pituitary Gland (Pars Distalis): Adenoma 

Overall rate 38/50 (76%) 35/49 (71%) 34/48 (71%) 35/50 (70%)
 

Adjusted rate 82.4% 75.7% 76.4% 79.6%
 

Terminal rate 21/26 (81%) 20/26 (77%) 17/22 (77%) 12/16 (75%)
 

First incidence (days) 477 469 546 478
 

Poly-3 test P=0.545 P=0.285N P=0.315N P=0.466N
 

Skin (Subcutaneous Tissue): Fibroma 

Overall rate 0/50 (0%) 0/50 (0%) 3/49 (6%) 2/50 (4%) 

Adjusted rate 0.0% 0.0% 7.5% 5.4% 

Terminal rate 0/26 (0%) 0/26 (0%) 2/22 (9%) 0/16 (0%) 

First incidence (days) — — 694 711 

Poly-3 test P=0.168 —f P=0.116 P=0.220 

Thyroid Gland (C-cell): Adenoma 

Overall rate 7/49 (14%) 5/49 (10%) 6/47 (13%) 5/48 (10%)
 

Adjusted rate 17.2% 12.0% 15.2% 13.5%
 

Terminal rate 3/26 (12%) 2/26 (8%) 3/22 (14%) 2/16 (13%)
 

First incidence (days) 477 679 547 438
 

Poly-3 test P=0.500N P=0.364N P=0.526N P=0.443N
 
124 Furfuryl Alcohol, NTP TR 482 

TABLE B3 

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Thyroid Gland (C-cell): Adenoma or Carcinoma 

Overall rate 8/49 (16%) 6/49 (12%) 8/47 (17%) 5/48 (10%)
 

Adjusted rate 19.4% 14.4% 20.1% 13.5%
 

Terminal rate 3/26 (12%) 2/26 (8%) 4/22 (18%) 2/16 (13%)
 

First incidence (days) 477 677 547 438
 

Poly-3 test P=0.367N P=0.374N P=0.582 P=0.342N
 

Tongue: Squamous Cell Papilloma or Squamous Cell Carcinoma 

Overall rate 0/50 (0%) 3/50 (6%) 0/49 (0%) 2/50 (4%) 

Adjusted rate 0.0% 7.1% 0.0% 5.3% 

Terminal rate 0/26 (0%) 2/26 (8%) 0/22 (0%) 0/16 (0%) 

First incidence (days) — 469 — 639 

Poly-3 test P=0.403 P=0.128 — P=0.222 

Uterus: Stromal Polyp 

Overall rate 6/50 (12%) 9/50 (18%) 6/49 (12%) 2/50 (4%) 

Adjusted rate 14.7% 21.2% 14.9% 5.3% 

Terminal rate 4/26 (15%) 5/26 (19%) 5/22 (23%) 0/16 (0%) 

First incidence (days) 581 637 547 599 

Poly-3 test P=0.058N P=0.314 P=0.612 P=0.158N 

Uterus: Stromal Polyp or Stromal Sarcoma 

Overall rate 6/50 (12%) 9/50 (18%) 6/49 (12%) 4/50 (8%) 

Adjusted rate 14.7% 21.2% 14.9% 10.2% 

Terminal rate 4/26 (15%) 5/26 (19%) 5/22 (23%) 0/16 (0%) 

First incidence (days) 581 637 547 429 

Poly-3 test P=0.200N P=0.314 P=0.612 P=0.397N 

All Organs: Mononuclear Cell Leukemia 

Overall rate 21/50 (42%) 19/50 (38%) 18/49 (37%) 29/50 (58%)
 

Adjusted rate 46.7% 44.0% 41.2% 66.3%
 

Terminal rate 8/26 (31%) 9/26 (35%) 5/22 (23%) 12/16 (75%)
 

First incidence (days) 456 628 518 438
 

Poly-3 test P=0.011 P=0.484N P=0.375N P=0.043
 

All Organs: Benign Neoplasms 

Overall rate 48/50 (96%) 47/50 (94%) 46/49 (94%) 43/50 (86%)
 

Adjusted rate 99.5% 96.6% 96.7% 93.8%
 

Terminal rate 26/26 (100%) 25/26 (96%) 22/22 (100%) 16/16 (100%)
 

First incidence (days) 470 469 546 438
 

Poly-3 test P=0.113N P=0.358N P=0.376N P=0.092N
 

All Organs: Malignant Neoplasms 

Overall rate 31/50 (62%) 28/50 (56%) 32/49 (65%) 36/50 (72%)
 

Adjusted rate 67.6% 59.2% 68.5% 77.8%
 

Terminal rate 15/26 (58%) 10/26 (39%) 12/22 (55%) 13/16 (81%)
 

First incidence (days) 456 428 518 429
 

Poly-3 test P=0.058 P=0.262N P=0.553 P=0.181 
125 

c 

Furfuryl Alcohol, NTP TR 482 

TABLE B3 

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

All Organs: Benign or Malignant Neoplasms 

Overall rate 49/50 (98%) 49/50 (98%) 49/49 (100%) 49/50 (98%) 

Adjusted rate 100.0% 98.0% 100.0% 99.9% 

Terminal rate 26/26 (100%) 25/26 (96%) 22/22 (100%) 16/16 (100%) 

First incidence (days) 456 428 518 429 

Poly-3 test P=0.649 P=0.505N P=1.000 P=1.000N 

(T)Terminal sacrifice 

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for adrenal gland, clitoral gland, 

pancreatic islets, pituitary gland, thyroid gland, and uterus; for other tissues, denominator is number of animals necropsied. b Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality 

Observed incidence at terminal kill 

d	 Beneath the chamber control incidence are the P values associated with the trend test. Beneath the exposed group incidence are the P values corresponding to 

pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for differential mortality in animals that do not reach terminal 

sacrifice. A negative trend or a lower incidence in an exposure group is indicated by N. e Not applicable; no neoplasms in animal group f Value of statistic cannot be computed. 
126 Furfuryl Alcohol, NTP TR 482 

TABLE B4a 

Historical Incidence of Nasal Adenoma in Chamber Control Female F344/N Ratsa 

Study Incidence in Controls 

Historical Incidence at Battelle Pacific Northwest Laboratories 

Acetonitrile 0/47 

"-Chloroacetophenone 0/48 

Cobalt Sulfate Heptahydrate 0/50 

Epinephrine Hydrochloride 1/50 

Hexachlorocyclopentadiene 0/50 

Isobutyraldehyde 0/49 

Molybdenum Trioxide 0/48 

Nitromethane 0/50 

o-Chlorobenzalmalononitrile 0/49 

Ozone 0/50 

Tetrafluoroethylene 0/50 

Tetrahydrofuran 0/49 

Overall Historical Incidence 

Total 1/892 (0.1%) 

Standard deviation 0.5% 

Range 0%-2% 

a Data as of 15 October 1996 

TABLE B4b 

Historical Incidence of Renal Tubule Neoplasms in Chamber Control Female F344/N Ratsa 

Incidence in Controls 

Study Adenoma Carcinoma Adenoma or 

Carcinoma 

Historical Incidence at Battelle Pacific Northwest Laboratories 

Acetonitrile 0/48 0/48 0/48 

"-Chloroacetophenone 0/49 0/49 0/49 

Cobalt Sulfate Heptahydrate 0/49 1/49 1/49 

Epinephrine Hydrochloride 0/50 0/50 0/50 

Hexachlorocyclopentadiene 0/50 1/50 1/50 

Isobutyraldehyde 0/49 0/49 0/49 

Molybdenum Trioxide 0/50 0/50 0/50 

Nitromethane 0/50 1/50 1/50 

o-Chlorobenzalmalononitrile 0/49 0/49 0/49 

Ozone 1/50 0/50 1/50 

Tetrafluoroethylene 0/50 0/50 0/50 

Tetrahydrofuran 0/50 1/50 1/50 

Overall Historical Incidence 

Total 1/898 (0.1%) 4/898 (0.5%) 5/898 (0.6%) 

Standard deviation 0.5% 0.9% 0.9% 

Range 0%-2% 0%-2% 0%-2% 

a Data as of 15 October 1996 
 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 127 

TABLE B5 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohola 

Chamber Control 2 ppm 8 ppm 32 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 23 21 24 32 

Natural deaths 1 3 3 2 

Survivors 

Died last week of study 1 

Terminal sacrifice 26 25 22 16 

Pregnant 1 

Animals examined microscopically 50 50 49 50 

Alimentary System 

Intestine large, colon (50) (47) (48) (48) 

Parasite metazoan 2 (4%) 3 (6%) 2 (4%) 3 (6%) 

Intestine large, rectum (50) (47) (47) (49) 

Parasite metazoan 4 (8%) 3 (6%) 3 (6%) 3 (6%) 

Intestine large, cecum (49) (47) (46) (48) 

Parasite metazoan 5 (10%) 4 (9%) 8 (17%) 4 (8%) 

Intestine small, ileum (49) (47) (46) (48) 

Parasite metazoan 1 (2%) 

Liver (50) (49) (49) (50) 

Angiectasis 3 (6%) 2 (4%) 3 (6%) 5 (10%) 

Basophilic focus 30 (60%) 31 (63%) 34 (69%) 22 (44%) 

Clear cell focus 5 (10%) 6 (12%) 6 (12%) 3 (6%) 

Cyst 1 (2%) 

Degeneration, cystic 1 (2%) 1 (2%) 

Degeneration, fatty 13 (26%) 9 (18%) 10 (20%) 17 (34%) 

Eosinophilic focus 3 (6%) 2 (4%) 4 (8%) 1 (2%) 

Hematopoietic cell proliferation 1 (2%) 

Hepatodiaphragmatic nodule 4 (8%) 7 (14%) 6 (12%) 4 (8%) 

Infiltration cellular, histiocyte 1 (2%) 

Inflammation, granulomatous 1 (2%) 

Mixed cell focus 9 (18%) 13 (27%) 9 (18%) 8 (16%) 

Necrosis 1 (2%) 1 (2%) 2 (4%) 

Regeneration 1 (2%) 1 (2%) 

Thrombosis 1 (2%) 

Vacuolization cytoplasmic, focal 1 (2%) 

Bile duct, hyperplasia 6 (12%) 7 (14%) 6 (12%) 7 (14%) 

Centrilobular, necrosis 6 (12%) 6 (12%) 8 (16%) 9 (18%) 

Mesentery (15) (8) (11) (7) 

Fat, hemorrhage 1 (7%) 

Fat, necrosis 13 (87%) 7 (88%) 11 (100%) 6 (86%) 

Oral mucosa (1) (1) (1) 

Pharyngeal, hyperplasia, squamous 1 (100%) 1 (100%) 

Pancreas (49) (49) (48) (50) 

Atrophy 10 (20%) 11 (22%) 11 (23%) 11 (22%) 

Basophilic focus 4 (8%) 1 (2%) 1 (2%) 1 (2%) 

Hyperplasia 1 (2%) 1 (2%) 

Metaplasia, hepatocyte 1 (2%) 

Salivary glands (49) (50) (49) (50) 

Atrophy 1 (2%) 

Necrosis 1 (2%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

128 Furfuryl Alcohol, NTP TR 482 

TABLE B5 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Alimentary System (continued) 

Stomach, forestomach (50) (50) (49) (50) 

Hyperplasia, squamous 1 (2%) 1 (2%) 

Inflammation, acute 1 (2%) 

Mineralization 1 (2%) 

Necrosis 5 (10%) 6 (12%) 5 (10%) 12 (24%) 

Stomach, glandular (50) (49) (49) (50) 

Mineralization 2 (4%) 2 (4%) 1 (2%) 1 (2%) 

Necrosis 1 (2%) 2 (4%) 3 (6%) 7 (14%) 

Tongue (1) (4) (1) (3) 

Hyperplasia, squamous 1 (33%) 

Tooth (1) (1) 

Degeneration 1 (100%) 

Pulp, necrosis 1 (100%) 

Cardiovascular System 

Blood vessel (1) 

Aorta, mineralization 1 (100%) 

Heart (50) (50) (49) (50) 

Cardiomyopathy 29 (58%) 24 (48%) 23 (47%) 19 (38%) 

Artery, mineralization 1 (2%) 

Atrium, thrombosis 3 (6%) 3 (6%) 

Endocrine System 

Adrenal cortex (50) (50) (48) (50) 

Angiectasis 1 (2%) 1 (2%) 

Degeneration, cystic 1 (2%) 

Hyperplasia 19 (38%) 22 (44%) 21 (44%) 23 (46%) 

Hypertrophy 2 (4%) 4 (8%) 6 (13%) 2 (4%) 

Necrosis 4 (8%) 1 (2%) 1 (2%) 

Vacuolization cytoplasmic 5 (10%) 3 (6%) 3 (6%) 8 (16%) 

Adrenal medulla (50) (50) (48) (50) 

Hyperplasia 12 (24%) 7 (14%) 10 (21%) 14 (28%) 

Islets, pancreatic (49) (48) (48) (50) 

Hyperplasia 2 (4%) 

Parathyroid gland (46) (43) (44) (46) 

Hyperplasia 1 (2%) 1 (2%) 1 (2%) 1 (2%) 

Pituitary gland (50) (49) (48) (50) 

Cyst 1 (2%) 

Pars distalis, angiectasis 3 (6%) 

Pars distalis, hyperplasia 8 (16%) 10 (20%) 7 (15%) 9 (18%) 

Thyroid gland (49) (49) (47) (48) 

C-cell, hyperplasia 40 (82%) 41 (84%) 35 (74%) 39 (81%) 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 129 

TABLE B5 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Genital System 

Clitoral gland (44) (45) (46) (45) 

Hyperplasia 1 (2%) 5 (11%) 2 (4%) 1 (2%) 

Inflammation, chronic active 2 (5%) 3 (7%) 1 (2%) 

Ovary (50) (50) (49) (50) 

Cyst 3 (6%) 5 (10%) 6 (12%) 7 (14%) 

Hematopoietic System 

Bone marrow (49) (48) (48) (50) 

Hyperplasia, histiocytic 2 (4%) 1 (2%) 1 (2%) 

Lymph node (4) (5) (8) (11) 

Renal, ectasia 1 (9%) 

Renal, hemorrhage 1 (20%) 1 (13%) 1 (9%) 

Renal, pigmentation 1 (13%) 

Lymph node, mesenteric (50) (50) (49) (50) 

Hemorrhage 1 (2%) 

Lymph node, mediastinal (43) (37) (45) (40) 

Hemorrhage 1 (2%) 1 (3%) 

Spleen (49) (49) (49) (50) 

Accessory spleen 2 (4%) 1 (2%) 

Fibrosis 5 (10%) 3 (6%) 3 (6%) 5 (10%) 

Hematopoietic cell proliferation 2 (4%) 4 (8%) 2 (4%) 5 (10%) 

Hemorrhage 1 (2%) 1 (2%) 

Hyperplasia, focal 1 (2%) 

Inflammation, granulomatous 1 (2%) 1 (2%) 

Metaplasia, lipocyte 1 (2%) 

Necrosis 1 (2%) 1 (2%) 

Integumentary System 

Mammary gland (50) (49) (49) (50) 

Galactocele 3 (6%) 2 (4%) 1 (2%) 5 (10%) 

Hyperplasia, atypical 1 (2%) 

Necrosis 1 (2%) 

Skin (50) (50) (48) (50) 

Cyst epithelial inclusion 1 (2%) 

Hyperkeratosis 1 (2%) 

Inflammation, chronic active 2 (4%) 

Subcutaneous tissue, necrosis 1 (2%) 

Tail, hyperkeratosis 1 (2%) 

Tail, inflammation, chronic active 5 (10%) 

Musculoskeletal System 

Bone (50) (50) (49) (50) 

Fibrous osteodystrophy 1 (2%) 1 (2%) 

Hyperostosis 8 (16%) 14 (28%) 12 (24%) 6 (12%) 

Inflammation, chronic 1 (2%) 

Nervous System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

130 Furfuryl Alcohol, NTP TR 482 

TABLE B5 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Respiratory System 

Larynx (50) (49) (49) (49) 

Epiglottis, metaplasia, squamous 1 (2%) 

Lung (50) (50) (49) (50) 

Foreign body 1 (2%) 

Infiltration cellular, histiocyte 2 (4%) 

Inflammation, granulomatous 1 (2%) 2 (4%) 3 (6%) 

Inflammation, suppurative 1 (2%) 

Mineralization 1 (2%) 

Alveolar epithelium, hyperplasia 9 (18%) 16 (32%) 13 (27%) 12 (24%) 

Mediastinum, inflammation, granulomatous 1 (2%) 

Perivascular, infiltration cellular,

 mononuclear cell 1 (2%) 

Nose (49) (50) (48) (49) 

Inflammation, suppurative 4 (8%) 1 (2%) 5 (10%) 23 (47%) 

Thrombosis 7 (14%) 3 (6%) 6 (13%) 5 (10%) 

Glands, hyperplasia 24 (50%) 46 (94%) 

Lateral wall, hyperplasia 39 (78%) 48 (100%) 49 (100%) 

Lateral wall, metaplasia, squamous 1 (2%) 24 (49%) 

Olfactory epithelium, atrophy 6 (12%) 44 (92%) 49 (100%) 

Olfactory epithelium, degeneration, hyaline 43 (88%) 50 (100%) 47 (98%) 48 (98%) 

Olfactory epithelium, fibrosis 16 (33%) 31 (63%) 

Olfactory epithelium, hyperplasia 31 (65%) 41 (84%) 

Olfactory epithelium, metaplasia 5 (10%) 37 (77%) 48 (98%) 

Respiratory epithelium, degeneration, hyaline 23 (47%) 39 (78%) 45 (94%) 6 (12%) 

Respiratory epithelium, hyperplasia 18 (36%) 40 (83%) 49 (100%) 

Respiratory epithelium, metaplasia, squamous 2 (4%) 10 (20%) 

Special Senses System 

Eye (1) (1) (1) 

Cataract 1 (100%) 1 (100%) 

Retina, atrophy 1 (100%) 1 (100%) 

Urinary System 

Kidney (50) (49) (49) (50) 

Cyst 1 (2%) 

Hydronephrosis 1 (2%) 

Infarct 2 (4%) 1 (2%) 

Infiltration cellular, histiocyte 1 (2%) 

Mineralization 1 (2%) 

Nephropathy 47 (94%) 45 (92%) 47 (96%) 47 (94%) 

Renal tubule, hyperplasia 2 (4%) 

Urinary bladder (49) (49) (49) (50) 

Transitional epithelium, hyperplasia 2 (4%) 1 (2%) 
131 

APPENDIX C
 

SUMMARY OF LESIONS IN MALE MICE
 

IN THE 2-YEAR INHALATION STUDY
 

OF FURFURYL ALCOHOL
 

TABLE C1	 Summary of the Incidence of Neoplasms in Male Mice 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 133
 

TABLE C2 Individual Animal Tumor Pathology of Male Mice 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 136
 

TABLE C3 Statistical Analysis of Primary Neoplasms in Male Mice 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 152
 

TABLE C4 Historical Incidence of Renal Tubule Neoplasms 

in Chamber Control Male B6C3F Mice 1 ............................................. 155
 

TABLE C5	 Summary of the Incidence of Nonneoplastic Lesions in Male Mice 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 156
 
132 Furfuryl Alcohol, NTP TR 482 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 133 

TABLE C1 

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohola 

Chamber Control 2 ppm 8 ppm 32 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 11 10 14 8 

Natural deaths 5 4 6 4 

Survivors 

Terminal sacrifice 34 36 30 38 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Intestine small, duodenum (48) (48) (46) (47) 

Intestine small, jejunum (47) (47) (45) (47) 

Carcinoma 1 (2%) 1 (2%) 

Intestine small, ileum (46) (48) (46) (47) 

Liver (50) (50) (49) (50) 

Hemangiosarcoma 5 (10%) 3 (6%) 

Hepatoblastoma 1 (2%) 

Hepatocellular carcinoma 13 (26%) 17 (34%) 11 (22%) 12 (24%) 

Hepatocellular carcinoma, multiple 2 (4%) 2 (4%) 3 (6%) 1 (2%) 

Hepatocellular adenoma 7 (14%) 12 (24%) 5 (10%) 11 (22%) 

Hepatocellular adenoma, multiple 6 (12%) 1 (2%) 5 (10%) 2 (4%) 

Hepatocholangiocarcinoma 1 (2%) 

Mesentery (7) (4) (7) (3) 

Hemangioma 1 (14%) 

Oral mucosa (1) 

Pharyngeal, squamous cell carcinoma 1 (100%) 

Pancreas (50) (49) (48) (49) 

Hemangiosarcoma 1 (2%) 

Stomach, forestomach (50) (49) (50) (50) 

Squamous cell carcinoma 1 (2%) 

Squamous cell papilloma 1 (2%) 

Stomach, glandular (50) (48) (47) (48) 

Sarcoma 1 (2%) 

Tooth (2) (1) (1) 

Odontoma 1 (50%) 1 (100%) 

Cardiovascular System 

Heart (50) (50) (50) (50) 

Hepatocholangiocarcinoma, metastatic, liver 1 (2%) 1 (2%) 

Endocrine System 

Adrenal cortex (50) (49) (49) (48) 

Adenoma 2 (4%) 

Hepatocellular carcinoma, metastatic, liver 1 (2%) 

Capsule, adenoma 4 (8%) 2 (4%) 1 (2%) 

Adrenal medulla (50) (49) (48) (48) 

Pheochromocytoma malignant 1 (2%) 

Islets, pancreatic (50) (49) (48) (48) 

Adenoma 2 (4%) 1 (2%) 2 (4%) 

Pituitary gland (50) (48) (48) (49) 

Schwannoma malignant, metastatic, nose 1 (2%) 

Pars distalis, adenoma 1 (2%) 

Thyroid gland (50) (49) (49) (48) 

Follicular cell, adenoma 1 (2%) 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

134 Furfuryl Alcohol, NTP TR 482 

TABLE C1 

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

General Body System 

None 

Genital System 

Epididymis (50) (50) (49) (50) 

Leiomyoma 1 (2%) 

Testes (50) (50) (49) (50) 

Interstitial cell, adenoma 1 (2%) 1 (2%) 

Hematopoietic System 

Lymph node (2) (2) (1) (1) 

Lymph node, bronchial (27) (22) (27) (28) 

Alveolar/bronchiolar carcinoma, metastatic,

 lung 1 (4%) 

Hepatocholangiocarcinoma, metastatic, liver 1 (5%) 1 (4%) 

Lymph node, mandibular (28) (33) (23) (28) 

Lymph node, mesenteric (50) (46) (46) (47) 

Lymph node, mediastinal (40) (39) (38) (31) 

Alveolar/bronchiolar carcinoma, metastatic,

 lung 1 (3%) 

Spleen (50) (49) (49) (50) 

Hemangiosarcoma 1 (2%) 

Thymus (35) (31) (36) (36) 

Hepatocholangiocarcinoma, metastatic, liver 1 (3%) 

Integumentary System 

Skin (50) (50) (48) (49) 

Hemangioma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Subcutaneous tissue, hemangioma 1 (2%) 

Subcutaneous tissue, hemangiosarcoma 1 (2%) 

Subcutaneous tissue, histiocytic sarcoma 1 (2%) 

Subcutaneous tissue, sarcoma, multiple 1 (2%) 

Subcutaneous tissue, schwannoma malignant 1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) (50) 

Maxilla, hemangiosarcoma 1 (2%) 

Skeletal muscle (1) (1) 

Hemangiosarcoma 1 (100%) 

Nervous System 

Brain (50) (50) (49) (50) 

Meningioma benign 1 (2%) 

Meninges, schwannoma malignant, metastatic,

 nose 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 135 

TABLE C1 

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar adenoma, multiple

Alveolar/bronchiolar carcinoma

Alveolar/bronchiolar carcinoma, multiple

Carcinoma, metastatic, harderian gland

Hepatocellular carcinoma, metastatic, liver

Hepatocholangiocarcinoma, metastatic, liver

Mediastinum, alveolar/bronchiolar carcinoma,

 metastatic, lung

Mediastinum, hepatocholangiocarcinoma,

 metastatic, liver

Nose 

Carcinoma, metastatic, harderian gland

Schwannoma malignant

(50) 

 14 (28%) 

 2 (4%) 

 3 (6%) 

 1 (2%) 

 1 (2%) 

 2 (4%) 

(50) 

 1 (2%) 

 1 (2%) 

(50) 

 15 (30%) 

 1 (2%) 

 7 (14%) 

 4 (8%) 

 1 (2%) 

 1 (2%) 

(49) 

(49) 

 9 (18%) 

 1 (2%) 

 7 (14%) 

 1 (2%) 

 3 (6%) 

 1 (2%) 

(49) 

(50) 

 12 (24%) 

 2 (4%) 

 8 (16%) 

 1 (2%) 

 4 (8%) 

 1 (2%) 

 1 (2%) 

(50) 

Special Senses System 

Harderian gland

Adenoma

Carcinoma

 (4)

 3 (75%) 

 1 (25%) 

(4)

 3 (75%) 

(5)

 5 (100%)

 (3) 

 2 (67%) 

 1 (33%) 

Urinary System 

Kidney 

Hepatocholangiocarcinoma, metastatic, liver

Renal tubule, adenoma

Renal tubule, carcinoma

Renal tubule, carcinoma, multiple

(50) (49) 

 1 (2%) 

(49) (50) 

 1 (2%) 

 2 (4%) 

 1 (2%) 

 1 (2%) 

Systemic Lesions 

Multiple organsb 

Histiocytic sarcoma

Lymphoma malignant

(50) 

 3 (6%) 

(50) 

 3 (6%) 

(50) 

 2 (4%) 

 1 (2%) 

(50) 

 2 (4%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 

Total primary neoplasms 

Total animals with benign neoplasms 

Total benign neoplasms 

Total animals with malignant neoplasms 

Total malignant neoplasms 

Total animals with metastatic neoplasms 

Total metastatic neoplasms 

42 

70 

31 

43 

22 

27 

4 

7 

44 

76 

31 

40 

30 

36 

5 

10 

41 

61 

25 

30 

26 

31 

5 

6 

39 

66 

29 

34 

25 

32 

7 

11 

a 

b 

c 

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

Number of animals with any tissue examined microscopically 

Primary neoplasms: all neoplasms except metastatic neoplasms 
 

 

 

 

 

 

 

 

 

 

 

136 Furfuryl Alcohol, NTP TR 482 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

3 4 4 4 5 5 5 5 5 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 8 6 8 9 3 4 6 6 9 5 6 8 9 9 1 2 3 3 3 3 3 3 3 3 3 

5 5 4 7 7 7 7 7 7 1 1 7 2 7 2 1 3 3 3 3 3 3 3 3 3 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

Carcass ID Number 1 3 4 0 4 1 3 4 1 4 3 3 2 4 0 1 0 0 0 0 0 0 0 1 1 

4 4 2 1 3 2 6 7 5 0 2 8 1 9 7 6 2 3 4 5 6 8 9 0 1 

Alimentary System 

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

Gallbladder + + + + + + + A A + A + + + + + + + + + + + + + + 

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

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

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

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

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

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

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

Hepatoblastoma X 

Hepatocellular carcinoma X X X X X X X X X X 

Hepatocellular carcinoma, multiple X X 

Hepatocellular adenoma X X 

Hepatocellular adenoma, multiple X X X 

Mesentery + + + + 

Oral mucosa 

Pharyngeal, squamous cell carcinoma 

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

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

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

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

Tooth + + 

Odontoma X 

Cardiovascular System 

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

Endocrine System 

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

Adenoma X X 

Capsule, adenoma X X 

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

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

Adenoma X 

Parathyroid gland + + + + + + M M M + + + M + M + + M + M + M + + M 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Schwannoma malignant, metastatic, nose X 

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

Follicular cell, adenoma X 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Leiomyoma 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Prostate + + + + M + + + + + + + + + + + + + + + + + + + + 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 

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

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

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 137 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Total 

Carcass ID Number 1 1 1 1 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 4 4 4 4 4 5 Tissues/ 

3 7 8 9 0 2 3 4 5 6 7 8 9 0 1 3 5 7 9 1 4 5 6 8 0 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder + + + + + + + + + + + M + + + + + + M + + + + + + 45 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, rectum + + + + + + + + M + + I + + + + + + + + + + + + + 48 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + I + + + + 46 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatoblastoma 1 

Hepatocellular carcinoma X X X 13 

Hepatocellular carcinoma, multiple 2 

Hepatocellular adenoma X X X X X 7 

Hepatocellular adenoma, multiple X X X 6 

Mesentery + + + 7 

Oral mucosa + 1 

Pharyngeal, squamous cell carcinoma X 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Tooth 2 

Odontoma 1 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma 2 

Capsule, adenoma X X 4 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X 2 

Parathyroid gland M + + M + M + + + + M + + + + + M + M M + M + M + 32 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Schwannoma malignant, metastatic, nose 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Follicular cell, adenoma 1 

General Body System 

None 

Genital System 

Epididymis	 + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Leiomyoma X 1 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 
 

 

 

 

 

 

 

 

 

 

138 Furfuryl Alcohol, NTP TR 482 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

3 4 4 4 5 5 5 5 5 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 8 6 8 9 3 4 6 6 9 5 6 8 9 9 1 2 3 3 3 3 3 3 3 3 3 

5 5 4 7 7 7 7 7 7 1 1 7 2 7 2 1 3 3 3 3 3 3 3 3 3 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

Carcass ID Number 1 3 4 0 4 1 3 4 1 4 3 3 2 4 0 1 0 0 0 0 0 0 0 1 1 

4 4 2 1 3 2 6 7 5 0 2 8 1 9 7 6 2 3 4 5 6 8 9 0 1 

Hematopoietic System 

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

Lymph node +
 

Lymph node, bronchial + + M + M + M + M M + M M M + + M M M + + + M M +
 

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

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

Lymph node, mediastinal + + + M + + M + + + + + + M + + + + + + + + + + +
 

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

Thymus + + M + + M M + + M + + M M + M + + + + + M M M +
 

Integumentary System 

Mammary gland M M M M M M M M M M M M M M M M M M M M M M M M M 

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

Subcutaneous tissue, sarcoma, multiple X 

Musculoskeletal System 

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

Maxilla, hemangiosarcoma X 

Nervous System 

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

Meninges, schwannoma malignant,

 metastatic, nose X 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 

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

Alveolar/bronchiolar adenoma X X X X X X 

Alveolar/bronchiolar adenoma, multiple X 

Alveolar/bronchiolar carcinoma 

Alveolar/bronchiolar carcinoma, multiple X 

Carcinoma, metastatic, harderian gland X 

Hepatocellular carcinoma, metastatic, liver X X 

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

Carcinoma, metastatic, harderian gland X 

Schwannoma malignant X 

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

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 

Harderian gland + + 

Adenoma X 

Carcinoma X 

Urinary System 

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

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

Systemic Lesions 

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

Lymphoma malignant X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 139 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Total 

Carcass ID Number 1 1 1 1 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 4 4 4 4 4 5 Tissues/ 

3 7 8 9 0 2 3 4 5 6 7 8 9 0 1 3 5 7 9 1 4 5 6 8 0 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node + 2 

Lymph node, bronchial + + + M + M + + M + + M + M + M M + M M + + + M + 27 

Lymph node, mandibular M + M + + M M + + M + + + M M M + + M M M + + + + 28 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node, mediastinal + + M M M + M + + + + + + + + + M M + + + + I + + 40 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Thymus + + + + + M + + M + + + M + + + + + M M + + + + + 35 

Integumentary System 

Mammary gland M M M M M M M M M M M M M M M M M M + M M M M M M 1 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Subcutaneous tissue, sarcoma, multiple 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Maxilla, hemangiosarcoma 1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Meninges, schwannoma malignant,

 metastatic, nose 1 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar adenoma X X X X X X X X 14 

Alveolar/bronchiolar adenoma, multiple X 2 

Alveolar/bronchiolar carcinoma X X X 3 

Alveolar/bronchiolar carcinoma, multiple 1 

Carcinoma, metastatic, harderian gland 1 

Hepatocellular carcinoma, metastatic, liver 2 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, harderian gland 1 

Schwannoma malignant 1 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Eye	 + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Harderian gland + + 4 

Adenoma X X 3 

Carcinoma 1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymphoma malignant X 3 
 

 

 

 

 

 

 

 

 

 

 

 

140 Furfuryl Alcohol, NTP TR 482 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

2 2 4 4 5 5 5 5 5 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 7 8 3 9 7 7 8 9 9 0 3 6 9 1 3 3 3 3 3 3 3 3 3 3 3 

0 7 3 7 4 7 2 0 8 1 2 5 3 5 3 3 3 3 3 3 3 3 3 3 3 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

Carcass ID Number 2 1 3 4 3 0 0 4 1 1 2 1 3 4 0 0 0 0 0 0 0 1 1 1 1 

1 3 4 2 9 3 8 6 8 0 2 7 0 3 1 2 4 5 6 7 9 1 2 4 5 

Alimentary System 

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

Gallbladder A M M + + M + + + + + + + A + + + + + M + + + + + 

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

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

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

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

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

Carcinoma X 

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

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

Hemangiosarcoma X X 

Hepatocellular carcinoma X X X X X X X X X X 

Hepatocellular carcinoma, multiple X X 

Hepatocellular adenoma X X X X X 

Hepatocellular adenoma, multiple X 

Hepatocholangiocarcinoma X 

Mesentery + + + 

Pancreas M + + + + + + + + + + + + + + + + + + + + + + + + 

Salivary glands A + + + + + + + + + + + + + + + + + + + + + + + + 

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

Squamous cell papilloma 

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

Tooth 

Odontoma 

Cardiovascular System 

Blood vessel + 

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

Hepatocholangiocarcinoma, metastatic, liver X 

Endocrine System 

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

Capsule, adenoma X 

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

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

Adenoma X 

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

Pituitary gland A + + + + + + + + + + + + + + + + + + + + + + + + 

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

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + +
 

Penis +
 

Preputial gland A + + + + + + + + + + + + + + + + + + + + + + + +
 

Prostate A + + + + + + + + + + + + + M + + + + + + + + + +
 

Seminal vesicle A + + + + + + + + + + + + A + + + + + + + + + + +
 

Testes + + + + + + + + + + + + + + + + + + + + + + + + +
 

Interstitial cell, adenoma 
 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 141 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

3 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 4 4 4 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Total 

Carcass ID Number 1 1 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 4 5 Tissues/ 

6 9 0 3 4 5 6 7 8 9 1 2 3 5 6 7 8 0 1 4 5 7 8 9 0 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder + M + + + + + + + + + + + + M + + + + + + + + + + 42 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Carcinoma 1 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma X X X 5 

Hepatocellular carcinoma X X X X X X X 17 

Hepatocellular carcinoma, multiple 2 

Hepatocellular adenoma X X X X X X X 12 

Hepatocellular adenoma, multiple 1 

Hepatocholangiocarcinoma 1 

Mesentery + 4 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Squamous cell papilloma X 1 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Tooth + 1 

Odontoma X 1 

Cardiovascular System 

Blood vessel 1 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocholangiocarcinoma, metastatic, liver 1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Capsule, adenoma X 2 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma 1 

Parathyroid gland M + + M M + + + + M + + + M M + + + + + + + + + M 32 

Pituitary gland + + + + + + + I + + + + + + + + + + + + + + + + + 48 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Penis + 2 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Interstitial cell, adenoma X 1 
 

 

 

 

 

 

 

 

 

 

 

 

142 Furfuryl Alcohol, NTP TR 482 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

2 2 4 4 5 5 5 5 5 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 7 

0 

8 

7 

3 

3 

9 

7 

7 

4 

7 

7 

8 

2 

9 

0 

9 

8 

0 

1 

3 

2 

6 

5 

9 

3 

1 

5 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 

Carcass ID Number 2 

1 

1 

3 

3 

4 

4 

2 

3 

9 

0 

3 

0 

8 

4 

6 

1 

8 

1 

0 

2 

2 

1 

7 

3 

0 

4 

3 

0 

1 

0 

2 

0 

4 

0 

5 

0 

6 

0 

7 

0 

9 

1 

1 

1 

2 

1 

4 

1 

5 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, bronchial 

Hepatocholangiocarcinoma, metastatic, liver 

Lymph node, mandibular 

Lymph node, mesenteric 

Lymph node, mediastinal 

Spleen 

Thymus 

Hepatocholangiocarcinoma, metastatic, liver 

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

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

X 

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

M + + + + + + M + + + + + + + 

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

M + + + + + + + + + + + + + + 

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

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ + + 

+ M + 

+ + + 

M + + 

+ M + 

+ + + 

+ + I 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ + 

M + 

+ + 

+ + 

+ + 

+ + 

+ + 

+ + 

+ + 

+ M 

+ + 

M + 

+ + 

M M 

Integumentary System 

Mammary gland 

Skin 

Hemangioma 

Subcutaneous tissue, hemangioma 

M M M M M M M M M M M M M M M M M M M M M M M M M 

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

Musculoskeletal System 

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

Nervous System 

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

Respiratory System 

Larynx 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar adenoma, multiple 

Alveolar/bronchiolar carcinoma 

Hepatocellular carcinoma, metastatic liver 

Hepatocholangiocarcinoma, metastatic, liver 

Mediastinum, hepatocholangiocarcinoma,

 metastatic, liver 

Nose 

Trachea 

A 

+ 

A 

A 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

A 

+ 

+ 

X 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

X 

+ 

+ 

Special Senses System 

Ear +
 

Eye A + + + + + + + + + + + + A + + + + + + + + + + +
 

Harderian gland + + +
 

Adenoma X X 

Urinary System 

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

Hepatocholangiocarcinoma, metastatic, liver X 

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

Systemic Lesions 

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

Lymphoma malignant X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 143 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

3 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 4 4 4 

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Total 

Carcass ID Number 1 1 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 4 5 Tissues/ 

6 9 0 3 4 5 6 7 8 9 1 2 3 5 6 7 8 0 1 4 5 7 8 9 0 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lymph node + + 2 

Lymph node, bronchial M M M M M M M M M M + M + M M M M M M + + + + + M 22 

Hepatocholangiocarcinoma, metastatic, liver 1 

Lymph node, mandibular + + M M + + M + + + + + M + M M M + M + M + M M M 33 

Lymph node, mesenteric + + + + + + + + + + + + M + + + + + + + + + + + + 46 

Lymph node, mediastinal + + + + + + + + + + M M M + + + + + + + + + + M + 39 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Thymus + M M M + M + M + + + + + M + + M + + M + + + M + 31 

Hepatocholangiocarcinoma, metastatic, liver 1 

Integumentary System 

Mammary gland + M M M M + M M M M M M M M M M M M M M M M M M M 2 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangioma X 1 

Subcutaneous tissue, hemangioma X 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Respiratory System 

Larynx 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar adenoma, multiple

Alveolar/bronchiolar carcinoma 

Hepatocellular carcinoma, metastatic, liver 

Hepatocholangiocarcinoma, metastatic, liver

Mediastinum, hepatocholangiocarcinoma,

 metastatic, liver

Nose 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

X

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

49 

50 

15 

1 

7 

4 

1 

1 

49 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Special Senses System 

Ear 1 

Eye 

Harderian gland 

Adenoma 

+ 

+

X

+ + + + + + + + + + + + + + + + + + + + + + + + 48 

4 

3 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hepatocholangiocarcinoma, metastatic, liver 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymphoma malignant X X 3 
 

 

 

 

 

 

 

144 Furfuryl Alcohol, NTP TR 482 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

2 3 4 4 4 4 4 4 5 5 5 5 5 6 6 6 6 6 6 7 7 7 7 7 7 

Number of Days on Study 8 1 0 5 7 7 8 9 0 3 4 7 8 3 5 6 6 6 6 1 3 3 3 3 3 

7 7 0 5 1 1 8 7 2 2 8 6 2 0 1 5 5 6 9 2 3 3 3 3 3 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 

Carcass ID Number 1 3 0 0 2 4 0 0 1 2 1 4 5 0 3 2 2 3 0 1 0 0 0 1 1 

6 5 1 3 4 3 6 4 4 0 8 8 0 9 9 6 7 0 7 9 2 5 8 0 1 

Alimentary System 

Esophagus + A + + + + + + + + + + + + + + + + + + + + + + + 

Gallbladder + A A + M + + + + A + + + + + + + + A M + + + + + 

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

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

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

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

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

Carcinoma X 

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

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

Hepatocellular carcinoma X X X X X X X X X X 

Hepatocellular carcinoma, multiple X X 

Hepatocellular adenoma X X 

Hepatocellular adenoma, multiple X 

Mesentery + + + + 

Hemangioma X 

Pancreas + A + + + + + + + M + + + + + + + + + + + + + + + 

Hemangiosarcoma 

Salivary glands + M + + + + + + + + + + + + + + + + + + + + + + + 

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

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

Sarcoma X 

Tooth + 

Cardiovascular System 

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

Endocrine System 

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

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

Pheochromocytoma malignant X 

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

Adenoma X X 

Parathyroid gland + M + M M + M + + M M + + + + + M M + + + M + + + 

Pituitary gland + A + + + + + + + + + + + + + + + + + + + + + + + 

Pars distalis, adenoma 

Thyroid gland + M + + + + + + + + + + + + + + + + + + + + + + + 

Follicular cell, adenoma 

General Body System 

None 

Genital System 

Epididymis + A + + + + + + + + + + + + + + + + + + + + + + + 

Preputial gland + A + + + + + + + + + + + + + + + + + + + + + + + 

Prostate + A + + + + + + + + + + + + + + + + + + + + + + + 

Seminal vesicle + A A + + + + + + A + + + + + + + + A + + + + + + 

Testes + A + + + + + + + + + + + + + + + + + + + + + + + 
 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 145 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 Total 

Carcass ID Number 1 1 1 1 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 Tissues/ 

2 3 5 7 1 2 3 5 8 9 1 2 3 4 6 7 8 0 1 2 4 5 6 7 9 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Gallbladder + + + + + + + + + + + + + + + + M + + + + + + + M 42 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine large, rectum + + + + + + + + + + M + + + + + + + + M + + + + + 46 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 45 

Carcinoma 1 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hepatocellular carcinoma X 11 

Hepatocellular carcinoma, multiple X 3 

Hepatocellular adenoma X X X 5 

Hepatocellular adenoma, multiple X X X X 5 

Mesentery + + + 7 

Hemangioma 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Hemangiosarcoma X 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Sarcoma 1 

Tooth 1 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Pheochromocytoma malignant 1 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Adenoma 2 

Parathyroid gland M M + + + + + M + + M + M + M + M + + + + + + M M 32 

Pituitary gland + + + + + + + + + + + + + + M + + + + + + + + + + 48 

Pars distalis, adenoma X 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Follicular cell, adenoma X 1 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Prostate + + + + + + + M + + + + + + + + + + + + + + + + + 48 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 49 
 

 

 

 

 

 

 

 

 

 

146 Furfuryl Alcohol, NTP TR 482 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

2 3 4 4 4 4 4 4 5 5 5 5 5 6 6 6 6 6 6 7 7 7 7 7 7 

Number of Days on Study 8 1 0 5 7 7 8 9 0 3 4 7 8 3 5 6 6 6 6 1 3 3 3 3 3 

7 7 0 5 1 1 8 7 2 2 8 6 2 0 1 5 5 6 9 2 3 3 3 3 3 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 

Carcass ID Number 1 3 0 0 2 4 0 0 1 2 1 4 5 0 3 2 2 3 0 1 0 0 0 1 1 

6 5 1 3 4 3 6 4 4 0 8 8 0 9 9 6 7 0 7 9 2 5 8 0 1 

Hematopoietic System 

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

Lymph node + 

Lymph node, bronchial M M M M + + M + + + + M M M + + + + M + + M + + + 

Alveolar/bronchiolar carcinoma, metastatic, lung X 

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

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

Lymph node, mediastinal + A M M + M + M + M M + + + M + + + + M + M + + + 

Alveolar/bronchiolar carcinoma, metastatic, lung X 

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

Hemangiosarcoma 

Thymus + A M + + + + M + M M + M + M + + + M + + + + + + 

Integumentary System 

Mammary gland M M M M + M M M M M + M M M M M M M M M M M M M M 

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

Histiocytic sarcoma 

Subcutaneous tissue, hemangiosarcoma X 

Subcutaneous tissue, histiocytic sarcoma 

Musculoskeletal System 

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

Skeletal muscle 

Nervous System 

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

Respiratory System 

Larynx + M + + + + + + + + + + + + + + + + + + + + + + + 

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

Alveolar/bronchiolar adenoma X X X X 

Alveolar/bronchiolar adenoma, multiple 

Alveolar/bronchiolar carcinoma X X X 

Alveolar/bronchiolar carcinoma, multiple 

Hepatocellular carcinoma, metastatic, liver X X X 

Mediastinum, alveolar/bronchiolar carcinoma,

 metastatic, lung X 

Nose + A + + + + + + + + + + + + + + + + + + + + + + + 

Trachea + A + + + + + + + A + + + + + + + + + + + + + + + 

Special Senses System 

Eye + A + + + + + + + + + + + + + + + + + + + + + + + 

Harderian gland + + 

Adenoma X X 

Urinary System 

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

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

Systemic Lesions 

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

Histiocytic sarcoma 

Lymphoma malignant X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 147 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

3 

4 

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 Total 

Carcass ID Number 1 

2 

1 

3 

1 

5 

1 

7 

2 

1 

2 

2 

2 

3 

2 

5 

2 

8 

2 

9 

3 

1 

3 

2 

3 

3 

3 

4 

3 

6 

3 

7 

3 

8 

4 

0 

4 

1 

4 

2 

4 

4 

4 

5 

4 

6 

4 

7 

4 

9 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lymph node

Lymph node, bronchial 

Alveolar/bronchiolar carcinoma, metastatic, lung 

Lymph node, mandibular 

Lymph node, mesenteric 

Lymph node, mediastinal 

Alveolar/bronchiolar carcinoma, metastatic, lung 

Spleen 

Hemangiosarcoma 

Thymus 

+ M + + M + + 

+ + M + + M + 

+ + + + + + + 

+ + + M + + + 

+ + + + + + + 

X

M M M + + + + 

M M + 

+ M + 

+ + + 

+ + + 

+ + + 

+ + + 

+ 

+ 

+ 

+ 

+ 

+ 

M M + M M M + + + M M M + M 

M M M M M + + + M + M M M + 

+ M + + + + + + + + + + + + 

+ + + + + + + M + + + + + + 

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

M + + + + + M + M + + + + + 

1 

27 

1 

23 

46 

38 

1 

49 

1 

36 

Integumentary System 

Mammary gland 

Skin 

M M M M M M M M M M M M M M M M M M M M M M M M M

+ + + + + + + + + M + + + + + + + + + + + + + + + 

2 

48 

Histiocytic sarcoma 

Subcutaneous tissue, hemangiosarcoma

Subcutaneous tissue, histiocytic sarcoma X 

X 1 

1 

1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Skeletal muscle + 1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Respiratory System 

Larynx 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar adenoma, multiple 

Alveolar/bronchiolar carcinoma 

Alveolar/bronchiolar carcinoma, multiple 

Hepatocellular carcinoma, metastatic liver

Mediastinum, alveolar/bronchiolar carcinoma,

 metastatic, lung

Nose 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X 

X 

+ 

+ 

+ 

X

+ 

+ 

+ 

X 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

X

+ 

+ 

+ 

X

+ 

+ 

+ 

+ 

+ 

+ 

+ 

49 

49 

9 

1 

7 

1 

3 

1 

49 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Harderian gland + + + 5 

Adenoma X X X 5 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma X X 2 

Lymphoma malignant 1 
 

 

 

 

 

 

 

 

 

 

 

 

148 Furfuryl Alcohol, NTP TR 482 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

3 4 5 5 5 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 8 1 8 8 9 3 4 0 0 0 1 2 3 3 3 3 3 3 3 3 3 3 3 3 3 

2 3 2 2 0 7 6 7 7 9 6 4 3 3 3 3 3 3 3 3 3 3 3 3 3 

6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 

Carcass ID Number 3 2 3 5 3 4 4 0 1 4 2 2 0 0 0 0 0 0 0 0 1 1 1 1 1 

2 5 7 0 4 8 3 4 8 1 9 0 1 2 3 5 6 7 8 9 0 1 2 3 4 

Alimentary System 

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

Gallbladder A + + + + + M + + A M A + M + + + + + + + + + + + 

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

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

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

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

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

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

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

Hemangiosarcoma X X 

Hepatocellular carcinoma X X X X X X X 

Hepatocellular carcinoma, multiple X 

Hepatocellular adenoma X X X X X 

Hepatocellular adenoma, multiple X 

Mesentery + + 

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

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

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

Squamous cell carcinoma 

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

Cardiovascular System 

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

Hepatocholangiocarcinoma, metastatic, liver X 

Endocrine System 

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

Hepatocellular carcinoma, metastatic, liver X 

Capsule, adenoma X 

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

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

Parathyroid gland + M + + + + + + + + + M M + + + + + M M + M M M + 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 

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

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 

Prostate + M + + + + + + + + + + + + + + + + + + + + + + + 

Seminal vesicle + + + + + + + + + + + A + + + + + + + + + + + + + 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 

Interstitial cell, adenoma X 

Hematopoietic System 

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

Lymph node +
 

Lymph node, bronchial M + + M + + + M + + + + + M M + + M + M M + + + M
 

Hepatocholangiocarcinoma, metastatic, liver X 
 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 149 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 

6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 Total 

Carcass ID Number 1 1 1 1 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 4 Tissues/ 

5 6 7 9 1 2 3 4 6 7 8 0 1 3 5 6 8 9 0 2 4 5 6 7 9 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + M + + + + + + + + + + 49 

Gallbladder + + + + + + + + + + + + + + + + M + + + + + + + + 43 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, rectum + + + + + + + + M + + + M + + + + + + + + + + + + 46 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma X 3 

Hepatocellular carcinoma X X X X X 12 

Hepatocellular carcinoma, multiple 1 

Hepatocellular adenoma X X X X X X 11 

Hepatocellular adenoma, multiple X 2 

Mesentery + 3 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Squamous cell carcinoma X 1 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocholangiocarcinoma, metastatic, liver 1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Hepatocellular carcinoma, metastatic,liver 1 

Capsule, adenoma 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Parathyroid gland + M + M + + + M M + M + + + + + + M + M + + + + + 35 

Pituitary gland + + + + + + + + + + + + + + + M + + + + + + + + + 49 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 48 

General Body System 

None 

Genital System 

Epididymis + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Preputial gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Prostate + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Seminal vesicle + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Testes + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Interstitial cell, adenoma 1 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymph node 1 

Lymph node, bronchial + M M + + M M + + M M M M M M + + + + M + M + M + 28 

Hepatocholangiocarcinoma, metastatic, liver 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

150 Furfuryl Alcohol, NTP TR 482 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

Number of Days on Study 

3 

8 

2 

4 

1 

3 

5 

8 

2 

5 

8 

2 

5 

9 

0 

6 

3 

7 

6 

4 

6 

7 

0 

7 

7 

0 

7 

7 

0 

9 

7 

1 

6 

7 

2 

4 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

Carcass ID Number 

6 

3 

2 

6 

2 

5 

6 

3 

7 

6 

5 

0 

6 

3 

4 

6 

4 

8 

6 

4 

3 

6 

0 

4 

6 

1 

8 

6 

4 

1 

6 

2 

9 

6 

2 

0 

6 

0 

1 

6 

0 

2 

6 

0 

3 

6 

0 

5 

6 

0 

6 

6 

0 

7 

6 

0 

8 

6 

0 

9 

6 

1 

0 

6 

1 

1 

6 

1 

2 

6 

1 

3 

6 

1 

4 

Hematopoietic System (continued)
 

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

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

Lymph node, mediastinal M M M + M + M M + M + + + + + + + + + + + M + + +
 

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

Thymus + + + M + M + M + M + + + + + M + + + + + M M M +
 

Integumentary System 

Mammary gland M M M M M M M M M M M M M M M M M M M M M M M M M 

Skin + + M + + + + + + + + + + + + + + + + + + + + + + 

Subcutaneous tissue, schwannoma malignant X 

Musculoskeletal System 

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

Skeletal muscle + 

Hemangiosarcoma X 

Nervous System 

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

Meningioma benign 

Spinal cord + 

Respiratory System 

Larynx + + + + + + + + + + + A + + + + + + + + + + + M + 

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

Alveolar/bronchiolar adenoma X X X X 

Alveolar/bronchiolar adenoma, multiple X 

Alveolar/bronchiolar carcinoma X X X 

Carcinoma, metastatic, harderian gland X 

Hepatocellular carcinoma, metastatic, liver X 

Hepatocholangiocarcinoma, metastatic, liver X 

Mediastinum, hepatocholangiocarcinoma,

 metastatic, liver X 

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

Trachea + + + + + + + + + + + A + + + + + + + + + + + + + 

Special Senses System 

Eye + + + + + + + + + + + A + + + + + + + + + + + + + 

Harderian gland + + 

Adenoma X 

Carcinoma X 

Zymbal’s gland 

Urinary System 

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

Hepatocholangiocarcinoma, metastatic, liver X 

Renal tubule, adenoma X 

Renal tubule, carcinoma 

Renal tubule, carcinoma, multiple 

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

Systemic Lesions 

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

Lymphoma malignant X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 151 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

Number of Days on Study 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

3 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

Carcass ID Number 

6 

1 

5 

6 

1 

6 

6 

1 

7 

6 

1 

9 

6 

2 

1 

6 

2 

2 

6 

2 

3 

6 

2 

4 

6 

2 

6 

6 

2 

7 

6 

2 

8 

6 

3 

0 

6 

3 

1 

6 

3 

3 

6 

3 

5 

6 

3 

6 

6 

3 

8 

6 

3 

9 

6 

4 

0 

6 

4 

2 

6 

4 

4 

6 

4 

5 

6 

4 

6 

6 

4 

7 

6 

4 

9 

Total 

Tissues/ 

Tumors 

Hematopoietic System (continued) 

Lymph node, mandibular M M M + + M + + M + + + + + + + + + + + + M + M + 28 

Lymph node, mesenteric + + + + + + + + + + + M + + + + + + + + + + + + + 47 

Lymph node, mediastinal M M M + + M + M + + M M M M M + + + + + + M + + + 31 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Thymus + + M + + + M + M + + M + M + + I + + + + + + + + 36 

Integumentary System 

Mammary gland M M M M M M M M M M M M M M M M M M M M M M M M M 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Subcutaneous tissue, schwannoma malignant 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Skeletal muscle 1 

Hemangiosarcoma 1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Meningioma benign X 1 

Spinal cord + 2 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar adenoma X X X X X X X X 12 

Alveolar/bronchiolar adenoma, multiple X 2 

Alveolar/bronchiolar carcinoma X X X X X 8 

Carcinoma, metastatic, harderian gland 1 

Hepatocellular carcinoma, metastatic, liver X X X 4 

Hepatocholangiocarcinoma, metastatic, liver 1 

Mediastinum, hepatocholangiocarcinoma,

 metastatic, liver 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Harderian gland + 3 

Adenoma X 2 

Carcinoma 1 

Zymbal’s gland + 1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocholangiocarcinoma, metastatic, liver 1 

Renal tubule, adenoma X 2 

Renal tubule, carcinoma X 1 

Renal tubule, carcinoma, multiple X 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymphoma malignant X 2 
152 Furfuryl Alcohol, NTP TR 482 

TABLE C3 

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Adrenal Cortex: Adenoma a Overall rate 6/50 (12%) 2/49 (4%) 0/49 (0%) 1/48 (2%) 

Adjusted rateb 13.7% 4.7% 0.0% 2.3% c Terminal rate 4/34 (12%) 2/36 (6%) 0/30 (0%) 0/37 (0%) e First incidence (days) 567 733 (T) — 646 

Poly-3 testd P=0.094N P=0.139N P=0.022N P=0.054N 

Harderian Gland: Adenoma 

Overall rate 3/50 (6%) 3/50 (6%) 5/50 (10%) 2/50 (4%) 

Adjusted rate 7.0% 6.9% 12.5% 4.4% 

Terminal rate 3/34 (9%) 2/36 (6%) 4/30 (13%) 1/38 (3%) 

First incidence (days) 733 (T) 632 317 716 

Poly-3 test P=0.330N P=0.661N P=0.315 P=0.472N 

Harderian Gland: Adenoma or Carcinoma 

Overall rate 4/50 (8%) 3/50 (6%) 5/50 (10%) 3/50 (6%) 

Adjusted rate 9.1% 6.9% 12.5% 6.5% 

Terminal rate 3/34 (9%) 2/36 (6%) 4/30 (13%) 1/38 (3%) 

First incidence (days) 465 632 317 707 

Poly-3 test P=0.427N P=0.508N P=0.442 P=0.474N 

Kidney (Renal Tubule): Adenoma or Carcinoma (Single Sections) 

Overall rate 0/50 (0%) 0/49 (0%) 0/49 (0%) 4/50 (8%) 

Adjusted rate 0.0% 0.0% 0.0% 8.7% 

Terminal rate 0/34 (0%) 0/36 (0%) 0/30 (0%) 4/38 (11%) 

First incidence (days) — — — 733 (T) 

Poly-3 test P=0.002 —f — P=0.068 

Kidney (Renal Tubule): Adenoma (Single and Step Sections) 

Overall rate 0/50 (0%) 0/49 (0%) 0/49 (0%) 3/50 (6%) 

Adjusted rate 0.0% 0.0% 0.0% 6.6% 

Terminal rate 0/34 (0%) 0/36 (0%) 0/30 (0%) 3/38 (8%) 

First incidence (days) — — — 733 (T) 

Poly-3 test P=0.009 — — P=0.130 

Kidney (Renal Tubule): Adenoma or Carcinoma (Single and Step Sections) 

Overall rate 0/50 (0%) 0/49 (0%) 0/49 (0%) 5/50 (10%) 

Adjusted rate 0.0% 0.0% 0.0% 10.9% 

Terminal rate 0/34 (0%) 0/36 (0%) 0/30 (0%) 5/38 (13%) 

First incidence (days) — — — 733 (T) 

Poly-3 test P<0.001 — — P=0.036 

Liver: Hemangiosarcoma 

Overall rate 0/50 (0%) 5/50 (10%) 0/49 (0%) 3/50 (6%) 

Adjusted rate 0.0% 11.5% 0.0% 6.5% 

Terminal rate 0/34 (0%) 3/36 (8%) 0/30 (0%) 2/38 (5%) 

First incidence (days) — 632 — 637 

Poly-3 test P=0.428 P=0.031 — P=0.131 

Liver: Hepatocellular Adenoma 

Overall rate 13/50 (26%) 13/50 (26%) 10/49 (20%) 13/50 (26%)
 

Adjusted rate 30.2% 29.0% 24.7% 27.4%
 

Terminal rate 13/34 (38%) 10/36 (28%) 7/30 (23%) 9/38 (24%)
 

First incidence (days) 733 (T) 433 471 582
 

Poly-3 test P=0.483N P=0.546N P=0.374N P=0.479N
 
Furfuryl Alcohol, NTP TR 482 153 

TABLE C3 

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Liver: Hepatocellular Carcinoma 

Overall rate 15/50 (30%) 19/50 (38%) 14/49 (29%) 13/50 (26%)
 

Adjusted rate 31.2% 39.8% 30.8% 26.9%
 

Terminal rate 3/34 (9%) 9/36 (25%) 3/30 (10%) 5/38 (13%)
 

First incidence (days) 465 270 400 382
 

Poly-3 test P=0.208N P=0.251 P=0.572N P=0.407N
 

Liver: Hepatocellular Adenoma or Carcinoma 

Overall rate 28/50 (56%) 27/50 (54%) 23/49 (47%) 22/50 (44%)
 

Adjusted rate 58.2% 56.6% 49.7% 45.0%
 

Terminal rate 16/34 (47%) 17/36 (47%) 10/30 (33%) 12/38 (32%)
 

First incidence (days) 465 270 400 382
 

Poly-3 test P=0.108N P=0.519N P=0.264N P=0.135N
 

Liver: Hepatocellular Carcinoma or Hepatoblastoma 

Overall rate 15/50 (30%) 19/50 (38%) 14/49 (29%) 13/50 (26%)
 

Adjusted rate 31.2% 39.8% 30.8% 26.9%
 

Terminal rate 3/34 (9%) 9/36 (25%) 3/30 (10%) 5/38 (13%)
 

First incidence (days) 465 270 400 382
 

Poly-3 test P=0.208N P=0.251 P=0.572N P=0.407N
 

Liver: Hepatocellular Adenoma, Hepatocellular Carcinoma, or Hepatoblastoma 

Overall rate 28/50 (56%) 27/50 (54%) 23/49 (47%) 22/50 (44%)
 

Adjusted rate 58.2% 56.6% 49.7% 45.0%
 

Terminal rate 16/34 (47%) 17/36 (47%) 10/30 (33%) 12/38 (32%)
 

First incidence (days) 465 270 400 382
 

Poly-3 test P=0.108N P=0.519N P=0.264N P=0.135N
 

Lung: Alveolar/bronchiolar Adenoma 

Overall rate 16/50 (32%) 16/50 (32%) 10/49 (20%) 14/50 (28%)
 

Adjusted rate 37.0% 36.1% 25.6% 30.2%
 

Terminal rate 15/34 (44%) 13/36 (36%) 9/30 (30%) 12/38 (32%)
 

First incidence (days) 697 287 712 582
 

Poly-3 test P=0.312N P=0.554N P=0.189N P=0.322N
 

Lung: Alveolar/bronchiolar Carcinoma 

Overall rate 4/50 (8%) 7/50 (14%) 8/49 (16%) 8/50 (16%)
 

Adjusted rate 9.2% 16.3% 19.9% 17.4%
 

Terminal rate 3/34 (9%) 7/36 (19%) 6/30 (20%) 7/38 (18%)
 

First incidence (days) 687 733 (T) 502 716
 

Poly-3 test P=0.324 P=0.254 P=0.140 P=0.205 

Lung: Alveolar/bronchiolar Adenoma or Carcinoma 

Overall rate 20/50 (40%) 23/50 (46%) 17/49 (35%) 20/50 (40%)
 

Adjusted rate 46.1% 51.9% 42.2% 43.1%
 

Terminal rate 18/34 (53%) 20/36 (56%) 14/30 (47%) 17/38 (45%)
 

First incidence (days) 687 287 502 582
 

Poly-3 test P=0.332N P=0.368 P=0.444N P=0.470N
 

All Organs: Hemangiosarcoma 

Overall rate 1/50 (2%) 5/50 (10%) 3/50 (6%) 4/50 (8%) 

Adjusted rate 2.3% 11.5% 7.6% 8.7% 

Terminal rate 1/34 (3%) 3/36 (8%) 2/30 (7%) 2/38 (5%) 

First incidence (days) 733 (T) 632 630 637 

Poly-3 test P=0.431 P=0.102 P=0.273 P=0.200 
154 

c 

Furfuryl Alcohol, NTP TR 482 

TABLE C3 

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

All Organs: Hemangioma or Hemangiosarcoma 

Overall rate 1/50 (2%) 7/50 (14%) 4/50 (8%) 4/50 (8%) 

Adjusted rate 2.3% 16.1% 10.2% 8.7% 

Terminal rate 1/34 (3%) 5/36 (14%) 3/30 (10%) 2/38 (5%) 

First incidence (days) 733 (T) 632 630 637 

Poly-3 test P=0.588N P=0.030 P=0.152 P=0.200 

All Organs: Malignant Lymphoma 

Overall rate 3/50 (6%) 3/50 (6%) 1/50 (2%) 2/50 (4%) 

Adjusted rate 6.9% 7.0% 2.5% 4.4% 

Terminal rate 1/34 (3%) 2/36 (6%) 0/30 (0%) 1/38 (3%) 

First incidence (days) 712 693 532 724 

Poly-3 test P=0.416N P=0.661 P=0.336N P=0.474N 

All Organs: Benign Neoplasms 

Overall rate 31/50 (62%) 31/50 (62%) 25/50 (50%) 29/50 (58%) 

Adjusted rate 68.8% 67.0% 58.9% 60.6% 

Terminal rate 26/34 (77%) 25/36 (69%) 18/30 (60%) 22/38 (58%) 

First incidence (days) 547 287 317 582 

Poly-3 test P=0.260N P=0.517N P=0.222N P=0.268N 

All Organs: Malignant Neoplasms 

Overall rate 23/50 (46%) 30/50 (60%) 26/50 (52%) 25/50 (50%) 

Adjusted rate 46.8% 61.8% 55.5% 50.8% 

Terminal rate 9/34 (27%) 18/36 (50%) 11/30 (37%) 15/38 (40%) 

First incidence (days) 385 270 400 382 

Poly-3 test P=0.418N P=0.099 P=0.259 P=0.424 

All Organs: Benign or Malignant Neoplasms 

Overall rate 43/50 (86%) 44/50 (88%) 41/50 (82%) 39/50 (78%) 

Adjusted rate 86.5% 88.9% 84.1% 78.0% 

Terminal rate 28/34 (82%) 31/36 (86%) 23/30 (77%) 27/38 (71%) 

First incidence (days) 385 270 317 382 

Poly-3 test P=0.091N P=0.476 P=0.477N P=0.197N 

(T)Terminal sacrifice 

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for adrenal gland, kidney, liver, 

and lung; for other tissues, denominator is number of animals necropsied. b Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality 

Observed incidence at terminal kill 

d	 Beneath the chamber control incidence are the P values associated with the trend test. Beneath the exposed group incidence are the P values corresponding to 

pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for differential mortality in animals that do not reach terminal 

sacrifice. A negative trend or a lower incidence in an exposure group is indicated by N. e Not applicable; no neoplasms in animal group f Value of statistic cannot be computed. 
Furfuryl Alcohol, NTP TR 482 155 

TABLE C4 

Historical Incidence of Renal Tubule Neoplasms in Chamber Control Male B6C3F a 1 Mice

Incidence in Controls 

Study Adenoma Carcinoma Adenoma or 

Carcinoma 

Historical Incidence at Battelle Pacific Northwest Laboratories 

1,3-Butadiene 0/50 0/50 0/50 

Acetonitrile 0/49 0/49 0/49 

Allyl Glycidyl Ether 0/49 0/49 0/49 

"-Chloroacetophenone 0/50 0/50 0/50 

Cobalt Sulfate Heptahydrate 0/49 0/49 0/49 

Epinephrine Hydrochloride 0/50 0/50 0/50 

Hexachlorocyclopentadiene 0/50 0/50 0/50 

Molybdenum Trioxide 0/49 0/49 0/49 

Nitromethane 0/50 0/50 0/50 

o-Chlorobenzalmalononitrile 0/49 0/49 0/49 

Ozone 1/50 1/50 2/50 

Tetrahydrofuran 1/49 0/49 1/49 

Overall Historical Incidence 

Total 3/1,093 (0.3%) 1/1,093 (0.1%) 4/1,093 (0.4%) 

Standard deviation 0.6% 0.4% 1.0% 

Range 0%-2% 0%-2% 0%-4% 

a Data as of 4 October 1996 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

156 Furfuryl Alcohol, NTP TR 482 

TABLE C5 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohola 

Chamber Control 2 ppm 8 ppm 32 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Moribund 11 10 14 8 

Natural deaths 5 4 6 4 

Survivors 

Terminal sacrifice 34 36 30 38 

Animals examined microscopically 50 50 50 50 

Alimentary System 

Gallbladder (45) (42) (42) (43) 

Degeneration, hyaline 1 (2%) 

Epithelium, hyperplasia 1 (2%) 1 (2%) 

Intestine large, rectum (48) (47) (46) (46) 

Anus, inflammation, chronic active 1 (2%) 

Intestine large, cecum (48) (47) (46) (48) 

Serosa, inflammation, chronic 1 (2%) 

Intestine small, duodenum (48) (48) (46) (47) 

Peyer’s patch, hyperplasia 1 (2%) 

Intestine small, ileum (46) (48) (46) (47) 

Peyer’s patch, hyperplasia 1 (2%) 

Liver (50) (50) (49) (50) 

Angiectasis 2 (4%) 

Basophilic focus 5 (10%) 

Clear cell focus 3 (6%) 3 (6%) 1 (2%) 

Degeneration, cystic 1 (2%) 

Degeneration, fatty 5 (10%) 1 (2%) 1 (2%) 

Eosinophilic focus 13 (26%) 18 (36%) 12 (24%) 14 (28%) 

Hematopoietic cell proliferation 2 (4%) 1 (2%) 1 (2%) 1 (2%) 

Inflammation, chronic 1 (2%) 1 (2%) 2 (4%) 

Necrosis 2 (4%) 4 (8%) 6 (12%) 2 (4%) 

Vacuolization cytoplasmic 1 (2%) 3 (6%) 

Bile duct, cyst 1 (2%) 1 (2%) 1 (2%) 

Bile duct, hyperplasia 1 (2%) 

Centrilobular, degeneration 1 (2%) 

Centrilobular, necrosis 1 (2%) 

Mesentery (7) (4) (7) (3) 

Fat, necrosis 7 (100%) 4 (100%) 6 (86%) 3 (100%) 

Pancreas (50) (49) (48) (49) 

Atrophy 7 (14%) 3 (6%) 4 (8%) 10 (20%) 

Hypertrophy 1 (2%) 2 (4%) 

Inflammation, chronic, focal 1 (2%) 

Duct, cyst 1 (2%) 1 (2%) 

Salivary glands (50) (49) (49) (50) 

Hyperplasia 1 (2%) 

Inflammation, chronic 1 (2%) 

Duct, hyperplasia 1 (2%) 

Stomach, forestomach (50) (49) (50) (50) 

Diverticulum 1 (2%) 

Hyperkeratosis 1 (2%) 

Inflammation, suppurative 1 (2%) 1 (2%) 

Ulcer 1 (2%) 

Epithelium, hyperplasia 2 (4%) 5 (10%) 2 (4%) 5 (10%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 157 

TABLE C5 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Alimentary System (continued) 

Stomach, glandular (50) (48) (47) (48) 

Inflammation, suppurative 1 (2%) 2 (4%) 2 (4%) 

Necrosis 2 (4%) 1 (2%) 

Tooth (2) (1) (1) 

Developmental malformation 1 (50%) 

Inflammation 1 (100%) 

Cardiovascular System 

Blood vessel (1) 

Inflammation 1 (100%) 

Heart (50) (50) (50) (50) 

Cardiomyopathy 46 (92%) 47 (94%) 43 (86%) 45 (90%) 

Atrium, thrombosis 1 (2%) 

Ventricle, thrombosis 1 (2%) 

Endocrine System 

Adrenal cortex (50) (49) (49) (48) 

Hyperplasia 1 (2%) 1 (2%) 5 (10%) 2 (4%) 

Hypertrophy 35 (70%) 37 (76%) 31 (63%) 28 (58%) 

Capsule, hyperplasia 1 (2%) 

Adrenal medulla (50) (49) (48) (48) 

Hyperplasia 1 (2%) 

Islets, pancreatic (50) (49) (48) (48) 

Hyperplasia 9 (18%) 7 (14%) 10 (21%) 5 (10%) 

Pituitary gland (50) (48) (48) (49) 

Pars distalis, hyperplasia 3 (6%) 4 (8%) 1 (2%) 2 (4%) 

Pars intermedia, hyperplasia 1 (2%) 

Thyroid gland (50) (49) (49) (48) 

Follicular cell, hyperplasia 8 (16%) 9 (18%) 6 (12%) 13 (27%) 

General Body System 

None 

Genital System 

Epididymis (50) (50) (49) (50) 

Hyperplasia 2 (4%) 

Inflammation, chronic 2 (4%) 1 (2%) 2 (4%) 

Mineralization 1 (2%) 

Spermatocele 2 (4%) 

Penis (2) 

Inflammation 1 (50%) 

Preputial gland (50) (49) (49) (50) 

Cyst 3 (6%) 3 (6%) 2 (4%) 6 (12%) 

Inflammation 3 (6%) 1 (2%) 2 (4%) 

Prostate (49) (48) (48) (49) 

Inflammation, suppurative 1 (2%) 1 (2%) 1 (2%) 

Seminal vesicle (50) (48) (46) (49) 

Inflammation 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

158 Furfuryl Alcohol, NTP TR 482 

TABLE C5 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Genital System (continued) 

Testes (50) (50) (49) (50) 

Angiectasis 1 (2%) 

Atrophy 4 (8%) 3 (6%) 5 (10%) 2 (4%) 

Degeneration 1 (2%) 

Inflammation, focal, granulomatous 1 (2%) 

Mineralization 1 (2%) 

Interstitial cell, hyperplasia 1 (2%) 

Hematopoietic System 

Bone marrow (50) (49) (49) (50) 

Hyperplasia 2 (4%) 2 (4%) 1 (2%) 

Lymph node, bronchial (27) (22) (27) (28) 

Hyperplasia 2 (7%) 

Lymph node, mandibular (28) (33) (23) (28) 

Hyperplasia 1 (4%) 

Lymph node, mesenteric (50) (46) (46) (47) 

Angiectasis 1 (2%) 2 (4%) 

Hematopoietic cell proliferation 1 (2%) 1 (2%) 

Hyperplasia 1 (2%) 2 (4%) 3 (6%) 

Lymph node, mediastinal (40) (39) (38) (31) 

Hematopoietic cell proliferation 1 (3%) 

Hyperplasia 2 (5%) 1 (3%) 1 (3%) 

Spleen (50) (49) (49) (50) 

Angiectasis 1 (2%) 

Hematopoietic cell proliferation 7 (14%) 12 (24%) 11 (22%) 9 (18%) 

Hyperplasia, lymphoid 2 (4%) 

Thymus (35) (31) (36) (36) 

Epithelial cell, hyperplasia 1 (3%) 

Integumentary System 

Skin (50) (50) (48) (49) 

Cyst epithelial inclusion 1 (2%) 

Inflammation, chronic 2 (4%) 

Inflammation, chronic active 1 (2%) 

Mineralization 1 (2%) 

Prepuce, inflammation, chronic active 3 (6%) 2 (4%) 3 (6%) 2 (4%) 

Subcutaneous tissue, inflammation, chronic

 active 2 (4%) 1 (2%) 

Subcutaneous tissue, inflammation, focal,

 granulomatous 1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) (50) 

Fibrous osteodystrophy 1 (2%) 2 (4%) 

Hyperostosis 1 (2%) 1 (2%) 1 (2%) 

Nervous System 

Brain (50) (50) (49) (50) 

Cyst epithelial inclusion 1 (2%) 

Meninges, infiltration cellular, mononuclear

 cell 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 159 

TABLE C5 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Respiratory System 

Larynx (50) (49) (49) (48) 

Hyperplasia 2 (4%) 1 (2%) 2 (4%) 1 (2%) 

Inflammation, suppurative 1 (2%) 1 (2%) 

Lung (50) (50) (49) (50) 

Hematopoietic cell proliferation 1 (2%) 

Hemorrhage 1 (2%) 1 (2%) 2 (4%) 

Infiltration cellular, histiocyte 4 (8%) 4 (8%) 5 (10%) 7 (14%) 

Inflammation, chronic, focal 1 (2%) 

Alveolar epithelium, hyperplasia 5 (10%) 2 (4%) 2 (4%) 2 (4%) 

Mediastinum, angiectasis 1 (2%) 

Nose (50) (49) (49) (50) 

Inflammation, suppurative 7 (14%) 11 (22%) 27 (55%) 28 (56%) 

Glands, hyperplasia 10 (20%) 48 (98%) 46 (92%) 

Glands, metaplasia, squamous 6 (12%) 35 (71%) 47 (94%) 

Lateral wall, metaplasia, squamous 9 (18%) 10 (20%) 20 (40%) 

Lateral wall, necrosis 3 (6%) 

Olfactory epithelium, atrophy 3 (6%) 15 (31%) 49 (100%) 50 (100%) 

Olfactory epithelium, degeneration, hyaline 2 (4%) 3 (6%) 21 (43%) 39 (78%) 

Olfactory epithelium, metaplasia 12 (24%) 49 (100%) 50 (100%) 

Respiratory epithelium, degeneration, hyaline 5 (10%) 18 (37%) 42 (86%) 45 (90%) 

Respiratory epithelium, hyperplasia, polypoid 1 (2%) 

Respiratory epithelium, metaplasia, squamous 2 (4%) 10 (20%) 20 (40%) 

Respiratory epithelium, necrosis 1 (2%) 1 (2%) 

Respiratory epithelium, regeneration 1 (2%) 13 (27%) 21 (42%) 

Trachea (50) (48) (48) (49) 

Metaplasia, squamous 2 (4%) 

Special Senses System 

Eye (50) (48) (49) (49) 

Cataract 2 (4%) 1 (2%) 3 (6%) 

Inflammation, chronic active 2 (4%) 1 (2%) 

Cornea, dysplasia 1 (2%) 

Cornea, hyperplasia 1 (2%) 2 (4%) 1 (2%) 

Cornea, inflammation, chronic active 1 (2%) 

Retina, atrophy 1 (2%) 

Urinary System 

Kidney (50) (49) (49) (50) 

Amyloid deposition 1 (2%) 

Cyst 1 (2%) 3 (6%) 

Hydronephrosis 2 (4%) 2 (4%) 1 (2%) 2 (4%) 

Inflammation, chronic active 2 (4%) 1 (2%) 

Metaplasia, osseous 3 (6%) 4 (8%) 4 (8%) 

Mineralization 1 (2%) 

Nephropathy 49 (98%) 48 (98%) 43 (88%) 47 (94%) 

Papilla, necrosis 1 (2%) 

Renal tubule, degeneration 1 (2%) 48 (96%) 

Renal tubule, hyperplasia 1 (2%) 3 (6%) 3 (6%) 

Renal tubule, hypertrophy 1 (2%) 1 (2%) 

Urinary bladder (50) (47) (47) (50) 

Inflammation, chronic active 3 (6%) 1 (2%) 

Inflammation, suppurative 1 (2%) 

Mineralization 1 (2%) 

Necrosis 1 (2%) 

Transitional epithelium, hyperplasia 1 (2%) 1 (2%) 
160 Furfuryl Alcohol, NTP TR 482 
161 

APPENDIX D 

SUMMARY OF LESIONS IN FEMALE MICE 

IN THE 2-YEAR INHALATION STUDY 

OF FURFURYL ALCOHOL 

TABLE D1 Summary of the Incidence of Neoplasms in Female Mice 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 162 

TABLE D2 Individual Animal Tumor Pathology of Female Mice 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 166 

TABLE D3 Statistical Analysis of Primary Neoplasms in Female Mice 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 188 

TABLE D4 Summary of the Incidence of Nonneoplastic Lesions in Female Mice 

in the 2-Year Inhalation Study of Furfuryl Alcohol .................................... 191 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

162 Furfuryl Alcohol, NTP TR 482 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohola 

Chamber Control 2 ppm 8 ppm 32 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Accidental deaths 1 1 

Moribund 11 12 15 8 

Natural deaths 5 3 2 2 

Survivors 

Terminal sacrifice 34 33 32 40 

Pregnant 1 

Animals examined microscopically 50 49 50 50 

Alimentary System 

Intestine large, rectum (49) (45) (49) (48) 

Anus, squamous cell carcinoma 1 (2%) 

Intestine small, duodenum (47) (46) (48) (48) 

Polyp adenomatous 1 (2%) 

Intestine small, jejunum (45) (46) (48) (48) 

Intestine small, ileum (45) (47) (48) (48) 

Liver (50) (49) (49) (49) 

Hemangiosarcoma 1 (2%) 

Hepatocellular carcinoma 8 (16%) 12 (24%) 5 (10%) 6 (12%) 

Hepatocellular carcinoma, multiple 1 (2%) 3 (6%) 2 (4%) 

Hepatocellular adenoma 5 (10%) 5 (10%) 9 (18%) 5 (10%) 

Hepatocellular adenoma, multiple 2 (4%) 2 (4%) 

Hepatocholangiocarcinoma 1 (2%) 

Histiocytic sarcoma 2 (4%) 

Sarcoma, metastatic, uncertain primary site 1 (2%) 

Mesentery (15) (6) (11) (10) 

Hemangiosarcoma 1 (9%) 

Hepatocholangiocarcinoma, metastatic, liver 1 (9%) 

Histiocytic sarcoma 1 (7%) 

Sarcoma, metastatic, skin 1 (10%) 

Pancreas (50) (48) (49) (49) 

Sarcoma, metastatic, uncertain primary site 1 (2%) 

Salivary glands (50) (49) (49) (50) 

Carcinoma, metastatic, harderian gland 1 (2%) 

Stomach, forestomach (50) (48) (49) (49) 

Squamous cell carcinoma 1 (2%) 

Squamous cell papilloma 3 (6%) 

Stomach, glandular (50) (46) (49) (48) 

Tooth (2) 

Adamantinoma malignant 1 (50%) 

Cardiovascular System 

Heart (50) (49) (49) (50) 

Sarcoma, metastatic, uncertain primary site 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 163 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Endocrine System 

Adrenal cortex (50) (49) (50) (49) 

Sarcoma, metastatic, uncertain primary site 1 (2%) 

Capsule, adenoma 2 (4%) 1 (2%) 

Adrenal medulla (48) (48) (49) (49) 

Pheochromocytoma benign 1 (2%) 1 (2%) 

Sarcoma, metastatic, uncertain primary site 1 (2%) 

Islets, pancreatic (49) (48) (49) (49) 

Adenoma 1 (2%) 1 (2%) 1 (2%) 

Pituitary gland (48) (48) (48) (49) 

Pars distalis, adenoma 7 (15%) 7 (15%) 4 (8%) 1 (2%) 

Pars intermedia, adenoma 1 (2%) 1 (2%) 

Thyroid gland (50) (49) (49) (49) 

Bilateral, follicular cell, adenoma 1 (2%) 

Follicular cell, adenoma 3 (6%) 1 (2%) 2 (4%) 5 (10%) 

Follicular cell, carcinoma 1 (2%) 

General Body System 

None 

Genital System 

Clitoral gland (43) (41) (31) (41) 

Histiocytic sarcoma 1 (2%) 

Ovary (50) (49) (48) (49) 

Alveolar/bronchiolar carcinoma, metastatic,

 lung 1 (2%) 

Cystadenoma 2 (4%) 1 (2%) 3 (6%) 2 (4%) 

Granulosa cell tumor benign 2 (4%) 

Histiocytic sarcoma 2 (4%) 

Luteoma 1 (2%) 1 (2%) 

Sarcoma, metastatic, uncertain primary site 1 (2%) 

Yolk sac carcinoma 1 (2%) 

Uterus (50) (49) (49) (49) 

Adenocarcinoma 1 (2%) 

Hemangioma 1 (2%) 

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

Leiomyoma 1 (2%) 

Leiomyosarcoma 1 (2%) 

Polyp stromal 2 (4%) 3 (6%) 4 (8%) 2 (4%) 

Sarcoma, metastatic, uncertain primary site 1 (2%) 

Hematopoietic System 

Bone marrow (50) (49) (49) (49) 

Hemangiosarcoma 2 (4%) 1 (2%) 1 (2%) 

Lymph node (6) (4) (5) (4) 

Lymph node, bronchial (33) (27) (30) (37) 

Alveolar/bronchiolar carcinoma, metastatic,

 lung 1 (3%) 1 (4%) 1 (3%) 

Hepatocholangiocarcinoma, metastatic, liver 1 (3%) 

Lymph node, mandibular (36) (40) (43) (40) 

Carcinoma, metastatic, harderian gland 1 (3%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

164 Furfuryl Alcohol, NTP TR 482 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Hematopoietic System (continued) 

Lymph node, mesenteric (48) (47) (47) (46) 

Lymph node, mediastinal (41) (34) (40) (40) 

Alveolar/bronchiolar carcinoma, metastatic,

 lung 1 (3%) 1 (3%) 

Hepatocholangiocarcinoma, metastatic, liver 1 (3%) 

Sarcoma, metastatic, uncertain primary site 1 (3%) 

Spleen (50) (48) (49) (49) 

Hemangioma 1 (2%) 

Hemangiosarcoma 1 (2%) 2 (4%) 

Histiocytic sarcoma 1 (2%) 

Thymus (42) (40) (46) (38) 

Alveolar/bronchiolar carcinoma, metastatic,

 lung 1 (2%) 

Sarcoma, metastatic, uncertain primary site 1 (2%) 

Integumentary System 

Mammary gland (50) (49) (49) (50) 

Carcinoma 2 (4%) 1 (2%) 

Skin (50) (49) (49) (50) 

Hemangiosarcoma 1 (2%) 

Subcutaneous tissue, hemangioma 1 (2%) 

Subcutaneous tissue, hemangioma, multiple 1 (2%) 

Subcutaneous tissue, hemangiosarcoma 1 (2%) 2 (4%) 1 (2%) 

Subcutaneous tissue, histiocytic sarcoma 1 (2%) 

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

Subcutaneous tissue, sarcoma, multiple 1 (2%) 

Musculoskeletal System 

Bone (50) (49) (50) (50) 

Hemangiosarcoma, metastatic, bone marrow 1 (2%) 

Osteosarcoma 1 (2%) 

Skeletal muscle (1) (1) (1) 

Alveolar/bronchiolar carcinoma, metastatic,

 lung 1 (100%) 

Sarcoma, metastatic, skin 1 (100%) 

Sarcoma, metastatic, uncertain primary site 1 (100%) 

Nervous System 

Brain (50) (49) (49) (49) 

Meninges, histiocytic sarcoma 1 (2%) 

Respiratory System 

Lung (50) (49) (49) (50) 

Alveolar/bronchiolar adenoma 2 (4%) 4 (8%) 8 (16%) 

Alveolar/bronchiolar carcinoma 4 (8%) 3 (6%) 3 (6%) 1 (2%) 

Alveolar/bronchiolar carcinoma, multiple 1 (2%) 1 (2%) 

Carcinoma, metastatic, harderian gland 2 (4%) 1 (2%) 

Carcinoma, metastatic, mammary gland 1 (2%) 

Hepatocellular carcinoma, metastatic, liver 2 (4%) 1 (2%) 3 (6%) 

Hepatocholangiocarcinoma, metastatic, liver 1 (2%) 

Histiocytic sarcoma 2 (4%) 
 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 165 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Respiratory System (continued) 

Lung (continued) 

Sarcoma, metastatic, skin

Sarcoma, metastatic, uncertain primary site

Mediastinum, alveolar/bronchiolar carcinoma,

 metastatic, lung

Mediastinum, hepatocholangiocarcinoma,

 metastatic, liver

Mediastinum, sarcoma, metastatic, skin

Nose 

Histiocytic sarcoma

Sarcoma, metastatic, uncertain primary site

(50) 

 1 (2%) 

(50) 

 1 (2%) 

(49) 

 1 (2%) 

(48) 

(49) 

 1 (2%) 

 1 (2%) 

 1 (2%) 

(49) 

 1 (2%) 

(50) 

 1 (2%) 

 1 (2%) 

(50) 

Special Senses System 

Eye 

Sarcoma, metastatic, uncertain primary site

Harderian gland

Adenoma

Carcinoma

Sarcoma, metastatic, uncertain primary site

(49) 

(2)

 2 (100%)

(49) 

(5)

 2 (40%) 

 2 (40%) 

(49) 

 1 (2%) 

(6)

 5 (83%) 

 1 (17%) 

(50) 

(6) 

 5 (83%) 

 1 (17%) 

Urinary System 

Kidney 

Hepatocholangiocarcinoma, metastatic, liver

Histiocytic sarcoma

Sarcoma, metastatic, uncertain primary site

Urinary bladder 

(50) 

 1 (2%) 

(49) 

(48) 

(45) 

(49) 

 1 (2%) 

 1 (2%) 

 1 (2%) 

(49) 

(49) 

(48) 

Systemic Lesions 

Multiple organsb 

Histiocytic sarcoma

Lymphoma malignant

(50) 

 2 (4%) 

 6 (12%) 

(49) 

 1 (2%) 

 3 (6%) 

(50) 

 2 (4%) 

 5 (10%) 

(50) 

 8 (16%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 

Total primary neoplasms 

Total animals with benign neoplasms 

Total benign neoplasms 

Total animals with malignant neoplasms 

Total malignant neoplasms 

Total animals with metastatic neoplasms 

Total metastatic neoplasms 

Total animals with malignant neoplasms

 of uncertain primary site 

36 

58 

23 

31 

20 

27 

5 

5 

37 

60 

23 

29 

25 

31 

4 

10 

39 

70 

29 

43 

23 

27 

4 

26 

1 

36 

51 

21 

26 

22 

25 

6 

8 

a 

b 

c 

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

Number of animals with any tissue examined microscopically 

Primary neoplasms: all neoplasms except metastatic neoplasms 
 

 

 

 

 

 

 

 

 

 

 

166 Furfuryl Alcohol, NTP TR 482 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

3 4 5 5 5 5 5 5 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 5 4 4 4 6 7 9 9 0 0 5 5 8 9 1 1 3 3 3 3 3 3 3 3 3 

2 8 7 7 6 3 5 6 4 9 1 1 9 3 2 5 4 4 4 4 4 4 4 4 4 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

Carcass ID Number 3 2 0 0 1 4 0 3 2 1 3 4 1 4 4 1 0 0 0 0 0 0 1 1 1 

2 9 1 5 4 1 7 4 7 1 5 5 9 4 2 8 2 3 4 6 8 9 0 2 3 

Alimentary System 

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

Gallbladder + A + + + A A + + + + + A + + + + + + + + + + M + 

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

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

Anus, squamous cell carcinoma X 

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

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

Polyp adenomatous 

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

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

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

Hepatocellular carcinoma X X X X X 

Hepatocellular carcinoma, multiple 

Hepatocellular adenoma X X X 

Hepatocellular adenoma, multiple 

Histiocytic sarcoma X X 

Mesentery + + + + + + 

Histiocytic sarcoma X 

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

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

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

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

Cardiovascular System 

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

Endocrine System 

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

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

Pheochromocytoma benign 

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

Adenoma 

Parathyroid gland M + + + + + M M M + M + + M + + + + M + + M M + + 

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

Pars distalis, adenoma X X 

Pars intermedia, adenoma X 

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

Follicular cell, adenoma X 

General Body System 

None 

Genital System 

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

Histiocytic sarcoma X 

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

Cystadenoma 

Histiocytic sarcoma X X 

Luteoma X 

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

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

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 167 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 1 1 1 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 5 Tissues/ 

5 6 7 0 1 2 3 4 5 6 8 0 1 3 6 7 8 9 0 3 6 7 8 9 0 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder + M + + + + M + + + + + + + + + + + + + + + + + + 43 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Anus, squamous cell carcinoma 1 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Polyp adenomatous X 1 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 45 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 45 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hepatocellular carcinoma X X X 8 

Hepatocellular carcinoma, multiple X 1 

Hepatocellular adenoma X X 5 

Hepatocellular adenoma, multiple X X 2 

Histiocytic sarcoma 2 

Mesentery + + + + + + + + + 15 

Histiocytic sarcoma 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + M + + + + + + + + + + + + + + + + + 48 

Pheochromocytoma benign X 1 

Islets, pancreatic + M + + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma X 1 

Parathyroid gland + M M M + M + + M M M + + + + + + + + + + M + + M 32 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Pars distalis, adenoma X X X X X 7 

Pars intermedia, adenoma 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Follicular cell, adenoma X X 3 

General Body System 

None 

Genital System 

Clitoral gland M + + + + + + + + + + + + + + + + + M + I + + + + 43 

Histiocytic sarcoma 1 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cystadenoma X X 2 

Histiocytic sarcoma 2 

Luteoma 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

168 Furfuryl Alcohol, NTP TR 482 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

3 4 5 5 5 5 5 5 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 5 4 4 4 6 7 9 9 0 0 5 5 8 9 1 1 3 3 3 3 3 3 3 3 3 

2 8 7 7 6 3 5 6 4 9 1 1 9 3 2 5 4 4 4 4 4 4 4 4 4 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

Carcass ID Number 3 2 0 0 1 4 0 3 2 1 3 4 1 4 4 1 0 0 0 0 0 0 1 1 1 

2 9 1 5 4 1 7 4 7 1 5 5 9 4 2 8 2 3 4 6 8 9 0 2 3 

Genital System (continued) 

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

Histiocytic sarcoma X X 

Leiomyoma X 

Leiomyosarcoma X 

Polyp stromal X 

Hematopoietic System 

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

Hemangiosarcoma X 

Lymph node + + + 

Lymph node, bronchial M M + M + M M + M M + M M + + + + + + + I + + + + 

Alveolar/bronchiolar carcinoma, metastatic, lung X 

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

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

Lymph node, mediastinal M M + + + + M + + M + + M + + + + + + + + + + + + 

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

Thymus M + + + M + + + M + + M + M + + + + M + M + + + + 

Integumentary System 

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

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

Subcutaneous tissue, hemangiosarcoma 

Subcutaneous tissue, sarcoma X 

Musculoskeletal System 

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

Hemangiosarcoma, metastatic, bone marrow X 

Nervous System 

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

Meninges, histiocytic sarcoma X 

Spinal cord + 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 

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

Alveolar/bronchiolar adenoma X 

Alveolar/bronchiolar carcinoma X X X 

Hepatocellular carcinoma, metastatic, liver X X 

Histiocytic sarcoma X X 

Sarcoma, metastatic, skin X 

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

Histiocytic sarcoma X 

Pleura + 

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

Special Senses System 

Eye + A + + + + + + + + + + + + + + + + + + + + + + + 

Harderian gland + 

Adenoma X 
 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 169 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 1 1 1 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 5 Tissues/ 

5 6 7 0 1 2 3 4 5 6 8 0 1 3 6 7 8 9 0 3 6 7 8 9 0 Tumors 

Genital System (continued) 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 2 

Leiomyoma 1 

Leiomyosarcoma 1 

Polyp stromal X 2 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma X 2 

Lymph node + + + 6 

Lymph node, bronchial + + M + + + + + M M M + M + + + M + + + + + + M + 33 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 

Lymph node, mandibular M M + M + M + + + + + + + + + + M + + M + + + + + 36 

Lymph node, mesenteric I + + + + + + + + + + + + + + + + + + + + + + + + 48 

Lymph node, mediastinal + + + + + + + + + + + + + + M + M + + M M + + + + 41 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Thymus + + + + + + + + + + + + + + + M + + + + + + + + + 42 

Integumentary System 

Mammary gland	 + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Subcutaneous tissue, hemangiosarcoma X 1 

Subcutaneous tissue, sarcoma 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma, metastatic, bone marrow 1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Meninges, histiocytic sarcoma 1 

Spinal cord + 2 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + M + + + + + + 49 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar adenoma X 2 

Alveolar/bronchiolar carcinoma X 4 

Hepatocellular carcinoma, metastatic, liver 2 

Histiocytic sarcoma 2 

Sarcoma, metastatic, skin 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Pleura 1 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Harderian gland + 2 

Adenoma X 2 
 

 

 

170 Furfuryl Alcohol, NTP TR 482 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

3 4 5 5 5 5 5 5 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 5 4 4 4 6 7 9 9 0 0 5 5 8 9 1 1 3 3 3 3 3 3 3 3 3 

2 8 7 7 6 3 5 6 4 9 1 1 9 3 2 5 4 4 4 4 4 4 4 4 4 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

Carcass ID Number 3 2 0 0 1 4 0 3 2 1 3 4 1 4 4 1 0 0 0 0 0 0 1 1 1 

2 9 1 5 4 1 7 4 7 1 5 5 9 4 2 8 2 3 4 6 8 9 0 2 3 

Urinary System 

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

Histiocytic sarcoma X 

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

Systemic Lesions 

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

Histiocytic sarcoma X X 

Lymphoma malignant X X X X X 
 

 

 

Furfuryl Alcohol, NTP TR 482 171 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: Chamber Control 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study	 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Total 

Carcass ID Number 1 1 1 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 5 Tissues/ 

5 6 7 0 1 2 3 4 5 6 8 0 1 3 6 7 8 9 0 3 6 7 8 9 0 Tumors 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 2 

Lymphoma malignant X 6 
 

 

 

 

 

 

 

 

 

 

 

172 Furfuryl Alcohol, NTP TR 482 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

2 4 4 4 4 5 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 6 4 4 5 9 2 0 0 4 4 8 8 8 2 2 3 3 3 3 3 3 3 3 3 

1 1 8 7 7 5 0 1 6 9 1 4 7 1 1 0 4 4 4 4 4 4 4 4 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

Carcass ID Number 1 4 4 1 1 0 3 0 3 2 1 1 4 0 3 2 0 0 0 0 0 0 1 1 

0 3 6 7 3 5 7 4 1 3 9 2 7 6 3 5 1 2 3 7 8 9 1 4 

Alimentary System 

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

Gallbladder + + A + + + + + + + + A + + + + + + + + + + + + 

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

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

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

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

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

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

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

Hepatocellular carcinoma X X X 

Hepatocellular carcinoma, multiple X X 

Hepatocellular adenoma X 

Hepatocellular adenoma, multiple X X 

Mesentery + + 

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

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

Carcinoma, metastatic, harderian gland X 

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

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

Cardiovascular System 

Blood vessel + 

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

Endocrine System 

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

Capsule, adenoma 

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

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

Parathyroid gland + M M + + + M + + M + + + + M M + M M + + + + + 

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

Pars distalis, adenoma X 

Pars intermedia, adenoma 

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

Follicular cell, adenoma 

Follicular cell, carcinoma 

General Body System 

None 

Genital System 

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

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

Alveolar/bronchiolar carcinoma, metastatic, lung X 

Cystadenoma X 

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

Hemangioma 

Polyp stromal X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 173 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 1 1 1 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 4 5 Tissues/ 

5 6 8 0 1 2 6 7 8 9 0 2 4 5 6 8 9 0 1 2 4 5 8 9 0 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Gallbladder + + + + + + + + + + + + + + M + + + M + + + + + + 45 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, rectum + + + + + + + + + + + + + + + + + M + + + + + + + 45 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hepatocellular carcinoma X X X X X X X X X 12 

Hepatocellular carcinoma, multiple X 3 

Hepatocellular adenoma X X X X 5 

Hepatocellular adenoma, multiple 2 

Mesentery + + + + 6 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Carcinoma, metastatic, harderian gland 1 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 46 

Cardiovascular System 

Blood vessel 1 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Capsule, adenoma X X 2 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Parathyroid gland M M + M + M M M M + I + + + + M + + + + + + + + + 32 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Pars distalis, adenoma X X X X X X 7 

Pars intermedia, adenoma X 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Follicular cell, adenoma X 1 

Follicular cell, carcinoma X 1 

General Body System 

None 

Genital System 

Clitoral gland + + I M + + + + + + + + M + + + + + M + + M + + M 41 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 

Cystadenoma 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hemangioma X 1 

Polyp stromal X X 3 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

174 Furfuryl Alcohol, NTP TR 482 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

2 4 4 4 4 5 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 6 4 4 5 9 2 0 0 4 4 8 8 8 2 2 3 3 3 3 3 3 3 3 3 

1 1 8 7 7 5 0 1 6 9 1 4 7 1 1 0 4 4 4 4 4 4 4 4 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

Carcass ID Number 1 4 4 1 1 0 3 0 3 2 1 1 4 0 3 2 0 0 0 0 0 0 1 1 

0 3 6 7 3 5 7 4 1 3 9 2 7 6 3 5 1 2 3 7 8 9 1 4 

Hematopoietic System 

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

Hemangiosarcoma X 

Lymph node + + 

Lymph node, bronchial + M + + M + M + M + M + + M M + M + M + M + M + 

Alveolar/bronchiolar carcinoma, metastatic, lung X 

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

Carcinoma, metastatic, harderian gland X 

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

Lymph node, mediastinal M M + + + + + + + + M + + M M + + M + + M M + M 

Alveolar/bronchiolar carcinoma, metastatic, lung X 

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

Hemangiosarcoma 

Histiocytic sarcoma 

Thymus + M + M M + + + + + + + + + + + + + M + M M + + 

Integumentary System 

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

Carcinoma X 

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

Hemangiosarcoma X 

Musculoskeletal System 

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

Skeletal muscle + 

Alveolar/bronchiolar carcinoma, metastatic, lung X 

Nervous System 

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

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + 

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

Alveolar/bronchiolar adenoma X X X 

Alveolar/bronchiolar carcinoma X X X 

Alveolar/bronchiolar carcinoma, multiple X 

Carcinoma, metastatic, harderian gland X X 

Hepatocellular carcinoma, metastatic,liver X 

Mediastinum, alveolar/bronchiolar carcinoma,

 metastatic, lung X 

Nose + + A + + + + + + + + + + + + + + + + + + + + + 

Trachea + + A + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + 

Harderian gland + + 

Adenoma 

Carcinoma X X 

Lacrimal gland + 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 175 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Total 

Carcass ID Number 1 1 1 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 4 5 Tissues/ 

5 6 8 0 1 2 6 7 8 9 0 2 4 5 6 8 9 0 1 2 4 5 8 9 0 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hemangiosarcoma 1 

Lymph node + + 4 

Lymph node, bronchial M M + + M + M + + M + M M + + M M + + + + M M + + 27 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 

Lymph node, mandibular + + + + + M + + M + + + + + + + M + + + + + M + M 40 

Carcinoma, metastatic, harderian gland 1 

Lymph node, mesenteric + + + + + + + + + + + + + M + + + + + + + + + + + 47 

Lymph node, mediastinal + + + M + + + M + + + + + M M + + + + M + M + + + 34 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Hemangiosarcoma X 1 

Histiocytic sarcoma X 1 

Thymus + + + + M + + + + + + + + + + I + + + + M + + + + 40 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Carcinoma X 2 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hemangiosarcoma 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Skeletal muscle 1 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Alveolar/bronchiolar adenoma X 4 

Alveolar/bronchiolar carcinoma 3 

Alveolar/bronchiolar carcinoma, multiple 1 

Carcinoma, metastatic, harderian gland 2 

Hepatocellular carcinoma, metastatic, liver 1 

Mediastinum, alveolar/bronchiolar carcinoma,

 metastatic, lung 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Harderian gland + + + 5 

Adenoma X X 2 

Carcinoma 2 

Lacrimal gland 1 
 

176 Furfuryl Alcohol, NTP TR 482 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

Number of Days on Study 

2 

6 

1 

4 

4 

1 

4 

4 

8 

4 

5 

7 

4 

9 

7 

5 

2 

5 

6 

0 

0 

6 

0 

1 

6 

4 

6 

6 

4 

9 

6 

8 

1 

6 

8 

4 

6 

8 

7 

7 

2 

1 

7 

2 

1 

7 

3 

0 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

Carcass ID Number 

3 

1 

0 

3 

4 

3 

3 

4 

6 

3 

1 

7 

3 

1 

3 

3 

0 

5 

3 

3 

7 

3 

0 

4 

3 

3 

1 

3 

2 

3 

3 

1 

9 

3 

1 

2 

3 

4 

7 

3 

0 

6 

3 

3 

3 

3 

2 

5 

3 

0 

1 

3 

0 

2 

3 

0 

3 

3 

0 

7 

3 

0 

8 

3 

0 

9 

3 

1 

1 

3 

1 

4 

Urinary System 

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

Urinary bladder + + A + + + + + + + + A + + + + + + + + + + + + 

Systemic Lesions 

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

Histiocytic sarcoma 

Lymphoma malignant X 
 

 

Furfuryl Alcohol, NTP TR 482 177 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 2 ppm 

Number of Days on Study 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

Carcass ID Number 

3 

1 

5 

3 

1 

6 

3 

1 

8 

3 

2 

0 

3 

2 

1 

3 

2 

2 

3 

2 

6 

3 

2 

7 

3 

2 

8 

3 

2 

9 

3 

3 

0 

3 

3 

2 

3 

3 

4 

3 

3 

5 

3 

3 

6 

3 

3 

8 

3 

3 

9 

3 

4 

0 

3 

4 

1 

3 

4 

2 

3 

4 

4 

3 

4 

5 

3 

4 

8 

3 

4 

9 

3 

5 

0 

Total 

Tissues/ 

Tumors 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Urinary bladder + + + + I + + + + + + + + + + + + + + + + + I + + 45 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Histiocytic sarcoma X 1 

Lymphoma malignant X X 3 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

178 Furfuryl Alcohol, NTP TR 482 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

4 4 4 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 

Number of Days on Study 1 1 6 8 0 1 2 3 3 3 3 6 6 6 8 9 9 9 3 3 3 3 3 3 3 

1 3 9 2 4 7 1 2 7 7 9 5 5 6 4 3 3 8 4 4 4 4 4 4 4 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

Carcass ID Number 3 2 4 3 5 4 4 0 0 2 4 3 4 1 2 0 1 4 0 0 0 0 0 0 1 

3 3 4 5 0 3 2 2 6 4 5 0 1 1 5 5 3 0 1 3 4 7 8 9 0 

Alimentary System 

Esophagus + + + + + + + + + + + + + + A + + + + + + + + + + 

Gallbladder M + A + + + + + + + + + + + A + + + + + + + + + + 

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

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

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

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

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

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

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

Hepatocellular carcinoma X X X X 

Hepatocellular adenoma X X X X X X 

Hepatocholangiocarcinoma X 

Sarcoma, metastatic, uncertain primary site X 

Mesentery + + + + + + 

Hemangiosarcoma X 

Hepatocholangiocarcinoma, metastatic,liver X 

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

Sarcoma, metastatic, uncertain primary site X 

Salivary glands + + + + + + + + + + + + + + A + + + + + + + + + + 

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

Squamous cell carcinoma X 

Squamous cell papilloma X 

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

Tooth + + 

Adamantinoma malignant X 

Cardiovascular System 

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

Sarcoma, metastatic, uncertain primary site X 

Endocrine System 

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

Sarcoma, metastatic, uncertain primary site X 

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

Sarcoma, metastatic, uncertain primary site X 

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

Adenoma 

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

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

Pars distalis, adenoma X X 

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

Bilateral, follicular cell, adenoma X 

Follicular cell, adenoma X 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 179 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

Number of Days on Study 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

4 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

7 

3 

5 

Carcass ID Number 

5 

1 

2 

5 

1 

4 

5 

1 

5 

5 

1 

6 

5 

1 

7 

5 

1 

8 

5 

1 

9 

5 

2 

0 

5 

2 

1 

5 

2 

2 

5 

2 

6 

5 

2 

7 

5 

2 

8 

5 

2 

9 

5 

3 

1 

5 

3 

2 

5 

3 

4 

5 

3 

6 

5 

3 

7 

5 

3 

8 

5 

3 

9 

5 

4 

6 

5 

4 

7 

5 

4 

8 

5 

4 

9 

Total 

Tissues/ 

Tumors 

Alimentary System 

Esophagus + + + + + + + + M + + + + + + + + + + + + + + + + 48 

Gallbladder + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hepatocellular carcinoma X 5 

Hepatocellular adenoma X X X 9 

Hepatocholangiocarcinoma 1 

Sarcoma, metastatic, uncertain primary site 1 

Mesentery + + + + + 11 

Hemangiosarcoma 1 

Hepatocholangiocarcinoma, metastatic, liver 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Sarcoma, metastatic, uncertain primary site 1 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Squamous cell carcinoma 1 

Squamous cell papilloma X X 3 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Tooth 2 

Adamantinoma malignant 1 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Sarcoma, metastatic, uncertain primary site 1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Sarcoma, metastatic, uncertain primary site 1 

Adrenal medulla + + + + + + + + + + + + + + + + + M + + + + + + + 49 

Sarcoma, metastatic, uncertain primary site 1 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma X 1 

Parathyroid gland M + + + M M M + + + I + M + + + + + M + + + M + M 29 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Pars distalis, adenoma X X 4 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Bilateral, follicular cell, adenoma 1 

Follicular cell, adenoma X 2 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

180 Furfuryl Alcohol, NTP TR 482 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

4 4 4 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 

Number of Days on Study 1 1 6 8 0 1 2 3 3 3 3 6 6 6 8 9 9 9 3 3 3 3 3 3 3 

1 3 9 2 4 7 1 2 7 7 9 5 5 6 4 3 3 8 4 4 4 4 4 4 4 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

Carcass ID Number 3 2 4 3 5 4 4 0 0 2 4 3 4 1 2 0 1 4 0 0 0 0 0 0 1 

3 3 4 5 0 3 2 2 6 4 5 0 1 1 5 5 3 0 1 3 4 7 8 9 0 

Genital System 

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

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

Cystadenoma X X X 

Granulosa cell tumor benign 

Sarcoma, metastatic, uncertain primary site X 

Yolk sac carcinoma X 

Uterus + + + + + + + + + + + + + + A + + + + + + + + + + 

Histiocytic sarcoma X 

Polyp stromal X X X 

Sarcoma, metastatic, uncertain primary site X 

Hematopoietic System 

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

Lymph node + + 

Lymph node, bronchial M + + + M M + + M + + + + M A + + M + M M + + M M 

Alveolar/bronchiolar carcinoma, metastatic, lung X 

Hepatocholangiocarcinoma, metastatic, liver X 

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

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

Lymph node, mediastinal + + + + + + M M M + + + M + A + + + + + + + + + + 

Alveolar/bronchiolar carcinoma, metastatic, lung X 

Hepatocholangiocarcinoma, metastatic, liver X 

Sarcoma, metastatic, uncertain primary site X 

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

Hemangiosarcoma X X 

Thymus + + + + + + + + + + M + + + + + + M + + + + + + M 

Alveolar/bronchiolar carcinoma, metastatic, lung X 

Sarcoma, metastatic, uncertain primary site X 

Integumentary System 

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

Carcinoma X 

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

Subcutaneous tissue, hemangioma, multiple 

Subcutaneous tissue, hemangiosarcoma X X 

Subcutaneous tissue, histiocytic sarcoma X 

Subcutaneous tissue, sarcoma 

Musculoskeletal System 

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

Skeletal muscle + 

Sarcoma, metastatic, uncertain primary site X 

Nervous System 

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

Peripheral nerve +
 

Spinal cord +
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 181 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 Total 

Carcass ID Number 1 1 1 1 1 1 1 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 Tissues/ 

2 4 5 6 7 8 9 0 1 2 6 7 8 9 1 2 4 6 7 8 9 6 7 8 9 Tumors 

Genital System 

Clitoral gland + + + + M M + + M + + M + + + + + + M + + + + + + 31 

Ovary + + + + + + + + + + + + + + + + + + + + M + + + + 48 

Cystadenoma 3 

Granulosa cell tumor benign X X 2 

Sarcoma, metastatic, uncertain primary site 1 

Yolk sac carcinoma 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Histiocytic sarcoma 1 

Polyp stromal X 4 

Sarcoma, metastatic, uncertain primary site 1 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lymph node + + + 5 

Lymph node, bronchial + M M + + + M + M + + + + M M M + + + + M M + + + 30 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 

Hepatocholangiocarcinoma, metastatic, liver 1 

Lymph node, mandibular M + + + + + + M + + + + + + + + + M + + + M + + + 43 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Lymph node, mediastinal + + M + + + + + + + + + M + + + + M + + + M + M + 40 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 

Hepatocholangiocarcinoma, metastatic, liver 1 

Sarcoma, metastatic, uncertain primary site 1 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hemangiosarcoma 2 

Thymus + + + + + + + + M + + + + + + + + + + + + + + + + 46 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 

Sarcoma, metastatic, uncertain primary site 1 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Carcinoma 1 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Subcutaneous tissue, hemangioma, multiple X 1 

Subcutaneous tissue, hemangiosarcoma 2 

Subcutaneous tissue, histiocytic sarcoma 1 

Subcutaneous tissue, sarcoma X 1 

Musculoskeletal System 

Bone 

Skeletal muscle

Sarcoma, metastatic, uncertain primary site 

+ + + + + + + + + + + + + + + + + + + + + + + + + 50 

1 

1 

Nervous System 

Brain 

Peripheral nerve

Spinal cord 

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

+

+ + + + + + + 49 

1 

2 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

182 Furfuryl Alcohol, NTP TR 482 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

4 4 4 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 

Number of Days on Study 1 1 6 8 0 1 2 3 3 3 3 6 6 6 8 9 9 9 3 3 3 3 3 3 3 

1 3 9 2 4 7 1 2 7 7 9 5 5 6 4 3 3 8 4 4 4 4 4 4 4 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

Carcass ID Number 3 2 4 3 5 4 4 0 0 2 4 3 4 1 2 0 1 4 0 0 0 0 0 0 1 

3 3 4 5 0 3 2 2 6 4 5 0 1 1 5 5 3 0 1 3 4 7 8 9 0 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 

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

Alveolar/bronchiolar adenoma X X 

Alveolar/bronchiolar carcinoma X 

Alveolar/bronchiolar carcinoma, multiple X 

Carcinoma, metastatic, mammary gland X 

Hepatocholangiocarcinoma, metastatic liver X 

Sarcoma, metastatic, uncertain primary site X 

Mediastinum, alveolar/bronchiolar carcinoma,

 metastatic, lung X 

Mediastinum, hepatocholangiocarcinoma,

 metastatic, liver X 

Nose + + + + + + + + + + + + + + A + + + + + + + + + + 

Sarcoma, metastatic, uncertain primary site X 

Trachea + + + + + + + + + + + + + + A + + + + + + + + + + 

Special Senses System 

Eye + + + + + + + + + + + + + + A + + + + + + + + + + 

Sarcoma, metastatic, uncertain primary site X 

Harderian gland + + + 

Adenoma X X 

Sarcoma, metastatic, uncertain primary site X 

Urinary System 

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

Hepatocholangiocarcinoma, metastatic, liver X 

Histiocytic sarcoma X 

Sarcoma, metastatic, uncertain primary site X 

Urinary bladder + + + + + + + + + + + + + + A + + + + + + + + + + 

Systemic Lesions 

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

Histiocytic sarcoma X X 

Lymphoma malignant X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 183 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 8 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 Total 

Carcass ID Number 1 1 1 1 1 1 1 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 Tissues/ 

2 4 5 6 7 8 9 0 1 2 6 7 8 9 1 2 4 6 7 8 9 6 7 8 9 Tumors 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Alveolar/bronchiolar adenoma X X X X X X 8 

Alveolar/bronchiolar carcinoma X X 3 

Alveolar/bronchiolar carcinoma, multiple 1 

Carcinoma, metastatic, mammary gland 1 

Hepatocholangiocarcinoma, metastatic, liver 1 

Sarcoma, metastatic, uncertain primary site 1 

Mediastinum, alveolar/bronchiolar carcinoma, 

metastatic, lung 1 

Mediastinum, hepatocholangiocarcinoma,

 metastatic, liver 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Sarcoma, metastatic, uncertain primary site 1 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Sarcoma, metastatic, uncertain primary site 1 

Harderian gland + + + 6 

Adenoma X X X 5 

Sarcoma, metastatic, uncertain primary site 1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hepatocholangiocarcinoma, metastatic, liver 1 

Histiocytic sarcoma 1 

Sarcoma, metastatic, uncertain primary site 1 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 2 

Lymphoma malignant X X X X 5 
 

 

 

 

 

 

 

 

184 Furfuryl Alcohol, NTP TR 482 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

5 5 5 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 7 7 8 0 0 6 6 8 9 1 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 9 2 0 9 3 5 9 3 3 4 4 4 4 4 4 4 4 4 4 4 4 5 5 5 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Carcass ID Number 3 3 1 2 1 2 0 3 4 0 0 0 0 0 0 0 0 1 1 1 1 1 1 1 1 

9 5 4 5 2 8 8 8 0 6 1 2 3 4 5 7 9 0 1 3 5 6 7 8 9 

Alimentary System 

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

Gallbladder + A + A M + + + + + + + + + + + + + + + + + + + + 

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

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

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

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

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

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

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

Hemangiosarcoma 

Hepatocellular carcinoma X X X 

Hepatocellular carcinoma, multiple 

Hepatocellular adenoma X X 

Mesentery + + + + + + + + 

Sarcoma, metastatic, skin X 

Oral mucosa 

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

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

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

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

Cardiovascular System 

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

Endocrine System 

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

Capsule, adenoma X 

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

Pheochromocytoma benign 

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

Adenoma 

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

Pituitary gland + A + + + + + + + + + + + + + + + + + + + + + + + 

Pars distalis, adenoma 

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

Follicular cell, adenoma X X X X 

General Body System 

None 

Genital System 

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

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

Cystadenoma X 

Luteoma X 

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

Adenocarcinoma X 

Polyp stromal 
 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 185 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 Total 

Carcass ID Number 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 5 Tissues/ 

0 1 2 3 4 6 7 9 0 1 2 3 4 6 7 1 2 3 4 5 6 7 8 9 0 Tumors 

Alimentary System 

Esophagus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Gallbladder M M + + + + + + + + + + M + + + M M + + + + + I + 41 

Intestine large, colon + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Intestine large, rectum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine large, cecum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, duodenum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, jejunum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Intestine small, ileum + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Liver + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hemangiosarcoma X 1 

Hepatocellular carcinoma X X X 6 

Hepatocellular carcinoma, multiple X X 2 

Hepatocellular adenoma X X X 5 

Mesentery + + 10 

Sarcoma, metastatic, skin 1 

Oral mucosa + 1 

Pancreas + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Salivary glands + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Stomach, forestomach + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Stomach, glandular + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Cardiovascular System 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Capsule, adenoma 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pheochromocytoma benign X 1 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Adenoma X 1 

Parathyroid gland M + M + M + + M M + I I M + + M M M + M + M + + M 26 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pars distalis, adenoma X 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Follicular cell, adenoma X 5 

General Body System 

None 

Genital System 

Clitoral gland + + + + + + + + + + + + M + + M + + + M + + + + + 41 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Cystadenoma X 2 

Luteoma 1 

Uterus + + + + + + + + + + + + + + + + + + I + + + + + + 49 

Adenocarcinoma 1 

Polyp stromal X X 2 
 

 

 

 

 

 

 

 

 

 

 

 

186 Furfuryl Alcohol, NTP TR 482 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

5 5 5 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 7 7 8 0 0 6 6 8 9 1 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

4 9 2 0 9 3 5 9 3 3 4 4 4 4 4 4 4 4 4 4 4 4 5 5 5 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Carcass ID Number 3 3 1 2 1 2 0 3 4 0 0 0 0 0 0 0 0 1 1 1 1 1 1 1 1 

9 5 4 5 2 8 8 8 0 6 1 2 3 4 5 7 9 0 1 3 5 6 7 8 9 

Hematopoietic System 

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

Hemangiosarcoma 

Lymph node + + 

Lymph node, bronchial + M + + + + + M + + + + + + + M + + + + + M + + + 

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

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

Lymph node, mediastinal + A M M M + M + + + + + + + M M M + + + + + + + + 

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

Hemangioma 

Thymus + A + + + M M + + + + + + + + + M M + + + + M + M 

Integumentary System 

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

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

Subcutaneous tissue, hemangioma 

Subcutaneous tissue, hemangiosarcoma 

Subcutaneous tissue, sarcoma X 

Subcutaneous tissue, sarcoma, multiple X 

Musculoskeletal System 

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

Osteosarcoma 

Skeletal muscle + 

Sarcoma, metastatic, skin X 

Nervous System 

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

Spinal cord 

Respiratory System 

Larynx + A + + + + + + + + + + + + + + + + + + + + + + + 

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

Alveolar/bronchiolar carcinoma 

Carcinoma, metastatic, harderian gland X 

Hepatocellular carcinoma, metastatic, liver X 

Sarcoma, metastatic, skin X 

Mediastinum, sarcoma, metastatic, skin X 

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

Trachea + A + A + + + + + + + + + + + + + + + + + + + + + 

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 

Harderian gland + + + + + 

Adenoma X X X X 

Carcinoma X 

Urinary System 

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

Urinary bladder + A + A + + + + + + + + + + + + + + + + + + + + + 

Systemic Lesions 

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

Lymphoma malignant X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 187 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol: 32 ppm 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 

5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 Total 

Carcass ID Number 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 5 Tissues/ 

0 1 2 3 4 6 7 9 0 1 2 3 4 6 7 1 2 3 4 5 6 7 8 9 0 Tumors 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hemangiosarcoma X 1 

Lymph node + + 4 

Lymph node, bronchial + + + M M + M M + M + + M + M M + + + + M + + + + 37 

Lymph node, mandibular + + M + M + + + + + M + + + + M + + M M + + + + + 40 

Lymph node, mesenteric + + + M + + + + + + + + + + + + + M + + + + + + + 46 

Lymph node, mediastinal + + + + + + + M + + + + + + M + + + + + + + + + + 40 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Hemangioma X 1 

Thymus + + + + M M + + + + + + + + M + + M + M + + + + + 38 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Subcutaneous tissue, hemangioma X 1 

Subcutaneous tissue, hemangiosarcoma X 1 

Subcutaneous tissue, sarcoma 1 

Subcutaneous tissue, sarcoma, multiple 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Osteosarcoma X 1 

Skeletal muscle 1 

Sarcoma, metastatic, skin 1 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Spinal cord + 1 

Respiratory System 

Larynx + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar carcinoma X 1 

Carcinoma, metastatic, harderian gland 1 

Hepatocellular carcinoma, metastatic, liver X X 3 

Sarcoma, metastatic, skin 1 

Mediastinum, sarcoma, metastatic, skin 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Special Senses System 

Eye + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Harderian gland + 6 

Adenoma X 5 

Carcinoma 1 

Urinary System 

Kidney + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Urinary bladder + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Systemic Lesions 

Multiple organs + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Lymphoma malignant X X X 8 
188 Furfuryl Alcohol, NTP TR 482 

TABLE D3 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Harderian Gland: Adenoma 

Overall ratea 

Adjusted rateb 2/50 (4%) 

4.6% 

2/49 (4%) 

4.7% 

5/50 (10%) 

11.6% 

5/50 (10%) 

10.6% 

Terminal ratec 1/34 (3%) 2/33 (6%) 4/32 (13%) 4/40 (10%) 

First incidence (days) 

Poly-3 testd 

712 

P=0.211 

734 (T) 

P=0.685 

693 

P=0.215 

600 

P=0.252 

Harderian Gland: Adenoma or Carcinoma 

Overall rate 2/50 (4%) 4/49 (8%) 5/50 (10%) 6/50 (12%) 

Adjusted rate 4.6% 9.3% 11.6% 12.7% 

Terminal rate 1/34 (3%) 2/33 (6%) 4/32 (13%) 5/40 (13%) 

First incidence (days) 712 525 693 600 

Poly-3 test P=0.210 P=0.332 P=0.215 P=0.162 

Liver: Hepatocellular Adenoma 

Overall rate 7/50 (14%) 7/49 (14%) 9/49 (18%) 5/49 (10%) 

Adjusted rate 16.0% 16.5% 20.8% 10.8% 

Terminal rate 5/34 (15%) 5/33 (15%) 5/32 (16%) 5/40 (13%) 

First incidence (days) 595 649 621 734 (T) 

Poly-3 test P=0.226N P=0.592 P=0.382 P=0.342N 

Liver: Hepatocellular Carcinoma 

Overall rate 9/50 (18%) 15/49 (31%) 5/49 (10%) 8/49 (16%) 

Adjusted rate 20.6% 34.5% 11.6% 17.1% 

Terminal rate 6/34 (18%) 11/33 (33%) 1/32 (3%) 7/40 (18%) 

First incidence (days) 651 525 665 582 

Poly-3 test P=0.174N P=0.111 P=0.198N P=0.440N 

Liver: Hepatocellular Adenoma or Carcinoma 

Overall rate 14/50 (28%) 19/49 (39%) 12/49 (24%) 12/49 (24%) 

Adjusted rate 31.7% 43.4% 27.5% 25.7% 

Terminal rate 10/34 (29%) 14/33 (42%) 6/32 (19%) 11/40 (28%) 

First incidence (days) 595 525 621 582 

Poly-3 test P=0.135N P=0.179 P=0.421N P=0.344N 

Lung: Alveolar/bronchiolar Adenoma 

Overall rate 2/50 (4%) 4/49 (8%) 8/49 (16%) 0/50 (0%) 

Adjusted rate 4.6% 9.4% 18.9% 0.0% 

Terminal rate 1/34 (3%) 2/33 (6%) 8/32 (25%) 0/40 (0%) 

First incidence (days) 693 649 734 (T) —e 

Poly-3 test P=0.058N P=0.328 P=0.040 P=0.221N 

Lung: Alveolar/bronchiolar Carcinoma 

Overall rate 4/50 (8%) 4/49 (8%) 4/49 (8%) 1/50 (2%) 

Adjusted rate 9.0% 9.3% 9.3% 2.1% 

Terminal rate 2/34 (6%) 3/33 (9%) 2/32 (6%) 1/40 (3%) 

First incidence (days) 547 448 469 734 (T) 

Poly-3 test P=0.099N P=0.626 P=0.628 P=0.164N 

Lung: Alveolar/bronchiolar Adenoma or Carcinoma 

Overall rate 6/50 (12%) 8/49 (16%) 11/49 (22%) 1/50 (2%) 

Adjusted rate 13.5% 18.5% 25.5% 2.1% 

Terminal rate 3/34 (9%) 5/33 (15%) 9/32 (28%) 1/40 (3%) 

First incidence (days) 547 448 469 734 (T) 

Poly-3 test P=0.011N P=0.364 P=0.122 P=0.049N 
Furfuryl Alcohol, NTP TR 482 189 

TABLE D3 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Ovary: Cystadenoma 

Overall rate 2/50 (4%) 1/49 (2%) 3/48 (6%) 2/49 (4%) 

Adjusted rate 4.6% 2.4% 7.2% 4.3% 

Terminal rate 2/34 (6%) 0/33 (0%) 1/31 (3%) 1/40 (3%) 

First incidence (days) 734 (T) 684 637 609 

Poly-3 test P=0.616 P=0.507N P=0.486 P=0.666N 

Pituitary Gland (Pars Distalis): Adenoma 

Overall rate 7/48 (15%) 7/48 (15%) 4/48 (8%) 1/49 (2%) 

Adjusted rate 16.8% 16.9% 9.5% 2.2% 

Terminal rate 7/33 (21%) 7/33 (21%) 2/32 (6%) 1/40 (3%) 

First incidence (days) 734 (T) 734 (T) 617 734 (T) 

Poly-3 test P=0.011N P=0.608 P=0.251N P=0.020N 

Stomach (Forestomach): Squamous Cell Papilloma 

Overall rate 0/50 (0%) 0/49 (0%) 3/50 (6%) 0/50 (0%)
 

Adjusted rate 0.0% 0.0% 7.0% 0.0%
 

Terminal rate 0/34 (0%) 0/33 (0%) 3/32 (9%) 0/40 (0%)
 

First incidence (days) — — 734 (T) —
 

Poly-3 test P=0.545N —f P=0.118 —
 

Stomach (Forestomach): Squamous Cell Papilloma or Squamous Cell Carcinoma 

Overall rate 0/50 (0%) 0/49 (0%) 4/50 (8%) 0/50 (0%)
 

Adjusted rate 0.0% 0.0% 9.3% 0.0%
 

Terminal rate 0/34 (0%) 0/33 (0%) 4/32 (13%) 0/40 (0%)
 

First incidence (days) — — 734 (T) —
 

Poly-3 test P=0.487N — P=0.059 —
 

Thyroid Gland (Follicular Cell): Adenoma 

Overall rate 3/50 (6%) 1/49 (2%) 3/49 (6%) 5/49 (10%) 

Adjusted rate 6.9% 2.4% 7.0% 10.8% 

Terminal rate 3/34 (9%) 1/33 (3%) 2/32 (6%) 5/40 (13%) 

First incidence (days) 734 (T) 734 (T) 617 734 (T) 

Poly-3 test P=0.159 P=0.313N P=0.657 P=0.393 

Thyroid Gland (Follicular Cell): Adenoma or Carcinoma 

Overall rate 3/50 (6%) 2/49 (4%) 3/49 (6%) 5/49 (10%) 

Adjusted rate 6.9% 4.7% 7.0% 10.8% 

Terminal rate 3/34 (9%) 2/33 (6%) 2/32 (6%) 5/40 (13%) 

First incidence (days) 734 (T) 734 (T) 617 734 (T) 

Poly-3 test P=0.223 P=0.511N P=0.657 P=0.393 

Uterus: Stromal Polyp 

Overall rate 2/50 (4%) 3/49 (6%) 4/50 (8%) 2/50 (4%) 

Adjusted rate 4.6% 7.1% 9.1% 4.3% 

Terminal rate 2/34 (6%) 3/33 (9%) 1/32 (3%) 2/40 (5%) 

First incidence (days) 734 (T) 734 (T) 582 734 (T) 

Poly-3 test P=0.434N P=0.489 P=0.347 P=0.666N 

All Organs: Hemangiosarcoma 

Overall rate 2/50 (4%) 2/49 (4%) 4/50 (8%) 2/50 (4%) 

Adjusted rate 4.6% 4.7% 9.1% 4.3% 

Terminal rate 1/34 (3%) 2/33 (6%) 1/32 (3%) 2/40 (5%) 

First incidence (days) 651 734 (T) 621 734 (T) 

Poly-3 test P=0.522N P=0.683 P=0.341 P=0.669N 
190 

c 

Furfuryl Alcohol, NTP TR 482 

TABLE D3 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

All Organs: Hemangioma or Hemangiosarcoma 

Overall rate 2/50 (4%) 3/49 (6%) 5/50 (10%) 4/50 (8%) 

Adjusted rate 4.6% 7.1% 11.4% 8.6% 

Terminal rate 1/34 (3%) 3/33 (9%) 2/32 (6%) 4/40 (10%) 

First incidence (days) 651 734 (T) 621 734 (T) 

Poly-3 test P=0.431 P=0.486 P=0.219 P=0.370 

All Organs: Malignant Lymphoma 

Overall rate 6/50 (12%) 3/49 (6%) 5/50 (10%) 8/50 (16%) 

Adjusted rate 13.4% 7.1% 11.5% 16.9% 

Terminal rate 2/34 (6%) 2/33 (6%) 4/32 (13%) 5/40 (13%) 

First incidence (days) 573 730 637 663 

Poly-3 test P=0.193 P=0.271N P=0.521N P=0.430 

All Organs: Benign Neoplasms 

Overall rate 23/50 (46%) 23/49 (47%) 29/50 (58%) 21/50 (42%) 

Adjusted rate 51.3% 53.8% 63.2% 44.2% 

Terminal rate 18/34 (53%) 19/33 (58%) 20/32 (63%) 19/40 (48%) 

First incidence (days) 573 649 582 600 

Poly-3 test P=0.152N P=0.490 P=0.168 P=0.316N 

All Organs: Malignant Neoplasms 

Overall rate 20/50 (40%) 25/49 (51%) 24/50 (48%) 22/50 (44%) 

Adjusted rate 41.7% 56.4% 50.3% 45.6% 

Terminal rate 9/34 (27%) 18/33 (55%) 11/32 (34%) 16/40 (40%) 

First incidence (days) 352 448 411 582 

Poly-3 test P=0.437N P=0.111 P=0.260 P=0.428 

All Organs: Benign or Malignant Neoplasms 

Overall rate 36/50 (72%) 37/49 (76%) 40/50 (80%) 36/50 (72%) 

Adjusted rate 73.4% 82.5% 81.7% 73.9% 

Terminal rate 22/34 (65%) 28/33 (85%) 24/32 (75%) 29/40 (73%) 

First incidence (days) 352 448 411 582 

Poly-3 test P=0.351N P=0.202 P=0.229 P=0.569 

(T)Terminal sacrifice 

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 Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality 

Observed incidence at terminal kill 

d	 Beneath the chamber control incidence are the P values associated with the trend test. Beneath the exposed group incidence are the P values corresponding to 

pairwise comparisons between the chamber controls and that exposed group. The Poly-3 test accounts for differential mortality in animals that do not reach terminal 

sacrifice. A negative trend or a lower incidence in an exposure group is indicated by N. e Not applicable; no neoplasms in animal group f Value of statistic cannot be computed. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 191 

TABLE D4 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohola 

Chamber Control 2 ppm 8 ppm 32 ppm 

Disposition Summary 

Animals initially in study 50 50 50 50 

Early deaths 

Accidental deaths 1 1 

Moribund 11 12 15 8 

Natural deaths 5 3 2 2 

Survivors 

Terminal sacrifice 34 33 32 40 

Pregnant 1 

Animals examined microscopically 50 49 50 50 

Alimentary System 

Esophagus (50) (49) (48) (50) 

Angiectasis 1 (2%) 

Inflammation 1 (2%) 

Gallbladder (43) (45) (47) (41) 

Degeneration, hyaline 1 (2%) 

Inflammation, suppurative 2 (4%) 

Intestine large, rectum (49) (45) (49) (48) 

Inflammation, suppurative 1 (2%) 

Metaplasia, squamous 1 (2%) 

Intestine small, duodenum (47) (46) (48) (48) 

Inflammation, chronic 1 (2%) 

Necrosis 1 (2%) 

Epithelium, hyperplasia 1 (2%) 

Intestine small, jejunum (45) (46) (48) (48) 

Peyer’s patch, hyperplasia 1 (2%) 

Intestine small, ileum (45) (47) (48) (48) 

Peyer’s patch, hyperplasia 1 (2%) 1 (2%) 

Liver (50) (49) (49) (49) 

Basophilic focus 2 (4%) 

Clear cell focus 2 (4%) 

Degeneration, fatty 1 (2%) 1 (2%) 1 (2%) 1 (2%) 

Eosinophilic focus 14 (28%) 19 (39%) 20 (41%) 8 (16%) 

Hematopoietic cell proliferation 1 (2%) 5 (10%) 5 (10%) 

Infiltration cellular, mixed cell 1 (2%) 

Inflammation, chronic 4 (8%) 4 (8%) 1 (2%) 

Inflammation, focal, granulomatous 1 (2%) 2 (4%) 

Karyomegaly 1 (2%) 

Necrosis 2 (4%) 1 (2%) 4 (8%) 2 (4%) 

Pigmentation, bile 1 (2%) 

Regeneration 1 (2%) 

Bile duct, cyst 1 (2%) 

Centrilobular, necrosis 1 (2%) 

Mesentery (15) (6) (11) (10) 

Angiectasis 1 (10%) 

Inflammation, chronic 1 (7%) 1 (10%) 

Fat, hemorrhage 1 (9%) 1 (10%) 

Fat, necrosis 13 (87%) 6 (100%) 8 (73%) 7 (70%) 

Oral mucosa (1) 

Pharyngeal, hyperplasia 1 (100%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

192 Furfuryl Alcohol, NTP TR 482 

TABLE D4 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Alimentary System (continued) 

Pancreas (50) (48) (49) (49) 

Atrophy 7 (14%) 3 (6%) 5 (10%) 9 (18%) 

Cytoplasmic alteration 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 1 (2%) 

Hypertrophy 1 (2%) 2 (4%) 1 (2%) 

Inflammation, chronic, focal 1 (2%) 1 (2%) 

Duct, cyst 1 (2%) 

Stomach, forestomach (50) (48) (49) (49) 

Infiltration cellular, mast cell 1 (2%) 

Inflammation, suppurative 2 (4%) 1 (2%) 

Ulcer 3 (6%) 1 (2%) 

Epithelium, hyperplasia 2 (4%) 8 (17%) 6 (12%) 3 (6%) 

Stomach, glandular (50) (46) (49) (48) 

Inflammation, suppurative 2 (4%) 2 (4%) 

Necrosis 1 (2%) 

Cardiovascular System 

Blood vessel (1) 

Inflammation 1 (100%) 

Heart (50) (49) (49) (50) 

Cardiomyopathy 36 (72%) 40 (82%) 46 (94%) 42 (84%) 

Mineralization 1 (2%) 

Endocrine System 

Adrenal cortex (50) (49) (50) (49) 

Angiectasis 1 (2%) 

Hematopoietic cell proliferation 1 (2%) 1 (2%) 

Hyperplasia 2 (4%) 

Hypertrophy 4 (8%) 1 (2%) 3 (6%) 3 (6%) 

Adrenal medulla (48) (48) (49) (49) 

Hyperplasia 4 (8%) 1 (2%) 2 (4%) 4 (8%) 

Islets, pancreatic (49) (48) (49) (49) 

Hyperplasia 2 (4%) 1 (2%) 2 (4%) 

Parathyroid gland (32) (32) (29) (26) 

Hyperplasia 1 (3%) 

Pituitary gland (48) (48) (48) (49) 

Angiectasis 1 (2%) 

Hemorrhage 1 (2%) 

Pars distalis, angiectasis 1 (2%) 1 (2%) 

Pars distalis, cyst 1 (2%) 

Pars distalis, hyperplasia 15 (31%) 17 (35%) 15 (31%) 17 (35%) 

Pars intermedia, hyperplasia 1 (2%) 

Thyroid gland (50) (49) (49) (49) 

Inflammation 1 (2%) 

Follicular cell, cyst 1 (2%) 

Follicular cell, hyperplasia 17 (34%) 21 (43%) 17 (35%) 30 (61%) 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 193 

TABLE D4 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Genital System 

Ovary (50) (49) (48) (49) 

Angiectasis 2 (4%) 1 (2%) 

Atrophy 4 (8%) 3 (6%) 1 (2%) 2 (4%) 

Cyst 14 (28%) 14 (29%) 18 (38%) 15 (31%) 

Hemorrhage 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 

Infiltration cellular, mononuclear cell 1 (2%) 

Inflammation, chronic 1 (2%) 

Inflammation, suppurative 1 (2%) 

Thrombosis 1 (2%) 

Corpus luteum, hemorrhage 1 (2%) 

Corpus luteum, hyperplasia 1 (2%) 

Germinal epithelium, hyperplasia 1 (2%) 

Interstitial cell, hyperplasia 1 (2%) 2 (4%) 1 (2%) 

Uterus (50) (49) (49) (49) 

Angiectasis 3 (6%) 4 (8%) 2 (4%) 

Hemorrhage 1 (2%) 1 (2%) 

Hydrometra 5 (10%) 5 (10%) 4 (8%) 3 (6%) 

Hyperplasia, cystic 4 (8%) 3 (6%) 2 (4%) 

Inflammation, chronic 1 (2%) 

Inflammation, suppurative 1 (2%) 1 (2%) 1 (2%) 

Thrombosis 1 (2%) 2 (4%) 1 (2%) 

Endometrium, hyperplasia 1 (2%) 1 (2%) 

Endometrium, metaplasia 1 (2%) 

Myometrium, hyperplasia 1 (2%) 

Hematopoietic System 

Bone marrow (50) (49) (49) (49) 

Hyperplasia 1 (2%) 1 (2%) 

Lymph node (6) (4) (5) (4) 

Angiectasis 4 (67%) 3 (75%) 2 (40%) 

Necrosis 1 (17%) 

Renal, hyperplasia 1 (25%) 1 (20%) 

Lymph node, bronchial (33) (27) (30) (37) 

Hyperplasia 1 (3%) 1 (4%) 1 (3%) 2 (5%) 

Lymph node, mandibular (36) (40) (43) (40) 

Hyperplasia 1 (3%) 2 (5%) 2 (5%) 

Infiltration cellular, mast cell 1 (2%) 

Lymph node, mesenteric (48) (47) (47) (46) 

Angiectasis 1 (2%) 2 (4%) 

Hematopoietic cell proliferation 1 (2%) 

Hyperplasia 2 (4%) 1 (2%) 1 (2%) 

Lymph node, mediastinal (41) (34) (40) (40) 

Hyperplasia 4 (10%) 1 (3%) 3 (8%) 2 (5%) 

Spleen (50) (48) (49) (49) 

Hematopoietic cell proliferation 11 (22%) 11 (23%) 12 (24%) 17 (35%) 

Hyperplasia, lymphoid 8 (16%) 8 (17%) 4 (8%) 5 (10%) 

Thymus (42) (40) (46) (38) 

Angiectasis 1 (3%) 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 1 (3%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

194 Furfuryl Alcohol, NTP TR 482 

TABLE D4 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Integumentary System 

Mammary gland (50) (49) (49) (50) 

Hyperplasia 2 (4%) 1 (2%) 2 (4%) 

Skin (50) (49) (49) (50) 

Hemorrhage 1 (2%) 

Inflammation, chronic active 1 (2%) 1 (2%) 1 (2%) 

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

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

Subcutaneous tissue, inflammation, focal,

 granulomatous 1 (2%) 

Musculoskeletal System 

Bone (50) (49) (50) (50) 

Fibrous osteodystrophy 16 (32%) 19 (39%) 15 (30%) 22 (44%) 

Fracture 1 (2%) 

Hyperostosis 1 (2%) 

Nervous System 

Brain (50) (49) (49) (49) 

Gliosis 1 (2%) 

Necrosis 2 (4%) 1 (2%) 

Meninges, infiltration cellular, mononuclear

 cell 4 (8%) 4 (8%) 2 (4%) 4 (8%) 

Peripheral nerve (1) 

Degeneration 1 (100%) 

Spinal cord (2) (2) (1) 

Degeneration 1 (50%) 

Respiratory System 

Larynx (49) (49) (50) (49) 

Hyperplasia 5 (10%) 9 (18%) 3 (6%) 5 (10%) 

Inflammation, suppurative 3 (6%) 1 (2%) 

Epiglottis, metaplasia, squamous 1 (2%) 

Lung (50) (49) (49) (50) 

Hematopoietic cell proliferation 1 (2%) 

Hemorrhage 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 

Infiltration cellular, histiocyte 3 (6%) 5 (10%) 2 (4%) 3 (6%) 

Inflammation, chronic, focal 1 (2%) 1 (2%) 

Pigmentation, hemosiderin 1 (2%) 

Alveolar epithelium, hyperplasia 2 (4%) 1 (2%) 2 (4%) 

Mediastinum, inflammation, chronic 1 (2%) 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

Furfuryl Alcohol, NTP TR 482 195 

TABLE D4 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Inhalation Study of Furfuryl Alcohol 

Chamber Control 2 ppm 8 ppm 32 ppm 

Respiratory System (continued) 

Nose (50) (48) (49) (50) 

Inflammation, suppurative 5 (10%) 12 (25%) 25 (51%) 42 (84%) 

Glands, hyperplasia 33 (69%) 46 (94%) 47 (94%) 

Glands, metaplasia, squamous 1 (2%) 1 (2%) 34 (69%) 46 (92%) 

Lateral wall, metaplasia, squamous 3 (6%) 14 (29%) 16 (33%) 36 (72%) 

Lateral wall, necrosis 4 (8%) 1 (2%) 

Olfactory epithelium, atrophy 2 (4%) 35 (73%) 49 (100%) 50 (100%) 

Olfactory epithelium, degeneration, hyaline 7 (14%) 14 (29%) 28 (57%) 45 (90%) 

Olfactory epithelium, metaplasia 31 (65%) 49 (100%) 49 (98%) 

Respiratory epithelium, degeneration, hyaline 19 (38%) 44 (92%) 49 (100%) 48 (96%) 

Respiratory epithelium, hyperplasia, polypoid 1 (2%) 

Respiratory epithelium, metaplasia, squamous 1 (2%) 9 (19%) 21 (43%) 39 (78%) 

Respiratory epithelium, necrosis 2 (4%) 3 (6%) 

Respiratory epithelium, regeneration 9 (18%) 13 (26%) 

Trachea (50) (48) (49) (48) 

Metaplasia, squamous 1 (2%) 

Special Senses System 

Eye (49) (49) (49) (50) 

Cataract 2 (4%) 1 (2%) 1 (2%) 

Inflammation, acute 1 (2%) 

Inflammation, chronic 1 (2%) 

Inflammation, chronic active 2 (4%) 

Cornea, degeneration 3 (6%) 1 (2%) 4 (8%) 26 (52%) 

Cornea, fibrosis 1 (2%) 

Cornea, hyperplasia 2 (4%) 4 (8%) 7 (14%) 

Cornea, inflammation, chronic active 1 (2%) 1 (2%) 3 (6%) 

Urinary System 

Kidney (50) (48) (49) (49) 

Metaplasia, osseous 1 (2%) 3 (6%) 2 (4%) 4 (8%) 

Mineralization 1 (2%) 

Nephropathy 41 (82%) 35 (73%) 40 (82%) 39 (80%) 
196 Furfuryl Alcohol, NTP TR 482 
197 

APPENDIX E
 

GENETIC TOXICOLOGY
 

SALMONELLA MUTAGENICITY TEST PROTOCOL ..................................................... 198
 

CHINESE HAMSTER OVARY CELL CYTOGENETICS PROTOCOLS ........................................ 198
 

MOUSE BONE MARROW CYTOGENETIC TEST PROTOCOLS ............................................ 199
 

RESULTS .................................................................................... 201
 

TABLE E1 Mutagenicity of Furfuryl Alcohol in Salmonella typhimurium ........................... 202
 

TABLE E2 Induction of Sister Chromatid Exchanges in Chinese Hamster Ovary Cells 

by Furfuryl Alcohol ............................................................... 204
 

TABLE E3 Induction of Chromosomal Aberrations in Chinese Hamster Ovary Cells 

by Furfuryl Alcohol ............................................................... 206
 

TABLE E4 Induction of Sister Chromatid Exchanges in Mouse Bone Marrow Cells 

by Furfuryl Alcohol ............................................................... 207
 

TABLE E5 Induction of Chromosomal Aberrations in Mouse Bone Marrow Cells 

by Furfuryl Alcohol ............................................................... 208
 

TABLE E6 Induction of Micronuclei in Bone Marrow Polychromatic Erythrocytes of Mice 

Treated with Furfuryl Alcohol by Intraperitoneal Injection ............................. 210
 
 

198 Furfuryl Alcohol, NTP TR 482 

GENETIC TOXICOLOGY 

SALMONELLA MUTAGENICITY TEST PROTOCOL 

Testing was performed as reported by Mortelmans et al. (1986). Furfuryl alcohol was sent to the laboratory as a 

coded aliquot from Radian Corporation (Austin, TX). It was incubated with the Salmonella typhimurium tester 

strains TA98, TA100, TA1535, and TA1537 either in buffer or S9 mix (metabolic activation enzymes and 

cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver) for 20 minutes at 37E C. 

Top agar supplemented with L-histidine and d-biotin was added, and the contents of the tubes were mixed and 

poured onto the surfaces of minimal glucose agar plates. Histidine-independent mutant colonies arising on these 

plates were counted following incubation for 2 days at 37E C. 

Each trial consisted of triplicate plates of concurrent positive and negative controls and five doses of furfuryl 

alcohol. The high dose was limited by experimental design to 10,000 μg/plate. All trials were repeated. 

In this assay, a positive response is defined as a reproducible, dose-related increase in histidine-independent 

(revertant) colonies in any one strain/activation combination. An equivocal response is defined as an increase in 

revertants that is not dose related, is not reproducible, or is not of sufficient magnitude to support a determination 

of mutagenicity. A negative response is obtained when no increase in revertant colonies is observed following 

chemical treatment. There is no minimum percentage or fold increase required for a chemical to be judged positive 

or weakly positive. 

CHINESE HAMSTER OVARY CELL CYTOGENETICS PROTOCOLS 

Testing was performed as reported by Galloway et al. (1987). Furfuryl alcohol was sent to the laboratory as a 

coded aliquot by Radian Corporation. It was tested in cultured Chinese hamster ovary (CHO) cells for induction 

of sister chromatid exchanges (SCEs) and chromosomal aberrations (Abs), both in the presence and absence of 

Aroclor 1254-induced male Sprague-Dawley rat liver S9 and cofactor mix. Cultures were handled under gold 

lights to prevent photolysis of bromodeoxyuridine-substituted DNA. Each test consisted of concurrent solvent and 

positive controls and of at least three doses of furfuryl alcohol; the high dose was limited by toxicity. A single 

flask per dose was used, and tests yielding equivocal or positive results were repeated. 

Sister Chromatid Exchange Test: In the SCE test without S9, CHO cells were incubated for 26 hours with 

furfuryl alcohol in supplemented McCoy’s 5A medium. Bromodeoxyuridine (BrdU) was added 2 hours after 

culture initiation. After 26 hours, the medium containing furfuryl alcohol was removed and replaced with fresh 

medium plus BrdU and Colcemid, and incubation was continued for 2 hours. Cells were then harvested by mitotic 

shake-off, fixed, and stained with Hoechst 33258 and Giemsa. In the SCE test with S9, cells were incubated with 

furfuryl alcohol, serum-free medium, and S9 for 2 hours. The medium was then removed and replaced with 

medium containing serum and BrdU and no furfuryl alcohol. Incubation proceeded for an additional 26 hours, 

with Colcemid present for the final 2 hours. Harvesting and staining were the same as for cells treated without S9. 

All slides were scored blind and those from a single test were read by the same person. Fifty second-division 

metaphase cells were scored for frequency of SCEs/cell from each dose level. Because significant chemicalinduced cell cycle delay was seen at 500 μg/mL in the second trial without S9, incubation time was lengthened to 

ensure a sufficient number of scorable (second-division metaphase) cells. 

Statistical analyses were conducted on the slopes of the dose-response curves and the individual dose points 

(Galloway et al., 1987). An SCE frequency 20% above the concurrent solvent control value was chosen as a 

statistically conservative positive response. The probability of this level of difference occurring by chance at one 

dose point is less than 0.01; the probability for such a chance occurrence at two dose points is less than 0.001. An 

increase of 20% or greater at any single dose was considered weak evidence of activity; increases at two or more 
 

Furfuryl Alcohol, NTP TR 482 199 

doses resulted in a determination that the trial was positive. A statistically significant trend (P<0.005) in the 

absence of any responses reaching 20% above background led to a call of equivocal. 

Chromosomal Aberrations Test: In the Abs test without S9, cells were incubated in McCoy’s 5A medium with 

furfuryl alcohol for 10 hours; Colcemid was added and incubation continued for 2 hours. The cells were then 

harvested by mitotic shake-off, fixed, and stained with Giemsa. For the Abs test with S9, cells were treated with 

furfuryl alcohol and S9 for 2 hours, after which the treatment medium was removed and the cells were incubated 

for 11 hours in fresh medium, with Colcemid present for the final 2 hours. Cells were harvested in the same 

manner as for the treatment without S9. The harvest time for the Abs test was based on the cell cycle information 

obtained in the SCE test. 

Cells were selected for scoring on the basis of good morphology and completeness of karyotype 

(21 ± 2 chromosomes). All slides were scored blind and those from a single test were read by the same person. 

Two hundred first-division metaphase cells were scored at each dose level. Classes of aberrations included simple 

(breaks and terminal deletions), complex (rearrangements and translocations), and other (pulverized cells, 

despiralized chromosomes, and cells containing 10 or more aberrations). 

Chromosomal aberration data are presented as percentage of cells with aberrations. To arrive at a statistical call 

for a trial, analyses were conducted on both the dose response curve and individual dose points. For a single trial, 

a statistically significant (P#0.05) difference for one dose point and a significant trend (P#0.015) were considered 

weak evidence for a positive response; significant differences for two or more doses indicated the trial was 

positive. A positive trend test in the absence of a statistically significant increase at any one dose resulted in an 

equivocal call (Galloway et al., 1987). Ultimately, the trial calls were based on a consideration of the statistical 

analyses as well as the biological information available to the reviewers. 

MOUSE BONE MARROW CYTOGENETIC TEST PROTOCOLS 

Sister Chromatid Exchange Test: A dose range-finding study was performed in the absence of adequate toxicity 

information from the literature; the high dose was limited by toxicity. Furfuryl alcohol was tested for the induction 

of SCEs in mouse bone marrow by two protocols. Male B6C3F1 mice (five animals per dose group) were injected

intraperitoneally with furfuryl alcohol dissolved in corn oil (injection volume=0.4 mL). Solvent control mice 

received equivalent injections of corn oil only. The positive control was dimethylbenzanthracene. 

The first protocol had a standard harvest time of 23 hours, and the second protocol had a delayed harvest time of 

42 hours. The mice were implanted subcutaneously with a BrdU tablet (McFee et al., 1983) 24 hours before 

harvest (1 hour before furfuryl alcohol treatment in the case of the standard protocol). The use of BrdU allowed 

selection of the appropriate cell population (cells in the second metaphase following furfuryl alcohol treatment) for 

scoring. Two hours before sacrifice, the mice received an intraperitoneal injection of colchicine in saline. The 

animals were killed 23 or 42 hours after treatment. One or both femurs were removed, and the marrow was 

flushed out with phosphate-buffered saline (pH 7.0). The cells were treated with a hypotonic salt solution, fixed, 

and dropped onto chilled slides. After a 24-hour drying period, the slides were stained with fluorescence-plusGiemsa and scored. 

Twenty-five second-division metaphase cells were scored from each of four animals per treatment. Responses 

were evaluated as SCEs/cell, and the data were analyzed by a trend test (Margolin et al., 1986). 

Chromosomal Aberrations Test: Doses were set based on the information obtained from the range-finding study 

conducted prior to the SCE test. Furfuryl alcohol was tested for induction of Abs in mouse bone marrow by two 

different protocols. The first protocol used a standard harvest time of 17 hours, and the second protocol used a 

delayed harvest time of 36 hours. 
200 Furfuryl Alcohol, NTP TR 482 

Male B6C3F1 mice (10 animals per dose group) were injected intraperitoneally with furfuryl alcohol dissolved in

corn oil (injection volume = 0.4 mL). Solvent control mice received equivalent injections of corn oil only. The 

positive control was dimethylbenzanthracene. The mice were subcutaneously implanted with a BrdU tablet 

(McFee et al., 1983) 18 hours before the scheduled harvest. (For the standard protocol, this required BrdU 

implantation to precede injection with furfuryl alcohol by 1 hour.) The use of BrdU allowed selection of the 

appropriate cell population for scoring. (Abs induced by chemical administration are present in maximum number 

at the first metaphase following treatment; they decline in number during subsequent nuclear divisions due to cell 

death.) Two hours before sacrifice, the mice received an intraperitoneal injection of colchicine in saline. The 

animals were killed 17 or 36 hours after furfuryl alcohol injection (18 hours after BrdU dosing). One or both 

femurs were removed and the marrow was flushed out with phosphate-buffered saline (pH 7.0). Cells were treated 

with a hypotonic salt solution, fixed, and dropped onto chilled slides. After a 24-hour drying period, the slides 

were stained and scored. 

Fifty first-division metaphase cells were scored from each of eight animals per treatment. Responses were 

evaluated as the percentage of aberrant metaphase cells, excluding gaps. The data were analyzed by a trend test, 

and pairwise comparisons were made between each dosed group and the control group (Margolin et al., 1986). 

Micronucleus Test: The standard three-exposure protocol is described in detail by Shelby et al. (1993). Male 

B6C3F1 mice were injected intraperitoneally three times at 24-hour intervals with furfuryl alcohol dissolved in

phosphate-buffered saline; the total dosing volume was 0.4 mL. Solvent control animals were injected with 

0.4 mL of phosphate-buffered saline only. The positive control animals received injections of cyclophosphamide. 

The mice were killed 24 hours after the third injection, and smears were prepared from bone marrow cells obtained 

from the femurs. Air-dried smears were fixed and stained; 2,000 polychromatic erythrocytes (PCEs) were scored 

for the frequency of micronucleated cells in each of five animals per dose group. In addition, the percentage of 

PCEs among the total erythrocyte population in the bone marrow was scored for each dose group as a measure of 

toxicity. 

The results were tabulated as the mean of the pooled results from all animals within a treatment group plus or 

minus the standard error of the mean. The frequency of micronucleated cells among PCEs was analyzed by a 

statistical software package that tested for increasing trend over dose groups with a one-tailed Cochran-Armitage 

trend test, followed by pairwise comparisons between each dosed group and the control group (Margolin et al., 

1990). In the presence of excess binomial variation, as detected by a binomial dispersion test, the binomial 

variance of the Cochran-Armitage test was adjusted upward in proportion to the excess variation. In the 

micronucleus test, an individual trial is considered positive if the trend test P value is less than or equal to 0.025 or 

if the P value for any single dose group is less than or equal to 0.025 divided by the number of dose groups. A 

final call of positive for micronucleus induction is preferably based on reproducibly positive trials (as noted 

above). Ultimately, the final call is determined by the scientific staff after considering the results of statistical 

analyses, the reproducibility of any effects observed, and the magnitude of those effects. 

RESULTS 

Furfuryl alcohol (33-10,000 μg/plate) was not mutagenic in Salmonella typhimurium strain TA98, TA100, 

TA1535, or TA1537, with or without S9 metabolic activation enzymes (Mortelmans et al., 1986; Table E1). It 

did induce sister chromatid exchanges in cultured CHO cells in each of two trials conducted in the absence of S9 

(Table E2). In the second trial without S9, significant cell cycle delay occurred at the highest dose (500 μg/mL) 

requiring harvest of additional cells at a later time (31 hours culture time) to provide sufficient cells for analysis. 

No induction of SCEs was noted following treatment with furfuryl alcohol in the presence of S9. Furfuryl alcohol 

did not induce Abs in cultured CHO cells treated with furfuryl alcohol in the absence of S9, but in the presence of 

S9, an equivocal result was obtained (Table E3). In the Abs test with S9, the first trial showed a clear dose-related 

increase in aberrations, with significant elevations seen at 500 and 1,000 μg/mL. Results of the second trial were 

negative, and the assay overall was determined to be equivocal. In vivo, no induction of SCEs (Table E4), Abs 
Furfuryl Alcohol, NTP TR 482 201 

(Table E5), or micronuclei (Table E6) was noted in bone marrow cells of male B6C3F1 mice after administration

of furfuryl alcohol by intraperitoneal injection. In the Abs test, results of the initial 36-hour trial were positive 

(P=0.003). However, results of two additional 36-hour trials were negative and the assay was concluded to be 

negative overall. 

In conclusion, with the exception of the positive response observed in the SCE test in cultured CHO cells in vitro, 

no indication of genetic activity was seen with furfuryl alcohol. 
202 Furfuryl Alcohol, NTP TR 482 

TABLE E1 

Mutagenicity of Furfuryl Alcohol in Salmonella typhimuriuma 

Revertants/plateb 

Strain Dose !S9 +10% hamster S9 +10% rat S9 

(μg/plate) Trial 1 Trial 2 Trial 1 Trial 2 Trial 1 Trial 2 

TA100 0 100 ± 6.2 95 ± 3.9 156 ± 4.5 144 ± 6.2 137 ± 4.6 129 ± 7.5 

100 122 ± 8.7 98 ± 9.6 152 ± 5.6 139 ± 1.8 158 ± 2.9 135 ± 7.2 

333 114 ± 6.2 104 ± 4.3 152 ± 1.2 141 ± 8.1 171 ± 20.7 137 ± 17.0 

1,000 116 ± 2.4 97 ± 6.5 157 ± 9.9 146 ± 14.4 145 ± 2.9 135 ± 5.6 

3,333 103 ± 12.0 93 ± 5.8 158 ± 13.3 135 ± 9.2 187 ± 2.9 154 ± 11.0 

10,000 Toxic 92 ± 8.0 61 ± 4.4 73 ± 8.7 117 ± 15.4 115 ± 2.7 

Trial summary Negative Negative Negative Negative Negative Negative 

Positive controlc 494 ± 20.0 620 ± 83.1 1,775 ± 96.1 2,509 ± 107.6 1,044 ± 25.4 1,091 ± 111.2 

TA1535 0 3 ± 0.7 5 ± 1.5 5 ± 0.3 4 ± 1.2 4 ± 1.8 4 ± 0.3 

100 3 ± 0.9 3 ± 1.2 3 ± 0.6 3 ± 0.9 3 ± 1.5 3 ± 0.0 

333 1 ± 0.0 1 ± 0.7 5 ± 0.3 4 ± 0.3 4 ± 0.3 3 ± 0.7 

1,000 7 ± 3.3 5 ± 3.7 3 ± 0.9 3 ± 0.3 2 ± 0.9 5 ± 1.8 

3,333 2 ± 0.7 2 ± 1.2 6 ± 0.3 3 ± 1.2 5 ± 0.6 4 ± 0.7 

10,000 3 ± 0.0 3 ± 1.3 4 ± 1.2 2 ± 1.2 2 ± 0.6 3 ± 0.7 

Trial summary Negative Negative Negative Negative Negative Negative 

Positive control 163 ± 28.0 108 ± 7.1 60 ± 1.0 93 ± 26.7 78 ± 11.8 115 ± 2.7 

!S9 +10% hamster S9 

Trial 1 Trial 2 Trial 1 Trial 2 Trial 3 

TA1537 0 3 ± 0.6 6 ± 2.4 5 ± 1.3 5 ± 0.6 10 ± 1.5 

33 3 ± 1.2 

100 2 ± 0.6 2 ± 0.9 5 ± 0.7 6 ± 1.2 15 ± 1.7 

333 2 ± 0.9 4 ± 1.5 3 ± 0.9 5 ± 0.9 12 ± 1.9 

1,000 2 ± 0.7 4 ± 0.3 4 ± 0.7 3 ± 0.7 10 ± 2.6 

3,333 3 ± 1.0 3 ± 1.5 8 ± 1.0 6 ± 0.9 13 ± 1.3 

10,000 0 ± 0.0 1 ± 0.3 Toxic 7 ± 1.5 

Trial summary Negative Negative Negative Negative Negative 

Positive control 787 ± 60.9 918 ± 78.8 110 ± 12.9 63 ± 1.3 675 ±15.3 

+10% rat S9 

Trial 1 Trial 2 Trial 3 

TA1537 0 2 ± 1.3 3 ± 0.5 12 ± 3.0 

100 1 ± 0.3 5 ± 1.9 14 ± 2.6 

333 3 ± 1.0 7 ± 1.3 12 ± 1.5 

1,000 7 ± 2.5 7 ± 1.0 16 ± 0.9 

3,333 6 ± 1.8 5 ± 1.8 14 ± 1.9 

10,000 1 ± 0.3 2 ± 1.3 8 ± 3.8 

Trial summary Negative Negative Negative 

Positive control 53 ± 4.4 79 ± 7.9 121 ± 4.1 
203 

c 

Furfuryl Alcohol, NTP TR 482 

TABLE E1 

Mutagenicity of Furfuryl Alcohol in Salmonella typhimurium 

Revertants/plate 

Strain Dose !S9 +10% hamster S9 +10% rat S9 

(μg/plate) Trial 1 Trial 2 Trial 1 Trial 2 Trial 1 Trial 2 

TA98 0 15 ± 2.0 15 ± 0.9 21 ± 1.9 23 ± 1.7 26 ± 1.2 20 ± 3.1 

33 14 ± 2.6 

100 11 ± 2.1 16 ± 3.3 18 ± 0.7 20 ± 1.3 24 ± 1.0 23 ± 1.9 

333 13 ± 2.4 15 ± 1.9 24 ± 0.9 23 ± 4.0 24 ± 2.3 20 ± 2.6 

1,000 12 ± 3.2 12 ± 0.3 26 ± 0.9 31 ± 4.0 23 ± 0.6 18 ± 4.3 

3,333 2 ± 0.6 12 ± 5.4 22 ± 0.3 23 ± 5.2 23 ± 0.9 17 ± 1.9 

10,000 Toxic 22 ± 1.5 22 ± 4.2 13 ± 2.3 15 ± 2.9 

Trial summary Negative Negative Negative Negative Negative Negative 

Positive control 156 ± 12.2 301 ± 5.3 2,223 ± 24.6 2,369 ± 46.4 462 ± 34.5 617 ± 103.7 

a Study was performed at Case Western Reserve University. The detailed protocol and these data are presented in Mortelmans et al. (1986). 

0 μg/plate was the solvent control. b	 Revertants are presented as mean ± standard error from three plates. 

The positive controls in the absence of metabolic activation were sodium azide (TA100 and TA1535), 9-aminoacridine (TA1537), and 

4-nitro-o-phenylenediamine (TA98). The positive control for metabolic activation with all strains was 2-aminoanthracene. 
204 Furfuryl Alcohol, NTP TR 482 

TABLE E2 

Induction of Sister Chromatid Exchanges in Chinese Hamster Ovary Cells by Furfuryl Alcohola 

Total No. of SCEs/ Relative 

Compound 

Concentration 

(μg/mL) 

Cells 

Scored 

Chromosomes No. of 

SCEs 

Chromosome SCEs/ 

Cell 

Hrs 

in BrdU 

Change of SCEs/ 

Chromosomeb 

(%) 

!S9 

Trial 1 

Summary: Weakly positive 

Dimethylsulfoxidec 50 1,045 422 0.40 8.4 26.0 

Mitomycin-Cd 0.0005 50 1,046 558 0.53 11.2 26.0 32.10 

0.0050 10 210 384 1.82 38.4 26.0 352.82

 Furfuryl alcohol 16 50 1,050 444 0.42 8.9 26.0 4.71 

50 50 1,051 451 0.42 9.0 26.0 6.26 

160 50 1,049 416 0.39 8.3 26.0 1.80 

500 50 1,051 572 0.54 11.4 26.0 34.77* 

P<0.001e

 Trial 2

 Summary: Positive

 Dimethylsulfoxide 50 1,049 459 0.43 9.2 26.0

 Mitomycin-C 0.0008 50 1,046 551 0.52 11.0 26.0 20.39 

0.0050 10 209 259 1.23 25.9 26.0 183.22

 Furfuryl alcohol 16 50 1,044 435 0.41 8.7 26.0 4.78 

50 50 1,048 436 0.41 8.7 26.0 4.92 

160 

500 

50 

3f 1,046 

61 

555 

41 

0.53 

0.67 

11.1 

13.7 

26.0 

26.0 

21.26* 

53.61* 

500 50 1,051 587 0.55 11.7 31.0 g 27.64* 

P<0.001 
205 

c 

Furfuryl Alcohol, NTP TR 482 

TABLE E2 

Induction of Sister Chromatid Exchanges in Chinese Hamster Ovary Cells by Furfuryl Alcohol 

Total No. of SCEs/ Relative 

Concentration Cells Chromo- No. of Chromo- SCEs/ Hrs Change of SCEs/ 

Compound (μg/mL) Scored somes SCEs some Cell in BrdU Chromosome 

(%) 

+S9 

Summary: Negative 

Dimethylsulfoxide	 50 1,050 452 0.43 9.0 26.0 

Cyclophosphamided 0.1 50 1,051 567 0.53 11.3 26.0 25.32 

0.6 10 210 202 0.96 20.2 26.0 123.45 

Furfuryl alcohol 16 50 1,049 400 0.38 8.0 26.0 11.42 

50 50 1,050 458 0.43 9.2 26.0 1.33 

160 50 1,050 482 0.45 9.6 26.0 6.64 

500 50 1,050 512 0.48 10.2 26.0 13.27 

P=0.001 

*	 Positive response ( 20% increase over solvent control) a Study was performed at Environmental Health Research and Testing, Inc. The detailed protocol is presented in Galloway et al. (1987). 

SCE=sister chromatid exchange; BrdU=bromodeoxyuridine b	 SCEs/chromosome in treated cells versus SCEs/chromosome in solvent control cells 

Solvent control 

d Positive control e Significance of SCEs/chromosome tested by the linear regression trend test versus log of the dose f	 Only three second-division metaphase cells were evaluated due to the cytostatic nature of the chemical at this concentration. This concentration 

was retested using an extended culture time. 

g	 Due to cell cycle delay, harvest time was extended to maximize the number of second-division metaphase cells available for analysis. 
206 Furfuryl Alcohol, NTP TR 482 

TABLE E3 

Induction of Chromosomal Aberrations in Chinese Hamster Ovary Cells by Furfuryl Alcohola 

Compound Concentration 

(μg/mL) 

Total Cells 

Scored 

Number 

of Aberrations 

Aberrations/ 

Cell 

Cells with 

Aberrations (%) 

!S9 

Harvest time: 12 hours 

Summary: Negative 

Dimethylsulfoxideb 200 3 0.02 1.5 

Mitomycin-Cc 0.0625 

0.25 

200 

50 

39 

20 

0.20 

0.40 

16.0 

36.0 

Furfuryl alcohol 160 

300 

500 

200 

200 

200 

3 

3 

7 

0.02 

0.02 

0.04 

1.5 

1.5 

3.5 

P=0.094d 

+S9 

Trial 1 

Harvest time: 13 hours 

Summary: Positive 

Dimethylsulfoxide 200 0 0.00 0.0 

Cyclophosphamidec 2.5 

7.5 

200 

50 

35 

21 

0.18 

0.42 

14.5 

32.0 

Furfuryl alcohol 300 

500 

1,000 

200 

200 

200 

1 

6 

11 

0.01 

0.03 

0.06 

0.5 

3.0* 

3.0* 

Trial 2 

Harvest time: 13 hours 

Summary: Negative 

P<0.001 

Dimethylsulfoxide 200 1 0.01 0.5 

Cyclophosphamide 2.5 

7.5 

200 

50 

22 

18 

0.11 

0.36 

10.5 

32.0 

Furfuryl alcohol 500 

1,000 

1,600 

200 

200 

200 

4 

6 

1 

0.02 

0.03 

0.01 

1.5 

3.0 

0.5 

P=0.286 

* Positive (P#0.05) a Study was performed at Environmental Health Research and Testing, Inc. The detailed protocol is presented in Galloway et al. (1987). b Solvent control 

Positive control d Significance of percent cells with aberrations tested by the linear regression trend test versus log of the dose 

c 
207 

c 

Furfuryl Alcohol, NTP TR 482 

TABLE E4 

Induction of Sister Chromatid Exchanges in Mouse Bone Marrow Cells by Furfuryl Alcohola 

Compound Dose SCEs/Cell 

(mg/kg) 

Trial 1 

Harvest time: 23 hours 

b Corn oil 0 4.47 ± 0.40 

c Dimethylbenzanthracene 2.5 9.15 ± 0.10 

Furfuryl alcohol 75 4.15 ± 0.73 

150 5.70 ± 0.50 

300 4.63 ± 1.03 

P=0.335d 

Trial 2 

Harvest time: 42 hours 

Corn oil 0 6.14 ± 1.06 

Dimethylbenzanthracene 100 18.39 ± 1.09 

Furfuryl alcohol 37.5 5.73 ± 0.44 

75 6.82 ± 1.00 

150 5.40 ± 0.84 

P=0.320 

a Study was performed at Oak Ridge Associated Universities. The detailed protocols are presented in McFee (1991). Data for SCEs/cell are given 

as mean ± standard error. SCE=sister chromatid exchange. Twenty-five second-division metaphase cells were analyzed from each of four animals 

per group. b Solvent control
 

Positive control
 d Significance tested by the one-tailed trend test; significant at P#0.025 (Margolin et al., 1986) 
208 Furfuryl Alcohol, NTP TR 482 

TABLE E5 

Induction of Chromosomal Aberrations in Mouse Bone Marrow Cells by Furfuryl Alcohola 

Compound Dose Total Aberrations/Cellb Cells with Aberrations Pairwise 

(mg/kg) Aberrations (%) P Valuesc 

Trial 1 

Harvest time: 17 hours 

Corn oild 1.1 0.02 2.00 

Dimethylbenzanthracenee 100 14.0 0.17 17.00 0.000 

Furfuryl alcohol 75 1.6 0.02 2.00 0.500 

150 2.6 0.04 4.00 0.097 

300 0.4 0.00 0.00 0.987 

P=0.935f 

Trial 2 

Harvest time: 36 hours 

Corn oilg 1.4 0.02 1.43 

Dimethylbenzanthracene 100 40.3 0.67 27.50 0.000 

Furfuryl alcohol 50 1.5 0.02 2.00 0.275 

100 2.9 0.04 4.00 0.017 

200 3.0 0.05 4.50 0.008 

P=0.003 

Trial 3 

Harvest time: 36 hours 

Corn oil 3.5 0.04 1.50 

Dimethylbenzanthraceneg 50 47.4 0.69 24.86 0.000 

Furfuryl alcohol 50 1.3 0.02 1.50 0.500 

100 1.1 0.02 1.75 0.390 

200 2.0 0.02 2.00 0.295 

P=0.267 
209 

c 

Furfuryl Alcohol, NTP TR 482 

TABLE E5 

Induction of Chromosomal Aberrations in Mouse Bone Marrow Cells by Furfuryl Alcohol 

Compound Dose Total Aberrations/Cell Cells with Aberrations Pairwise 

(mg/kg) Aberrations (%) P Values 

Trial 4 

Harvest time: 36 hours 

Corn oil 2.0 0.02 1.75 

Dimethylbenzanthracene 50 25.3 0.33 18.00 0.000 

Furfuryl alcohol 50 0.9 0.01 1.25 0.720 

100 0.5 0.01 0.75 0.899 

200 1.0 0.02 1.50 0.610 

P=0.603 

a Study was performed at Oak Ridge Associated Universities. The detailed protocols are presented in McFee (1991). Fifty cells were scored in each 

of eight animals per dose group unless otherwise noted. b Mean
 

Comparison of individual treatment groups to the concurrent solvent control. Significant at P#0.008.
 d Solvent control e Positive control 

f Significance tested by the one-tailed trend test; significant at P#0.025 (Margolin et al., 1986) 

g n=7 
210 

c 

Furfuryl Alcohol, NTP TR 482 

TABLE E6 

Induction of Micronuclei in Bone Marrow Polychromatic Erythrocytes of Mice 

Treated with Furfuryl Alcohol by Intraperitoneal Injectiona 

b Compound Dose Number of Mice Micronucleated PCEs/ Pairwise PCEs (%) 

(mg/kg) with Erythrocytes 1,000 PCEsb P Valuesc 

Scored 

Phosphate-buffered salined 5 1.00 ± 0.16 53.22 ± 2.68 

e Cyclophosphamide 15 5 8.80 ± 1.34 0.000 48.04 ± 2.56 

Furfuryl alcohol 15.625 5 1.50 ± 0.69 0.159 55.22 ± 2.03 

31.25 5 1.00 ± 0.32 0.500 58.74 ± 4.04 

62.5 5 1.40 ± 0.56 0.207 59.18 ± 2.11 

125 5 1.40 ± 0.19 0.207 52.98 ± 3.34 

250 Lethal 

P=0.266f 

a Study was performed at Environmental Health Research and Testing, Inc. The detailed protocol is presented in Shelby et al. (1993). 

PCE=polychromatic erythrocyte. b Mean ± standard error 

Comparison of individual treatment groups to the concurrent solvent control, significant at P#0.006 

d Solvent control e Positive control 

f Significance of micronucleated PCEs/1,000 PCEs tested by the one-tailed trend test, significant at P#0.025 (ILS, 1990) 
211 

APPENDIX F
 

HEMATOLOGY AND
 

CLINICAL CHEMISTRY RESULTS
 

TABLE F1	 Hematology and Clinical Chemistry Data for Rats in the 14-Week Inhalation Study 

of Furfuryl Alcohol ............................................................... 212 
212 Furfuryl Alcohol, NTP TR 482 

TABLE F1 

Hematology and Clinical Chemistry Data for Rats in the 14-Week Inhalation Study of Furfuryl Alcohola 

Chamber 

Control 2 ppm 4 ppm 8 ppm 16 ppm 32 ppm 

Male 

n 

Day 3 10 10 10 10 10 10 

Day 23 10 9 9 10 10 10 

Week 14 10 10 10 10 10 10 

Hematology 

Hematocrit (mL/dL) 

Day 3 39.8 ± 0.3 40.3 ± 0.3 42.9 ± 1.0** 40.7 ± 0.6* 42.3 ± 0.3** 41.8 ± 0.4** 

Day 23 42.9 ± 0.4 42.7 ± 0.5 43.0 ± 0.4 42.1 ± 0.3 42.9 ± 0.4 43.0 ± 0.4 

Week 14 46.0 ± 0.5 46.7 ± 0.3 46.2 ± 0.5 46.5 ± 0.4 46.6 ± 0.2 46.6 ± 0.2 

Hemoglobin (g/dL) 

Day 3 12.9 ± 0.1 13.1 ± 0.1 13.9 ± 0.3** 13.3 ± 0.2* 13.7 ± 0.1** 13.6 ± 0.1** 

Day 23 15.0 ± 0.1 15.0 ± 0.2 15.1 ± 0.1 14.7 ± 0.1 14.9 ± 0.1 15.0 ± 0.1 

Week 14 15.1 ± 0.2 15.1 ± 0.2 14.9 ± 0.1 15.1 ± 0.1 15.2 ± 0.1 15.2 ± 0.0 

Erythrocytes (10 /μL) 6 

Day 3 6.63 ± 0.07 6.73 ± 0.07 7.28 ± 0.18** 6.90 ± 0.12* 7.15 ± 0.06** 7.02 ± 0.12** 

Day 23 7.81 ± 0.09 7.78 ± 0.10 7.84 ± 0.09 7.68 ± 0.09 7.77 ± 0.07 7.75 ± 0.09 

Week 14 8.81 ± 0.11 8.96 ± 0.04 8.86 ± 0.08 8.95 ± 0.06 9.05 ± 0.04 8.94 ± 0.02 

Reticulocytes (10 /μL) 6 

Day 3 0.49 ± 0.02 0.52 ± 0.03 0.49 ± 0.03 0.46 ± 0.03 0.42 ± 0.03 0.43 ± 0.02 

Day 23 0.14 ± 0.01 0.11 ± 0.01 0.12 ± 0.01 0.13 ± 0.01 0.15 ± 0.01 0.18 ± 0.01* 

Week 14 0.14 ± 0.01 0.14 ± 0.01 0.13 ± 0.01 0.15 ± 0.01 0.15 ± 0.02 0.11 ± 0.01 

Nucleated erythrocytes (10 /μL) 3 

Day 3 0.19 ± 0.03 0.14 ± 0.03 0.11 ± 0.03 0.12 ± 0.03 0.11 ± 0.03 0.08 ± 0.02 

Day 23 0.02 ± 0.01 0.00 ± 0.00 0.01 ± 0.01 0.01 ± 0.01 0.01 ± 0.01 0.01 ± 0.01 

Week 14 0.02 ± 0.01 0.01 ± 0.01 0.01 ± 0.01 0.03 ± 0.02 0.02 ± 0.01 0.02 ± 0.01 

Mean cell volume (fL) 

Day 3 60.0 ± 0.2 59.9 ± 0.3 59.0 ± 0.3 59.0 ± 0.5 59.3 ± 0.3 59.5 ± 0.5 

Day 23 55.0 ± 0.3 54.9 ± 0.4 54.9 ± 0.3 54.6 ± 0.3 55.3 ± 0.2 55.5 ± 0.3 

Week 14 52.3 ± 0.2 52.2 ± 0.1 52.0 ± 0.0 51.9 ± 0.4* 51.5 ± 0.2** 52.0 ± 0.1* 

Mean cell hemoglobin (pg) 

Day 3 19.4 ± 0.1 19.4 ± 0.1 19.1 ± 0.1 19.3 ± 0.1 19.2 ± 0.1 19.4 ± 0.2 

Day 23 19.2 ± 0.1 19.3 ± 0.1 19.3 ± 0.1 19.1 ± 0.1 19.2 ± 0.0 19.3 ± 0.1 

Week 14 17.1 ± 0.1 16.8 ± 0.1 16.9 ± 0.0 16.9 ± 0.1 16.8 ± 0.1 17.0 ± 0.1 

Mean cell hemoglobin concentration (g/dL) 

Day 3 32.4 ± 0.2 32.5 ± 0.1 32.3 ± 0.1 32.7 ± 0.1 32.4 ± 0.1 32.5 ± 0.1 

Day 23 34.9 ± 0.1 35.2 ± 0.1 35.1 ± 0.1 34.9 ± 0.1 34.8 ± 0.1 34.8 ± 0.1 

Week 14 32.7 ± 0.1 32.3 ± 0.2 32.4 ± 0.1 32.5 ± 0.1 32.7 ± 0.1 32.6 ± 0.1 

Platelets (10 /μL) 3 

Day 3 750.6 ± 12.3 773.7 ± 6.4 762.9 ± 12.5 758.0 ± 17.0 785.2 ± 15.4 792.6 ± 43.4 

Day 23 

Week 14 

537.5 ± 9.2 

489.2 ± 7.3b 

543.0 ± 15.4 

474.9 ± 10.2 

540.3 ± 17.5 

507.0 ± 6.3 

546.9 ± 7.1 

517.3 ± 10.4 

539.0 ± 7.2 

481.4 ± 8.1 

552.5 ± 7.5 

486.2 ± 9.2 

Leukocytes (10 /μL) 3 

Day 3 7.78 ± 0.31 8.49 ± 0.29 8.62 ± 0.28 8.16 ± 0.38 8.75 ± 0.44 7.62 ± 0.53 

Day 23 5.81 ± 0.32 6.16 ± 0.32 6.84 ± 0.33 5.99 ± 0.13 6.44 ± 0.31 6.43 ± 0.31 

Week 14 6.70 ± 0.30 7.14 ± 0.34 7.32 ± 0.39 6.87 ± 0.26 5.89 ± 0.29 6.27 ± 0.24 

Segmented neutrophils (10 /μL) 3 

Day 3 1.29 ± 0.09 1.18 ± 0.09 1.01 ± 0.10 1.10 ± 0.09 1.07 ± 0.22* 0.78 ± 0.07** 

Day 23 0.57 ± 0.04 0.64 ± 0.07 0.78 ± 0.12 0.86 ± 0.07** 1.01 ± 0.11** 0.92 ± 0.10** 

Week 14 1.19 ± 0.08 1.02 ± 0.08 1.13 ± 0.17 0.98 ± 0.08 1.06 ± 0.06 1.08 ± 0.11 
Furfuryl Alcohol, NTP TR 482 213 

TABLE F1 

Hematology and Clinical Chemistry Data for Rats in the 14-Week Inhalation Study of Furfuryl Alcohol 

Chamber 

Control 2 ppm 4 ppm 8 ppm 16 ppm 32 ppm 

Male (continued) 

n 

Day 3 10 10 10 10 10 10 

Day 23 10 9 9 10 10 10 

Week 14 10 10 10 10 10 10 

Hematology (continued) 

Lymphocytes (10 /μL) 3 

Day 3 6.05 ± 0.22 6.87 ± 0.26 7.27 ± 0.30* 6.79 ± 0.32 7.33 ± 0.36* 6.67 ± 0.49 

Day 23 5.14 ± 0.31 5.39 ± 0.29 5.86 ± 0.36 4.94 ± 0.12 5.22 ± 0.27 5.10 ± 0.26 

Week 14 5.37 ± 0.26 5.99 ± 0.30 6.08 ± 0.29 5.72 ± 0.26 4.73 ± 0.25 5.00 ± 0.19 

Monocytes (10 /μL) 3 

Day 3 0.40 ± 0.08 0.38 ± 0.06 0.33 ± 0.06 0.21 ± 0.04 0.31 ± 0.05 0.16 ± 0.03** 

Day 23 0.10 ± 0.02 0.09 ± 0.03 0.18 ± 0.04 0.15 ± 0.04 0.14 ± 0.03 0.30 ± 0.04** 

Week 14 0.09 ± 0.02 0.08 ± 0.03 0.08 ± 0.02 0.09 ± 0.03 0.05 ± 0.02 0.07 ± 0.02 

Eosinophils (10 /μL) 3 

Day 3 0.05 ± 0.02 0.05 ± 0.02 0.00 ± 0.00 0.06 ± 0.02 0.04 ± 0.01 0.02 ± 0.01 

Day 23 0.01 ± 0.01 0.04 ± 0.02 0.01 ± 0.01 0.04 ± 0.02 0.07 ± 0.03 0.10 ± 0.04* 

Week 14 0.06 ± 0.02 0.05 ± 0.02 0.03 ± 0.02 0.07 ± 0.02 0.04 ± 0.02 0.12 ± 0.03 

Clinical Chemistry 

Urea nitrogen (mg/dL) 

Day 3 12.4 ± 0.5 11.6 ± 0.4 12.6 ± 0.7 11.2 ± 0.3 12.9 ± 0.6 13.4 ± 0.3 

Day 23 12.6 ± 0.4 12.8 ± 0.3 13.1 ± 0.3 12.7 ± 0.3 13.3 ± 0.2 12.8 ± 0.3 

Week 14 17.9 ± 0.6 18.7 ± 0.6 18.9 ± 0.7 17.5 ± 0.7 17.8 ± 0.5 17.1 ± 0.7 

Creatinine (mg/dL) 

Day 3 0.45 ± 0.02 0.51 ± 0.01 0.47 ± 0.02 0.45 ± 0.02 0.46 ± 0.02 0.46 ± 0.02 

Day 23 0.74 ± 0.02 0.77 ± 0.02 0.73 ± 0.02 0.69 ± 0.02 0.74 ± 0.02 0.78 ± 0.01 

Week 14 0.67 ± 0.02 0.70 ± 0.02 0.65 ± 0.02 0.64 ± 0.02 0.64 ± 0.02 0.66 ± 0.02 

Total protein (g/dL) 

Day 3 5.2 ± 0.0 5.4 ± 0.1 5.6 ± 0.2** 5.4 ± 0.1* 5.5 ± 0.1** 5.5 ± 0.1** 

Day 23 6.4 ± 0.1 6.5 ± 0.1 6.4 ± 0.1 6.2 ± 0.1* 6.2 ± 0.1* 6.2 ± 0.1* 

Week 14 7.1 ± 0.1 7.0 ± 0.1 7.0 ± 0.1 7.0 ± 0.1 7.1 ± 0.1 6.9 ± 0.1 

Albumin (g/dL) 

Day 3 3.2 ± 0.0 3.2 ± 0.0 3.4 ± 0.1 3.3 ± 0.1 3.4 ± 0.1* 3.4 ± 0.1* 

Day 23 4.4 ± 0.1 4.4 ± 0.1 4.3 ± 0.0 4.2 ± 0.1 4.4 ± 0.1 4.4 ± 0.1 

Week 14 3.9 ± 0.1 4.0 ± 0.0 4.0 ± 0.0 4.0 ± 0.1 4.1 ± 0.0 3.9 ± 0.0 

Globulin (g/dL) 

Day 3 2.0 ± 0.1 2.1 ± 0.0 2.2 ± 0.1 2.1 ± 0.1 2.1 ± 0.1 2.1 ± 0.0 

Day 23 2.0 ± 0.1 2.1 ± 0.1 2.1 ± 0.0 2.0 ± 0.1 1.8 ± 0.1* 1.8 ± 0.1* 

Week 14 3.1 ± 0.1 3.0 ± 0.1 3.0 ± 0.1 3.0 ± 0.1 3.0 ± 0.1 3.0 ± 0.1 

A/G ratio 

Day 3 1.6 ± 0.1 1.5 ± 0.0 1.6 ± 0.0 1.6 ± 0.1 1.7 ± 0.1 1.6 ± 0.0 

Day 23 2.2 ± 0.1 2.1 ± 0.1 2.1 ± 0.1 2.2 ± 0.1 2.5 ± 0.1* 2.6 ± 0.1* 

Week 14 1.3 ± 0.1 1.3 ± 0.0 1.4 ± 0.0 1.3 ± 0.0 1.4 ± 0.0 1.3 ± 0.0 

Alanine aminotransferase (IU/L) 

Day 3 47 ± 1 44 ± 1* 44 ± 2 42 ± 3* 38 ± 1** 41 ± 1** 

Day 23 

Week 14 

35 ± 1 

66 ± 4 

36 ± 1 

66 ± 4b 

39 ± 3 

60 ± 3 

35 ± 1 

72 ± 3 

34 ± 1 

65 ± 4 

33 ± 1 

53 ± 2* 
214 Furfuryl Alcohol, NTP TR 482 

TABLE F1 

Hematology and Clinical Chemistry Data for Rats in the 14-Week Inhalation Study of Furfuryl Alcohol 

Chamber 

Control 2 ppm 4 ppm 8 ppm 16 ppm 32 ppm 

Male (continued) 

n 

Day 3 10 10 10 10 10 10 

Day 23 10 9 9 10 10 10 

Week 14 10 10 10 10 10 10 

Clinical Chemistry (continued) 

Alkaline phosphatase (IU/L) 

Day 3 692 ± 12 718 ± 12 679 ± 12 647 ± 12 580 ± 12** 641 ± 20** 

Day 23 568 ± 16 579 ± 17 561 ± 17 570 ± 18 554 ± 14 576 ± 15 

Week 14 294 ± 7 285 ± 7 271 ± 8 273 ± 10 296 ± 9 283 ± 3 

Creatine kinase (IU/L) 

Day 3 408 ± 25 374 ± 20 360 ± 26 496 ± 86 391 ± 54 507 ± 50 

Day 23 238 ± 32 379 ± 58 250 ± 22 310 ± 48 287 ± 36 259 ± 39 

Week 14 143 ± 14 167 ± 20 138 ± 19 143 ± 15 138 ± 17 149 ± 20 

Sorbitol dehydrogenase (IU/L) 

Day 3 8 ± 1 7 ± 0 7 ± 1 6 ± 1 7 ± 1 8 ± 1 

Day 23 

Week 14 

8 ± 0 

12 ± 0 

8 ± 1 

12 ± 1b 

9 ± 2 

12 ± 1 

9 ± 1 

12 ± 1 

9 ± 0 

12 ± 1 

10 ± 0* 

10 ± 1 

Bile acids (μmol/L) 

Day 3 8.4 ± 1.0 7.1 ± 0.7 8.5 ± 0.9 6.4 ± 1.1 6.2 ± 0.4 7.6 ± 0.7 

Day 23 

Week 14 

5.4 ± 0.6 

4.4 ± 0.3 

7.2 ± 1.7 

4.2 ± 0.7b 

6.1 ± 0.8 

6.5 ± 1.1 

4.4 ± 0.5 

4.7 ± 0.7 

8.1 ± 2.5 

4.6 ± 0.8 

5.0 ± 0.5 

4.2 ± 0.9 

Female 

n 10 10 10 10 10 10 

Hematology 

Hematocrit (mL/dL) 

Day 3 41.5 ± 0.5 42.3 ± 0.2 42.8 ± 0.7 42.9 ± 0.4* 43.4 ± 0.5* 43.7 ± 0.6* 

Day 23 44.7 ± 0.3 43.6 ± 0.3 44.3 ± 0.4 44.8 ± 0.3 44.1 ± 0.4 44.1 ± 0.3 

Week 14 47.1 ± 0.4 48.0 ± 0.3 47.8 ± 0.4 48.1 ± 0.5 47.6 ± 0.7 47.8 ± 0.6 

Hemoglobin (g/dL) 

Day 3 13.6 ± 0.2 14.0 ± 0.1* 14.1 ± 0.2* 14.1 ± 0.1* 14.2 ± 0.2* 14.3 ± 0.2** 

Day 23 15.6 ± 0.1 15.3 ± 0.1 15.6 ± 0.1 15.7 ± 0.1 15.5 ± 0.1 15.5 ± 0.1 

Week 14 15.3 ± 0.1 15.5 ± 0.1 15.5 ± 0.1 15.5 ± 0.1 15.3 ± 0.3 15.5 ± 0.1 

Erythrocytes (10 /μL) 6 

Day 3 7.17 ± 0.09 7.39 ± 0.05 7.53 ± 0.15* 7.42 ± 0.08* 7.62 ± 0.11** 7.56 ± 0.12** 

Day 23 8.03 ± 0.07 7.91 ± 0.07 8.02 ± 0.08 8.10 ± 0.07 7.97 ± 0.11 7.96 ± 0.06 

Week 14 8.50 ± 0.07 8.62 ± 0.05 8.62 ± 0.08 8.68 ± 0.08 8.55 ± 0.13 8.61 ± 0.11 

Reticulocytes (10 /μL) 6 

Day 3 0.29 ± 0.02 0.28 ± 0.02 0.30 ± 0.02 0.29 ± 0.01 0.24 ± 0.02 0.31 ± 0.03 

Day 23 0.10 ± 0.01 0.07 ± 0.01 0.12 ± 0.01 0.11 ± 0.01 0.11 ± 0.01 0.11 ± 0.01 

Week 14 0.19 ± 0.01 0.18 ± 0.02 0.19 ± 0.02 0.16 ± 0.01 0.16 ± 0.01 0.16 ± 0.02 

Nucleated erythrocytes (10 /μL) 3 

Day 3 0.15 ± 0.03 0.13 ± 0.04 0.19 ± 0.03 0.11 ± 0.03 0.04 ± 0.03 0.08 ± 0.03 

Day 23 0.02 ± 0.01 0.00 ± 0.00 0.01 ± 0.01 0.01 ± 0.01 0.00 ± 0.00 0.01 ± 0.01 

Week 14 0.04 ± 0.02 0.04 ± 0.02 0.04 ± 0.02 0.03 ± 0.02 0.05 ± 0.02 0.06 ± 0.02 
Furfuryl Alcohol, NTP TR 482 215 

TABLE F1 

Hematology and Clinical Chemistry Data for Rats in the 14-Week Inhalation Study of Furfuryl Alcohol 

Chamber 

Control 2 ppm 4 ppm 8 ppm 16 ppm 32 ppm 

Female (continued) 

n 10 10 10 10 10 10 

Hematology (continued) 

Mean cell volume (fL) 

Day 3 58.0 ± 0.2 57.2 ± 0.2 56.9 ± 0.4 57.9 ± 0.2 56.8 ± 0.5* 57.9 ± 0.4 

Day 23 55.6 ± 0.2 55.1 ± 0.2 55.1 ± 0.2 55.4 ± 0.3 55.2 ± 0.4 55.3 ± 0.3 

Week 14 55.3 ± 0.2 55.8 ± 0.1 55.6 ± 0.2 55.6 ± 0.2 55.5 ± 0.2 55.5 ± 0.3 

Mean cell hemoglobin (pg) 

Day 3 19.0 ± 0.1 19.0 ± 0.1 18.7 ± 0.1 19.0 ± 0.1 18.7 ± 0.1 18.9 ± 0.1 

Day 23 19.5 ± 0.1 19.4 ± 0.1 19.5 ± 0.1 19.4 ± 0.1 19.5 ± 0.2 19.5 ± 0.1 

Week 14 18.0 ± 0.0 18.0 ± 0.1 18.0 ± 0.1 17.9 ± 0.1 17.9 ± 0.2 18.0 ± 0.1 

Mean cell hemoglobin concentration (g/dL) 

Day 3 32.7 ± 0.1 33.1 ± 0.1 32.8 ± 0.1 32.8 ± 0.1 32.8 ± 0.1 32.7 ± 0.1 

Day 23 35.0 ± 0.1 35.2 ± 0.1 35.3 ± 0.1 35.0 ± 0.1 35.2 ± 0.1 35.3 ± 0.1 

Week 14 32.5 ± 0.1 32.4 ± 0.1 32.5 ± 0.1 32.3 ± 0.1 32.2 ± 0.2 32.4 ± 0.2 

Platelets (10 /μL) 3 

Day 3 781.8 ± 14.8 786.0 ± 17.4 774.5 ± 24.3 786.4 ± 15.9 769.6 ± 25.2 774.0 ± 29.4 

Day 23 544.8 ± 7.5 512.5 ± 17.8 532.8 ± 9.7 534.3 ± 9.2 499.5 ± 18.1 528.6 ± 12.0 

Week 14 506.2 ± 7.6 520.3 ± 9.1 516.7 ± 10.6 526.9 ± 7.2 502.2 ± 10.8 521.7 ± 5.4 

Leukocytes (10 /μL) 3 

Day 3 8.75 ± 0.41 8.50 ± 0.36 8.77 ± 0.44 8.55 ± 0.46 8.78 ± 0.35 8.61 ± 0.47 

Day 23 8.03 ± 0.57 7.91 ± 0.22 8.22 ± 0.43 7.57 ± 0.36 7.50 ± 0.41 6.07 ± 0.24** 

Week 14 7.23 ± 0.34 6.94 ± 0.45 6.60 ± 0.46 7.87 ± 0.64 6.81 ± 0.56 7.14 ± 0.55 

Segmented neutrophils (10 /μL) 3 

Day 3 0.87 ± 0.11 1.05 ± 0.12 0.90 ± 0.09 0.92 ± 0.09 1.01 ± 0.13 0.90 ± 0.08 

Day 23 0.83 ± 0.10 0.68 ± 0.07 0.78 ± 0.09 0.99 ± 0.14 0.72 ± 0.11 0.94 ± 0.11 

Week 14 1.03 ± 0.11 1.00 ± 0.14 0.99 ± 0.10 1.11 ± 0.12 0.99 ± 0.08 1.01 ± 0.17 

Lymphocytes (10 /μL) 3 

Day 3 7.62 ± 0.34 7.24 ± 0.28 7.56 ± 0.40 7.38 ± 0.41 7.60 ± 0.37 7.40 ± 0.46 

Day 23 6.96 ± 0.51 6.97 ± 0.21 7.18 ± 0.40 6.31 ± 0.32 6.46 ± 0.33 4.93 ± 0.18** 

Week 14 6.05 ± 0.31 5.77 ± 0.38 5.48 ± 0.44 6.55 ± 0.57 5.65 ± 0.48 5.95 ± 0.43 

Monocytes (10 /μL) 3 

Day 3 0.20 ± 0.05 0.18 ± 0.06 0.28 ± 0.09 0.22 ± 0.05 0.12 ± 0.03 0.26 ± 0.05 

Day 23 0.22 ± 0.05 0.22 ± 0.05 0.22 ± 0.06 0.23 ± 0.05 0.20 ± 0.05 0.15 ± 0.03 

Week 14 0.15 ± 0.03 0.12 ± 0.04 0.08 ± 0.03 0.13 ± 0.04 0.08 ± 0.02 0.06 ± 0.03 

Eosinophils (10 /μL) 3 

Day 3 0.06 ± 0.02 0.04 ± 0.02 0.03 ± 0.01 0.04 ± 0.01 0.05 ± 0.02 0.05 ± 0.02 

Day 23 0.03 ± 0.02 0.04 ± 0.02 0.05 ± 0.02 0.04 ± 0.01 0.12 ± 0.03 0.05 ± 0.02 

Week 14 0.01 ± 0.01 0.04 ± 0.02 0.04 ± 0.02 0.08 ± 0.03* 0.10 ± 0.04** 0.12 ± 0.02** 

Clinical Chemistry 

Urea nitrogen (mg/dL) 

Day 3 15.9 ± 0.8 14.6 ± 0.6 13.7 ± 0.6 14.0 ± 0.6 14.7 ± 0.6 13.5 ± 0.6 

Day 23 14.7 ± 0.5 14.8 ± 0.4 14.3 ± 0.5 15.7 ± 0.4 13.8 ± 0.4 14.1 ± 0.7 

Week 14 19.0 ± 0.8 18.0 ± 0.5 18.0 ± 0.4 18.7 ± 0.6 17.9 ± 0.5 16.6 ± 0.7 

Creatinine (mg/dL) 

Day 3 0.52 ± 0.01 0.52 ± 0.02 0.53 ± 0.02 0.51 ± 0.02 0.50 ± 0.02 0.46 ± 0.02 

Day 23 0.68 ± 0.01 0.65 ± 0.02 0.70 ± 0.02 0.70 ± 0.02 0.66 ± 0.02 0.66 ± 0.02 

Week 14 0.67 ± 0.03 0.63 ± 0.02 0.65 ± 0.02 0.60 ± 0.00 0.64 ± 0.02 0.62 ± 0.02 
216 Furfuryl Alcohol, NTP TR 482 

TABLE F1 

Hematology and Clinical Chemistry Data for Rats in the 14-Week Inhalation Study of Furfuryl Alcohol 

Chamber 

Control 2 ppm 4 ppm 8 ppm 16 ppm 32 ppm 

Female (continued) 

n 10 10 10 10 10 10 

Clinical Chemistry (continued) 

Total protein (g/dL) 

Day 3 5.2 ± 0.1 5.5 ± 0.1 5.4 ± 0.1 5.3 ± 0.1 5.2 ± 0.1 5.3 ± 0.1 

Day 23 6.3 ± 0.1 6.1 ± 0.1 6.2 ± 0.1 6.3 ± 0.0 6.2 ± 0.1 6.0 ± 0.1 

Week 14 7.2 ± 0.1 7.1 ± 0.1 7.2 ± 0.1 7.2 ± 0.0 7.1 ± 0.1 7.1 ± 0.1 

Albumin (g/dL) 

Day 3 3.3 ± 0.1 3.5 ± 0.0 3.5 ± 0.1 3.4 ± 0.1 3.5 ± 0.1 3.4 ± 0.1 

Day 23 4.5 ± 0.1 4.2 ± 0.1** 4.3 ± 0.0 4.5 ± 0.0 4.4 ± 0.1 4.4 ± 0.1 

Week 14 4.3 ± 0.1 4.3 ± 0.1 4.3 ± 0.0 4.3 ± 0.0 4.3 ± 0.1 4.3 ± 0.1 

Globulin (g/dL) 

Day 3 1.9 ± 0.1 1.9 ± 0.1 1.9 ± 0.0 2.0 ± 0.1 1.8 ± 0.1 1.9 ± 0.1 

Day 23 1.8 ± 0.1 1.9 ± 0.1 1.9 ± 0.1 1.9 ± 0.1 1.8 ± 0.1 1.6 ± 0.1 

Week 14 2.9 ± 0.1 2.8 ± 0.1 2.9 ± 0.1 3.0 ± 0.1 2.8 ± 0.0 2.8 ± 0.1 

A/G ratio 

Day 3 1.8 ± 0.1 1.9 ± 0.1 1.9 ± 0.1 1.7 ± 0.1 2.0 ± 0.1 1.9 ± 0.1 

Day 23 2.5 ± 0.1 2.2 ± 0.1 2.4 ± 0.1 2.4 ± 0.1 2.5 ± 0.1 2.7 ± 0.1 

Week 14 1.5 ± 0.1 1.5 ± 0.1 1.5 ± 0.0 1.5 ± 0.0 1.5 ± 0.0 1.5 ± 0.0 

Alanine aminotransferase (IU/L) 

Day 3 40 ± 1 44 ± 2 41 ± 1 43 ± 1 42 ± 1 38 ± 1 

Day 23 29 ± 2 30 ± 1 33 ± 1 30 ± 1 28 ± 2 24 ± 1 

Week 14 44 ± 3 48 ± 3 47 ± 3 44 ± 1 48 ± 2 42 ± 2 

Alkaline phosphatase (IU/L) 

Day 3 543 ± 9 548 ± 15 528 ± 11 519 ± 15 485 ± 19* 421 ± 15** 

Day 23 443 ± 14 430 ± 10 459 ± 17 453 ± 13 440 ± 12 412 ± 19 

Week 14 234 ± 9 232 ± 6 240 ± 11 232 ± 10 234 ± 8 224 ± 6 

Creatine kinase (IU/L) 

Day 3 428 ± 29 352 ± 15 364 ± 39 407 ± 44 419 ± 41 487 ± 52 

Day 23 205 ± 28 327 ± 44 294 ± 42 248 ± 26 230 ± 19 285 ± 45 

Week 14 90 ± 10 85 ± 12 105 ± 12 99 ± 11 113 ± 9 107 ± 12 

Sorbitol dehydrogenase (IU/L) 

Day 3 9 ± 1 10 ± 1 10 ± 1 10 ± 1 9 ± 0 7 ± 0 

Day 23 11 ± 1 12 ± 0 11 ± 0 11 ± 1 11 ± 1 10 ± 1 

Week 14 9 ± 1 8 ± 1 8 ± 1 8 ± 1 9 ± 1 8 ± 0 

Bile acids (μmol/L) 

Day 3 9.1 ± 1.1 11.8 ± 2.0 11.9 ± 1.3 10.1 ± 1.2 9.1 ± 1.0 6.5 ± 0.7 

Day 23 5.5 ± 0.9 6.2 ± 1.1 7.1 ± 1.1 7.7 ± 1.9 9.9 ± 2.9 8.5 ± 2.1 

Week 14 14.5 ± 3.7 11.4 ± 2.2 9.0 ± 1.9 11.5 ± 2.7 15.7 ± 5.1 11.4 ± 4.5 

* Significantly different (P#0.05) from the chamber control group by Dunn’s or Shirley’s test 

** P#0.01 a Mean ± standard error. Statistical tests were performed on unrounded data. b n=9 
217 

APPENDIX G 

ORGAN WEIGHTS AND 

ORGAN-WEIGHT-TO-BODY-WEIGHT RATIOS 

TABLE G1 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats 

in the 16-Day Inhalation Study of Furfuryl Alcohol ................................... 218 

TABLE G2 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats 

in the 14-Week Inhalation Study of Furfuryl Alcohol .................................. 219 

TABLE G3 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice 

in the 16-Day Inhalation Study of Furfuryl Alcohol ................................... 220 

TABLE G4 Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice 

in the 14-Week Inhalation Study of Furfuryl Alcohol .................................. 221 
218 Furfuryl Alcohol, NTP TR 482 

TABLE G1 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats in the 16-Day Inhalation Study of Furfuryl Alcohola 

Chamber 

Control 16 ppm 31 ppm 63 ppm 125 ppm 

Male 

n 5 5 5 5 4 

Necropsy body wt 186 ± 5 194 ± 4 172 ± 3 174 ± 6 159 ± 7** 

Heart 

Absolute 0.674 ± 0.021 0.696 ± 0.015 0.622 ± 0.011 0.660 ± 0.042 0.578 ± 0.027* 

Relative 3.62 ± 0.03 3.58 ± 0.05 3.62 ± 0.07 3.80 ± 0.19 3.64 ± 0.06 

R. Kidney 

Absolute 0.814 ± 0.034 0.878 ± 0.017 0.786 ± 0.012 0.822 ± 0.027 0.800 ± 0.014 

Relative 4.37 ± 0.10 4.52 ± 0.10 4.58 ± 0.09 4.74 ± 0.02* 5.07 ± 0.16** 

Liver 

Absolute 8.684 ± 0.365 9.660 ± 0.272 8.140 ± 0.162 8.578 ± 0.322 7.553 ± 0.370 

Relative 46.58 ± 1.05 49.68 ± 0.47* 47.35 ± 0.52 49.40 ± 0.55 47.66 ± 1.44 

Lung 

Absolute 1.494 ± 0.079 1.406 ± 0.035 1.366 ± 0.080 1.206 ± 0.079** 1.073 ± 0.048** 

Relative 8.01 ± 0.31 7.26 ± 0.32 7.96 ± 0.51 6.97 ± 0.48 6.79 ± 0.32 

R. Testis 

Absolute 1.053 ± 0.030 1.080 ± 0.041 1.027 ± 0.018 1.032 ± 0.041 1.047 ± 0.031 

Relative 5.65 ± 0.10 5.55 ± 0.14 5.98 ± 0.17 5.94 ± 0.07 6.62 ± 0.15** 

Thymus 

Absolute 0.422 ± 0.023 0.492 ± 0.019 0.474 ± 0.020 0.443 ± 0.012 0.343 ± 0.033* 

Relative 2.26 ± 0.09 2.55 ± 0.16 2.76 ± 0.10* 2.57 ± 0.12* 2.15 ± 0.15 

Female 

n 5 5 5 5 5 

Necropsy body wt 130 ± 4 131 ± 4 125 ± 3 126 ± 2 113 ± 4** 

Heart 

Absolute 0.506 ± 0.014 0.546 ± 0.016 0.486 ± 0.005 0.504 ± 0.027 0.444 ± 0.017* 

Relative 3.90 ± 0.08 4.16 ± 0.13 3.89 ± 0.04 4.00 ± 0.21 3.92 ± 0.07 

R. Kidney 

Absolute 0.592 ± 0.013 0.638 ± 0.018 0.618 ± 0.012 0.638 ± 0.014 0.600 ± 0.024 

Relative 4.57 ± 0.08 4.86 ± 0.09 4.95 ± 0.06* 5.06 ± 0.12** 5.31 ± 0.15** 

Liver 

Absolute 5.520 ± 0.163 5.884 ± 0.191 5.568 ± 0.126 5.802 ± 0.144 5.226 ± 0.231 

Relative 42.50 ± 0.19 44.77 ± 0.81 44.58 ± 0.90 46.02 ± 1.18* 46.20 ± 1.44* 

Lung 

Absolute 1.136 ± 0.043 1.188 ± 0.076 1.048 ± 0.093 1.248 ± 0.056 0.878 ± 0.027* 

Relative 8.76 ± 0.29 9.00 ± 0.35 8.39 ± 0.74 9.90 ± 0.46 7.80 ± 0.39 

Thymus 

Absolute 0.372 ± 0.014 0.393 ± 0.016 0.383 ± 0.014 0.374 ± 0.023 0.287 ± 0.022* 

Relative 2.89 ± 0.19 2.99 ± 0.13 3.07 ± 0.14 2.96 ± 0.18 2.54 ± 0.20 

* Significantly different (P#0.05) from the chamber control group by Williams’ or Dunnett’s test 

** P#0.01 a Organ weights (absolute weights) and body weights are given in grams; organ-weight-to-body-weight ratios (relative weights) are given as 

mg organ weight/g body weight (mean ± standard error). All 250 ppm rats died before the end of the study. 
Furfuryl Alcohol, NTP TR 482 219 

TABLE G2 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats in the 14-Week Inhalation Study of Furfuryl Alcohola 

Chamber 

Control 2 ppm 4 ppm 8 ppm 16 ppm 32 ppm 

n 10 10 10 10 10 10 

Male 

Necropsy body wt 325 ± 7 322 ± 7 332 ± 5 323 ± 5 307 ± 4 311 ± 6 

Heart 

Absolute 0.925 ± 0.030 0.923 ± 0.016 0.959 ± 0.017 0.925 ± 0.012 0.908 ± 0.016 0.928 ± 0.021 

Relative 2.84 ± 0.05 2.87 ± 0.03 2.89 ± 0.03 2.87 ± 0.03 2.96 ± 0.03* 2.99 ± 0.02** 

R. Kidney 

Absolute 1.048 ± 0.025 1.053 ± 0.026 1.092 ± 0.021 1.104 ± 0.023 1.050 ± 0.013 1.082 ± 0.023 

Relative 3.23 ± 0.05 3.27 ± 0.02 3.29 ± 0.04 3.42 ± 0.07** 3.42 ± 0.04** 3.48 ± 0.03** 

Liver 

Absolute 10.667 ± 0.188 11.035 ± 0.381 11.317 ± 0.324 11.471 ± 0.395 10.629 ± 0.368 10.362 ± 0.385 

Relative 32.87 ± 0.33 34.20 ± 0.73 34.10 ± 0.80 35.46 ± 0.83 34.59 ± 0.97 33.30 ± 0.73 

Lung 

Absolute 1.531 ± 0.037 1.511 ± 0.051 1.572 ± 0.043 1.708 ± 0.072 1.570 ± 0.054 1.668 ± 0.101 

Relative 4.74 ± 0.17 4.69 ± 0.13 4.74 ± 0.10 5.28 ± 0.19 5.11 ± 0.15 5.35 ± 0.24* 

R. Testis 

Absolute 1.323 ± 0.016 1.297 ± 0.033 1.368 ± 0.021 1.322 ± 0.024 1.314 ± 0.023 1.363 ± 0.032 

Relative 4.08 ± 0.07 4.03 ± 0.08 4.12 ± 0.04 4.10 ± 0.07 4.29 ± 0.09 4.39 ± 0.06** 

Thymus 

Absolute 0.337 ± 0.010 0.327 ± 0.011 0.354 ± 0.010 0.320 ± 0.016 0.315 ± 0.010b 0.303 ± 0.014 

Relative 1.04 ± 0.03 1.02 ± 0.04 1.07 ± 0.04 0.99 ± 0.04 1.02 ± 0.04b 0.97 ± 0.03 

Female 

Necropsy body wt 198 ± 4 198 ± 3 197 ± 4 189 ± 3 188 ± 3 178 ± 4** 

Heart 

Absolute 0.619 ± 0.012 0.622 ± 0.008 0.631 ± 0.014 0.624 ± 0.006 0.619 ± 0.008 0.595 ± 0.010 

Relative 3.14 ± 0.05 3.14 ± 0.03 3.20 ± 0.06 3.31 ± 0.05* 3.29 ± 0.07* 3.36 ± 0.06** 

R. Kidney 

Absolute 0.641 ± 0.013 0.646 ± 0.010 0.656 ± 0.018 0.689 ± 0.048 0.635 ± 0.009 0.617 ± 0.011 

Relative 3.25 ± 0.05 3.27 ± 0.04 3.32 ± 0.06 3.64 ± 0.24 3.38 ± 0.05 3.48 ± 0.08 

Liver 

Absolute 6.164 ± 0.194 6.022 ± 0.088 6.258 ± 0.140 6.093 ± 0.095 6.037 ± 0.131 5.560 ± 0.134* 

Relative 31.16 ± 0.58 30.43 ± 0.23 31.71 ± 0.34 32.29 ± 0.62 32.06 ± 0.51 31.34 ± 0.59 

Lung 

Absolute 1.117 ± 0.033 1.116 ± 0.026 1.067 ± 0.034 1.093 ± 0.023 1.077 ± 0.030 1.002 ± 0.026** 

Relative 5.65 ± 0.11 5.64 ± 0.10 5.40 ± 0.12 5.80 ± 0.15 5.72 ± 0.13 5.65 ± 0.13 

Thymus 

Absolute 0.271 ± 0.008 0.254 ± 0.008 0.275 ± 0.008 0.247 ± 0.010 0.251 ± 0.009 0.244 ± 0.008 

Relative 1.38 ± 0.05 1.28 ± 0.04 1.39 ± 0.04 1.30 ± 0.04 1.33 ± 0.03 1.37 ± 0.04 

* Significantly different (P#0.05) from the chamber control group by Williams’ or Dunnett’s test 

** P#0.01 a Organ weights (absolute weights) and body weights are given in grams; organ-weight-to-body-weight ratios (relative weights) are given as 

mg organ weight/g body weight (mean ± standard error). b n=9 
220 Furfuryl Alcohol, NTP TR 482 

TABLE G3 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice in the 16-Day Inhalation Study of Furfuryl Alcohola 

Chamber 

Control 16 ppm 31 ppm 63 ppm 125 ppm 

Male 

n 5 5 5 5 5 

Necropsy body wt 27.8 ± 0.5 28.5 ± 0.3 27.8 ± 0.7 25.8 ± 0.3* 24.5 ± 0.7** 

Heart 

Absolute 0.126 ± 0.002 0.142 ± 0.007 0.124 ± 0.004 0.112 ± 0.002* 0.114 ± 0.002* 

Relative 4.54 ± 0.11 5.00 ± 0.29 4.45 ± 0.06 4.33 ± 0.06 4.66 ± 0.12 

R. Kidney 

Absolute 0.278 ± 0.005 0.298 ± 0.007 0.268 ± 0.009 0.250 ± 0.000* 0.256 ± 0.007* 

Relative 10.01 ± 0.16 10.47 ± 0.17 9.63 ± 0.25 9.68 ± 0.10 10.44 ± 0.18 

Liver 

Absolute 1.536 ± 0.042 1.656 ± 0.035 1.584 ± 0.047 1.524 ± 0.030 1.574 ± 0.071 

Relative 55.22 ± 0.58 58.20 ± 1.19 56.87 ± 0.31 58.97 ± 0.91* 64.11 ± 1.58** 

Lung 

Absolute 0.210 ± 0.004 0.218 ± 0.010 0.206 ± 0.007 0.196 ± 0.005 0.198 ± 0.009 

Relative 7.55 ± 0.11 7.67 ± 0.38 7.40 ± 0.19 7.59 ± 0.26 8.07 ± 0.20 

R. Testis 

Absolute 0.107 ± 0.003 0.103 ± 0.001 0.103 ± 0.002 0.104 ± 0.003 0.103 ± 0.004 

Relative 3.83 ± 0.04 3.64 ± 0.06 3.72 ± 0.13 4.04 ± 0.11 4.21 ± 0.07** 

Thymus 

Absolute 0.045 ± 0.003 0.044 ± 0.003 0.045 ± 0.002 0.041 ± 0.002 0.033 ± 0.004** 

Relative 1.63 ± 0.12 1.55 ± 0.09 1.63 ± 0.09 1.59 ± 0.08 1.33 ± 0.17 

Female 

n 5 5 5 5 4 

Necropsy body wt 22.6 ± 0.3 23.2 ± 0.3 22.6 ± 0.4 21.1 ± 0.3** 19.9 ± 0.2** 

Heart 

Absolute 0.110 ± 0.003 0.114 ± 0.002 0.108 ± 0.004 0.098 ± 0.002** 0.093 ± 0.003** 

Relative 4.86 ± 0.12 4.91 ± 0.09 4.77 ± 0.10 4.64 ± 0.05 4.65 ± 0.08 

R. Kidney 

Absolute 0.190 ± 0.004 0.194 ± 0.005 0.192 ± 0.004 0.172 ± 0.005* 0.165 ± 0.005** 

Relative 8.39 ± 0.14 8.36 ± 0.23 8.49 ± 0.20 8.14 ± 0.14 8.29 ± 0.17 

Liver 

Absolute 1.230 ± 0.034 1.360 ± 0.018 1.300 ± 0.040 1.158 ± 0.039 1.248 ± 0.043 

Relative 54.30 ± 0.96 58.58 ± 0.69 57.41 ± 1.34 54.80 ± 1.40 62.64 ± 1.43** 

Lung 

Absolute 0.192 ± 0.009 0.198 ± 0.006 0.200 ± 0.005 0.178 ± 0.010 0.183 ± 0.008 

Relative 8.47 ± 0.29 8.53 ± 0.24 8.84 ± 0.27 8.42 ± 0.42 9.16 ± 0.27 

Thymus 

Absolute 0.069 ± 0.004 0.070 ± 0.005 0.068 ± 0.002 0.062 ± 0.003 0.049 ± 0.003** 

Relative 3.03 ± 0.17 3.02 ± 0.25 3.03 ± 0.11 2.95 ± 0.15 2.47 ± 0.14 

* Significantly different (P#0.05) from the chamber control group by Williams’ or Dunnett’s test 

** P#0.01 a Organ weights (absolute weights) and body weights are given in grams; organ-weight-to-body-weight ratios (relative weights) are given as 

mg organ weight/g body weight (mean ± standard error). All 250 ppm mice died before the end of the study. 
Furfuryl Alcohol, NTP TR 482 221 

TABLE G4 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice in the 14-Week Inhalation Study of Furfuryl Alcohola 

Chamber 

Control 2 ppm 4 ppm 8 ppm 16 ppm 32 ppm 

n 10 10 10 10 10 10 

Male 

Necropsy body wt 34.5 ± 0.6 36.9 ± 0.8 36.3 ± 0.8 36.6 ± 0.8 36.5 ± 0.6 34.0 ± 0.8 

Heart 

Absolute 0.160 ± 0.004 0.158 ± 0.003 0.162 ± 0.002 0.160 ± 0.004 0.161 ± 0.002 0.143 ± 0.003** 

Relative 4.65 ± 0.12 4.29 ± 0.04* 4.47 ± 0.08 4.38 ± 0.07 4.42 ± 0.09 4.22 ± 0.06** 

R. Kidney 

Absolute 0.307 ± 0.011 0.330 ± 0.009 0.335 ± 0.008 0.332 ± 0.007 0.322 ± 0.004 0.306 ± 0.006 

Relative 8.88 ± 0.23 8.95 ± 0.17 9.24 ± 0.19 9.09 ± 0.18 8.85 ± 0.20 9.03 ± 0.13 

Liver 

Absolute 1.617 ± 0.043 1.616 ± 0.060 1.644 ± 0.033 1.654 ± 0.036 1.604 ± 0.026 1.523 ± 0.043 

Relative 46.85 ± 0.91 43.78 ± 1.14 45.36 ± 0.79 45.25 ± 0.67 44.05 ± 0.79 44.84 ± 0.67 

Lung 

Absolute 0.244 ± 0.005 0.248 ± 0.008 0.243 ± 0.008 0.242 ± 0.010 0.247 ± 0.007 0.219 ± 0.007 

Relative 7.07 ± 0.12 6.74 ± 0.20 6.70 ± 0.19 6.63 ± 0.27 6.80 ± 0.25 6.44 ± 0.13 

R. Testis 

Absolute 0.124 ± 0.003 0.131 ± 0.003 0.128 ± 0.003 0.129 ± 0.002 0.131 ± 0.004 0.122 ± 0.003 

Relative 3.59 ± 0.07 3.55 ± 0.10 3.54 ± 0.13 3.54 ± 0.10 3.59 ± 0.12 3.59 ± 0.09 

Thymus 

Absolute 0.036 ± 0.001 0.040 ± 0.002 0.038 ± 0.002 0.037 ± 0.002 0.041 ± 0.003 0.040 ± 0.003 

Relative 1.03 ± 0.04 1.08 ± 0.04 1.06 ± 0.05 1.02 ± 0.03 1.11 ± 0.06 1.18 ± 0.11 

Female 

Necropsy body wt 30.9 ± 0.9 31.7 ± 1.0 32.1 ± 1.0 31.3 ± 1.0 32.3 ± 0.9 30.2 ± 0.8 

Heart 

Absolute 0.139 ± 0.002 0.136 ± 0.003 0.136 ± 0.003 0.135 ± 0.002 0.133 ± 0.002 0.126 ± 0.002** 

Relative 4.53 ± 0.14 4.31 ± 0.11 4.27 ± 0.10 4.34 ± 0.12 4.15 ± 0.12 4.19 ± 0.09 

R. Kidney 

Absolute 0.210 ± 0.006 0.221 ± 0.003 0.221 ± 0.005 0.226 ± 0.003 0.225 ± 0.005 0.207 ± 0.004 

Relative 6.82 ± 0.18 7.02 ± 0.18 6.92 ± 0.17 7.27 ± 0.21 7.01 ± 0.22 6.88 ± 0.11 

Liver 

Absolute 1.437 ± 0.034 1.471 ± 0.029 1.552 ± 0.043 1.510 ± 0.041 1.560 ± 0.034 1.418 ± 0.042 

Relative 46.61 ± 0.36 46.58 ± 0.76 48.54 ± 1.01 48.37 ± 0.88 48.44 ± 0.92 47.06 ± 0.95 

Lung 

Absolute 0.222 ± 0.006 0.225 ± 0.007 0.224 ± 0.006 0.228 ± 0.006 0.227 ± 0.006 0.221 ± 0.007 

Relative 7.21 ± 0.17 7.13 ± 0.21 7.01 ± 0.13 7.32 ± 0.21 7.05 ± 0.19 7.35 ± 0.25 

Thymus 

Absolute 0.055 ± 0.002 0.057 ± 0.002 0.059 ± 0.003 0.057 ± 0.003 0.062 ± 0.004 0.059 ± 0.003 

Relative 1.78 ± 0.06 1.79 ± 0.05 1.83 ± 0.08 1.83 ± 0.09 1.93 ± 0.10 1.95 ± 0.09 

* Significantly different (P#0.05) from the chamber control group by Williams’ or Dunnett’s test 

** P#0.01 a Organ weights (absolute weights) and body weights are given in grams; organ-weight-to-body-weight ratios (relative weights) are given as 

mg organ weight/g body weight (mean ± standard error). 
222 Furfuryl Alcohol, NTP TR 482 
223 

APPENDIX H 

REPRODUCTIVE TISSUE EVALUATIONS 

AND ESTROUS CYCLE CHARACTERIZATION 

TABLE H1 Summary of Reproductive Tissue Evaluations for Male Rats 

in the 14-Week Inhalation Study of Furfuryl Alcohol .................................. 224 

TABLE H2 Estrous Cycle Characterization for Female Rats in the 14-Week Inhalation Study 

of Furfuryl Alcohol ............................................................... 224 

TABLE H3 Summary of Reproductive Tissue Evaluations for Male Mice 

in the 14-Week Inhalation Study of Furfuryl Alcohol .................................. 225 

TABLE H4 Estrous Cycle Characterization for Female Mice in the 14-Week Inhalation Study 

of Furfuryl Alcohol ............................................................... 225 
224 Furfuryl Alcohol, NTP TR 482 

TABLE H1 

Summary of Reproductive Tissue Evaluations for Male Rats in the 14-Week Inhalation Study 

of Furfuryl Alcohola 

Chamber 

Control 2 ppm 8 ppm 32 ppm 

n 10 10 10 10 

Weights (g) 

Necropsy body wt 

L. cauda epididymis 

L. epididymis 

L. testis 

325 ± 7 

0.1637 ± 0.0079 

0.4514 ± 0.0184 

1.3579 ± 0.0389 

322 ± 7 

0.1627 ± 0.0042 

0.4406 ± 0.0085 

1.3626 ± 0.0262 

323 ± 5 

0.1578 ± 0.0064 

0.4315 ± 0.0098 

1.3569 ± 0.0278 

311 ± 6 

0.1626 ± 0.0064 

0.4586 ± 0.0075 

1.4049 ± 0.0304 

Spermatid measurements 

Spermatid heads (10 /g testis) 7 

Spermatid heads (10 /testis) 7 

Spermatid count 

(mean/10 mL suspension) !4 

10.43 ± 0.57 

14.26 ± 0.96 

71.30 ± 4.80 

12.20 ± 0.68 

16.65 ± 1.05 

83.25 ± 5.25 

12.32 ± 0.61* 

16.65 ± 0.74 

83.23 ± 3.69 

12.96 ± 0.54** 

18.13 ± 0.61** 

90.63 ± 3.07** 

Epididymal spermatozoal measurements 

Motility (%) 

Concentration 

 (10 /g cauda epididymal tissue) 6 

87.48 ± 7.80 

443 ± 46 

93.35 ± 1.16 

511 ± 21 

88.02 ± 4.91 

460 ± 19 

92.53 ± 0.58 

442 ± 15 

* Significantly different (P#0.05) from the chamber control group by Shirley’s test 

** P#0.01 a Data are presented as mean ± standard error. Differences from the chamber control group are not significant by Dunnett’s test (body and tissue 

weights) or Dunn’s test (epididymal spermatozoal measurements). 

TABLE H2 

Estrous Cycle Characterization for Female Rats in the 14-Week Inhalation Study of Furfuryl Alcohola 

Chamber 

Control 2 ppm 8 ppm 32 ppm 

n 10 10 10 10 

Necropsy body wt (g) 198 ± 4 198 ± 3 189 ± 3 178 ± 4** 

Estrous cycle length (days) 4.80 ± 0.11 4.85 ± 0.11 4.90 ± 0.10 4.80 ± 0.11 

Estrous stages (% of cycle) 

Diestrus 42.5 42.5 39.2 40.0 

Proestrus 19.2 15.8 15.8 14.2 

Estrus 21.7 22.5 25.0 28.3 

Metestrus 16.7 18.3 16.7 15.0 

Uncertain diagnoses 0.0 0.8 3.3 2.5 

** Significantly different (P#0.05) from the chamber control group by Williams’ test a Necropsy body weight and estrous cycle length data are presented as mean ± standard error. Differences from the chamber control group for 

estrous cycle length are not significant by Dunn’s test. By multivariate analysis of variance, exposed females do not differ significantly from the 

chamber control females in the relative length of time spent in the estrous stages. 
Furfuryl Alcohol, NTP TR 482 225 

TABLE H3 

Summary of Reproductive Tissue Evaluations for Male Mice in the 14-Week Inhalation Study 

of Furfuryl Alcohola 

Chamber 

Control 2 ppm 8 ppm 32 ppm 

n 10 10 10 10 

Weights (g) 

Necropsy body wt 

L. cauda epididymis 

L. epididymis 

L. testis 

34.5 ± 0.6 

0.0162 ± 0.0008 

0.0462 ± 0.0016 

0.1187 ± 0.0027 

36.9 ± 0.8 

0.0173 ± 0.0009 

0.0472 ± 0.0010 

0.1264 ± 0.0022 

36.6 ± 0.8 

0.0155 ± 0.0006 

0.0453 ± 0.0009 

0.1229 ± 0.0011 

34.0 ± 0.8 

0.0162 ± 0.0010 

0.0439 ± 0.0014 

0.1134 ± 0.0031 

Spermatid measurements 

Spermatid heads (10 /g testis) 7 

Spermatid heads (10 /testis) 7 

Spermatid count 

(mean/10 mL suspension) !4 

24.94 ± 0.76 

2.95 ± 0.08 

92.18 ± 2.57 

24.31 ± 0.88 

3.06 ± 0.08 

95.63 ± 2.57 

24.26 ± 1.06 

2.98 ± 0.13 

93.10 ± 3.95 

25.56 ± 1.24 

2.87 ± 0.09 

89.80 ± 2.92 

Epididymal spermatozoal measurements 

Motility (%) 

Concentration 

 (10 /g cauda epididymal tissue) 6 

91.17 ± 1.52 

996 ± 56 

90.27 ± 1.49 

914 ± 63 

94.26 ± 0.97 

1,029 ± 40 

93.34 ± 0.84 

876 ± 93 

a Data are presented as mean ± standard error. Differences from the chamber control group were not significant by Dunnett’s test (body and tissue 

weights) or Dunn’s test (spermatid and epididymal spermatozoal measurements). 

TABLE H4 

Estrous Cycle Characterization for Female Mice in the 14-Week Inhalation Study of Furfuryl Alcohola 

Chamber 

Control 2 ppm 8 ppm 32 ppm 

n 10 10 10 10 

Necropsy body wt (g) 30.9 ± 0.9 31.7 ± 1.0 31.3 ± 1.0 30.2 ± 0.8 

Estrous cycle length (days) 4.10 ± 0.10 4.20 ± 0.13 4.40 ± 0.22 4.10 ± 0.07 

Estrous stages (% of cycle) 

Diestrus 31.7 30.8 32.5 34.2 

Proestrus 14.2 20.0 22.5 22.5 

Estrus 35.8 30.8 27.5 28.3 

Metestrus 16.7 18.3 15.0 14.2 

Uncertain diagnoses 1.7 0.0 2.5 0.8 

a Necropsy body weight and estrous cycle length data are presented as mean ± standard error. Differences from the chamber control group are not 

significant by Dunnett’s test (body weights) or Dunn’s test (estrous cycle length). By multivariate analysis of variance, exposed females do not 

differ significantly from the chamber control females in the relative length of time spent in the estrous stages. 
226 Furfuryl Alcohol, NTP TR 482 
227 

APPENDIX I
 

URINARY METABOLITE STUDY
 

TABLE I1	 Urinary Metabolite Data for Rats in the 2-Year Inhalation Study 

of Furfuryl Alcohol ............................................................... 228 
228 

c 

Furfuryl Alcohol, NTP TR 482 

TABLE I1 

Urinary Metabolite Data for Rats in the 2-Year Inhalation Study of Furfuryl Alcohola 

Chamber 

Control 2 ppm 8 ppm 32 ppm 

Male 

n 5 5 3 0d 

Volume (mL/16 hr) 

Creatinine (mg/16 hr) 

Furoylglycine (μg/16 hr) 

Furanacryloylglycine (μg/16 hr) 

8.9 ± 1.2 

6.92 ± 0.94 

16.8 ± 4.1 

3.50 ± 1.70b 

10.6 ± 1.3 

8.90 ± 0.66 

1,000.6 ± 155.9** 

46.20 ± 7.69c 

12.8 ± 1.5 

8.47 ± 0.07 

3,920.3 ± 136.1** 

369.47 ± 108.26* 

Female 

n 5 5 5 5 

Volume (mL/16 hr) 

Creatinine (mg/16 hr) 

Furoylglycine (μg/16 hr) 

Furanacryloylglycine (μg/16 hr) 

5.5 ± 0.5 

4.96 ± 0.32 

13.6 ± 1.0 

3.15 ± 0.25b 

6.2 ± 0.9 

4.94 ± 0.82 

516.8 ± 128.4** 

24.96 ± 5.19 

5.4 ± 0.5 

5.12 ± 0.61 

2,387.8 ± 332.7** 

98.18 ± 11.49** 

5.7 ± 0.5 

4.52 ± 0.25 

7,598.0 ± 942.6** 

328.48 ± 61.11** 

* Significantly different (P#0.05) from the chamber control group by Dunn’s or Shirley’s test 

** P#0.01 a Mean ± standard error. Statistical tests were performed on unrounded data. b n=2 

n=3 

d No data available due to 100% mortality in this exposure group 
229 

APPENDIX J
 

CHEMICAL CHARACTERIZATION AND
 

GENERATION OF CHAMBER CONCENTRATIONS
 

PROCUREMENT AND CHARACTERIZATION OF FURFURYL ALCOHOL .................................... 230
 

VAPOR GENERATION AND EXPOSURE SYSTEM ...................................................... 231
 

VAPOR CONCENTRATION MONITORING ........................................................... 232
 

CHAMBER ATMOSPHERE CHARACTERIZATION ..................................................... 232
 

FIGURE J1 Infrared Absorption Spectrum of Furfuryl Alcohol .................................... 234
 

FIGURE J2 Nuclear Magnetic Resonance Spectrum of Furfuryl Alcohol ............................ 235
 

FIGURE J3a Schematic of the Generation and Delivery System in the 16-Day and 14-Week Studies ..... 236
 

FIGURE J3b Schematic of the Generation and Delivery System in the 2-Year Studies ................. 237
 

TABLE J1 Summary of Chamber Concentrations in the 16-Day Inhalation Studies 

of Furfuryl Alcohol ............................................................... 238
 

TABLE J2 Summary of Chamber Concentrations in the 14-Week Inhalation Studies 

of Furfuryl Alcohol ............................................................... 238
 

TABLE J3 Summary of Chamber Concentrations in the 2-Year Inhalation Studies 

of Furfuryl Alcohol ............................................................... 239
 
230 Furfuryl Alcohol, NTP TR 482 

CHEMICAL CHARACTERIZATION AND 

GENERATION OF CHAMBER CONCENTRATIONS 

PROCUREMENT AND CHARACTERIZATION OF FURFURYL ALCOHOL 

Furfuryl alcohol was obtained from QO Chemicals, Inc. (Memphis, TN), in one lot (7B19M-2), which was used 

during the 16-day, 14-week, 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 furfuryl alcohol studies are on file at the National Institute of Environmental Health Sciences. 

The chemical, a clear yellow liquid, was identified as furfuryl alcohol by infrared, ultraviolet/visible, and nuclear 

magnetic resonance spectroscopy. All spectra were consistent with the literature spectra (Sadtler Standard 

Spectra, 1970; Weast, 1975) of furfuryl alcohol. The infrared and nuclear magnetic spectra are presented in 

Figures J1 and J2. 

The purity of lot 7B19M-2 was determined by elemental analyses, Karl Fischer water analysis, and gas 

chromatography. Gas chromatography was performed using a flame ionization detector. Two systems were used: 

A) 20% SP-2100/0.1% Carbowax 1500 on 100/120 Supelcoport glass column, with a nitrogen 

carrier gas at a flow rate of 70 mL/minute and an oven temperature program of 50E C for 

5 minutes, then 50E to 170E C at 10E C per minute, and 

B) DB-Wax capillary fused silica column, with a helium carrier gas at a flow rate of 8 mL/minute, a 

nitrogen makeup gas at a flow rate of 22 mL/minute, and an oven temperature program of 50E C 

for 5 minutes, then 50E to 225E C at 10E C per minute. 

Elemental analyses for carbon and hydrogen were in agreement with the theoretical values for furfuryl alcohol. 

Karl Fischer water analysis indicated 0.098% ± 0.008% water. Gas chromatography by each system indicated one 

major peak and five impurities with areas greater than 0.1% relative to the major peak area; the combined impurity 

peak areas were 1.36% for system A and 1.17% for system B. Major peak comparison between lot 7B19M-2 and 

lot Q0112979, a previously analyzed lot not used in the current studies, indicated a purity of 100.9% ± 0.6% for 

lot 7B19M-2 relative to lot Q0112979. The overall purity was determined to be greater than 98%. 

Stability studies of lot Q0112979 of the bulk chemical performed by the analytical chemistry laboratory indicated 

that furfuryl alcohol was stable as a bulk chemical when stored at or below 25E C, protected from light, and under 

a nitrogen headspace. Literature obtained from the manufacturer indicated that furfuryl alcohol was stable up to 

6 months at ambient temperatures and that stability during storage was improved by maintaining the chemical 

under nitrogen. 

During the studies, the bulk chemical was stored under a nitrogen blanket in its original shipping containers at 

approximately !20E C. Stability was monitored by the study laboratory throughout all studies with gas 

chromatography; no degradation of the bulk chemical was detected. 
Furfuryl Alcohol, NTP TR 482 231 

VAPOR GENERATION AND EXPOSURE SYSTEM 

Schematic diagrams of the furfuryl alcohol generation and delivery system are shown in Figures J3a and J3b. 

Furfuryl alcohol was pumped through a calibrated volume tube into the top of a glass evaporation column filled 

with glass beads, which increased the surface area for evaporation. A heated nitrogen stream entered the column 

from below, vaporized the furfuryl alcohol, and carried it to a heated condenser column. During the 2-year studies, 

the evaporation column was heated by wrapping with heat tape; additional heated nitrogen was added to the 

furfuryl alcohol vapor leaving the evaporation column to dilute the vapor. Condensation in the condenser 

controlled the furfuryl alcohol vapor concentration produced by the generator; condensate was collected in a waste 

flask at the bottom of the condenser. The refluxing action also tended to remove less volatile impurities from the 

vapor. The saturated vapor leaving the condenser was transported to the exposure room through a heated Teflon 

line to prevent condensation. During the 16-day and 14-week studies, the vapor was drawn through the heated line 

and injected into the inlet air stream of a mixing chamber (an exposure chamber with the cages removed) and then 

pumped through a pneumatic valve into the distribution line. The charcoal- and HEPA-filtered air was 

conditioned to room temperature and maintained at minimum relative humidity to prevent the vapor from 

condensing. During the 16-day studies, condensation particles were filtered from the vapor with Teflon-membrane 

filters before entering the distribution line. In the 2-year studies, no mixing chamber was used; the vapor was 

mixed with additional heated air at the entrance of a short vapor distribution manifold. An automatic controller 

maintained constant flow (and thus constant concentration) in the distribution manifold. 

From the distribution manifold, individual temperature-controlled delivery lines carried the vapor to each exposure 

chamber (Harford Systems Division of Lab Products, Inc., Aberdeen, MD). The study laboratory designed the 

inhalation exposure chamber so that uniform vapor concentrations could be maintained throughout the chamber 

with the catch pans in place. The total active mixing volume of each chamber was 1.7 m . 

3 Vapor was drawn 

through the system by compressed-air-driven vacuum pumps located at the chamber end of each delivery line. A 

three-way valve, mounted in the line from the distribution manifold to each chamber, directed vapor to the 

exposure chamber exhaust until the generation system was stable. When equilibrium was reached, each valve was 

opened to allow the flow of vapor into the chamber. At each chamber, the vapor was injected into the chamber 

inlet duct where it was further diluted with filtered chamber air to achieve the desired exposure concentration. A 

small particle detector (Type CN, Gardner Associates, Schenectady, NY) was used with and without animals in the 

exposure chambers to ensure that furfuryl alcohol vapor, and not aerosol, was produced. The minimum resolvable 

level of the detector is approximately 200 particles per cubic centimeter. During the 16-day studies, no particles 

were detected in the distribution line. Without animals in the chambers, particle concentrations were below the 3 limit of detection in the 16 and 31 ppm chambers but ranged up to 600 particles/cm in the 63 ppm chambers and 3 8,400 particles/cm in the 125 ppm chambers; concentrations in the 250 ppm chambers ranged from 8,400 to

36,000 particles/cm . 

3 With animals in the chambers, concentrations were below the limit of detection in all but the 3 125 and 250 ppm chambers, which had concentrations of 1,470 and 11,200 particles/cm , respectively. During 3 the 14-week studies, particle concentrations in the 32 ppm chamber were 200 particles/cm without animals 3 present and 245 particles/cm with animals; concentrations in all other chambers were below the limit of detection,

with and without animals present. During the 2-year study prestart phase, the 32 ppm mouse chamber had a 3 concentration of 370 particles/cm with no animals present; all other rat and mouse chambers, with and without

animals present, had concentrations below the limit of detection. 
 

 

 

 

232 Furfuryl Alcohol, NTP TR 482 

VAPOR CONCENTRATION MONITORING 

The chamber concentrations of furfuryl alcohol were monitored by a Hewlett-Packard Model 5890 on-line gas 

chromatograph (Hewlett-Packard, Palo Alto, CA). During the 2-year studies, samples were drawn from each 

exposure chamber, the control chamber, the exposure suite, on-line standards, and a nitrogen blank approximately 

every 36 minutes through a 12-port stream select valve. 

The monitoring system was calibrated against a gravimetrically prepared standard of furfuryl alcohol in nitrogen. 

Additionally, the on-line monitor was calibrated by a comparison of chamber concentration data to grab samples 

analyzed by an off-line gas chromatograph at least once per month. The operation of the chamber monitor was 

checked throughout the day against an on-line standard. The grab samples were collected in bubblers containing 

dimethylformamide and analyzed by an off-line gas chromatograph. The volumes of gas were sampled at a 

constant flow rate ensured by a calibrated critical orifice. The off-line gas chromatograph was calibrated with 

gravimetrically prepared furfuryl alcohol standards in dimethylformamide. 

Summaries of the chamber concentrations during the studies are presented in Tables J1 through J3. 

CHAMBER ATMOSPHERE CHARACTERIZATION 

The buildup of vapor concentration in the chamber to 90% of its final stable concentration (T ) at the beginning of 90 

exposure and the decay of concentration at the end of exposure to 10% (T ) were measured with and without 10 

animals in the chambers. At a chamber airflow rate of 15 air changes/hour, the theoretical value for both T90 and 

T10 is approximately 12.5 minutes. For the 16-day studies without animals present, the values of T90 ranged from 8

to 12 minutes and T10 from 8 to 11 minutes; with animals present, the values for both T90 10 and T ranged from 11

to 18 minutes. For the 14-week studies without animals present, the values of T90 10 and T ranged from 10 to

13 minutes; with animals present, the values ranged from 16 to 20 minutes for T and 13 to 21 minutes for T . 90 10 

For the 2-year studies without animals present, the values of T90 were 11 to 12 minutes for rats and 11 minutes for 

mice; the values of T10 ranged from 11 to 13 minutes for rats and 10 to 13 minutes for mice. With animals 

present, a much slower buildup phase was noted. The values of T90 ranged from 12 to 25 minutes for rats and 15 

to 22 minutes for mice and the values for T10 were between 30 and 33 minutes for rats and 33 and 59 minutes for 

mice. To compensate for the slow buildup, additional vapor was delivered to the exposure chambers during the 

first 30 to 60 minutes. A value for T10 could not be determined for the 2 ppm chambers because 10% of the target 

concentration (0.2 ppm) was below the limit of quantitation (0.27 ppm). A T90 of 12 minutes was initially used for 

all studies. However, because the actual T90 values for the 14-week studies were considerably longer than 

12 minutes (16 to 20 minutes), the T90 was increased to 20 minutes on the seventeenth exposure day; this value 

was used until the end of the studies. 

Vapor concentration uniformity in the exposure chambers without animals in the chambers was measured before 

each of the studies began. Concentration uniformity with animals present was measured once during the 16-day 

and 14-week studies and at approximately 90-day intervals during the 2-year studies. Vapor concentration was 

measured by the on-line gas chromatograph with the automatic 12-port sample valve disabled to allow continuous 

monitoring from a single input line. Samples taken from several positions within each exposure chamber were 

analyzed. Chamber concentration uniformity was maintained throughout the studies. 

In order to determine the persistence of furfuryl alcohol in the chambers after exposure, the time for the 

concentration to decay to less than 1% of the stable concentration was measured in the 250 ppm (16-day study) or 

32 ppm (14-week and 2-year studies) chamber. Monitoring was performed before the start of the studies without 

animals and during the studies with animals present. In the 16-day studies, the concentration of furfuryl alcohol 

fell to below 1% in approximately 30 minutes without animals present and in approximately 50 minutes with 

animals in the chambers. In the 14-week studies, the concentration fell to below 1% in approximately 27 minutes 

without animals present and in approximately 103 minutes with animals present. In the 2-year studies, the 

concentration of furfuryl alcohol in the rat chambers failed to fall below 1% within 945 minutes with animals in 
Furfuryl Alcohol, NTP TR 482 233 

the chamber, although the concentration decayed to less than 1% in 52 minutes without animals. The 

concentration of furfuryl alcohol in the mouse chambers fell to less than 1% within 367 minutes with animals 

present and within 58 minutes without animals in the chamber. 

Furfuryl alcohol samples collected with bubblers or gas sampling tubes from the vapor generator reservoir were 

tested for stability during the 16-day and 14-week studies by gas chromatography with a furfuryl alcohol reference. 

Results indicated that furfuryl alcohol was stable in the reservoir for 8 hours at room temperature under a blanket 

of nitrogen. Although a brown-black tar, indicative of polymerization, was noted in the evaporation column, the 

refluxing action of the condenser column apparently removed the heavier, less volatile degradation products; no 

significant degeneration of furfuryl alcohol was detected. During prestudy testing, 0.5% furfural was detected in 

the transport line, although concentrations elsewhere in the exposure system ranged from 0.02% to 0.17%; the 

furfural in the transport line was considered to be a sampling artifact. Furoic acid, furan, and formaldehyde 

concentrations were at or below the limits of detection. Additionally, aged samples of furfuryl alcohol were 

analyzed with gas chromatography/mass spectroscopy and gas chromatography/Fourier transform infrared 

spectroscopy; eight degradation products were tentatively identified in the aged furfuryl alcohol sample. 

During the 16-day studies, stability was monitored by testing furfuryl alcohol samples for furfural, formaldehyde, 

and volatile organic impurities by gas chromatography. Samples were collected with bubblers or gas sampling 

tubes from the generator reservoir, transport and distribution lines, and the 16 and 250 ppm chambers, with and 

without animals present. An impurity with a relative area of 0.1% was detected in the 16 ppm chamber, and two 

impurities with a combined relative area of approximately 0.4% were detected in the occupied 250 ppm chamber. 

No more than 0.4% furfural (approximately the amount present in the bulk chemical) was detected in any sample; 

formaldehyde concentrations were at or below the limit of detection. During the 14-week studies, samples 

collected by gas sampling tube from the distribution line and the 2 and 32 ppm chambers, with animals present, 

were tested by gas chromatography for oxidation products, polymers, dimers, and the oxazolidine derivatives 

formaldehyde and 2-furaldehyde; major peak comparisons of samples from the evaporation and condenser column 

collection flasks and the generator reservoir were also performed with gas chromatography. No degradation of 

furfuryl alcohol was detected; 2-furaldehyde concentrations in the exposure system ranged from approximately 

0.1% to 0.2%, similar to the concentration detected in the bulk chemical (0.22%), and formaldehyde 

concentrations were at or below the limit of detection in all samples. Stability in the 2-year studies was monitored 

by gas chromatographic analysis of 2-furaldehyde concentrations in the generator reservoir, condenser column 

collection flask, distribution line, and 0, 2, and 32 ppm chambers with animals present. Concentrations of 

2-furaldehyde ranged from 0.11% in the condenser column collection flask to 0.35% in the 2 ppm chamber (at the 

end of an exposure day), indicating that no degradation of furfuryl alcohol occurred. 
 

 

234 Furfuryl Alcohol, NTP TR 482
 

Figure J1 

Infrared Absorption Spectrum of Furfuryl Alcohol 
 

 

Furfuryl Alcohol, NTP TR 482
 235 

FIGURE J2 

Nuclear Magnetic Resonance Spectrum of Furfuryl Alcohol 
236 Furfuryl Alcohol, NTP TR482 

Figure J3a 

Schematic of the Generation and Delivery System 

in the 16-Day and 14-Week Studies 
Furfuryl Alcohol, NTP TR482 237 

FIGURE J3B 

Schematic of the Generation and Delivery System 

in the 2-Year Studies 
238 Furfuryl Alcohol, NTP TR 482 

TABLE J1 

Summary of Chamber Concentrations in the 16-Day Inhalation Studies of Furfuryl Alcohol 

Target Concentration 

(ppm) 

Total Number of Readings Average Concentrationa 

(ppm) 

Rat Chambers 

16 

31 

63 

125 

250 

144 

142 

141 

141 

21 

15.5 ± 1.0 

30.0 ± 1.8 

61.4 ± 3.9 

119 ± 9.0 

229 ± 7.3 

Mouse Chambers 

16 

31 

63 

125 

250 

146 

143 

141 

141 

34 

15.5 ± 1.0 

30.2 ± 1.7 

61.8 ± 3.8 

120 ± 9.1 

226 ± 33 

a Mean ± standard deviation 

TABLE J2 

Summary of Chamber Concentrations in the 14-Week Inhalation Studies of Furfuryl Alcohol 

Target Concentration Total Number of Readings Average Concentrationa 

(ppm) (ppm) 

Rat Chambers 

2 743 2.0 ± 0.10 

4 742 4.0 ± 0.21 

8 737 8.1 ± 0.38 

16 735 16.1 ± 0.77 

32 739 32.2 ± 1.43 

Mouse Chambers 

2 754 2.0 ± 0.10 

4 753 4.0 ± 0.20 

8 749 8.1 ± 0.38 

16 746 16.1 ± 0.72 

32 750 32.2 ± 1.41 

a Mean ± standard deviation 
Furfuryl Alcohol, NTP TR 482 239 

TABLE J3 

Summary of Chamber Concentrations in the 2-Year Inhalation Studies of Furfuryl Alcohol 

Target Concentration Total Number of Readings Average Concentrationa 

(ppm) (ppm) 

Rat Chambers 

2 4,769 2.01 ± 0.11 

8 4,759 8.02 ± 0.43 

32 4,786 32.3 ± 1.93 

Mouse Chambers 

2 5,161 1.99 ± 0.12 

8 5,194 8.01 ± 0.45 

32 5,198 31.9 ± 2.07 

a Mean ± standard deviation 
240 Furfuryl Alcohol, NTP TR 482 
241 

APPENDIX K 

INGREDIENTS, NUTRIENT COMPOSITION, 

AND CONTAMINANT LEVELS 

IN NIH-07 RAT AND MOUSE RATION 

TABLE K1 

TABLE K2 

TABLE K3 

TABLE K4 

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 ................................ 

242 

242 

243 

244 
242 Furfuryl Alcohol, NTP TR 482 

TABLE K1 

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 K2 

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 
Furfuryl Alcohol, NTP TR 482 243 

TABLE K3 

Nutrient Composition of NIH-07 Rat and Mouse Ration 

Mean ± Standard 

Nutrient Deviation Range Number of Samples 

Protein (% by weight) 23.35 ± 0.52 22.2 ) 24.3 24 

Crude fat (% by weight) 5.38 ± 0.18 5.10 ) 5.90 24 

Crude fiber (% by weight) 3.24 ± 0.35 2.60 ) 4.30 24 

Ash (% by weight) 6.37 ± 0.23 5.94 ) 6.81 24 

Amino Acids (% of total diet) 

Arginine 1.273 ± 0.083 1.100 ) 1.390 12 

Cystine 0.307 ± 0.068 0.181 ) 0.400 12 

Glycine 1.152 ± 0.051 1.060 ) 1.220 12 

Histidine 0.581 ± 0.029 0.531 ) 0.630 12 

Isoleucine 0.913 ± 0.034 0.867 ) 0.965 12 

Leucine 1.969 ± 0.053 1.850 ) 2.040 12 

Lysine 1.269 ± 0.050 1.200 ) 1.370 12 

Methionine 0.436 ± 0.104 0.306 ) 0.699 12 

Phenylalanine 0.999 ± 0.114 0.665 ) 1.110 12 

Threonine 0.899 ± 0.059 0.824 ) 0.985 12 

Tryptophan 0.216 ± 0.146 0.107 ) 0.671 12 

Tyrosine 0.690 ± 0.091 0.564 ) 0.794 12 

Valine 1.079 ± 0.057 0.962 ) 1.170 12 

Essential Fatty Acids (% of total diet) 

Linoleic 2.389 ± 0.223 1.830 ) 2.570 11 

Linolenic 0.273 ± 0.034 0.210 ) 0.320 11 

Vitamins 

Vitamin A (IU/kg) 6,602 ± 572 5,730 ) 8,800 24 

Vitamin D (IU/kg) 4,450 ± 1,382 3,000 ) 6,300 4 

"-Tocopherol (ppm) 35.24 ± 8.58 22.5 ) 48.9 12 

Thiamine (ppm) 16.58 ± 2.32 13.0 ) 22.0 24 

Thiamine (ppm) 17.13 ± 2.03 14.0 ) 22.0 23 

Riboflavin (ppm) 7.78 ± 0.899 6.10 ) 9.00 12 

Niacin (ppm) 98.73 ± 23.21 65.0 ) 150.0 12 

Pantothenic acid (ppm) 32.94 ± 8.92 23.0 ) 59.2 12 

Pyridoxine (ppm) 9.28 ± 2.49 5.60 ) 14.0 12 

Folic acid (ppm) 2.56 ± 0.70 1.80 ) 3.70 12 

Biotin (ppm) 0.265 ± 0.046 0.190 ) 0.354 12 

Vitamin B (ppb) 41.6 ± 18.6 10.6 ) 65.0 12 12 

Choline (ppm) 2,955 ± 382 2,300 ) 3,430 11 

Minerals 

Calcium (%) 1.13 ± 0.04 1.06 ) 1.20 24 

Phosphorus (%) 0.91 ± 0.05 0.76 ) 1.00 24 

Potassium (%) 0.886 ± 0.059 0.772 ) 0.971 10 

Chloride (%) 0.531 ± 0.082 0.380 ) 0.635 10 

Sodium (%) 0.316 ± 0.031 0.258 ) 0.370 12 

Magnesium (%) 0.165 ± 0.010 0.148 ) 0.180 12 

Sulfur (%) 0.266 ± 0.060 0.208 ) 0.420 11 

Iron (ppm) 348.0 ± 83.7 255.0 ) 523.0 12 

Manganese (ppm) 93.27 ± 5.62 81.7 ) 102.0 12 

Zinc (ppm) 59.42 ± 9.73 46.1 ) 81.6 12 

Copper (ppm) 11.63 ± 2.46 8.09 ) 15.4 12 

Iodine (ppm) 3.49 ± 1.14 1.52 ) 5.83 11 

Chromium (ppm) 1.57 ± 0.53 0.60 ) 2.09 12 

Cobalt (ppm) 0.81 ± 0.27 0.49 ) 1.23 8 
244 Furfuryl Alcohol, NTP TR 482 

TABLE K4 

Contaminant Levels in NIH-07 Rat and Mouse Rationa 

Mean ± Standard 

Deviationb Range Number of Samples 

Contaminants 

Arsenic (ppm) 0.54 ± 0.11 0.30 ) 0.70 24 

Cadmium (ppm) 0.09 ± 0.07 0.04 ) 0.20 24 

Lead (ppm) 0.33 ± 0.13 0.20 ) 0.70 24 c Mercury (ppm) 0.02 ± 0.0 0.02 ) 0.03 24 

Selenium (ppm) 0.36 ± 0.08 0.10 ) 0.50 24 

Aflatoxins (ppb) <5.0 24 

Nitrate nitrogen (ppm)d 6.88 ± 2.86 2.90 ) 14.0 24 

Nitrite nitrogen (ppm)d 0.60 ± 0.87 0.10 ) 3.50 24 e BHA (ppm) 2.29 ± 4.20 1.00 ) 20.0 24 e BHT (ppm) 1.54 ± 1.02 1.0 ) 5.0 24 

Aerobic plate count (CFU/g) 95,150 ± 164,754 7,200 ) 710,000 24 

Coliform (MPN/g) 4 ± 4 3 ) 23 24 

Escherichia coli (MPN/g) <3 24 

Salmonella (MPN/g) Negative 24 

Total nitrosoamines (ppb)f 10.82 ± 4.49 4.7 ) 23.0 24 

N-Nitrosodimethylamine (ppb)f 8.56 ± 4.53 2.9 ) 21.0 24 

N-Nitrosopyrrolidine (ppb)f 2.26 ± 1.20 1.0 ) 6.0 24 

Pesticides (ppm) 

"-BHC <0.01 24 

$-BHC <0.02 24 

(-BHC <0.01 24 

*-BHC <0.01 24 

Heptachlor <0.01 24 

Aldrin <0.01 24 

Heptachlor epoxide <0.01 24 

DDE <0.01 24 

DDD <0.01 24 

DDT <0.01 24 

HCB <0.01 24 

Mirex <0.01 24 

Methoxychlor <0.05 24 

Dieldrin <0.01 24 

Endrin <0.01 24 

Telodrin <0.01 24 

Chlordane <0.05 24 

Toxaphene <0.10 24 

Estimated PCBs <0.20 24 

Ronnel <0.01 24 

Ethion <0.02 24 

Trithion <0.05 24 

Diazinon <0.10 24 

Methyl parathion <0.02 24 

Ethyl parathion <0.02 24 

Malathion 0.13 ± 0.13 0.05 ) 0.53 24 

Endosulfan I <0.01 24 

Endosulfan II <0.01 24 

Endosulfan sulfate <0.03 24 

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. 

All values except for the lots milled September, November, and December 1991 were less than the detection limit. The detection limit is 

given as the mean. d Sources of contamination: alfalfa, grains, and fish meal e Sources of contamination: soy oil and fish meal f All values were corrected for percent recovery. 

c 
245 

APPENDIX L 

SENTINEL ANIMAL PROGRAM 

METHODS ................................................................................... 

RESULTS .................................................................................... 

246 

248 
246 Furfuryl Alcohol, NTP TR 482 

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 rats and mice during the 14-week and 2-year studies. 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 

RATS 

14-Week Study 

ELISA 

PVM (pneumonia virus of mice) Study termination 

RCV/SDA (rat coronavirus/ Study termination

 sialodacryoadenitis virus) 

Sendai Study termination 

Hemagglutination Inhibition 

H-1 (Toolan’s H-1 virus) Study termination 

KRV (Kilham rat virus) Study termination 

2-Year Study 

ELISA 

Mycoplasma arthritidis Study termination 

Mycoplasma pulmonis Study termination 

PVM 6, 12, and 18 months, study termination 

RCV/SDA 6, 12, and 18 months, study termination 

Sendai 6, 12, and 18 months, study termination 

Immunofluorescence Assay 

PVM 18 months 

Sendai 18 months 

Hemagglutination Inhibition 

6, 12, and 18 months, study termination 

KRV 6, 12, and 18 months, study termination 

H-1 
Furfuryl Alcohol, NTP TR 482 247 

Method and Test 

MICE 

14-Week Study 

ELISA 

Ectromelia virus 

GDVII (mouse encephalomyelitis virus) 

MVM (minute virus of mice) 

Mouse adenoma virus 

MHV (mouse hepatitis virus) 

PVM 

Reovirus 3 

Sendai 

Immunofluorescence Assay 

EDIM (epizootic diarrhea of infant mice) 

LCM (lymphocytic choriomeningitis virus) 

Hemagglutination Inhibition 

K (papovavirus) 

Polyoma virus 

2-Year Study 

ELISA 

Ectromelia virus 

EDIM 

GDVII 

LCM 

Mouse adenoma virus-FL 

MHV 

M. arthritidis 

M. pulmonis 

PVM
 

Reovirus 3
 

Sendai
 

Immunofluorescence Assay 

EDIM 

Hemagglutination Inhibition 

K 

MVM 

Polyoma virus 

Time of Analysis 

Study termination 

Study termination 

Study termination 

Study termination 

Study termination 

Study termination 

Study termination 

Study termination 

Study termination 

Study termination 

Study termination 

Study termination 

6, 12, and 18 months, study termination 

6, 12, and 18 months, study termination 

6, 12, and 18 months, study termination 

6, 12, and 18 months, study termination 

6, 12, and 18 months, study termination 

6, 12, and 18 months, study termination 

Study termination 

Study termination 

6, 12, and 18 months, study termination 

6, 12, and 18 months, study termination 

6, 12, and 18 months, study termination 

12 and 18 months, study termination 

6, 12, and 18 months, study termination 

6, 12, and 18 months, study termination 

6, 12, and 18 months, study termination 
248 Furfuryl Alcohol, NTP TR 482 

RESULTS 

One rat was positive for M. arthritidis at the end of the 2-year study. 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 a positive 

titer. Accordingly, the M. arthritidis-positive titer was considered a false positive.