NTP TECHNICAL REPORT
 

ON THE 

TOXICOLOGY AND CARCINOGENESIS
 

STUDIES OF COCONUT OIL ACID
 

DIETHANOLAMINE CONDENSATE
 

(CAS NO. 68603-42-9)
 

IN F344/N RATS AND B6C3F1 MICE
 

(DERMAL STUDIES)
 

NATIONAL TOXICOLOGY PROGRAM
 

P.O. Box 12233
 

Research Triangle Park, NC 27709
 

January 2001
 

NTP TR 479
 

NIH Publication No. 01-3969
 

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 and Prevention. 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. 

Details about ongoing and completed NTP studies are available at the NTP’s World Wide Web site: 

http://ntp-server.niehs.nih.gov. Abstracts of all NTP Technical Reports and full versions of the most recent 

reports and other publications are available from the NIEHS’ Environmental Health Information Service 

(EHIS) http://ehis.niehs.nih.gov (800-315-3010 or 919-541-3841). In addition, printed copies of these 

reports are available from EHIS as supplies last. A listing of all the NTP reports printed since 1982 

appears on the inside back cover. 
NTP TECHNICAL REPORT
 

ON THE
 

TOXICOLOGY AND CARCINOGENESIS
 

STUDIES OF COCONUT OIL ACID
 

DIETHANOLAMINE CONDENSATE
 

(CAS NO. 68603-42-9)
 

IN F344/N RATS AND B6C3F1 MICE
 

(DERMAL STUDIES)
 

NATIONAL TOXICOLOGY PROGRAM
 

P.O. Box 12233
 

Research Triangle Park, NC 27709
 

January 2001
 

NTP TR 479
 

NIH Publication No. 01-3969
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

National Institutes of Health
 
2 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

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. 

J.R. Leininger, D.V.M., Ph.D. 

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

D.P. Orzech, M.S. 

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, Inc. 

Battelle Columbus Laboratories 

Conducted studies, evaluated pathology findings 

P.J. Kurtz, Ph.D., Principal Investigator

 (14-week and 2-year studies) 

M.R. Hejtmancik, Ph.D., Principal Investigator

 (2-year studies) 

J.D. Toft II, D.V.M., M.S. (14-week and 2-year rats) 

M.J. Ryan, D.V.M., Ph.D. (14-week mice) 

A.W. Singer, D.V.M. (2-year mice) 

Experimental Pathology Laboratories, Inc. 

Provided pathology quality assurance 

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

S. Botts, M.S., D.V.M., Ph.D. 

P. Mann, D.V.M. 

Dynamac Corporation 

Prepared quality assurance audits 

S. Brecher, Ph.D., Principal Investigator 

NTP Pathology Working Group 

Evaluated slides, prepared pathology report on rats 

(27 March 1997) 

M. Butt, D.V.M., Chairperson 

Pathology Associates International 

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

National Toxicology Program 

J.R. Leininger, D.V.M., Ph.D. 

National Toxicology Program 

P. Mann, D.V.M. 

Experimental Pathology Laboratories, Inc. 

R. Miller, D.V.M., Ph.D. 

North Carolina State University 

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

National Toxicology Program 

Evaluated slides, prepared pathology report on mice 

(8 May 1997) 

M. Butt, D.V.M., Chairperson 

Pathology Associates International 

S. Botts, M.S., D.V.M., Ph.D. 

Experimental Pathology Laboratories, Inc. 

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

National Toxicology Program 

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

National Toxicology Program 

J.R. Leininger, D.V.M., Ph.D. 

National Toxicology Program 

R. Miller, D.V.M., Ph.D. 

North Carolina State University 

A. Yoshida, D.V.M., Ph.D., Observer 

National Toxicology Program 

Analytical Sciences, Inc. 

Provided statistical analyses 

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

S.R. Lloyd, M.S. 

N.G. Mintz, B.S. 

Biotechnical Services, Inc. 

Prepared Technical Report 

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

J.R. Dias, M.S. 

L.M. Harper, B.S. 

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

D.P. Shaw, B.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 ........................................................ 15 
 

MATERIALS AND METHODS ............................................... 17 
 

RESULTS .............................................................. 27 
 

DISCUSSION AND CONCLUSIONS ........................................... 51 
 

REFERENCES .......................................................... 57 
 

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

of Coconut Oil Acid Diethanolamine Condensate ........................ 61 
 

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

of Coconut Oil Acid Diethanolamine Condensate ........................ 89 
 

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

of Coconut Oil Acid Diethanolamine Condensate ........................ 115 
 

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

of Coconut Oil Acid Diethanolamine Condensate ........................ 147 
 

APPENDIX E Genetic Toxicology ............................................. 179 
 

APPENDIX F Hematology and Clinical Chemistry Results ............................ 195 
 

APPENDIX G Organ Weights and Organ-Weight-to-Body-Weight Ratios .................. 201 
 

APPENDIX H Reproductive Tissue Evaluations and Estrous Cycle Characterization .......... 205 
 

APPENDIX I Chemical Characterization and Dose Formulation Studies .................. 209 
 

APPENDIX J Ingredients, Nutrient Composition, and Contaminant Levels
 

in NIH-07 Rat and Mouse Ration .................................. 219 
 

APPENDIX K Sentinel Animal Program ........................................ 223 
 
4 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 
 

 

 

 

5 

ABSTRACT
 

n = 7, 9, 11, 13, or 15 

COCONUT OIL ACID DIETHANOLAMINE CONDENSATE 

CAS No. 68603-42-9 

Chemical Formula: C(7+n)H(15+2n)O3N Molecular Weight: 280-290 

Synonyms:	 Cocamide DEA; cocamide diethanolamine; coconut oil diethanolamine; N,N-bis(hydroxyethyl)coco amides; 

N,N-bis(hydroxyethyl)coco fatty amides 

Trade names:	 Clindrol 200CGN; Clindrol 202CGN; Clindrol Superamide 100CG; Comperlan KD; Comperlan LS; Comperlan PD; 

Conco Emulsifier K; Elromid KD 80; Empilan CDE; Ethylan LD; Ethylan A 15; Lauridit KDG; Marlamid D 1218; 

Monamid 150D; Monamid 150DB; Ninol 1281; Ninol 2012E; Ninol 2012 Extra; Ninol P 621; P and G Amide 72; 

Purton CFD; Schercomid CDA; Steinamid DC 2129; Steinamid DC 2129E; Varamide A 2; Varamide A 10; Varamide A 

83; Witcamide 82; Witcamide 5133 

Coconut oil acid diethanolamine condensate, a mixture of fatty acid diethanolamides of the acids found 

in coconut oil, is widely used in cosmetics, shampoos, 

soaps, and related consumer products. Because of the 

lack of information about potential risks associated 

with long-term exposure, coconut oil acid diethanolamine condensate was selected as a representative of 

the diethanolamine chemical class for evaluation of 

toxicity and carcinogenic potential. 

Male and female F344/N rats and B6C3F1 mice 

received dermal applications of coconut oil acid 

diethanolamine condensate for 14 weeks or 2 years. 

Genetic toxicology studies were conducted in 

Salmonella typhimurium, L5178Y mouse lymphoma 

cells, cultured Chinese hamster ovary cells, and 

mouse peripheral blood erythrocytes. 

14-WEEK STUDY IN RATS 

Groups of 10 male and 10 female F344/N rats 

received dermal applications of 0, 25, 50, 100, 200, 

or 400 mg coconut oil acid diethanolamine condensate/kg body weight in ethanol, five times per week 

for 14 weeks. All rats survived until the end of the 

study. Final mean body weights and body weight 

gains of 200 and 400 mg/kg males and females were 

significantly less than those of the vehicle controls. 

Clinical findings included irritation of the skin at the 

site of application in 100, 200, and 400 mg/kg males 

and females. Cholesterol concentrations were significantly decreased in 200 and 400 mg/kg males and in 

females administered 100 mg/kg or greater; triglyceride concentrations were also decreased in 200 

and 400 mg/kg males. Histopathologic lesions of the 

skin at the site of application included epidermal 
 

 

 

 

6 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

hyperplasia, sebaceous gland hyperplasia, chronic 

active inflammation, parakeratosis, and ulcer. The 

incidences and severities of these skin lesions 

generally increased with increasing dose in males and 

females. The incidences of renal tubule regeneration 

in 100, 200, and 400 mg/kg females were significantly greater than the vehicle control incidence, 

and the severities in 200 and 400 mg/kg females were 

increased. 

14-WEEK STUDY IN MICE 

Groups of 10 male and 10 female B6C3F1 mice 

received dermal applications of 0, 50, 100, 200, 400, 

or 800 mg coconut oil acid diethanolamine condensate/kg body weight in ethanol, five times per 

week for 14 weeks. All mice survived until the end 

of the study. Final mean body weights and body 

weight gains of dosed males and females were similar 

to those of the vehicle controls. The only treatmentrelated clinical finding was irritation of the skin at the 

site of application in males and females administered 

800 mg/kg. Weights of the liver and kidney of 

800 mg/kg males and females, the liver of 400 mg/kg 

females, and the lung of 800 mg/kg females were 

significantly increased compared to the vehicle 

controls. Epididymal spermatozoal concentration was 

significantly increased in 800 mg/kg males. Histopathologic lesions of the skin at the site of application 

included epidermal hyperplasia, sebaceous gland 

hyperplasia, chronic active inflammation, parakeratosis, and ulcer. The incidences and severities of 

these skin lesions generally increased with increasing 

dose in males and females. 

2-YEAR STUDY IN RATS 

Groups of 50 male and 50 female F344/N rats 

received dermal applications of 0, 50, or 100 mg 

coconut oil acid diethanolamine condensate/kg body 

weight in ethanol five times a week for 104 weeks. 

Survival, Body Weights, and Clinical Findings 

The survival rates of treated male and female rats 

were similar to those of the vehicle controls. The 

mean body weights of dosed males and females were 

similar to those of the vehicle controls throughout 

most of the study. The only chemical-related clinical 

finding was irritation of the skin at the site of 

application in 100 mg/kg females. 

Pathology Findings 

There were marginal increases in the incidences of 

renal tubule adenoma or carcinoma (combined) in 

50 mg/kg females. The severity of nephropathy 

increased with increasing dose in female rats. Nonneoplastic lesions of the skin at the site of application 

included epidermal hyperplasia, sebaceous gland 

hyperplasia, parakeratosis, and hyperkeratosis, and 

the incidences and severities of these lesions increased 

with increasing dose. The incidences of chronic 

active inflammation, epithelial hyperplasia, and epithelial ulcer of the forestomach increased with dose in 

female rats, and the increases were significant in the 

100 mg/kg group. 

2-YEAR STUDY IN MICE 

Groups of 50 male and 50 female B6C3F1 mice 

received dermal applications of 0, 100, or 200 mg 

coconut oil acid diethanolamine condensate/kg body 

weight in ethanol five times a week for 104 to 

105 weeks. 

Survival, Body Weights, and Clinical Findings 

Survival of dosed male and female mice was generally 

similar to that of the vehicle controls. Mean body 

weights of 100 mg/kg females from week 93 and 

200 mg/kg females from week 77 were less than those 

of the vehicle controls. The only clinical finding 

attributed to treatment was irritation of the skin at the 

site of application in males administered 200 mg/kg. 

Pathology Findings 

The incidences of hepatic neoplasms (hepatocellular 

adenoma, hepatocellular carcinoma, and hepatoblastoma) were significantly increased in male and/or 

female mice. Most of the incidences exceeded the 

historical control ranges. The incidences of eosinophilic foci in dosed groups of male mice were 

increased relative to that in the vehicle controls. 
 

 

__________ 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 7 

The incidences of renal tubule adenoma and renal 

tubule adenoma or carcinoma (combined) were 

significantly increased in 200 mg/kg males. 

Several nonneoplastic lesions of the skin at the site of 

application were considered treatment related. Incidences of epidermal hyperplasia, sebaceous gland 

hyperplasia, and hyperkeratosis were greater in all 

dosed groups of males and females than in the vehicle 

controls. The incidences of ulcer in 200 mg/kg males 

and inflammation and parakeratosis in 200 mg/kg 

females were greater than those in the vehicle 

controls. 

The incidences of thyroid gland follicular cell 

hyperplasia in all dosed groups of males and females 

were significantly greater than those in the vehicle 

control groups. 

GENETIC TOXICOLOGY 

Coconut oil acid diethanolamine condensate did not 

show genotoxic activity in vitro. It was not mutagenic 

in Salmonella typhimurium, nor did it produce an 

increase in mutant L5178Y mouse lymphoma cell 

colonies. In addition, no increases in the frequencies 

of sister chromatid exchanges or chromosomal aberrations were observed in Chinese hamster ovary cells 

after incubation with coconut oil acid diethanolamine 

condensate. All these in vitro assays were conducted 

with and without induced S9 activation enzymes. In 

contrast to the uniformly negative results in vitro, 

positive results were obtained in a peripheral blood 

micronucleus test in male and female mice from the 

14-week dermal study. 

CONCLUSIONS 

Under the conditions of these 2-year dermal studies, 

there was no evidence of carcinogenic activity* of 

coconut oil acid diethanolamine condensate in male 

F344/N rats administered 50 or 100 mg/kg. There 

was equivocal evidence of carcinogenic activity in 

female F344/N rats based on a marginal increase in 

the incidences of renal tubule neoplasms. There was 

clear evidence of carcinogenic activity in male 

B6C3F1 mice based on increased incidences of hepatic 

and renal tubule neoplasms and in female B6C3F1 

mice based on increased incidences of hepatic 

neoplasms. These increases were associated with the 

concentration of free diethanolamine present as a 

contaminant in the diethanolamine condensate. 

Exposure of rats to coconut oil acid diethanolamine 

condensate by dermal application in ethanol for 

2 years resulted in epidermal hyperplasia, sebaceous 

gland hyperplasia, hyperkeratosis, and parakeratosis 

in males and females and ulcer in females at the site 

of application. There were increases in the incidences 

of chronic inflammation, epithelial hyperplasia, and 

epithelial ulcer in the forestomach of female rats. The 

severities of nephropathy in dosed female rats were 

increased. 

Exposure of mice to coconut oil acid diethanolamine 

condensate by dermal application for 2 years resulted 

in increased incidences of eosinophilic foci of the liver 

in males. Increased incidences of epidermal hyperplasia, sebaceous gland hyperplasia, and hyperkeratosis in males and females, ulcer in males, and 

parakeratosis and inflammation in females at the site 

of application and of follicular cell hyperplasia in the 

thyroid gland of males and females were chemical 

related. 

* 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 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies 

of Coconut Oil Acid Diethanolamine Condensate 

Male Female Male Female
 

F344/N Rats F344/N Rats B6C3F1 Mice B6C3F1 Mice
 

Doses in ethanol	 Vehicle control, 50, or 

100 mg/kg by dermal 

application 

Body weights	 Dosed groups similar to 

vehicle controls 

Survival rates	 8/50, 12/50, 11/50 

Nonneoplastic	 Skin, site of application: 

epidermal hyperplasia effects 

(0/50, 46/50, 50/50); 

sebaceous gland 

hyperplasia (0/50, 45/50, 

50/50); parakeratosis 

(0/50, 9/50, 28/50); 

hyperkeratosis (0/50, 

36/50, 48/50); 

Neoplastic effects	 None 

Uncertain findings	 None 

Vehicle control, 50, or 

100 mg/kg 

Dosed groups similar to 

vehicle controls 

28/50, 24/50, 22/50 

Skin, site of application: 

epidermal hyperplasia 

(3/50, 46/50, 50/50); 

sebaceous gland 

hyperplasia (2/50, 46/50, 

49/50); parakeratosis 

(1/50, 11/50, 23/50); 

hyperkeratosis (3/50, 

45/50, 47/50); ulcer 

(2/50, 0/50, 9/50) 

Forestomach: chronic 

active inflammation 

(1/50, 3/50, 10/50); 

epithelial hyperplasia 

(2/50, 5/50, 13/50); 

epithelial ulcer (1/50, 

3/50, 11/50) 

Kidney: severity of 

nephropathy (1.6, 2.1, 

2.7) 

None 

Kidney: renal tubule 

adenoma or carcinoma 

(standard evaluation -

0/50, 2/50, 0/50 ; 

standard and extended 

evaluations combined -

0/50, 4/50, 1/50) 

Vehicle control, 100, or 

200 mg/kg 

Dosed groups similar to 

vehicle controls 

41/50, 37/50, 36/50 

Liver: eosinophilic foci 

(20/50, 29/50, 31/50) 

Skin, site of application: 

epidermal hyperplasia 

(5/50, 47/50, 50/50); 

sebaceous gland 

hyperplasia (0/50, 44/50, 

49/50); hyperkeratosis 

(0/50, 24/50, 23/50); 

ulcer (1/50, 0/50, 7/50) 

Thyroid gland: follicular 

cell hyperplasia (11/50, 

20/50, 23/50) 

Liver: hepatocellular 

adenoma (22/50, 35/50, 

45/50); hepatoblastoma 

(1/50, 1/50, 10/50); 

hepatocellular adenoma, 

carcinoma, or 

hepatoblastoma (29/50, 

39/50, 49/50) 

Kidney: renal tubule 

adenoma (1/50, 1/50, 

7/50); renal tubule 

adenoma or carcinoma 

(1/50, 1/50, 9/50) 

None 

Vehicle control, 100, or 

200 mg/kg 

Dosed groups less than 

vehicle controls 

35/50, 36/50, 26/50 

Skin, site of application: 

epidermal hyperplasia 

(9/50, 47/50, 50/50); 

sebaceous gland 

hyperplasia (0/50, 42/50, 

48/50); hyperkeratosis 

(5/50, 30/50, 40/50); 

chronic active 

inflammation (3/50, 2/50, 

11/50); parakeratosis 

(3/50, 4/50, 16/50) 

Thyroid gland: follicular 

cell hyperplasia (27/50, 

36/50, 33/50) 

Liver: hepatocellular 

adenoma (32/50, 44/50, 

43/50); hepatocellular 

carcinoma (3/50, 21/50, 

32/50); hepatocellular 

adenoma, carcinoma, or 

hepatoblastoma (33/50, 

46/50, 48/50) 

None 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 9 

Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies 

of Coconut Oil Acid Diethanolamine Condensate 

Male Female Male Female 

F344/N Rats F344/N Rats B6C3F1 Mice B6C3F1 Mice 

Level of evidence 

of carcinogenic 

activity 

No evidence Equivocal evidence Clear evidence Clear evidence 

Genetic toxicology 

Salmonella typhimurium gene mutations: 

Mouse lymphoma gene mutations: 

Sister chromatid exchanges

 Cultured Chinese hamster ovary cells in vitro: 

Chromosomal aberrations

 Cultured Chinese hamster ovary cells in vitro: 

Micronucleated erythrocytes

 Mouse peripheral blood in vivo: 

Negative in strains TA97, TA98, TA100, and TA1535 

Negative with or without S9 

Negative with or without S9 

Negative with or without S9 

Positive in males and females 
10 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

EXPLANATION OF LEVELS OF EVIDENCE OF CARCINOGENIC ACTIVITY 

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

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

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

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

indicate that exposure to the chemical has the potential for hazard to humans. Other organizations, such as the International Agency for 

Research on Cancer, assign a strength of evidence for conclusions based on an examination of all available evidence, including animal 

studies such as those conducted by the NTP, epidemiologic studies, and estimates of exposure. Thus, the actual determination of risk to 

humans from chemicals found to be carcinogenic in laboratory animals requires a wider analysis that extends beyond the purview of these 

studies. 

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

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

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

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

in March 1986 for use in the Technical Report series to incorporate more specifically the concept of actual weight of evidence of 

carcinogenic activity. For each separate experiment (male rats, female rats, male mice, female mice), one of the following five categories is 

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

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

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

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

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

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

required for clear evidence.
 

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

of neoplasms that may be chemical related. 

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

increases in malignant or benign neoplasms.
 

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

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

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

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

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

between two adjacent levels. These considerations should include: 

• adequacy of the experimental design and conduct;
 

• occurrence of common versus uncommon neoplasia;
 

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

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

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

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

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

or tissue;
 

• latency in tumor induction; 

•	 multiplicity in site-specific neoplasia; 

•	 metastases; 

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

lesion in another sex or species); 

• presence or absence of dose relationships; 

•	 statistical significance of the observed tumor increase; 

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

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

•	 structure-activity correlations; and 

• in some cases, genetic toxicology. 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 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 coconut oil acid diethanolamine condensate on 9 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. 

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., Principal Reviewer 

Kirkland Air Force Base Integrated Laboratory Systems 

Albuquerque, NM Research Triangle Park, NC 

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

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., Principal Reviewer Jose Russo, M.D. 

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 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

SUMMARY OF TECHNICAL REPORTS REVIEW SUBCOMMITTEE COMMENTS
 

On 9 December 1997, the draft Technical Report on 

the toxicology and carcinogenesis studies of coconut 

oil acid diethanolamine condensate received public 

review by the National Toxicology Program’s Board 

of Scientific Counselors’ 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 toxicology 

and carcinogenesis studies of coconut oil acid diethanolamine condensate 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 compound-related 

neoplastic and nonneoplastic lesions in rats and mice. 

The proposed conclusions were no evidence of 

carcinogenic activity in male F344/N rats, equivocal 

evidence of carcinogenic activity in female F344/N 

rats, and clear evidence of carcinogenic activity in 

male and female B6C3F1 mice. 

Dr. Irwin discussed a logistic regression model 

designed to quantitatively evaluate the association 

between hepatocellular neoplasms in female mice and 

free diethanolamine concentration. He said that this 

model tended to strengthen the hypothesis that 

increased incidences of hepatocellular neoplasms in 

mice are associated with diethanolamine exposure. 

This model was also applied to the other two diethanolamine condensates tested. 

Dr. I. Russo, the first principal reviewer, agreed with 

the proposed conclusions. She questioned the use of 

ethanol as the solvent, because coconut oil acid diethanolamine condensate is water soluble. Dr. Irwin 

responded that the primary purpose for using ethanol 

as the solvent was to allow comparison of results from 

all three of the diethanolamides, the other two of 

which are not water soluble. Furthermore, when 

water is used as the solvent in dermal studies, the 

solutions tend to become beaded and do not spread 

well. 

Dr. Goldsworthy, the second principal reviewer, 

agreed with the proposed conclusions. However, he 

argued that the statement attributing all the neoplasm 

responses to free diethanolamine does not appear 

warranted because the association is mainly supported 

by data for female mice, while there are gaps of 

information and a lack of definitive conclusions for 

the liver as well as for other neoplasm sites. He said 

that correlations were not assessed for liver neoplasms 

in male mice. Furthermore, the link between hepatic 

neoplasm formation and concentrations of free 

diethanolamine clearly does not apply to hepatoblastoma occurrence. Dr. Irwin agreed that there 

may be other neoplastic responses not associated with 

diethanolamine. 

Dr. Hecht, the third principal reviewer, agreed with 

the proposed conclusions. He said that it would have 

been more satisfactory to have tested the diethanolamides in the absence of diethanolamine, although he 

realized that the strategy was to test the product as it 

actually is used. Dr. J.R. Bucher, NIEHS, agreed but 

stated that because this is a safety assessment issue, 

the determining factor was the diethanolamide as it is 

used in cosmetics. Dr. Hecht asked for some discussion of the significance of the liver neoplasms in a 

strain of mouse that already has a considerable 

spontaneous incidence of such neoplasms. Spontaneous incidences, along with the fact that no other 

substantial neoplasm responses were observed, 

suggest that coconut oil acid diethanolamine condensate is a weak carcinogen. 

Dr. L. Loretz, The Cosmetic, Toiletry, and Fragrance 

Association (CTFA), said that there was inadequate 

documentation and analysis of the test materials, 

particularly when attributing neoplasm effects of the 

condensates to diethanolamine content. Furthermore, 

the test animals appeared to have ingested some of the 

material, and the inappropriate use of ethanol as the 

vehicle complicated interpretation of study results in 

that The International Agency for Research on Cancer 

(IARC) lists ethanol in beverages as a known human 

carcinogen. Finally, Dr. Loretz asked that the level 

of evidence for male mice, which was based on 

kidney neoplasms, be changed from clear to some 

evidence of carcinogenic activity because the response 

was limited to one species, one gender, and one dose 

and consisted primarily of benign neoplasms. 
 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 13 

Dr. I. Russo moved that the Technical Report on 

coconut oil acid diethanolamine condensate be 

accepted with the revisions discussed and the 

conclusions as written with the addition of the word 

“marginal” before “increased” in the conclusion for 

female rats. Dr. Fischer seconded the motion. 

Dr. Goldsworthy moved that the motion be amended 

such that the last sentence of the conclusions for 

carcinogenicity be changed from “These increases 

were attributed to the concentration of free diethanolamine present as a contaminant” to “These 

increases were associated with the concentration of 

free diethanolamine present as a contaminant.” 

Dr. Belinsky seconded the amendment, which was 

accepted by seven yes votes and one abstention 

(Dr. Bus). The amended motion was then accepted 

by seven yes votes and one abstention (Dr. Bus). 
14 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 
 

 

 

15 

INTRODUCTION
 

n = 7, 9, 11, 13, or 15 

COCONUT OIL ACID DIETHANOLAMINE CONDENSATE 

CAS No. 68603-42-9 

Chemical Formula: C(7+n)H(15+2n)O3N Molecular Weight: 280-290 

Synonyms:	 Cocamide DEA; cocamide diethanolamine; coconut oil diethanolamine; N,N-bis(hydroxyethyl)coco amides; 

N,N-bis(hydroxyethyl)coco fatty amides 

Trade names:	 Clindrol 200CGN; Clindrol 202CGN; Clindrol Superamide 100CG; Comperlan KD; Comperlan LS; Comperlan PD; 

Conco Emulsifier K; Elromid KD 80; Empilan CDE; Ethylan LD; Ethylan A 15; Lauridit KDG; Marlamid D 1218; 

Monamid 150D; Monamid 150DB; Ninol 1281; Ninol 2012E; Ninol 2012 Extra; Ninol P 621; P and G Amide 72; 

Purton CFD; Schercomid CDA; Steinamid DC 2129; Steinamid DC 2129E; Varamide A 2; Varamide A 10; Varamide A 

83; Witcamide 82; Witcamide 5133 

CHEMICAL AND PHYSICAL PROPERTIES 

Coconut oil is a mixture of fatty acids composed of 

approximately 48.2% lauric acid, 18% myristic acid, 

8.5% palmitic acid, 8% caprylic (n-octanoic) acid, 

7% capric (n-decanoic) acid, 6% oleic acid, 

2.3% stearic acid, and 2% linoleic acid (Source Book 

for Food Scientists, 1978). Therefore, coconut oil 

acid diethanolamine condensate is a mixture of 

diethanolamides of these constituent fatty acids. 

Coconut oil acid diethanolamine condensate is available in several grades which differ on the basis of the 

molar ratio of coconut oil methyl esters and diethanolamine used during manufacture; the purest 

product is obtained with a molar ratio of 1:1. Free 

diethanolamine is present in the final product at 

concentrations ranging from 4% to 8.5%. Coconut 

oil acid diethanolamine condensate has a melting point 

range of 23E to 35E C; at room temperature and 

atmospheric pressure, most preparations are clear, 

amber-colored liquids with a faint coconut odor. 

Coconut oil acid diethanolamine condensate is soluble 

in water and produces a slightly alkaline aqueous 

solution (CTFA, 1985). 

PRODUCTION, USE, 

AND HUMAN EXPOSURE 

Coconut oil acid diethanolamine condensate is prepared by the condensation of coconut oil fatty acid 

methyl esters with diethanolamine at temperatures up 

to 170E C and in the presence of a catalyst (CTFA, 

1985). Fatty acid diethanolamides, including coconut 

oil acid diethanolamine condensate, are widely used in 

cosmetics. Coconut oil acid diethanolamine condensate is present in approximately 584 cosmetic 

formulations of bath oils, shampoos, conditioners, 

lipsticks, and hair dyes. In these preparations, the 

concentration of diethanolamide may range from 1% 

to 25%. Noncosmetic applications include use as a 

surfactant in bar soaps, light-duty detergents, and 

dishwashing detergents and as a delinting agent for 

cottonseed (CTFA, 1985). The National Occupational 
 

16 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

Exposure Survey (1981-1983) estimated that 589,000 

workers were exposed to coconut oil acid diethanolamine annually (NIOSH, 1990). 

ABSORPTION, DISTRIBUTION, 

METABOLISM, AND EXCRETION 

No information on the absorption, distribution, 

metabolism, or excretion of coconut oil acid diethanolamine condensate in experimental animals or 

humans was found in the literature. 

TOXICITY 

Experimental Animals 

In a 16-day study in male Sprague-Dawley rats, 

undiluted coconut oil acid diethanolamine condensate 

administered by gavage was slightly toxic and had an 

LD50 of 12.2 g/kg body weight; 10% or 12% dilutions 

had no effect. Dermal application of a 30% solution 

of coconut oil acid diethanolamine condensate to the 

shaved dorsal skin of a rabbit for 23 hours was judged 

to be moderately irritating (CTFA, 1985). 

Humans 

There have been several reports of skin irritation in 

humans exposed to consumer products where patch 

testing demonstrated that the offending substance was 

coconut oil acid diethanolamine condensate. The skin 

irritation was reported following exposure to a hand 

gel (Nurse, 1980), shampoos (De Groot et al., 1987), 

hydraulic oil (Hindson and Lawlor, 1983), and 

handwashing liquids and barrier creams (Kanerva 

et al., 1993; Pinola et al., 1993). 

CARCINOGENICITY 

No information on the carcinogenicity of coconut oil 

acid diethanolamine condensate in experimental 

animals or epidemiology studies in humans was found 

in the literature. 

GENETIC TOXICITY 

Coconut oil acid diethanolamine condensate was not 

mutagenic in Salmonella typhimurium strain TA97, 

TA98, TA100, or TA1535, with or without S9 

metabolic activation (Zeiger et al., 1988). No other 

published mutagenicity data for coconut oil acid 

diethanolamine condensate were identified. 

STUDY RATIONALE 

Coconut oil acid diethanolamine condensate is widely 

used in cosmetics, shampoos, soaps, and related 

consumer products to which humans are exposed 

extensively. These products are typically used on a 

daily basis for the majority of the human life span. 

Because of the lack of information about potential 

risks associated with long-term exposure, coconut oil 

acid diethanolamine condensate, lauric acid diethanolamine condensate, and oleic acid diethanolamine 

condensate were selected by the National Cancer 

Institute as representatives of the class of diethanolamides for evaluation of toxicity and carcinogenic 

potential. Because diethanolamine is a frequent 

contaminant of commercial preparations of diethanolamides, its toxicity and carcinogenic potential were 

also evaluated. 
 

 

 

17 

MATERIALS AND METHODS
 

PROCUREMENT 

AND CHARACTERIZATION 

Coconut Oil Acid 

Diethanolamine Condensate 

Coconut oil acid diethanolamine condensate was 

obtained from Henkel Corporation (Mauldin, SC) in 

one lot (1G01742286). Identity and purity analyses 

were conducted by the study laboratory. Stability 

studies were performed by the analytical chemistry 

laboratory, Midwest Research Institute (Kansas City, 

MO). Reports on analyses performed in support of 

the coconut oil acid diethanolamine condensate studies 

are on file at the National Institute of Environmental 

Health Sciences. 

The chemical, a viscous yellow liquid, was identified 

as coconut oil acid diethanolamine condensate by 

infrared and nuclear magnetic resonance spectroscopy. The purity of lot 1G01742286 was determined 

by high-performance liquid chromatography and 

nitrosamine quantitation. 

High-performance liquid chromatography indicated 

one major peak and 15 smaller peaks with areas of at 

least 0.5% relative to the major peak area. 

Lot 1G01742286 was composed primarily of diethanolamides of coconut oil acids, with unreacted 

diethanolamine, alkanolamides of unsaturated acids, 

and amine salts of the acids. The polar nitrosamine, 

N-nitrosodiethanolamine, was detected at a concentration of 219 ppb, which was considered consistent 

with the anticipated composition of commercial 

coconut oil acid diethanolamine condensate. No 

nonpolar nitrosamines were detected. 

Stability studies of lot DS42578C0 of the bulk chemical were performed by the analytical chemistry 

laboratory on using nonaqueous titration of amine 

function of diethanolamine with perchloric acid. 

Coconut oil acid diethanolamine condensate showed 

some instability when stored in glass tubes for 

2 weeks at 60E C. Stability was monitored during the 

14-week and 2-year studies using high-performance 

liquid chromatography. No degradation of the bulk 

chemical was detected. To ensure stability, the bulk 

chemical was stored at room temperature, protected 

from light, in amber glass bottles sealed with Teflon®-

lined caps. 

Ethanol 

Ethanol (95%) was obtained from Aaper Alcohol and 

Chemical Company (Shelbyville, KY) in 14 lots. The 

purity of the 95% ethanol used in these studies was 

monitored at the beginning and end of the 14-week 

studies and every 2 to 4 months during the 2-year 

studies using gas chromatography with a flame 

ionization detector. USP/NF ethanol reference standards were analyzed concomitantly. Purity of the 

bulk chemical ranged from 96.6% to 103.4% relative 

to that of the reference standard, except for one 

sample taken during the 2-year studies which measured 109.6%. This result was considered to be 

spurious because analysis of the same material 

approximately 2 months later indicated a relative 

purity of 101.1%. 

PREPARATION AND ANALYSIS 

OF DOSE FORMULATIONS 

The dose formulations were prepared every 3 weeks 

by mixing coconut oil acid diethanolamine condensate 

and 95% ethanol to give the required concentration 

(Table I1). The dose formulations were stored at 

room temperature, protected from light, in amber 

glass bottles for up to 28 days. 

The study laboratory performed stability studies of a 

10 mg/mL formulation using high-performance liquid 

chromatography. When stored in sealed glass containers and protected from ultraviolet light, the stability of the dose formulation was confirmed for at 

least 28 days between –20E C and room temperature. 

When left open to air and light, the stability of coconut oil acid diethanolamine condensate was confirmed 

for 3 hours; however, a narrow-mouth bottle was 

suggested for storage during dose administration to 

decrease evaporation of the ethanol. 
 

18 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

Periodic analyses of the dose formulations of coconut 

oil acid diethanolamine condensate were conducted at 

the study laboratory using high-performance liquid 

chromatography. For the 14-week studies, dose 

formulations from the beginning, middle, and end of 

the studies were analyzed (Table I2). During the 

2-year studies, dose formulations were analyzed 

approximately every 2 months (Table I3). During the 

14-week studies, 13 of 15 dose formulations for rats 

and all 15 dose formulations for mice were within 

10% of the target concentrations; two dose formulations for rats were remixed, and the remixes were 

determined to be within 10% of the target concentrations. All 48 dose formulations analyzed and used 

during the 2-year studies were within 10% of the 

target concentrations. In addition to dose formulation 

analyses prior to dosing, samples collected after 

dosing (animal room samples) were analyzed 

periodically. All animal room samples analyzed 

during the 14-week studies were within 10% of the 

target concentration. For the 2-year studies, 14 of 16 

were within 10% of target concentration; two samples 

were 112% and 116% of target concentrations, apparently due to evaporation of the 95% ethanol from 

improperly sealed dosing bottles. 

14-WEEK STUDIES 

The 14-week studies were conducted to evaluate the 

cumulative toxic effects of repeated exposure to 

coconut oil acid diethanolamine condensate and to 

determine the appropriate doses to be used in the 

2-year studies. 

Male and female F344/N rats and B6C3F1 mice were 

obtained from Taconic Farms (Germantown, NY). 

On receipt, the rats and mice were 4 weeks old. 

Animals were quarantined for 14 to 17 days and were 

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

initiation of the studies, 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 control rats 

and mice using the protocols of the NTP Sentinel 

Animal Program (Appendix K). 

Groups of 10 male and 10 female core study rats and 

10 male and 10 female special study rats received 

dermal applications of 0, 25, 50, 100, 200, or 400 mg 

coconut oil acid diethanolamine condensate per kg 

body weight in ethanol (0, 30, 61, 121, 243, or 

485 mg/mL ethanol). Groups of 10 male and 

10 female mice received dermal applications of 0, 50, 

100, 200, 400, or 800 mg/kg in ethanol (0, 20, 40, 

80, 160, or 320 mg/mL ethanol). Feed and water 

were available ad libitum. Rats and mice were 

housed individually. The animals were weighed 

initially, weekly, and at the end of the studies. 

Clinical findings were recorded weekly. Details of 

the study design and animal maintenance are 

summarized in Table 1. 

On days 4 and 24, blood was collected from the 

retroorbital sinus of clinical pathology study male and 

female rats from each dose group for hematology and 

clinical chemistry analyses. At the end of the 

14-week studies, blood was collected from the 

retroorbital sinus of all core study rats for hematology 

and clinical chemistry analyses. At all time points, 

the rats were anesthetized with a carbon dioxide/ 

oxygen mixture. Blood for hematology was collected 

into tubes containing potassium EDTA and gently 

inverted on an aliquot mixer to prevent clotting. 

Blood for clinical chemistry was collected into serum 

separator tubes with no anticoagulant and allowed to 

clot, and the serum was obtained by centrifugation. 

The parameters measured are listed in Table 1. 

Hematology determinations, including erythrocyte and 

leukocyte counts, hemoglobin concentration, hematocrit, mean cell volume, mean cell hemoglobin, and 

mean cell hemoglobin concentration, were performed 

on a Serono-Baker 9000 hematology analyzer 

(Serono-Baker Diagnostics, Allentown, PA). Differential leukocyte counts were determined by light 

microscopy from blood smears stained with modified 

Wright-Giemsa. Smears made from blood samples 

stained with new methylene blue were examined 

microscopically for a quantitation of reticulocytes. 

Clinical chemistry parameters were measured with a 

Hitachi 704® chemistry analyzer (Boehringer 

Mannheim, Indianapolis, IN) using commercially 

available reagents. 

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

collected for sperm motility and vaginal cytology 

evaluations on rats administered 0, 100, 200, or 

400 mg/kg and mice receiving 0, 200, 400, or 

800 mg/kg. The parameters evaluated are listed in 

Table 1. Methods used were those described in the 

NTP’s sperm morphology and vaginal cytology eval-
 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 19 

uations 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. 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. 

Homogenization-resistant spermatid nuclei were 

counted with a hemacytometer. 

A necropsy was performed on all core study rats and 

all mice. 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 0 and 400 mg/kg core study rats and on 0 and 

800 mg/kg mice. Table 1 lists the tissues and organs 

routinely examined. 

2-YEAR STUDIES 

Study Design 

Groups of 50 male and 50 female rats received dermal 

applications of 0, 50, or 100 mg coconut oil acid 

diethanolamine condensate/kg body weight in ethanol 

(0, 85, or 170 mg/mL ethanol). Groups of 50 male 

and 50 female mice received dermal applications of 0, 

100, or 200 mg/kg in ethanol (0, 50, or 100 mg/mL 

ethanol). 

Source and Specification of Animals 

Male and female F344/N rats and B6C3F1 mice were 

obtained from Taconic Laboratory Animals and 

Services (Germantown, NY) for use in the 2-year 

studies. Rats and mice were quarantined for 11 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 K). 

Animal Maintenance 

Rats and mice were housed individually. Feed and 

water were available ad libitum. Cages and racks 

were rotated twice weekly. Further details of animal 

maintenance are given in Table 1. Information on 

feed composition and contaminants is provided in 

Appendix J. 

Clinical Examinations and Pathology 

All animals were observed twice daily. Body weights 

were recorded at the beginning of the study, weekly 

for the first 13 weeks, at 4-week intervals thereafter, 

and at the end of the study. Clinical findings were 

recorded at the beginning of the study, and at 4-week 

intervals thereafter, and at the end of the study. 

Complete necropsies and microscopic examinations 

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. 

Tissues examined microscopically are listed in 

Table 1. 
 

20 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

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 clitoral 

gland, forestomach, kidney, pancreas (males), preputial gland, prostate gland, skin (site of application), 

and thyroid gland (males) of rats and the bone marrow, kidney, liver, skin (site of application), spleen, 

and thyroid gland of mice. 

The quality assessment report and the reviewed slides 

were submitted to the NTP Pathology Working Group 

(PWG) chairperson, who reviewed the selected tissues 

and addressed any inconsistencies in the diagnoses 

made by the laboratory and quality assessment 

pathologists. Representative histopathology slides 

containing examples of lesions related to chemical 

administration, examples of disagreements in diagnoses between the laboratory and quality assessment 

pathologists, or lesions of general interest were 

presented by the chairperson to the PWG for review. 

The PWG consisted of the quality assessment pathologist and other pathologists experienced in rodent 

toxicologic pathology. This group examined the 

tissues without any knowledge of dose groups or 

previously rendered diagnoses. When the PWG 

consensus differed from the opinion of the laboratory 

pathologist, the diagnosis was changed. Final diagnoses for reviewed lesions represent a consensus 

between the laboratory pathologist, reviewing pathologist(s), and the PWG. Details of these review procedures have been described, in part, by Maronpot 

and Boorman (1982) and Boorman et al. (1985). For 

subsequent analyses of the pathology data, the decision of whether to evaluate the diagnosed lesions for 

each tissue type separately or combined was generally 

based on the guidelines of McConnell et al. (1986). 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 21 

TABLE 1 

Experimental Design and Materials and Methods in the Dermal Studies 

of Coconut Oil Acid Diethanolamine Condensate 

14-Week Studies	 2-Year Studies 

Study Laboratory 

Battelle Columbus Laboratories 

(Columbus, OH) 

Strain and Species 

Rats: F344/N 

Mice: B6C3F1 

Animal Source 

Taconic Farms 

(Germantown, NY) 

Time Held Before Studies 

Rats: 14 days (males) or 15 days (females) 

Mice: 16 days (males) or 17 days (females) 

Average Age When Studies Began 

6 weeks 

Date of First Dose 

Rats: 10 February 1992 (males) 

11 February 1992 (females) 

Mice: 12 February 1992 (males) 

13 February 1992 (females) 

Duration of Dosing 

Five exposures per week for 14 weeks 

Date of Last Dose 

Rats:	 3 March 1992 (clinical pathology males) 

4 March 1992 (clinical pathology females) 

11 May 1992 (males) 

12 May 1992 (females) 

Mice:	 13 May 1992 (males) 

14 May 1992 (females) 

Necropsy Dates 

Rats: 12 May 1992 (males) 

13 May 1992 (females) 

Mice: 14 May 1992 (males) 

15 May 1992 (females) 

Average Age at Necropsy 

20 weeks 

Size of Study Groups 

10 males and 10 females 

Method of Distribution 

Animals were distributed randomly into groups of approximately 

equal initial mean body weights. 

Animals per Cage 

Battelle Columbus Laboratories 

(Columbus, OH) 

Rats: F344/N 

Mice: B6C3F1 

Taconic Laboratory Animals and Services 

(Germantown, NY) 

Rats: 11 days (males) or 12 days (females) 

Mice: 13 days (males) or 14 days (females) 

6 weeks 

Rats: 1 February 1993 (males) 

2 February 1993 (females) 

Mice: 20 January 1993 (males) 

21 January 1993 (females) 

Five exposures per week for 104 weeks (rats) or 104 to 105 weeks 

(mice) 

Rats: 27 January 1995 (males) 

30 January 1995 (females) 

Mice: 17 January 1995 (males) 

19 January 1995 (females) 

Rats: 30-31 January 1995 

Mice: 16-20 January 1995 

110 weeks (rats) or 111 weeks (mice) 

50 males and 50 females 

Same as 14-week studies 

1 1 
22 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE 1 

Experimental Design and Materials and Methods in the Dermal Studies 

of Coconut Oil Acid Diethanolamine Condensate 

14-Week Studies	 2-Year Studies 

Method of Animal Identification 

Tail tattoo 

Diet 

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

Gardners, PA), available ad libitum and changed weekly 

Water 

Tap water (Columbus municipal supply) via automatic watering 

system (Edstrom Industries, Inc., Waterford, WI), available 

ad libitum and cleaned every 2 weeks 

Cages 

Polycarbonate (Lab Products, Inc., Maywood, NJ), changed weekly 

and rotated every 2 weeks 

Bedding 

Sani-Chip® heat-treated hardwood chips (P.J. Murphy Forest 

Products Corp., Montville, NJ), changed weekly 

Cage Filters 

Spun-bonded polyester DuPont 2024 (Snow Filtration Co., 

Cincinnati, OH), changed every 2 weeks 

Racks 

Stainless steel drawer-type (Lab Products, Inc., Maywood, NJ), 

changed and rotated every 2 weeks 

Animal Room Environment 

Temperature: 22.2E-23.9E C (rats) 

20.6E-22.8E C (mice) 

Relative humidity: 38%-55% (rats) 

41%-58% (mice) 

Room fluorescent light: 12 hours/day 

Room air changes: 10/hour 

Dose Levels, Concentrations, and Volume 

Rats:	 0, 25, 50, 100, 200, or 400 mg/kg (0, 30, 61, 121, 243, or 

485 mg/mL) in ethanol applied to shaved skin. Dosing 

volume varied with animal weight. 

Mice:	 0, 50, 100, 200, 400, or 800 mg/kg (0, 20, 40, 80, 160, or 

320 mg/mL) in ethanol applied to shaved skin. Dosing 

volume varied with animal weight. 

Type and Frequency of Observation 

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

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

Method of Sacrifice 

Carbon dioxide asphyxiation 

Tail tattoo 

Same as 14-week studies 

Same as 14-week studies 

Same as 14-week studies 

Same as 14-week studies 

Same as 14-week studies 

Same as 14-week studies 

Temperature: 20.0E-23.9E C (rats) 

20.6E-23.9E C (mice) 

Relative humidity: 33%-70% (rats) 

30%-67% (mice) 

Room fluorescent light: 12 hours/day 

Room air changes: 10/hour 

Rats:	 0, 50, or 100 mg/kg (0, 85, or 170 mg/mL) in ethanol 

applied to shaved skin. Dosing volume varied with animal 

weight. 

Mice: 0, 100, or 200 mg/kg (0, 50, or 100 mg/mL) in ethanol 

applied to shaved skin. Dosing volume varied with animal 

weight. 

Observed twice daily; animals were weighed initially, weekly 

during weeks 1 through 13, at 4-week intervals thereafter, and at 

the end of the studies; clinical findings were recorded initially, at 4-

week intervals during the study, and at the end of the study. 

Same as 14-week studies 
 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 23 

TABLE 1 

Experimental Design and Materials and Methods in the Dermal Studies 

of Coconut Oil Acid Diethanolamine Condensate 

14-Week Studies 2-Year Studies 

Necropsy 

Necropsy was performed on all core study rats and mice. Organs 

weighed were heart, right kidney, liver, lung, right testis, and 

thymus. 

Clinical Pathology 

Blood for hematology and clinical chemistry was collected from the 

retroorbital sinus of anesthetized supplemental rats on days 4 and 24 

and from anesthetized core study rats at the end of the study. 

Hematology: hematocrit; hemoglobin concentration; erythrocyte, 

reticulocyte, nucleated erythrocyte, and platelet counts; mean cell 

volume; mean cell hemoglobin; mean cell hemoglobin concentration; 

and leukocyte count and differentials 

Clinical chemistry: urea nitrogen, creatinine, total protein, albumin, 

cholesterol, triglycerides, alanine aminotransferase, alkaline 

phosphatase, sorbitol dehydrogenase, and total bile acids 

Histopathology 

Complete histopathology was performed on 0 and 400 mg/kg core 

study rats and 0 and 800 mg/kg mice. In addition to gross lesions 

and tissue masses, the following tissues were examined: adrenal 

gland, bone and marrow, brain, clitoral gland, esophagus, 

gallbladder (mice), heart, large intestine (cecum, colon, rectum), 

small intestine (duodenum, jejunum, ileum), kidney, liver, lung, 

lymph nodes (mandibular and mesenteric), mammary gland, nose, 

ovary, pancreas, parathyroid gland, pituitary gland, preputial gland, 

prostate gland, salivary gland, spleen, stomach (forestomach and 

glandular), testis (and epididymis and seminal vesicle), thymus, 

thyroid gland, trachea, urinary bladder, and uterus. In addition, the 

skin (site of application) was examined in all core study groups, and 

the kidney was examined in core study male and female rats. 

Sperm Motility and Vaginal Cytology 

At the end of the studies, samples were collected for sperm motility 

or vaginal cytology from all rats in the 0, 100, 200, and 400 mg/kg 

groups and mice in the 0, 200, 400, and 800 mg/kg groups. The 

following sperm motility parameters were evaluated: spermatid 

heads per gram of testis, spermatid heads per testis, spermatid count, 

and epididymal spermatozoal motility and concentration. 

The left cauda epididymis, epididymis, and testis were weighed. 

Vaginal samples for cytology evaluations were collected for 

12 consecutive days prior to the end of the studies from all female 

rats in the 0, 100, 200, and 400 mg/kg groups and female mice in 

the 0, 200, 400, and 800 mg/kg groups. The length of the estrous 

cycle and the length of time spent in each stage of the cycle were 

evaluated. 

Necropsy was performed on all animals. 

None 

Complete histopathology was performed on all rats and mice. In 

addition to gross lesions and tissue masses, the following tissues 

were examined: adrenal gland, bone and marrow, brain, clitoral 

gland, esophagus, gallbladder (mice), heart, large intestine (cecum, 

colon, rectum), small intestine (duodenum, jejunum, ileum), 

kidney, liver, lung, lymph nodes (mandibular and mesenteric), 

mammary gland, nose, ovary, pancreas, parathyroid gland, 

pituitary gland, preputial gland, prostate gland, salivary gland, 

skin, spleen, stomach (forestomach and glandular), testis (and 

epididymis and seminal vesicle), thymus, thyroid gland, trachea, 

urinary bladder, and uterus. 

None 
 

 

 

 

24 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

STATISTICAL METHODS 

Survival Analyses 

The probability of survival was estimated by the 

product-limit procedure of Kaplan and Meier (1958) 

and is presented in the form of graphs. Animals 

found dead of other than natural causes or missing 

were censored from the survival analyses; animals 

dying from natural causes were not censored. Statistical analyses for possible dose-related 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, A4, B1, B5, C1, C5, 

D1, and D5 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. Tables A3, B3, C3, and D3 also give the 

survival-adjusted neoplasm rate for each group and 

each site-specific 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 quantalresponse procedure that modifies the CochranArmitage 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 over time (Bailer and Portier, 1988). Unless 

otherwise specified, a value of k=3 was used in the 

analysis of site-specific 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 B6C3F1 mice (Portier 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 dosed group with controls and a test for an 

overall dose-related trend. Continuity-corrected 

Poly-3 tests were used in the analysis of lesion 

incidence, and reported P values are one sided. The 

significance of lower incidences or decreasing trends 

in lesions are represented as 1!P with the letter N 

added (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 dosed and 

control groups in the analysis of continuous variables. 

Organ and body weight data, which historically 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 
 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 25 

Dunn (1964). Jonckheere’s test (Jonckheere, 1954) 

was used to assess the significance of the dose-related 

trends and to determine whether a trend-sensitive 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 dose levels. 

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 coconut oil acid diethanolamine 

condensate was assessed by testing the ability of the 

chemical to induce mutations in various strains of 

Salmonella typhimurium, mutations in L5178Y mouse 

lymphoma cells, sister chromatid exchanges and 

chromosomal aberrations in cultured Chinese hamster 

ovary cells, and increases in the frequency of micronucleated erythrocytes in peripheral blood of mice. 

The protocols for these studies and the results are 

given in Appendix E. 

The genetic toxicity studies of coconut oil acid diethanolamine condensate 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 chemicalinduced DNA damage and to predict carcinogenicity 

in animals, based on the electrophilicity theory of 

chemical mutagenesis and the somatic mutation theory 

of cancer (Miller and Miller, 1977; Straus, 1981; 

Crawford, 1985). 

There is a strong correlation between a chemical’s 

potential electrophilicity (structural alert to DNA 

reactivity), mutagenicity in Salmonella, and carcinogenicity in rodents. The combination of electrophilicity and Salmonella mutagenicity is highly 

correlated with the induction of carcinogenicity in rats 

and mice and/or at multiple tissue sites (Ashby and 

Tennant, 1991). Other in vitro genetic toxicity tests 

correlate less well with rodent carcinogenicity 

(Tennant et al., 1987; Zeiger et al., 1990), although 

these other tests can provide information on the types 

of DNA and chromosome effects that can be induced 

by the chemical being investigated. Data from NTP 

studies show that a positive response in Salmonella is 

the most predictive in vitro test for rodent carcinogenicity (89% of the Salmonella mutagens are rodent 

carcinogens), and that there is no complementarity 

among the in vitro genetic toxicity tests. That is, no 

battery of tests that included the Salmonella test improved the predictivity of the Salmonella test alone. 

The predictivity for carcinogenicity of a positive 

response in bone marrow chromosome aberration or 

micronucleus tests appears to be less than the 
26 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

Salmonella test (Shelby et al., 1993; Shelby and Witt, observed associations between induced genetic damage 

1995). Positive responses in long-term peripheral and adverse effects in somatic and germ cells, the 

blood micronucleus tests have not been formally determination of in vivo genetic effects is important to 

evaluated for their predictivity for rodent carcino- the overall understanding of the risks associated with 

genicity. But, because of the theoretical and exposure to a particular chemical. 
 

 

 

27 

RESULTS
 

RATS 

14-WEEK STUDY 

All rats survived until the end of the study (Table 2). Irritation of the skin at the site of application was 

Final mean body weights and body weight gains of observed in nearly all 200 and 400 mg/kg males and 

200 and 400 mg/kg males and females were females and in two males and one female administered 

significantly less than those of the vehicle controls. 100 mg/kg. 

TABLE 2 

Survival and Body Weights of Rats in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Dose 

(mg/kg) 

Survivala Initial

Mean Body Weightb (g) 

Final Change 

Final Weight 

Relative to Controls 

(%) 

Male 

0 

25 

50 

100 

200 

400 

10/10 

10/10 

10/10 

10/10 

10/10 

10/10 

146 ± 3 

143 ± 4 

144 ± 4 

145 ± 3 

143 ± 3 

145 ± 4 

352 ± 6 

342 ± 7 

338 ± 5 

338 ± 9 

317 ± 7** 

283 ± 9** 

206 ± 6 

199 ± 6 

194 ± 5 

193 ± 8 

174 ± 6** 

137 ± 8** 

97 

96 

96 

90 

80 

Female 

0 

25 

50 

100 

200 

400 

10/10 

10/10 

10/10 

10/10 

10/10 

10/10 

117 ± 2 

115 ± 3 

117 ± 3 

117 ± 2 

117 ± 2 

115 ± 2 

192 ± 3 

193 ± 4 

188 ± 3 

194 ± 6 

177 ± 3* 

167 ± 4** 

76 ± 2 

78 ± 2 

71 ± 3 

77 ± 5 

60 ± 3** 

52 ± 3** 

101 

98 

101 

92 

87 

* Significantly different (P#0.05) from the vehicle control group by Williams’ test 

** P#0.01 a Number of animals surviving at 14 weeks/number initially in group b Weights and weight changes are given as mean ± standard error. 

The hematology and clinical chemistry data for rats in females on day 24. The anemia was evidenced by 

the 14-week dermal study of coconut oil acid decreases in hematocrit values, hemoglobin condiethanolamine condensate are listed in Table F1. At centrations, and erythrocyte counts. Microcytic and 

week 14, a minimal microcytic, normochromic, non- normochromic erythrocytes were evidenced by 

responsive anemia occurred in the 100 and 200 mg/kg decreased mean cell volumes and the lack of change 

females and 400 mg/kg males and females. The in the mean cell hemoglobin concentration, respecanemia also occurred in the 400 mg/kg males and tively. The lack of an erythropoietic response was 
 

28 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

evidenced by no change in the reticulocyte counts. 

Increased segmented neutrophil counts occurred in 

400 mg/kg males and females at week 14 and in 

400 mg/kg females on day 24. 

There was an indication of altered lipid metabolism, 

evidenced by decreases of cholesterol and triglyceride 

concentrations. At all time points, the cholesterol 

concentration was decreased in 400 mg/kg male and 

female rats; on day 24 and at week 14, 100 mg/kg 

females and 200 mg/kg males and females were also 

affected. A transient decrease in cholesterol concentration also occurred in the 50 mg/kg female rats 

on day 24. Triglyceride concentration was decreased 

in 200 and 400 mg/kg male rats only at week 14. At 

week 14, there was a minimal concentration-related 

increase of serum albumin concentration in all treated 

groups of females and in 100 mg/kg or greater male 

rats; on day 24, increased albumin concentration 

occurred in the 400 mg/kg females. The increased 

albumin concentrations were reflected by increased 

total protein concentrations in 200 and 400 mg/kg 

female rats on day 24 and at week 14. There were 

minimal increases of urea nitrogen concentration that 

occurred in the 200 and 400 mg/kg female rats on 

day 24 and at week 14. At week 14, an increase in 

alanine aminotransferase activity occurred in 

50 mg/kg or greater male rats. Additionally, alkaline 

phosphatase activity was increased in 400 mg/kg 

males. Increased activities of these enzymes could 

indicate altered hepatocellular integrity or cholestasis. 

However, the female rats were not affected, and other 

biomarkers of hepatocellular leakage and/or function 

(serum sorbitol dehydrogenase activity and bile salt 

concentration) were not affected. 

Left epididymis weights of 200 and 400 mg/kg males 

were significantly less than those of the vehicle 

controls, but this was most likely secondary to 

decreased mean body weights in these groups 

(Table H1). Estrous cycle lengths of dosed females 

were similar to those of the vehicle controls 

(Table H2). 

Kidney weights of females administered 50 mg/kg or 

greater were significantly greater than those of the 

vehicle control group (Table G1). 

The incidences of epidermal hyperplasia in all dosed 

groups of males and in females administered 

50 mg/kg or greater were significantly greater than 

those in the vehicle controls (Table 3). Compared to 

the vehicle controls, the incidences of sebaceous gland 

hyperplasia were significantly increased in males 

administered 50 mg/kg or greater and in females 

administered 100 mg/kg or greater. The incidences of 

chronic active inflammation in 100, 200, and 

400 mg/kg males and females significantly exceeded 

the vehicle control incidences. The incidences of 

parakeratosis and ulcer in 200 and 400 mg/kg males 

and females were significantly greater than in the 

vehicle controls. The severities of these skin lesions 

generally increased with increasing dose in males and 

females. 

Males in the 400 mg/kg group had a significantly 

lower incidence of minimal renal tubule regeneration 

than did the vehicle controls. The incidences of renal 

tubule regeneration in 100, 200, and 400 mg/kg 

females were significantly greater than the vehicle 

control incidence, and the severities were greater at 

200 and 400 mg/kg. 
29 

c 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE 3 

Incidences of Selected Nonneoplastic Lesions in Rats in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate

 Vehicle 25 mg/kg 50 mg/kg 100 mg/kg 200 mg/kg 400 mg/kg Control

Male 

Skin, Site of Applicationa 

 Epidermis, Hyperplasiab 

 Sebaceous Gland, Hyperplasia 

 Inflammation, Chronic, Active 

 Parakeratosis 

 Ulcer 

10 

0 

0 

0 

0 

0 

10 

7** (1.1)c 

0 

0 

0 

0 

10 

10** (1.4) 

6** (1.0) 

0 

0 

0 

10 

10** (2.3) 

9** (1.7) 

8** (1.0) 

3 (1.0) 

1 (1.0) 

10 

10** (2.9) 

10** (3.0) 

10** (1.9) 

9** (3.1) 

6** (3.2) 

10

10** (3.0)

10** (3.0)

10** (2.9)

10** (3.9)

7** (4.0) 

Kidney 

 Renal Tubule, Regeneration 

10 

9 (1.0) 

10 

9 (1.2) 

10 

9 (1.1) 

10 

9 (1.1) 

10 

5 (1.0) 

10

3** (1.0) 

Female 

Skin, Site of Application 

 Epidermis, Hyperplasia 

 Sebaceous Gland, Hyperplasia 

 Inflammation, Chronic Active 

 Parakeratosis 

 Ulcer 

10 

0 

0 

0 

0 

0 

10 

2 

0 

0 

0 

0 

(1.0) 

10 

10** (1.5) 

0 

0 

0 

0 

10 

10** (1.8) 

7** (1.3) 

9** (1.0) 

0 

0 

10 

10** (3.0) 

10** (3.0) 

10** (2.8) 

10** (3.4) 

10** (3.8) 

10

10** (3.0)

10** (3.0)

10** (3.0)

10** (4.0)

10** (3.9) 

Kidney 

 Renal Tubule, Regeneration 

10 

3 (1.0) 

10 

5 (1.0) 

10 

7 (1.0) 

10 

10** (1.0) 

10 

10** (1.6) 

10

10** (2.0) 

** Significantly different (P#0.01) from the vehicle control group by the Fisher exact test a Number of animals with tissue examined 

b Number of animals with lesion
 

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

Dose Selection Rationale: Doses of 200 or ulceration, were less than at 200 mg/kg, and in 

400 mg/kg were associated with reduced mean body general, the severities were minimal to mild. 

weights, mild anemia, and significantly increased Therefore, 100 mg/kg was selected as the high dose 

incidences and severities of lesions of the skin at the for the 2-year rat study. The responses observed at 

site of application. Therefore, these doses were 25 and 50 mg/kg were very similar and, therefore, 

considered inappropriate for a 2-year study. At 50 mg/kg was selected as the low dose. 

100 mg/kg, the incidences of skin lesions, especially 
 

30 

c 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

2-YEAR STUDY 

Survival 

Estimates of 2-year survival probabilities for male and 

female rats are shown in Table 4 and in the 

Kaplan-Meier survival curves (Figure 1). Survival 

rates of dosed male and female rats were similar to 

those of the vehicle controls. 

TABLE 4 

Body Weights and Clinical Findings 

The mean body weights of dosed male and female rats 

were similar to those of the vehicle controls 

throughout most of the study (Tables 5 and 6 and 

Figure 2). The only clinical finding attributed to 

dosing was irritation of the skin at the site of 

application in 100 mg/kg females. 

Survival of Rats in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate
 

Vehicle Control 50 mg/kg 100 mg/kg 

Male 

Animals initially in study	 50 50 50 

Accidental deatha 1 0 0 

Moribund 28 27 25 

Natural deaths 13 11 14 

Animals surviving to study termination 8 12 11 

Percent probability of survival at end of studyb 16 24 22 

Mean survival (days)c 594 633 629 

Survival analysisd	 P=0.324N P=0.270N P=0.350N 

Female 

Animals initially in study	 50 50 50 

Moribund 7 15 10 

Natural deaths 15 11 18 

Animals surviving to study termination 28 24 22e 

Percent probability of survival at end of study 56 48 44 

Mean survival (days) 683 638 621 

Survival analysis	 P=0.142 P=0.350 P=0.165 

a Censored from survival analyses b	 Kaplan-Meier determinations 

Mean of all deaths (uncensored, censored, and terminal sacrifice) d	 The result of the life table trend test (Tarone, 1975) is in the vehicle control column, and the results of the life table pairwise comparison 

(Cox, 1972) with the vehicle controls are in the dosed group columns. A negative trend or lower mortality in a dose group is indicated 

by N. e Includes one animal that died during the last week of the study 
C o c o nut Oil Acid Diethanolamine Condensat e, NTP TR 479 3 1
 

F i g u re 1 

Kaplan-Meier Surv ival Curves for Male and Female Rats Administered 

C o c o nut Oil Acid Diethanolamine Condensate Derm a l ly for 2 Ye a rs
 
 

32 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE 5 

Mean Body Weights and Survival of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Weeks Vehicle Control 50 mg/kg 100 mg/kg

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

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

1 129 50 129 100 50 129 100 50 

2 167 50 165 99 50 165 99 50 

3 200 50 197 99 50 196 98 50 

4 229 50 226 99 50 224 98 50 

5 244 50 242 99 50 237 97 50 

6 263 50 259 99 50 255 97 50 

7 278 50 271 98 50 267 96 50 

8 292 50 285 98 50 279 96 50 

9 306 50 298 97 50 292 96 50 

10 311 50 303 97 50 296 95 50 

11 321 50 312 97 50 306 95 50 

12 332 50 321 97 50 315 95 50 

13 340 50 330 97 50 323 95 50 

17 368 49 355 96 50 347 94 50 

21 390 49 374 96 50 365 94 50 

25 407 49 391 96 50 381 94 50 

29 418 49 404 97 50 394 94 50 

33 429 49 415 97 50 403 94 50 

37 430 49 416 97 50 404 94 50 

41 438 49 422 97 50 410 94 50 

45 448 49 435 97 50 420 94 50 

49 456 48 441 97 50 427 94 49 

53 464 48 450 97 50 436 94 49 

57 475 46 459 97 49 444 94 48 

61 475 46 463 97 49 447 94 47 

65 476 45 462 97 48 450 94 47 

69 481 41 465 97 47 452 94 46 

73 474 40 463 98 45 446 94 45 

77 469 38 460 98 42 448 95 42 

81 457 34 452 99 40 442 97 39 

85 444 31 446 101 34 436 98 34 

89 435 26 425 98 30 426 98 31 

93 436 18 428 98 24 421 96 25 

97 415 15 417 101 21 394 95 23 

101 378 13 388 103 18 393 104 14 

Mean for weeks 

1-13 262 257 98 253 97 

14-52 420 406 97 395 94 

53-101 452 444 99 433 96 
 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 33 

TABLE 6 

Mean Body Weights and Survival of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Weeks Vehicle Control 50 mg/kg 100 mg/kg

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

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

1 106 50 106 100 50 106 100 50 

2 123 50 122 99 50 123 100 50 

3 135 50 134 100 50 135 100 50 

4 149 50 148 99 50 148 100 50 

5 156 50 155 99 50 155 99 50 

6 164 50 162 99 50 162 99 50 

7 169 50 166 98 50 166 98 50 

8 175 50 172 98 50 172 98 50 

9 180 50 177 98 50 175 97 50 

10 183 50 179 98 50 177 97 50 

11 187 50 184 98 50 181 97 50 

12 191 50 186 98 50 185 97 50 

13 193 50 189 98 50 187 97 50 

17 204 50 201 98 50 199 98 50 

21 208 50 205 99 50 203 97 50 

25 216 50 213 99 50 211 97 50 

29 226 50 221 98 50 220 97 50 

33 233 50 227 98 49 226 97 50 

37 237 50 231 97 49 227 96 50 

41 246 50 240 98 47 233 95 49 

45 254 50 248 97 47 245 97 47 

49 263 50 258 98 47 254 97 46 

53 274 49 267 98 47 262 96 46 

57 283 49 275 97 45 274 97 42 

61 286 49 280 98 44 279 98 42 

65 291 49 285 98 44 281 97 42 

69 296 49 290 98 43 287 97 41 

73 297 48 293 99 43 291 98 40 

77 301 47 294 98 42 290 96 39 

81 304 46 296 97 40 297 98 35 

85 303 45 301 99 35 296 98 34 

89 305 42 304 100 34 293 96 34 

93 307 37 297 97 33 291 95 31 

97 307 35 291 95 32 289 94 27 

101 312 32 295 95 28 276 88 26 

Mean for weeks 

1-13 162 160 99 159 98 

14-52 232 227 98 224 97 

53-101 297 290 98 285 96 
3 4 C o c o nut Oil Acid Diethanolamine Condensat e, NTP TR 479
 

F i g u re 2 

G rowth Curves for Male and Female Rats Administere d
 

C o c o nut Oil Acid Diethanolamine Condensate Derm a l ly for 2 Ye a rs
 
 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 35 

Pathology and Statistical Analyses 

This section describes the statistically significant or 

biologically noteworthy changes in the incidences of 

neoplasms and/or nonneoplastic lesions of the skin, 

kidney, forestomach, and pancreas. 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 mention in this 

section are presented in Appendix A for male rats and 

Appendix B for female rats. 

Skin: No neoplasms of the skin were attributed to 

treatment with coconut oil acid diethanolamine condensate. Incidences of squamous cell papilloma, 

keratoacanthoma, trichoepithelioma, basal cell adenoma, or carcinoma (combined) were significantly 

TABLE 7 

decreased in 100 mg/kg male rats (6/50, 9/50, 1/50; 

Table A3). Incidences of epidermal hyperplasia, 

sebaceous gland hyperplasia, parakeratosis, and 

hyperkeratosis in all dosed groups were significantly 

greater than those in the vehicle control groups 

(Tables 7, A5, and B5). The severities of these 

lesions generally increased with increasing dose and 

ranged from minimal to mild. No skin lesions were 

observed at the site of application in vehicle control 

males. Females in the 100 mg/kg group had a significantly greater incidence of ulceration at the site of 

application than did the vehicle controls. Epidermal 

hyperplasia and sebaceous gland hyperplasia consisted 

of increased numbers of cells in the epidermis or 

sebaceous glands. The epidermis and sebaceous 

glands were thickened because of the hyperplasia. 

Hyperkeratosis was characterized by increased keratin 

on the surface. 

Incidences of Nonneoplastic Lesions of the Skin at the Site of Application in Rats 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Male 

Number Examined Microscopically 

 Epidermis, Hyperplasiaa

 Sebaceous Gland, Hyperplasia

 Parakeratosis

 Hyperkeratosis

50 

0 

0 

0

 0 

50 

46** 

45** 

9** 

36** 

(1.5)b 

(1.5) 

(1.2) 

(1.4) 

50

50** 

50** 

28** 

48** 

(2.4)

(2.2)

(1.9)

(1.9) 

Female 

Number Examined 

 Epidermis, Hyperplasia 

 Sebaceous Gland, Hyperplasia 

 Parakeratosis 

 Hyperkeratosis 

 Ulcer 

50 

3

2

1

3 

2

 (2.3) 

 (1.5) 

 (1.0) 

(1.3) 

 (2.5)

50 

46** 

46** 

11** 

45** 

0

(1.7) 

(1.7) 

(1.2) 

(1.6) 

50

50** 

49** 

23** 

47** 

 9* 

(2.3)

(2.0)

(2.0)

(1.7)

(2.2) 

* Significantly different (P#0.05) from the vehicle 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 
 

 

 

36 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

Kidney: Initially, single sections of each kidney were 

evaluated. Incidences of renal tubule hyperplasia in 

dosed females were significantly greater than those of 

the vehicle controls, and the incidence of renal tubule 

adenoma in 50 mg/kg males was marginally increased 

(Tables 8, A3, and B5). The incidences of renal 

tubule adenoma in all groups of males and of renal 

tubule carcinoma in 50 mg/kg females exceeded the 

historical control ranges (Tables 8, A4, and B4). An 

extended evaluation of the kidney revealed additional 

renal tubule adenomas in vehicle control and dosed 

males, and renal tubule adenomas and/or carcinomas 

in dosed females. Additional incidences of renal 

tubule hyperplasia were observed in all groups. 

When the single and step sections were combined, the 

incidences of renal tubule hyperplasia in dosed 

females and of renal tubule adenoma or carcinoma 

(combined) in 50 mg/kg females were significantly 

greater than those of the controls. 

Incidences of chronic nephropathy were similar 

between vehicle control and dosed groups of male and 

female rats (Tables 8, A5, and B5); however, the 

severity of nephropathy increased with increasing 

dose in female rats. 

TABLE 8 

Incidences of Neoplasms and Nonneoplastic Lesions of the Kidney in Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Male 

Number Examined Microscopically 50 50 50 

Single Sections (Standard Evaluation)

 Chronic Nephropathy 

 Renal Tubule Hyperplasiaa 49 

13

(2.8) 

 (2.2)b 

50 

13 

(2.7) 

(1.9) 

49 

15 

(2.7)

(2.3)

 Renal Tubule Adenomac 

 Renal Tubule Carcinoma 

 Renal Tubule Adenoma or Carcinomad 

3 

0 

3 

6 

1 

7 

3

0

3 

Step Sections (Extended Evaluation)

 Renal Tubule Hyperplasia 8 8 14

 Renal Tubule Adenoma

 Renal Tubule Carcinoma 

 Renal Tubule Adenoma or Carcinoma 

8 

0 

8 

8 

1 

9 

8

0

8 

Single and Step Sections (Combined)

 Renal Tubule Hyperplasia 16 17 23

 Renal Tubule Adenoma 

 Renal Tubule Carcinoma 

 Renal Tubule Adenoma or Carcinoma 

11 

0

11 

10 

2

11 

10

 0

10 
 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 37 

TABLE 8 

Incidences of Neoplasms and Nonneoplastic Lesions of the Kidney in Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Female 

Number Examined Microscopically 50 50 50 

Single Sections (Standard Evaluation)

 Chronic Nephropathy 47 (1.6) 46 (2.1) 46 (2.7)

 Renal Tubule Hyperplasia 2 (2.0) 8* (2.5) 15** (1.9)

 Renal Tubule Carcinomae 0 2 0 

Step Sections (Extended Evaluation)

 Renal Tubule Hyperplasia 2 (1.0) 2 (2.0) 4 (2.8)

 Renal Tubule Adenoma 0 2 1

 Renal Tubule Carcinoma 0 1 0

 Renal Tubule Adenoma or Carcinoma 0 3 1 

Single and Step Sections (Combined)

 Renal Tubule Hyperplasia 4 (1.5) 10* (2.4) 17** (2.2)

 Renal Tubule Adenoma 0 2 1

 Renal Tubule Carcinoma 0 2 0

 Renal Tubule Adenoma or Carcinoma

 Overall ratef 0/50 (0%) 4/50 (8%) 1/50 (2%) 

 Adjusted rateg

 Terminal rateh

 First incidence (days)

 Poly-3 testi

 0.0%

 0/28 (0%)

 —j

 P=0.293 

10.6% 

3/24 (13%) 

719 

P=0.045 

2.8% 

1/22 (5%) 

728 (T) 

P=0.464 

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

** P#0.01 

(T) Terminal sacrifice a Number of animals with lesion 

b Average severity grade of lesions in affected animals: 1=minimal, 2=mild, 3=moderate, 4=marked c Historical incidence for 2-year NTP dermal studies with ethanol vehicle controls (mean ± standard deviation):
 

8/302 (2.7% ± 3.0%); range, 0%-6%
 d	 Historical incidence: 9/302 (3.0% ± 3.5%); range, 0%-8% e Historical incidence: 0/301 

f	 Number of animals with neoplasm per number of animals with kidney examined microscopically 

g	 Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality h Observed incidence at terminal kill 

i	 Beneath the vehicle control incidence are the P values associated with the trend test. Beneath the dosed group incidence are the P 

values corresponding to pairwise comparisons between the vehicle controls and that dosed group. The Poly-3 test accounts for 

differential mortality in animals that do not reach terminal sacrifice. j Not applicable, no neoplasms in animal group 
38 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

Forestomach: The incidences of chronic active 

inflammation (vehicle control, 1/50; 50 mg/kg, 3/50; 

100 mg/kg,10/50), epithelial hyperplasia (2/50, 5/50, 

13/50), and epithelial ulcer (1/50, 3/50, 11/50) were 

significantly increased in the forestomach of 

100 mg/kg females (Table B5). The severities of 

these lesions were similar among all groups 

(inflammation: 3.0, 2.3, 2.8; epithelial hyperplasia: 

2.5, 2.6, 2.9; epithelial ulcer: 4.0, 4.0, 3.5). 

Pancreas: The incidence of pancreatic acinar atrophy 

in 100 mg/kg male rats was significantly greater than 

that in the vehicle controls (11/50, 22/50, 25/50; 

Table A5). 
 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 39 

MICE 

14-WEEK STUDY 

All mice survived until the end of the study (Table 9). 

Final mean body weights and body weight gains of 

dosed males and females were similar to those of the 

vehicle controls. The only treatment-related clinical 

finding was irritation of the skin at the site of 

application in all males and females administered 

800 mg/kg. 

The absolute and relative liver and right kidney 

weights of 800 mg/kg males and females and the 

absolute and relative liver weights of 400 mg/kg 

females were significantly greater than those of the 

vehicle controls (Table G2). The absolute and 

relative lung weights of 800 mg/kg females were also 

significantly greater than those of the vehicle controls. 

The epididymal spermatozoal concentration of 

800 mg/kg males was significantly greater than that of 

the vehicle controls (Table H3). Estrous cycle lengths 

of dosed females were similar to that of the vehicle 

controls (Table H4). 

TABLE 9 

Survival and Body Weights of Mice in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Mean Body Weightb (g) Final Weight 

Dose Survivala Initial Final Change Relative to Controls 

(mg/kg) (%)

 Male 

0 10/10 24.4 ± 0.2 37.8 ± 1.2 13.4 ± 1.1 

50 10/10 24.4 ± 0.2 36.0 ± 0.5 11.7 ± 0.4 95 

100 10/10 24.4 ± 0.2 36.3 ± 0.7 11.9 ± 0.7 96 

200 10/10 24.1 ± 0.3 37.2 ± 1.0 13.1 ± 1.0 99 

400 10/10 24.8 ± 0.3 37.1 ± 1.2 12.4 ± 1.1 98 

800 10/10 24.6 ± 0.2 37.4 ± 1.1 12.8 ± 1.0 99

 Female 

0 10/10 20.2 ± 0.4 31.0 ± 1.0 10.8 ± 0.7 

50 10/10 19.7 ± 0.2 31.2 ± 0.6 11.5 ± 0.5 101 

100 10/10 20.1 ± 0.4 32.7 ± 1.2 12.6 ± 1.0 105 

200 10/10 20.2 ± 0.4 29.4 ± 0.4 9.2 ± 0.3 95 

400 10/10 20.2 ± 0.3 29.9 ± 0.5 9.8 ± 0.4 96 

800 10/10 20.2 ± 0.2 29.4 ± 0.5 9.2 ± 0.4 95 

a Number of animals surviving at 14 weeks/number initially in group b	 Weights and weight changes are given as mean ± standard error. Differences from the control group are not significant by Williams’ 

or Dunnett’s test. 
 

40 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

In all dosed groups, the incidences of epidermal 

hyperplasia and sebaceous gland hyperplasia at the 

site of application were significantly greater than 

those in vehicle controls, and the severities of these 

lesions generally increased with increasing dose 

(Table 10). The incidences of chronic active 

inflammation of the skin in 200, 400, and 800 mg/kg 

males and females were significantly greater than 

TABLE 10 

those in the vehicle controls, and the severities were 

increased in the 800 mg/kg groups. Compared to the 

vehicle controls, the incidences of parakeratosis in 

200, 400, and 800 mg/kg males and 400 and 

800 mg/kg females were significantly greater than 

those in the vehicle controls. The incidences of skin 

ulceration in 800 mg/kg males and females were 

significantly greater than the vehicle control 

incidences. 

Incidences of Nonneoplastic Lesions of the Skin at the Site of Application in Mice 

in the 14-Week Dermal Study of Coconut Oil Acid Diethanolamine Condensate

 Vehicle 50 mg/kg 100 mg/kg 200 mg/kg 400 mg/kg 800 mg/kg Control

Male 

Number Examined 10 10 10 10 10 10

Microscopically 

 Epidermis, Hyperplasiaa 0 7** (1.0)b 9** (1.1) 10** (1.8) 8** (1.8) 10** (2.2)

 Sebaceous Gland, Hyperplasia 0 7** (1.1) 10** (1.2) 10** (1.5) 9** (1.8) 10** (2.3)

 Inflammation, Chronic, Active 0 0 0 8** (1.0) 7** (1.0) 9** (1.4)

 Parakeratosis 0 0 0 5* (1.0) 7** (1.0) 9** (1.6)

 Ulcer 0 0 0 1 (1.0) 4* (1.0) 6** (1.2) 

Female 

Number Examined 10 10 10 10 10 10

Microscopically 

 Epidermis, Hyperplasia 0 4* (1.0) 9** (1.1) 10** (1.6) 10** (1.7) 10** (2.7)

 Sebaceous Gland, Hyperplasia 0 4* (1.3) 10** (1.1) 10** (1.8) 10** (2.0) 10** (3.4)

 Inflammation, Chronic, Active 0 0 1 (1.0) 6** (1.0) 7** (1.0) 9** (1.8)

 Parakeratosis 0 0 0 2 (1.0) 5* (1.0 ) 7** (1.7)

 Ulcer 0 0 0 0 0 5* (1.0) 

* Significantly different (P#0.05) from the vehicle 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 

Dose Selection Rationale: Exposure to coconut oil 

acid diethanolamine condensate for 14 weeks 

produced only a minimal toxic response in mice 

except in the skin at the site of application. The 

incidences of chronic active inflammation as well as 

several other skin lesions were significantly increased 

at doses of 200 mg/kg and greater in both male and 

female mice. The incidences of ulceration were 

increased in males exposed to 400 and 800 mg/kg and 

in females exposed to 800 mg/kg. Therefore, 400 and 

800 mg/kg were considered inappropriate for a 2-year 

study. However, ulceration was present in only one 

200 mg/kg male and no females, and the severities of 

these lesions in all affected groups were minimal to 

mild. Below 200 mg/kg, the incidences of skin 

lesions decreased markedly with a minor difference in 

response between 50 and 100 mg/kg. Therefore, 

200 mg/kg was selected as the high dose and 

100 mg/kg as the low dose for the 2-year mouse 

study. 
 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 41 

2-YEAR STUDY 

Survival 

Estimates of 2-year survival probabilities for male and 

female mice are shown in Table 11 and in the 

Kaplan-Meier survival curves (Figure 3). The survival of dosed males and 100 mg/kg females was 

similar to that of the vehicle controls. Survival of the 

200 mg/kg group of female mice was reduced 

compared to the vehicle control group, but the 

difference was not significant. 

Body Weights and Clinical Findings 

Mean body weights of dosed males were similar to 

those of the vehicle controls throughout most of the 

study; those of 100 and 200 mg/kg females were less 

than those of the vehicle controls from weeks 93 and 

77, respectively (Figure 4 and Tables 12 and 13). 

The only treatment-related clinical finding was 

irritation of the skin at the site of application in males 

that received 200 mg/kg. 

TABLE 11 

Survival of Mice in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Male 

Animals initially in study	 50 50 50 

Moribund 5 7 7 

Natural deaths 4 6 7 

Animals surviving to study termination 41 37 36 

Percent probability of survival at end of studya 82 74 72 

Mean survival (days)b 704 688 695 

Survival analysisc	 P=0.318 P=0.456 P=0.356 

Female 

Animals initially in study	 50 50 50 

Moribund 11 11 15 

Natural deaths 4 3 9 

Animals surviving to study termination 35 36d 26 

Percent probability of survival at end of study 70 72 52 

Mean survival (days) 700 696 665 

Survival analysis	 P=0.056 P=1.000N P=0.070 

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 vehicle control column, and the results of the life table pairwise 

comparisons (Cox, 1972) with the vehicle controls are in the dosed columns. A lower mortality in a dose group is indicated by N. 

d	 Includes one animal that died during the last week of study 

c 
4 2 C o c o nut Oil Acid Diethanolamine Condensat e, NTP TR 479
 

F i g u re 3 

Kaplan-Meier Surv ival Curves for Male and Female Mice Administere d
 

C o c o nut Oil Acid Diethanolamine Condensate Derm a l ly for 2 Ye a rs
 
C o c o nut Oil Acid Diethanolamine Condensat e, NTP TR 479 4 3
 

F i g u re 4
 

G rowth Curves for Male and Female Mice Administered 

C o c o nut Oil Acid Diethanolamine Condensate Derm a l ly for 2 Ye a rs
 
44 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE 12 

Mean Body Weights and Survival of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Weeks Vehicle Control 100 mg/kg 200 mg/kg 

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

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

1 23.9 50 23.8 100 50 23.9 100 50 

2 24.6 50 25.2 102 50 24.9 101 50 

3 25.7 50 26.6 104 50 26.2 102 50 

4 26.6 50 27.6 104 50 27.2 102 50 

5 27.8 50 28.9 104 50 28.5 103 50 

6 28.7 50 29.9 104 50 29.6 103 50 

7 29.4 50 30.9 105 50 30.4 103 50 

8 30.4 50 32.1 106 50 31.4 103 50 

9 31.4 50 32.8 105 50 32.1 102 50 

10 32.4 50 34.0 105 50 33.5 103 50 

11 32.7 50 34.8 106 50 33.8 103 50 

12 33.9 50 36.3 107 50 35.7 105 50 

13 34.7 50 36.8 106 50 36.1 104 50 

17 38.4 50 40.6 106 50 39.5 103 50 

21 40.3 50 42.2 105 50 41.5 103 50 

25 42.7 50 44.7 105 50 44.0 103 50 

29 45.0 50 46.7 104 50 46.3 103 50 

33 46.7 50 49.0 105 50 48.4 104 50 

37 48.5 50 49.6 102 50 49.9 103 50 

41 48.1 50 49.9 104 50 49.5 103 50 

45 48.8 50 50.5 104 49 50.5 104 50 

49 49.6 50 51.5 104 49 51.3 103 50 

53 49.5 50 51.9 105 48 51.5 104 50 

57 50.6 50 52.5 104 48 52.3 103 50 

61 50.6 49 52.5 104 48 53.0 105 49 

65 51.2 49 52.4 102 48 52.8 103 49 

69 50.9 49 52.3 103 47 53.0 104 48 

73 50.7 48 52.5 104 47 53.0 105 47 

77 51.2 48 53.4 104 46 53.6 105 47 

81 48.9 48 51.8 106 46 51.8 106 46 

85 50.3 47 52.1 104 45 50.8 101 46 

89 49.8 46 50.9 102 44 49.9 100 44 

93 50.6 44 50.2 99 44 48.6 96 43 

97 49.4 43 48.3 98 40 46.0 93 41 

101 49.8 41 48.4 97 38 44.4 89 39 

Mean for weeks 

1-13 29.4 30.7 104 30.3 103 

14-52 45.3 47.2 104 46.8 103 

53-101 50.3 51.5 102 50.8 101 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 45 

TABLE 13 

Mean Body Weights and Survival of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Weeks Vehicle Control 100 mg/kg 200 mg/kg 

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

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

1 20.1 50 20.2 101 50 20.0 100 50 

2 21.5 50 21.7 101 50 21.7 101 50 

3 22.9 50 23.2 101 50 23.2 101 50 

4 23.5 50 23.6 100 50 23.7 101 50 

5 25.0 50 25.3 101 50 25.1 100 50 

6 25.8 50 26.3 102 50 26.2 102 50 

7 26.7 50 27.0 101 50 26.9 101 50 

8 27.2 50 27.1 100 50 27.0 99 50 

9 28.1 50 28.3 101 50 28.0 100 50 

10 29.1 50 29.4 101 50 29.3 101 50 

11 30.5 50 30.5 100 50 30.3 99 50 

12 31.6 50 31.8 101 50 31.4 99 50 

13 32.1 50 32.2 100 50 31.8 99 50 

17 35.3 50 35.6 101 50 35.5 101 49 

21 37.9 50 37.5 99 50 37.2 98 49 

25 40.4 50 40.7 101 50 40.6 101 49 

29 43.4 50 43.8 101 50 43.5 100 49 

33 45.6 50 46.5 102 50 45.8 100 49 

37 47.8 50 48.5 102 50 48.0 100 49 

41 48.1 50 48.6 101 50 47.8 99 49 

44 49.6 50 50.7 102 50 49.7 100 49 

49 51.2 50 52.1 102 50 50.7 99 49 

53 52.8 50 53.8 102 50 52.5 99 49 

57 54.5 50 55.6 102 50 53.9 99 48 

61 54.6 50 56.4 103 50 54.5 100 48 

65 56.0 49 56.8 101 50 55.0 98 47 

69 55.6 49 56.0 101 49 54.3 98 47 

73 56.5 48 56.9 101 49 54.4 96 47 

77 58.0 47 56.8 98 49 53.4 92 46 

81 56.3 47 54.5 97 48 50.9 90 45 

85 56.1 46 54.8 98 45 49.8 89 42 

89 55.6 44 52.7 95 43 45.8 82 40 

93 55.8 44 52.2 94 40 43.9 79 37 

96 51.9 43 47.9 92 39 40.9 79 32 

101 51.6 40 46.0 89 36 40.9 79 31 

Mean for weeks 

1-13 26.5 26.7 101 26.5 100 

14-52 44.4 44.9 101 44.3 100 

53-101 55.0 53.9 98 50.0 91 
 

46 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

Pathology and Statistical Analyses 

This section describes the statistically significant or 

biologically noteworthy changes in the incidences of 

neoplasms and/or nonneoplastic lesions of the liver, 

kidney, skin, and thyroid gland. 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 C for male 

mice and Appendix D for female mice. 

Liver: Dosed male and female mice had significantly 

greater incidences of hepatic neoplasms than the 

vehicle controls (Tables 14, C3, and D3). These 

neoplasms included hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma (males). 

The incidences of hepatocellular adenoma, hepatocellular carcinoma, or hepatoblastoma (combined) in 

200 mg/kg males and 100 and 200 mg/kg females 

exceeded the historical control ranges (Tables 14, 

C4a, and D4). The incidences of eosinophilic foci in 

dosed groups of males were increased relative to that 

in the vehicle controls; the incidences in dosed 

females were also increased, but the differences from 

the vehicle controls were not significant (Tables 14, 

C5, and D5). 

There was a morphologic continuum from adenoma to 

carcinoma, with less differentiation and typical 

trabecular formations in the carcinomas. Carcinomas 

were often a centimeter or more in diameter, whereas 

adenomas were generally smaller and more discrete. 

Carcinomas metastasized to the lung in a few males 

and females. Adenomas, carcinomas, and hepatoblastomas displaced normal liver parenchyma, and 

none contained normal lobular architecture. Hepatoblastomas were characterized by well-demarcated 

focal areas composed of bundles of deeply basophilic, 

spindle-shaped cells. 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 47 

TABLE 14 

Incidences of Neoplasms and Nonneoplastic Lesions of the Liver in Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Male 

Number Examined Microscopically 50 50 50 

Eosinophilic Focusa 20 29* 31* 

Hepatocellular Adenoma, Multiple 11 24 41 

Hepatocellular Adenoma (includes multiple)b 

Overall ratec 22/50 (44%) 35/50 (70%) 45/50 (90%) 

Adjusted rated 46.2% 75.4% 91.4% 

Terminal ratee 18/41 (44%) 29/37 (78%) 34/36 (94%) 

First incidence (days) 612 507 401 

Poly-3 testf P<0.001 P=0.002 P<0.001 

Hepatocellular Carcinoma, Multiple 5 2 8 

Hepatocellular Carcinoma (includes multiple)g 

Overall rate 12/50 (24%) 12/50 (24%) 20/50 (40%) 

Adjusted rate 25.4% 26.2% 43.0% 

Terminal rate 9/41 (22%) 7/37 (19%) 15/36 (42%) 

First incidence (days) 584 576 456 

Poly-3 test P=0.041 P=0.561 P=0.055 

Hepatocellular Adenoma or Carcinoma (includes multiple) 

Overall rate 28/50 (56%) 39/50 (78%) 47/50 (94%) 

Adjusted rate 58.0% 82.4% 95.3% 

Terminal rate 22/41 (54%) 30/37 (81%) 34/36 (94%) 

First incidence (days) 584 507 401 

Poly-3 test P<0.001 P=0.007 P<0.001 

Hepatoblastoma, Multiple 1 0 0 

Hepatoblastoma (includes multiple)h 

Overall rate 1/50 (2%) 1/50 (2%) 10/50 (20%) 

Adjusted rate 2.1% 2.2% 22.1% 

Terminal rate 0/41 (0%) 0/37 (0%) 8/36 (22%) 

First incidence (days) 664 507 692 

Poly-3 test P<0.001 P=0.753 P=0.003 

Hepatocellular Adenoma, Hepatocellular Carcinoma, or Hepatoblastoma (includes multiple)i 

Overall rate 29/50 (58%) 39/50 (78%) 49/50 (98%) 

Adjusted rate 59.8% 82.4% 99.3% 

Terminal rate 22/41 (54%) 30/37 (81%) 36/36 (100%) 

First incidence (days) 584 507 401 

Poly-3 test P<0.001 P=0.011 P<0.001 

* Significantly different (P#0.05) from the vehicle control group by the Poly-3 test a Number of animals with lesion 

b Historical incidence for 2-year NTP dermal studies with ethanol vehicle controls (mean ± standard deviation): 118/249 (47.4% ± 

8.9%); range, 38%-62% 

Number of animals with neoplasm per number of animals with liver examined microscopically d Poly-3 estimated neoplasm incidence after adjustment for intercurrent mortality e Observed incidence at terminal kill 

f Beneath the vehicle control incidence are the P values associated with the trend test. Beneath the dosed group incidence are the P values 

corresponding to pairwise comparisons between the vehicle controls and that dosed group. The Poly-3 test accounts for differential 

mortality in animals that do not reach sacrifice. 

c 
48 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE 14 

Incidences of Neoplasms and Nonneoplastic Lesions of the Liver in Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Female 

Number Examined Microscopically 50 50 50 

Eosinophilic Focus 18 25 24 

Hepatocellular Adenoma, Multiple 24 39 38 

Hepatocellular Adenoma (includes multiple)j 

Overall rate 32/50 (64%) 44/50 (88%) 43/50 (86%) 

Adjusted rate 69.0% 90.3% 90.7% 

Terminal rate 26/35 (74%) 32/36 (89%) 25/26 (96%) 

First incidence (days) 568 561 366 

Poly-3 test P=0.002 P=0.006 P=0.005 

Hepatocellular Carcinoma, Multiple 2 4 16 

Hepatocellular Carcinoma (includes multiple)k 

Overall rate 3/50 (6%) 21/50 (42%) 32/50 (64%) 

Adjusted rate 6.6% 45.8% 70.4% 

Terminal rate 1/35 (3%) 17/36 (47%) 18/26 (69%) 

First incidence (days) 681 584 366 

Poly-3 test P<0.001 P<0.001 P<0.001 

Hepatocellular Adenoma or Carcinoma (includes multiple) 

Overall rate 33/50 (66%) 46/50 (92%) 48/50 (96%) 

Adjusted rate 70.9% 94.4% 99.0% 

Terminal rate 26/35 (74%) 34/36 (94%) 26/26 (100%) 

First incidence (days) 568 561 366 

Poly-3 test P<0.001 P<0.001 P<0.001 

Hepatoblastoma, Multiple 0 0 1 

Hepatoblastomal

 (includes multiple) 

Overall rate 0/50 (0%) 1/50 (2%) 3/50 (6%) 

Adjusted rate 0.0% 2.2% 7.3% 

Terminal rate 0/35 (0%) 0/36 (0%) 1/26 (4%) m First incidence (days) — 629 567 

Poly-3 test P=0.054 P=0.498 P=0.103 

Hepatocellular Adenoma, Hepatocellular Carcinoma, or Hepatoblastoma (includes multiple)n 

Overall rate 33/50 (66%) 46/50 (92%) 48/50 (96%) 

Adjusted rate 70.9% 94.4% 99.0% 

Terminal rate 26/35 (74%) 34/36 (94%) 26/26 (100%) 

First incidence (days) 568 561 366 

Poly-3 test P<0.001 P<0.001 P<0.001 

g Historical incidence: 54/249 (21.7% ± 2.5%); range, 18%-24% h Historical incidence: 1/249 (0.4% ± 0.9%); range, 0%-2% i Historical incidence: 154/249 (61.8% ± 9.1%); range, 56%-78% j Historical incidence: 133/252 (52.8% ± 11.4%); range, 38%-64% k Historical incidence: 35/252 (13.9% ± 7.3%); range, 6%-23% l Historical incidence: 1/252 (0.4% ± 0.9%); range, 0%-2% m Not applicable; no neoplasms in animal group n Historical incidence: 149/252 (59.1% ± 6.4%); range, 52%-66% 
 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 49 

Kidney: The incidences of renal tubule adenoma 

(1/50, 1/50, 7/50) and of renal tubule adenoma or 

carcinoma (combined) (1/50, 1/50, 9/50) in 

200 mg/kg males were significantly greater than those 

in the vehicle controls (Table C3) and exceeded the 

historical control ranges for these neoplasms 

[adenoma: 2/299 (0.7% ± 1.0%), range 0%-2%; 

adenoma or carcinoma 4/299 (1.3% ± 2.4%), range 

0%-6%; Table C4b]. One 200 mg/kg female also had 

a renal tubule adenoma (Table D1). To further 

evaluate the response in female mice, an extended 

kidney analysis was conducted but no additional renal 

tubule neoplasms were found. The incidence of 

nephropathy in 200 mg/kg females was significantly 

less than that in the vehicle controls (27/50, 24/50, 

15/50; Table D5). 

Renal tubule hyperplasia, adenoma, and carcinoma 

formed a morphological continuum. Adenomas were 

TABLE 15 

focal, compressive masses approximately five or more 

tubules in diameter; carcinomas were morphologically 

similar to adenomas but were larger and often showed 

cellular debris and/or mineralization. Renal tubule 

neoplasms were located in the cortex or outer 

medulla. Focal proliferative masses less than five 

tubules in diameter were classified as focal 

hyperplasia. 

Skin: No neoplasms of the skin were attributed to 

treatment with coconut oil acid diethanolamine 

condensate. Several nonneoplastic lesions of the skin 

at the site of application were determined to be 

chemical related. Incidences of epidermal hyperplasia, sebaceous gland hyperplasia, and hyperkeratosis in all dosed groups of males and females 

were significantly greater than those in the vehicle 

control groups (Tables 15, C5, and D5). The 

incidences of ulceration in 200 mg/kg males and 

Incidences of Nonneoplastic Lesions of the Skin at the Site of Application in Mice 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Male 

Number Examined 

Microscopically 

 Epidermis Hyperplasiaa 

 Sebaceous Gland, Hyperplasia 

 Inflammation 

 Parakeratosis 

 Hyperkeratosis 

Ulcer 

50 

5 

0 

2 

1 

0 

1 

(2.0)b 

(3.5) 

(2.0) 

(4.0) 

50 

47** (2.2) 

44** (1.9) 

2 (1.0) 

4 (1.0) 

24** (1.2) 

0 

50

50** (2.9)

49** (2.0)

2 (2.5)

5 (1.0)

23** (1.4)

7* (2.3) 

Female 

Number Examined 

Microscopically 

 Epidermis Hyperplasia 

 Sebaceous Gland, Hyperplasia 

 Inflammation 

 Parakeratosis 

 Hyperkeratosis 

Ulcer 

50 

9 

0 

3 

3 

5 

1 

(2.1) 

(1.3) 

(2.7) 

(1.4) 

(1.0) 

50 

47** (2.4) 

42** (2.0) 

2 (1.0) 

4 (1.0) 

30** (1.2) 

0 

50

50** (3.0)

48** (1.9)

11* (1.5)

16** (1.3)

40** (1.9)

3 (1.3) 

* Significantly different (P#0.05) from the vehicle 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 
 

 

 

 

 

 

50 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

inflammation and parakeratosis in 200 mg/kg females 

were increased. Epidermal hyperplasia consisted of 

increased thickness of the epidermis and varied in 

severity from mild to moderate. Hyperkeratosis was 

usually of minimal to mild severity and consisted of 

increased keratin on the surface. In some cases, cells 

that had not shed their nuclei were undergoing 

keratinization, which is the basis for a diagnosis of 

parakeratosis. Parakeratosis was seen only with 

hyperkeratosis and was not considered to be biologically significant. 

Thyroid Gland: The incidences of follicular cell 

hyperplasia in all dosed groups of males (vehicle 

control, 11/50; 100 mg/kg, 20/50; 200 mg/kg, 23/50; 

Table C5) and females (27/50, 36/50, 33/50; 

Table D5) were significantly greater than those in the 

vehicle controls. Follicular cell hyperplasia consisted 

of focal areas of thyroid gland follicles lined with 

increased numbers of epithelial cells, which formed 

papillary projections in some instances. The incidences of follicular cell adenoma (2/50, 5/50, 3/50; 

Table D3) in female mice administered 100 or 

200 mg/kg were slightly, but not significantly, greater 

than that in the vehicle controls. While the incidence 

of follicular cell adenoma in 100 mg/kg females 

exceeded the historical control range [17/302 

(5.6% ± 2.0%; range; 4%–8%), there was no doserelated pattern in the incidence of these neoplasms. 

GENETIC TOXICOLOGY 

Results of in vitro assays for genotoxicity with 

coconut oil acid diethanolamine condensate were 

uniformly negative. It did not induce mutations in 

Salmonella typhimurium strain TA97, TA98, TA100, 

or TA1535, with or without S9 metabolic activation 

(Zeiger et al., 1988; Table E1). The highest concentration was limited to 200 μg/plate by toxicity. No 

increase in mutant L5178Y mouse lymphoma cell 

colonies was observed after exposure to coconut oil 

acid diethanolamine condensate, with or without S9 

(Table E2). A single positive response noted at 

8 nL/mL in the second trial conducted without S9 was 

not reproducible and the test results overall were 

considered to be negative. In tests for induction of 

chromosomal damage, no increases in the frequencies 

of sister chromatid exchanges (Table E3) or 

chromosomal aberrations (Table E4) were observed in 

cultured Chinese hamster ovary cells after incubation 

with coconut oil acid diethanolamine condensate, with 

or without S9. 

In contrast to the negative results obtained in in vitro 

assays, positive results were obtained in the 14-week 

study. At the end of 14 weeks, significant increases 

in the frequencies of micronucleated normochromatic 

erythrocytes were seen in peripheral blood of both 

male and female mice (Table E5). Statistical analysis 

of the data showed positive trends for both data sets as 

well as significantly elevated micronucleus frequencies at the highest dose tested (800 mg/kg) in male 

and female mice. 
 

51 

DISCUSSION AND CONCLUSIONS
 

Coconut oil diethanolamide is a member of a group of 

fatty acid diethanolamine condensates widely used as 

emollients, thickeners, and foam stabilizers in 

cosmetics, shampoos, conditioners, and hair dyes. 

Because of the extensive human exposure to these 

compounds and the absence of information concerning 

the consequences of long-term exposure, lauric acid 

diethanolamine condensate, oleic acid diethanolamine 

condensate, and coconut oil acid diethanolamine 

condensate were selected for evaluation of carcinogenic potential as representatives of this class of 

compounds. Because diethanolamine is used in the 

synthesis of all the diethanolamides, and free diethanolamine is present at varying concentrations as a 

contaminant of commercial diethanolamide preparations, the carcinogenic potential of diethanolamine 

was also evaluated. The primary route of human 

exposure to products containing diethanolamides is by 

contact with the skin. Therefore, this series of studies 

was conducted by dermal administration. 

During the 14-week studies in rats, doses of 200 or 

400 mg coconut oil acid diethanolamine condensate/kg 

body weight were associated with reduced mean body 

weights and the presence of a minimal microcytic, 

normochromic, unresponsive anemia. The absence of 

a reticulocyte response or of any indication of 

hemosiderin in the spleen suggests that accelerated 

removal of erythrocytes was not involved. A similar 

anemia was observed in rats in the 14-week studies of 

diethanolamine. Because the coconut oil acid diethanolamine condensate preparation used in these 

studies contained approximately 18.2% free diethanolamine by weight, the anemia observed in this study 

may be associated with the contaminating diethanolamine. There was also an indication of altered lipid 

metabolism in the present study, as evidenced by 

decreases in cholesterol and triglyceride concentrations in the 200 and 400 mg/kg groups. Cholesterol and triglycerides were not measured in the 

diethanolamine study; however, diethanolamine is 

extensively incorporated into phospholipids (Matthews 

et al., 1995), and in vitro, the choline analogs monomethyl and dimethylethanolamine inhibited incorporation of oleic acid into cholesteryl esters and triacylglycerols by 40% (Maziere et al., 1990). 

Therefore, the unreacted diethanolamine may also be 

responsible for the changes in the cholesterol and 

triglyceride levels. 

No neoplasms of the skin were associated with 

exposure to coconut oil acid diethanolamine condensate. At the end of the 2-year studies, the incidences 

of skin lesions at the site of application were 

significantly increased in all dosed groups of rats, but 

there were only slight differences in severities 

between the 50 and 100 mg/kg males or among any 

groups of females. In mice, the skin response was 

also rather mild; in males, the incidences of chronic 

inflammation were not increased at the site of 

application in groups exposed to coconut oil acid 

diethanolamine condensate, and in females, the 

incidences of ulcer were not increased in the dosed 

groups. In male and female mice, the severities of 

skin lesions were not increased by exposure to 

coconut oil acid diethanolamine condensate. 

Renal tubule neoplasms were present in dosed groups 

of male and female rats. Six 50 mg/kg male rats had 

adenomas and one had a carcinoma; however, three 

vehicle control and three 100 mg/kg males had 

adenomas, and the incidences of hyperplasia were not 

increased. In female rats, there was a significant 

dose-related increase in the incidence of hyperplasia, 

and renal tubule carcinomas were present in two 

animals from the 50 mg/kg group, but there were no 

renal tubule neoplasms in the 100 mg/kg group. 

In order to evaluate this response in greater detail, the 

kidneys from rats were step sectioned, and an 

extended evaluation of all kidney sections conducted. 

The extended evaluation identified additional renal 

tubule hyperplasias, adenomas, and a carcinoma in 

males and additional renal tubule hyperplasias and 

neoplasms in females. The number of renal tubule 

neoplasms in male rats identified by the extended 

evaluation was unusually large, but analysis of single 

and step sections combined indicates that the incidence 
 

 

 

 

52 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

of renal tubule neoplasms in male rats was not 

increased by dermal exposure to coconut oil acid 

diethanolamine condensate, nor was there an increase 

in the incidence of renal tubule hyperplasia. 

In female rats, the combined single and step section 

evaluations of the kidney revealed a significant doserelated increase in the incidence of renal tubule 

hyperplasia and two adenomas and two carcinomas in 

the 50 mg/kg group but only one neoplasm, an 

adenoma, in the 100 mg/kg group. Renal tubule 

neoplasms are uncommon in female F344/N rats, and 

the presence of four neoplasms in the 50 mg/kg 

group, combined with the increased incidence of 

hyperplasia, is suggestive of an association with 

chemical exposure. However, the absence of an 

increase in neoplasms the 100 mg/kg group in the 

presence of increased hyperplasia makes the association with chemical exposure uncertain. 

The incidences of hepatocellular adenoma, hepatocellular carcinoma, or hepatoblastoma (combined) 

were significantly increased in dosed male and female 

mice. The incidences of hepatoblastoma alone were 

significantly increased in male mice but not in female 

mice. Hepatoblastomas are uncommon phenotypic 

variants of hepatocellular carcinomas that appear to 

arise within existing hepatocellular carcinomas. 

In addition, the incidences of renal tubule neoplasms 

were significantly increased in the 200 mg/kg group 

of male mice. A renal tubule adenoma was also present in one 200 mg/kg female mouse; however, an 

extended analysis of kidney sections failed to identify 

additional renal tubule neoplasms in any groups of 

female mice. 

This pattern of response involving the liver of female 

mice and the liver and kidney of male mice is the 

same as that observed in mice in the 2-year studies of 

diethanolamine (NTP, 1999a) and fits into a pattern of 

response observed in the 2-year studies of the other 

diethanolamine condensates (NTP, 1999b,c). Comparison of the results of these studies reveals a strong 

association between the concentration of free 

diethanolamine contaminant present in the different 

diethanolamide preparations and the incidence of 

hepatocellular neoplasms in male and female mice and 

renal tubule neoplasms in male mice. The 

comparison also reveals a clear gender difference in 

the responses of male and female mice to 

diethanolamine administration. 

The strongest response occurred with diethanolamine 

(purity greater than 99%) and involved male and 

female mice (NTP, 1998a). In the diethanolamine 

study, mice received doses of 0, 40, 80, or 

160 mg/kg. In addition to increased incidences of 

hepatocellular neoplasms, administration of diethanolamine was also associated with significant increases in 

the multiplicity and size of hepatocellular adenomas 

and carcinomas in males and females and increased 

incidences of hepatoblastoma in males. Mean body 

weights of dosed female mice were depressed more 

than those of dosed males, and survival of female 

mice in the 160 mg/kg group was reduced. In addition to the neoplastic response in the liver, increased 

incidences of renal tubule neoplasms occurred in 

dosed male mice. 

The next strongest response was observed in the 

present study and involved significant increases in 

hepatocellular neoplasms in mice but no corresponding increases in the multiplicity or size of neoplasms, 

as was observed in the diethanolamine study. The 

incidences of hepatoblastoma were significantly 

increased in males but not in females. Mean body 

weights and survival of 200 mg/kg female mice were 

less than those of vehicle controls. In addition, the 

incidences of renal tubule neoplasms were increased 

in 200 mg/kg male mice. The coconut oil acid diethanolamine condensate used for the present studies 

contained 18.2% free diethanolamine by weight. 

Therefore, mice in this study were exposed to 18.2 or 

36.4 mg free diethanolamine/kg body weight. 

The weakest positive response occurred in the lauric 

acid diethanolamine condensate study (NTP, 1999b), 

in which the incidences of hepatocellular neoplasms 

were increased only in female mice. Moreover, 

although the combined incidences of hepatocellular 

adenoma or carcinoma in dosed female mice were 

significantly greater than that in the vehicle controls, 

the incidences of hepatocellular adenoma or hepatocellular carcinoma alone were not significantly 

increased in 200 mg/kg female mice. Also, survival 

of females was similar to that of the vehicle controls, 

and no response was observed in the kidney of dosed 

male mice. Lauric acid diethanolamine condensate 

contained 0.83% free diethanolamine by weight, and, 
 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 53 

therefore, mice in that study were exposed to 0.83 or 

1.66 mg free diethanolamine/kg body weight. 

No carcinogenic response occurred in the oleic acid 

diethanolamine condensate study (NTP, 1999c). The 

oleic acid diethanolamine condensate had a free diethanolamine content of 0.19%, less than the 0.83% for 

lauric acid diethanolamine condensate. Also, mice 

were given doses of only 15 or 30 mg oleic acid 

diethanolamine condensate/kg body weight, compared 

to the other studies in which mice were administered 

100 or 200 mg of the diethanolamide/kg body weight. 

Therefore, mice in the oleic acid diethanolamine 

condensate study were exposed to 0.028 or 0.056 mg 

free diethanolamine/kg body weight, the lowest concentration in any of the four studies. 

To quantify the association between the incidence of 

hepatocellular neoplasms and diethanolamine concentration, a logistic regression model was fitted to 

individual animal neoplasm incidences and survival 

data from the four studies. The model predicts the 

incidence of hepatocellular neoplasms as a function of 

diethanolamine dose (mg/kg) and survival (days). 

This analysis compares observed liver neoplasm rates 

in female mice with the rates predicted by the logistic 

regression model (Figure 5). The close agreement 

between observed and predicted rates strongly 

supports the conclusion that the liver neoplasm 

response in the diethanolamine study and the three 

diethanolamine condensate studies is determined 

primarily by the concentration of free diethanolamine. 

The composition and purity of the bulk diethanolamide preparations used in these studies varied 

considerably. Lauric acid diethanolamine condensate 

was approximately 90% lauric acid diethanolamine 

condensate, 0.83% free diethanolamine, and 9.17% 

other organic impurities. Oleic acid diethanolamine 

condensate was 47.5% oleic acid diethanolamine 

condensate, 0.19% free diethanolamine, approximately 30% other fatty acid alkanolamides, and 

23.31% other organic impurities (most probably 

unreacted fatty acids). Coconut oil itself is a fatty 

acids mixture, which typically contains as much as 

40% lauric acid, and this was reflected in the composition of coconut oil acid diethanolamine condensate, 

in which lauric acid diethanolamine condensate was 

the major constituent. With animals exposed to preparations of such widely varying diethanolamide 

composition, it seems improbable that the strong 

correlation between liver neoplasm response and 

diethanolamine content could have occurred by chance 

or that the response that occurred in the diethanolamide studies would involve the same species, 

gender, and target tissues as observed for 100% 

diethanolamine. 

Absorption, distribution, and metabolism studies of 

lauric acid diethanolamine condensate revealed that 

this diethanolamide is well absorbed after dermal 

exposure or oral administration and eliminated 

primarily in the urine as the half amides of succinic 

and adipic acid (Matthews et al., 1996). No parent 

diethanolamide, diethanolamine, or diethanolaminederived metabolites were detected in urine even after 

oral doses of 1,000 mg/kg. This suggests that lauric 

acid diethanolamine condensate metabolism involves 

T-hydroxylation followed by $-oxidation to half 

amides that are eliminated in urine. Therefore, no 

additional bioavailable diethanolamine was released as 

a result of metabolic cleavage of the amide linkage, 

specifically for lauric acid diethanolamine condensate 

and quite likely for coconut oil diethanolamine 

condensate and oleic acid diethanolamine condensate. 

The results of the diethanolamine study and the other 

diethanolamine condensate studies are consistent with 

an association between the increased incidences of 

hepatocellular neoplasms in male and female mice, the 

increased incidences of renal tubule neoplasms in 

male mice, and the presence of free, unreacted 

diethanolamine. 

The incidences of thyroid gland follicular cell 

hyperplasia were increased in male and female mice 

in the coconut oil acid diethanolamine condensate 

study. Similar increases in the incidences of thyroid 

gland follicular cell hyperplasia occurred in male and 

female mice in the diethanolamine study and in male 

mice in the lauric acid diethanolamine condensate 

study; no increase in the incidences of follicular cell 

hyperplasia occurred in male or female mice in the 
5 4 C o c o nut Oil Acid Diethanolamine Condensat e, NTP TR 479 

F i g u re 5 

O b s e rved and Predicted Liver Neoplasm Incidences in Female B6C3F1 Mice as a Function of Dose and Surv iva l 

(• = Observed, ---- = Predicted). Predicted rates are based on the logistic regression model, P=1/[1+ex p ( T ) ] , 

wh e re P is the pro b ability of observing a neoplasm. For carcinoma, T = 3 . 2 4 2 5 – 0 . 2 9 2 0 D – 0 . 0 0 2 2 6 S, and fo r 

a d e n o m a / c a rcinoma, T = 6 . 3 8 2 0 – 0 . 6 8 2 2 D – 0 . 0 0 9 7 9 S, wh e re D = d o s e1 / 2 in mg diethanolamine/kg body we i g h t 

and S = s u rv ival in day s. 
 

__________ 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 55 

oleic acid diethanolamine condensate study. Therefore, increased incidences of follicular cell 

hyperplasia also appear to be associated with dermal 

exposure to diethanolamine. 

CONCLUSIONS 

Under the conditions of these 2-year dermal studies, 

there was no evidence of carcinogenic activity* of 

coconut oil acid diethanolamine condensate in male 

F344/N rats administered 50 or 100 mg/kg. There 

was equivocal evidence of carcinogenic activity in 

female F344/N rats based on a marginal increase in 

the incidences of renal tubule neoplasms. There was 

clear evidence of carcinogenic activity in male 

B6C3F1 mice based on increased incidences of hepatic 

and renal tubule neoplasms and in female B6C3F1 

mice based on increased incidences of hepatic 

neoplasms. These increases were associated with the 

concentration of free diethanolamine present as a 

contaminant in the diethanolamine condensate. 

Exposure of rats to coconut oil acid diethanolamine 

condensate by dermal application in ethanol for 

2 years resulted in epidermal hyperplasia, sebaceous 

gland hyperplasia, hyperkeratosis, and parakeratosis 

in males and females and ulcer in females at the site 

of application. There were increases in the incidences 

of chronic inflammation, epithelial hyperplasia, and 

epithelial ulcer in the forestomach of female rats. The 

severities of nephropathy in dosed female rats were 

increased. 

Exposure of mice to coconut oil acid diethanolamine 

condensate by dermal application for 2 years resulted 

in increased incidences of eosinophilic foci of the liver 

in males. Increased incidences of epidermal hyperplasia, sebaceous gland hyperplasia, and hyperkeratosis in males and females, ulcer in males, and 

parakeratosis and inflammation in females at the site 

of application and of follicular cell hyperplasia in the 

thyroid gland of males and females were chemical 

related. 

* 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. 
56 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 
 

 

 

 

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Service, NIH, Bethesda, MD. 
 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 59 

National Toxicology Program (NTP) (1987). 

Technical Protocol for Sperm Morphology and 

Vaginal Cytology Evaluations in Toxicity Testing for 

Rats and Mice. 10/31/82 version (updated December 

1987). Research Triangle Park, NC. 

National Toxicology Program (NTP) (1999a). 

Toxicology and Carcinogenesis Studies of 

Diethanolamine (CAS No. 111-42-2) in F344/N Rats 

and B6C3F1 Mice (Dermal Studies). Technical 

Report Series No. 478. NIH Publication 

No. 99-3968. U.S. Department of Health and Human 

Services, Public Health Service, National Institutes of 

Health, Research Triangle Park, NC. 

National Toxicology Program (NTP) (1999b). 

Toxicology and Carcinogenesis Studies of Lauric 

Acid Diethanolamine Condensate (CAS No. 120-40-1) 

in F344/N Rats and B6C3F1 Mice (Dermal Studies). 

Technical Report Series No. 480. NIH Publication 

No. 99-3970. U.S. Department of Health and Human 

Services, Public Health Service, National Institutes of 

Health, Research Triangle Park, NC. 

National Toxicology Program (NTP) (1999c). 

Toxicology and Carcinogenesis Studies of Oleic Acid 

Diethanolamine Condensate (CAS No. 93-83-4) in 

F344/N Rats and B6C3F1 Mice (Dermal Studies). 

Technical Report Series No. 481. NIH Publication 

No. 99-3971. U.S. Department of Health and Human 

Services, Public Health Service, National Institutes of 

Health, Research Triangle Park, NC. 

Nurse, D.S. (1980). Sensitivity to coconut 

diethanolamide. Contact Dermatitis 6, 502. 

Piegorsch, W.W., and Bailer, A.J. (1997). Statistics 

for Environmental Biology and Toxicology, 

Section 6.3.2. Chapman and Hall, London. 

Pinola, A., Estlander, T., Jolanki, R., Tarvainen, K., 

and Kanerva, L. (1993). Occupational allergic 

contact dermatitis due to coconut diethanolamide 

(cocamide DEA). Contact Dermatitis 29, 262-265. 

Portier, C.J., and Bailer, A.J. (1989). Testing for 

increased carcinogenicity using a survival-adjusted 

quantal response test. Fundam. Appl. Toxicol. 12, 

731-737. 

Portier, C.J., Hedges, J.C., and Hoel, D.G. (1986). 

Age-specific models of mortality and tumor onset for 

historical control animals in the National Toxicology 

Program’s carcinogenicity experiments. Cancer Res. 

46, 4372-4378. 

Shelby, M.D., and Witt, K.L. (1995). Comparison 

of results from mouse bone marrow chromosome 

aberration and micronucleus tests. Environ. Mol. 

Mutagen. 25, 302-313. 

Shelby, M.D., Erexson, G.L., Hook, G.J., and 

Tice, R.R. (1993). Evaluation of a three-exposure 

mouse bone marrow micronucleus protocol: Results 

with 49 chemicals. Environ. Mol. Mutagen. 21, 

160-179. 

Shirley, E. (1977). A non-parametric equivalent of 

Williams’ test for contrasting increasing dose levels of 

a treatment. Biometrics 33, 386-389. 

Source Book for Food Scientists (1978). (H.W. 

Ockerman, Ed.) p. 471. AVI Publishing Co., Inc., 

Westport, CT. 

Straus, D.S. (1981). Somatic mutation, cellular 

differentiation, and cancer causation. JNCI 67, 

233-241. 

Tarone, R.E. (1975). Tests for trend in life table 

analysis. Biometrika 62, 679-682. 

Tennant, R.W., Margolin, B.H., Shelby, M.D., 

Zeiger, E., Haseman, J.K., Spalding, J., 

Caspary, W., Resnick, M., Stasiewicz, S., 

Anderson, B., and Minor, R. (1987). Prediction of 

chemical carcinogenicity in rodents from in vitro 

genetic toxicity assays. Science 236, 933-941. 

Williams, D.A. (1971). A test for differences 

between treatment means when several dose levels are 

compared with a zero dose control. Biometrics 27, 

103-117. 

Williams, D.A. (1972). The comparison of several 

dose levels with a zero dose control. Biometrics 28, 

519-531. 
60 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

Zeiger, E., Anderson, B., Haworth, S., Lawlor, T., Zeiger, E., Haseman, J.K., Shelby, M.D., 

and Mortelmans, K. (1988). Salmonella mutagenicity Margolin, B.H., and Tennant, R.W. (1990). 

test: IV. Results from the testing of 300 chemicals. Evaluation of four in vitro genetic toxicity tests for 

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earlier results with 41 additional chemicals. Environ. 

Mol. Mutagen. 16 (Suppl. 18), 1-14. 
61 

APPENDIX A
 

SUMMARY OF LESIONS IN MALE RATS
 

IN THE 2-YEAR DERMAL STUDY
 

OF COCONUT OIL ACID
 

DIETHANOLAMINE CONDENSATE
 

TABLE A1 Summary of the Incidence of Neoplasms in Male Rats 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ......... 63 
 

TABLE A2 Individual Animal Tumor Pathology of Male Rats 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ......... 66 
 

TABLE A3 Statistical Analysis of Primary Neoplasms in Male Rats 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ......... 78 
 

TABLE A4 Historical Incidence of Renal Tubule Neoplasms in Vehicle Control Male F344/N Rats ... 83 
 

TABLE A5 Summary of the Incidence of Nonneoplastic Lesions in Male Rats
 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ......... 84 
 
62 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 63 

TABLE A1 

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 50 mg/kg 100 mg/kg 

Disposition Summary 

Animals initially in study 50 50 50 

Early deaths 

Accidental death 1 

Moribund 28 27 25 

Natural deaths 13 11 14 

Survivors 

Terminal sacrifice 8 12 11 

Animals examined microscopically 50 50 50 

Alimentary System 

Esophagus (50) (50) (50) 

Thymoma malignant, metastatic, thymus 1 (2%) 

Intestine large, colon (50) (50) (50) 

Polyp adenomatous 1 (2%) 1 (2%) 

Intestine small, ileum (50) (50) (50) 

Liver (50) (50) (50) 

Mesentery (8) (7) (6) 

Fat, fibrosarcoma 1 (14%) 

Oral mucosa (1) (2) (2) 

Gingival, squamous cell carcinoma 1 (50%) 

Pharyngeal, squamous cell papilloma 1 (100%) 

Pancreas (50) (50) (50) 

Acinus, adenoma 1 (2%) 

Salivary glands (50) (50) (50) 

Stomach, forestomach (50) (50) (50) 

Squamous cell papilloma 3 (6%) 1 (2%) 

Squamous cell papilloma, multiple 1 (2%) 

Stomach, glandular (50) (50) (50) 

Cardiovascular System 

Heart (50) (50) (50) 

Endocrine System 

Adrenal cortex (50) (50) (50) 

Adenoma 1 (2%) 

Adrenal medulla (50) (50) (50) 

Ganglioneuroma 1 (2%) 

Pheochromocytoma malignant 1 (2%) 

Pheochromocytoma benign 6 (12%) 4 (8%) 5 (10%) 

Bilateral, pheochromocytoma benign 1 (2%) 1 (2%) 

Islets, pancreatic (50) (50) (50) 

Adenoma 3 (6%) 4 (8%) 3 (6%) 

Pituitary gland (50) (50) (49) 

Sarcoma, metastatic, brain 1 (2%) 

Pars distalis, adenoma 37 (74%) 39 (78%) 36 (73%) 

Thyroid gland (50) (50) (50) 

C-cell, adenoma 3 (6%) 4 (8%) 4 (8%) 

C-cell, carcinoma 1 (2%) 

Follicular cell, adenoma 3 (6%) 1 (2%) 

Follicular cell, carcinoma 2 (4%) 1 (2%) 
 

 

64 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A1 

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

General Body System 

Peritoneum (1) 

Genital System 

Epididymis 

Preputial gland 

Adenoma 

Carcinoma 

Bilateral, adenoma 

Prostate 

Carcinoma 

Seminal vesicle 

Testes 

Bilateral, interstitial cell, adenoma 

Interstitial cell, adenoma 

(50) 

(50) 

1 (2%) 

2 (4%) 

(50) 

(50) 

11 (22%) 

12 (24%) 

(50) 

(50) 

2 (4%) 

1 (2%) 

(50) 

(50) 

(50) 

9 (18%) 

11 (22%) 

(50) 

(50) 

1 (2%) 

2 (4%) 

(50) 

(50) 

(50) 

12 (24%) 

7 (14%) 

(50) 

Hematopoietic System 

Bone marrow 

Lymph node 

Mediastinal, fibrosarcoma, metastatic, skin 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Hemangiosarcoma 

Thymus 

Thymoma malignant 

(50) 

(35) 

(50) 

(49) 

(50) 

(50) 

(30) 

1 (3%) 

(50) 

(50) 

(50) 

1 (2%) 

(47) 

(50) 

(37) 

(50) 

(50) 

(50) 

(45) 

1 (2%) 

(48) 

Integumentary System 

Mammary gland 

Adenoma 

Carcinoma 

Fibroadenoma 

Skin 

Basal cell carcinoma 

Keratoacanthoma 

Squamous cell papilloma 

Trichoepithelioma 

Pinna, squamous cell papilloma 

Sebaceous gland, carcinoma 

Sebaceous gland, skin, site of application, adenoma 

Skin, site of application, basal cell adenoma 

Skin, site of application, basal cell carcinoma 

Skin, site of application, keratoacanthoma 

Subcutaneous tissue, fibroma 

Subcutaneous tissue, fibrosarcoma 

Subcutaneous tissue, skin, site of application,

 fibrosarcoma 

(48) 

1 (2%) 

2 (4%) 

(50) 

1 (2%) 

2 (4%) 

1 (2%) 

1 (2%) 

1 (2%) 

1 (2%) 

3 (6%) 

(49) 

1 (2%) 

1 (2%) 

(50) 

4 (8%) 

1 (2%) 

1 (2%) 

1 (2%) 

1 (2%) 

2 (4%) 

3 (6%) 

2 (4%) 

(50) 

1 (2%) 

1 (2%) 

(50) 

1 (2%) 

1 (2%) 

1 (2%) 

1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) 

Osteosarcoma 1 (2%) 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 65 

TABLE A1 

Summary of the Incidence of Neoplasms in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Nervous System 

Brain 

Cranial nerve, schwannoma malignant 

Meninges, sarcoma 

(50) 

1 (2%) 

1 (2%) 

(50) (50) 

Respiratory System 

Lung 

Thymoma malignant, metastatic, thymus 

Nose 

Squamous cell carcinoma 

(50) 

(50) 

(50) 

(50) 

(50) 

1 (2%) 

(50) 

1 (2%) 

Special Senses System 

Zymbal’s gland 

Carcinoma 

(1) 

1 (100%) 

(2) 

2 (100%) 

Urinary System 

Kidney 

Lipoma 

Thymoma malignant, metastatic, thymus 

Renal tubule, adenoma 

Renal tubule, adenoma, multiple 

Renal tubule, carcinoma 

Urinary bladder 

(50) 

3 (6%) 

(50) 

(50) 

1 (2%) 

4 (8%)

2 (4%) 

1 (2%) 

(50) 

(50) 

1 (2%) 

3 (6%) 

(50) 

Systemic Lesions 

Multiple organsb 

Leukemia granulocytic 

Leukemia mononuclear 

Mesothelioma malignant 

(50) 

16 (32%) 

2 (4%) 

(50) 

1 (2%) 

10 (20%) 

1 (2%) 

(50) 

12 (24%) 

1 (2%) 

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 

49 

119 

48 

92 

25 

27 

1 

1 

49 

125 

49 

101 

20 

24 

1 

1 

49 

101 

47 

78 

21 

23 

1 

3 

a Number of animals examined microscopically at the site and the number of animals with neoplasm b Number of animals with any tissue examined microscopically 

Primary neoplasms: all neoplasms except metastatic neoplasms c 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

66 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

1333444444555555555555666 

Number of Days on Study 1389456679224456688899001 

0492283705160361333913377 

0000000000000000000000000 

Carcass ID Number 2331021233044224124202241 

7136443686193592438860268 

Alimentary System 

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

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

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

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

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

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

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

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

Mesentery + + + + 

Oral mucosa + 

Pharyngeal, squamous cell papilloma X 

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

Acinus, adenoma 

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

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

Squamous cell papilloma X 

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

Cardiovascular System 

Blood vessel 

Heart 

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

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

Endocrine System 

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

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

Pheochromocytoma benign X 

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

Adenoma X 

Parathyroid gland ++M++++M+++++++++++++++++ 

Pituitary gland +++++++++++++++++++++++++ 

Sarcoma, metastatic, brain X 

Pars distalis, adenoma XXXXXXXX XXXXXX XXXXXX 

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

C-cell, adenoma X 

Follicular cell, carcinoma X 

General Body System 

None 

Genital System 

Epididymis +++++++++++++++++++++++++ 

Penis + 

Preputial gland +++++++++++++++++++++++++ 

Bilateral, adenoma 

Prostate +++++++++++++++++++++++++ 

Carcinoma 

Seminal vesicle +++++++++++++++++++++++++ 

Testes +++++++++++++++++++++++++ 

Bilateral, interstitial cell, adenoma X X X 

Interstitial cell, adenoma X X X X 

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

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

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 67 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

Number of Days on Study 

6666666666667777777777777 

1123344556780011222222222 

8811202068702533399999999 

Carcass ID Number 

0000000000000000000000000 

0310013104035413301123444 

7292514037890020795715145 

Total 

Tissues/ 

Tumors 

Alimentary System 

Esophagus 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Mesentery

Oral mucosa 

Pharyngeal, squamous cell papilloma 

Pancreas 

Acinus, adenoma

Salivary glands 

Stomach, forestomach 

Squamous cell papilloma

Stomach, glandular 

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

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

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

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

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

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

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

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

+ + + + 

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

X 

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

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

X X 

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

50 

50 

50 

50 

50 

50 

50 

50 

8 

1 

1 

50 

1 

50 

50 

3 

50 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma benign XXX X X 6 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X X 3 

Parathyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 48 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Sarcoma, metastatic, brain 1 

Pars distalis, adenoma X X X X X X X X X X X X X X X X X 37 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, adenoma X X 3 

Follicular cell, carcinoma X 2 

General Body System 

None 

Genital System 

Epididymis +++++++++++++++++++++++++ 50 

Penis 1 

Preputial gland +++++++++++++++++++++++++ 50 

Bilateral, adenoma X 1 

Prostate +++++++++++++++++++++++++ 50 

Carcinoma X X 2 

Seminal vesicle +++++++++++++++++++++++++ 50 

Testes +++++++++++++++++++++++++ 50 

Bilateral, interstitial cell, adenoma X X X XXXX X 11 

Interstitial cell, adenoma X X X XX X X X 12 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

68 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

1333444444555555555555666 

Number of Days on Study 1389456679224456688899001 

0492283705160361333913377 

0000000000000000000000000 

Carcass ID Number 2331021233044224124202241 

7136443686193592438860268 

Hematopoietic System 

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

Lymph node + + + +++++++++++ + +++ 

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

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

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

Thymus +M+++++++++++++++++++MM++ 

Integumentary System 

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

Adenoma X 

Fibroadenoma 

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

Basal cell carcinoma 

Keratoacanthoma X 

Squamous cell papilloma 

Sebaceous gland, skin, site of application, adenoma X 

Skin, site of application, basal cell carcinoma X 

Skin, site of application, keratoacanthoma 

Subcutaneous tissue, fibroma X 

Musculoskeletal System 

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

Nervous System 

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

Cranial nerve, schwannoma malignant X 

Meninges, sarcoma X 

Peripheral nerve + 

Spinal cord + 

Respiratory System 

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

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

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

Special Senses System 

Eye 

Zymbal’s gland + 

Carcinoma X 

Urinary System 

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

Renal tubule, adenoma X 

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

Systemic Lesions 

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

Leukemia mononuclear XXX XX X 

Mesothelioma malignant X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 69 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

6666666666667777777777777 

Number of Days on Study 1123344556780011222222222 

8811202068702533399999999 

0000000000000000000000000 Total 

Carcass ID Number 0310013104035413301123444 Tissues/ 

7292514037890020795715145 Tumors 

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++ 50 

Lymph node + + ++++++++ ++++++ + 35 

Lymph node, mandibular +++++++++++++++++++++++++ 50 

Lymph node, mesenteric +++++++++M+++++++++++++++ 49 

Spleen +++++++++++++++++++++++++ 50 

Thymus +++++++++++++++++++++++++ 47 

Integumentary System 

Mammary gland +++++++++++M+++M+++++++++ 48 

Adenoma 1 

Fibroadenoma X X 2 

Skin +++++++++++++++++++++++++ 50 

Basal cell carcinoma X 1 

Keratoacanthoma X 2 

Squamous cell papilloma X 1 

Sebaceous gland, skin, site of application, adenoma 

1 

Skin, site of application, basal cell carcinoma 1 

Skin, site of application, keratoacanthoma X 1 

Subcutaneous tissue, fibroma X X 3 

Musculoskeletal System 

Bone +++++++++++++++++++++++++ 50 

Nervous System 

Brain +++++++++++++++++++++++++ 50 

Cranial nerve, schwannoma malignant 1 

Meninges, sarcoma 1 

Peripheral nerve + + 3 

Spinal cord + + 3 

Respiratory System 

Lung +++++++++++++++++++++++++ 50 

Nose +++++++++++++++++++++++++ 50 

Trachea +++++++++++++++++++++++++ 50 

Special Senses System 

Eye + + 2 

Zymbal’s gland 1 

Carcinoma 1 

Urinary System 

Kidney +++++++++++++++++++++++++ 50 

Renal tubule, adenoma X X 3 

Urinary bladder +++++++++++++++++++++++++ 50 

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++ 50 

Leukemia mononuclear XXXXX X X XX X 16 

Mesothelioma malignant X 2 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

70 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 50 mg/kg 

3444455555555555566666666 

Number of Days on Study 8479912235677788801111222 

0445913948145906901177001 

0000000000000000000000000 

Carcass ID Number 8758775776979575586956668 

3594268714495634272830598 

Alimentary System 

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

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

Polyp adenomatous 

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

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

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

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

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

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

Mesentery + + 

Fat, fibrosarcoma 

Oral mucosa + 

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

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

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

Squamous cell papilloma, multiple 

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

Cardiovascular System 

Blood vessel 

Heart 

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

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

Endocrine System 

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

Adenoma X 

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

Ganglioneuroma X 

Pheochromocytoma malignant 

Pheochromocytoma benign X 

Bilateral, pheochromocytoma benign X 

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

Adenoma X 

Parathyroid gland +M+++++++++++++++++++++++ 

Pituitary gland +++++++++++++++++++++++++ 

Pars distalis, adenoma XXX XX XXXXXXXXXXXX XXX 

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

C-cell, adenoma X 

Follicular cell, adenoma 

General Body System 

Peritoneum 

Genital System 

Coagulating gland + 

Epididymis +++++++++++++++++++++++++ 

Preputial gland +++++++++++++++++++++++++ 

Adenoma X 

Carcinoma X 

Prostate +++++++++++++++++++++++++ 

Seminal vesicle +++++++++++++++++++++++++ 

Testes +++++++++++++++++++++++++ 

Bilateral, interstitial cell, adenoma 

Interstitial cell, adenoma X X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 71 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 50 mg/kg 

6666666777777777777777777 

Number of Days on Study 2557789011222222222222222 

6660765803058999999999999 

0000000000000000000000001 Total 

Carcass ID Number 5888989999579566666778890 Tissues/ 

7695310692107513678480210 Tumors 

Alimentary System 

Esophagus +++++++++++++++++++++++++ 50 

Intestine large, colon +++++++++++++++++++++++++ 50 

Polyp adenomatous X 1 

Intestine large, rectum +++++++++++++++++++++++++ 50 

Intestine large, cecum +++++++++++++++++++++++++ 50 

Intestine small, duodenum +++++++++++++++++++++++++ 50 

Intestine small, jejunum +++++++++++++++++++++++++ 50 

Intestine small, ileum +++++++++++++++++++++++++ 50 

Liver +++++++++++++++++++++++++ 50 

Mesentery + + + ++ 7 

Fat, fibrosarcoma X 1 

Oral mucosa + 2 

Pancreas +++++++++++++++++++++++++ 50 

Salivary glands +++++++++++++++++++++++++ 50 

Stomach, forestomach +++++++++++++++++++++++++ 50 

Squamous cell papilloma, multiple X 1 

Stomach, glandular +++++++++++++++++++++++++ 50 

Cardiovascular System 

Blood vessel +++++++++++++++++++++++++ 50 

Heart +++++++++++++++++++++++++ 50 

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++ 50 

Adenoma 1 

Adrenal medulla +++++++++++++++++++++++++ 50 

Ganglioneuroma 1 

Pheochromocytoma malignant X 1 

Pheochromocytoma benign X X X 4 

Bilateral, pheochromocytoma benign 1 

Islets, pancreatic +++++++++++++++++++++++++ 50 

Adenoma X X X 4 

Parathyroid gland ++++M++++++M+++++++++M+++ 46 

Pituitary gland +++++++++++++++++++++++++ 50 

Pars distalis, adenoma XX XXXX XXXXXXX XX XXXX 39 

Thyroid gland +++++++++++++++++++++++++ 50 

C-cell, adenoma X X X 4 

Follicular cell, adenoma X X X 3 

General Body System 

Peritoneum + 1 

Genital System 

Coagulating gland + + 3 

Epididymis +++++++++++++++++++++++++ 50 

Preputial gland +++++++++++++++++++++++++ 50 

Adenoma X 2 

Carcinoma 1 

Prostate +++++++++++++++++++++++++ 50 

Seminal vesicle +++++++++++++++++++++++++ 50 

Testes +++++++++++++++++++++++++ 50 

Bilateral, interstitial cell, adenoma XX X X XXX XX 9 

Interstitial cell, adenoma X X X X X 11 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

72 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 50 mg/kg 

3444455555555555566666666 

Number of Days on Study 8479912235677788801111222 

0445913948145906901177001 

0000000000000000000000000 

Carcass ID Number 8758775776979575586956668 

3594268714495634272830598 

Hematopoietic System 

Bone marrow 

Lymph node 

Mediastinal, fibrosarcoma, 

metastatic, skin 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Hemangiosarcoma

Thymus 

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

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

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

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

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

X 

++++M+M++++++++M+++++++++ 

Integumentary System 

Mammary gland 

Carcinoma 

Fibroadenoma 

Skin 

Keratoacanthoma

Squamous cell papilloma

Pinna, squamous cell papilloma 

Sebaceous gland, carcinoma

Skin, site of application, basal cell adenoma 

Skin, site of application, keratoacanthoma 

Subcutaneous tissue, fibroma 

Subcutaneous tissue, fibrosarcoma 

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

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

X 

X 

X 

Musculoskeletal System 

Bone 

Osteosarcoma 

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

Nervous System 

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

Respiratory System 

Lung 

Nose 

Trachea 

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

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

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

Special Senses System 

Eye 

Zymbal’s gland

Carcinoma

 +

 X

 + 

X 

Urinary System 

Kidney 

Lipoma 

Renal tubule, adenoma

Renal tubule, adenoma, multiple 

Renal tubule, carcinoma 

Urinary bladder 

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

X 

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

Systemic Lesions 

Multiple organs 

Leukemia granulocytic

Leukemia mononuclear

Mesothelioma malignant 

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

X 

X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 73 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 50 mg/kg 

6666666777777777777777777 

Number of Days on Study 2557789011222222222222222 

6660765803058999999999999 

0000000000000000000000001 Total 

Carcass ID Number 5888989999579566666778890 

7695310692107513678480210 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow 

Lymph node 

Mediastinal, fibrosarcoma, 

metastatic, skin

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Hemangiosarcoma 

Thymus 

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

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

X 

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

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

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

+++M++++M++++++++++++++++ 

50 

30 

1 

50 

50 

50 

1 

45 

Integumentary System 

Mammary gland 

Carcinoma

Fibroadenoma

Skin 

Keratoacanthoma

Squamous cell papilloma 

Pinna, squamous cell papilloma

Sebaceous gland, carcinoma 

Skin, site of application, basal cell adenoma

Skin, site of application, keratoacanthoma 

Subcutaneous tissue, fibroma 

Subcutaneous tissue, fibrosarcoma

++++++++++M++++++++++++++ 

X 

X 

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

X X X 

X 

X 

X X 

X X X 

X X 

49 

1 

1 

50 

4 

1 

1 

1 

1 

2 

3 

2 

Musculoskeletal System 

Bone 

Osteosarcoma

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

X 

50 

1 

Nervous System 

Brain +++++++++++++++++++++++++ 50 

Respiratory System 

Lung 

Nose 

Trachea 

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

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

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

50 

50 

50 

Special Senses System 

Eye

Zymbal’s gland 

Carcinoma 

+ + + 3 

2 

2 

Urinary System 

Kidney 

Lipoma

Renal tubule, adenoma

Renal tubule, adenoma, multiple

Renal tubule, carcinoma

Urinary bladder 

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

X 

X X X 

X X 

X 

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

50 

1 

4 

2 

1 

50 

Systemic Lesions 

Multiple organs 

Leukemia granulocytic 

Leukemia mononuclear

Mesothelioma malignant

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

X X X X X 

X 

50 

1 

10 

1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

74 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

3344455555555555566666666 

Number of Days on Study 2827800256666788900222234 

9914558920025926377016720 

1111111111111111111111111 

Carcass ID Number 2443301210210011402323134 

8761462387973894394775505 

Alimentary System 

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

Thymoma malignant, metastatic, thymus X 

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

Polyp adenomatous 

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

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

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

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

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

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

Mesentery + ++ + 

Oral mucosa 

Gingival, squamous cell carcinoma 

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

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

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

Squamous cell papilloma X 

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

Cardiovascular System 

Blood vessel 

Heart 

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

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

Endocrine System 

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

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

Pheochromocytoma benign X X 

Bilateral, pheochromocytoma benign 

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

Adenoma 

Parathyroid gland M+++++M++++++++++++++++++ 

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

Pars distalis, adenoma X X XXXXXXX XXXXXXXXXX XX 

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

C-cell, adenoma X 

C-cell, carcinoma 

Follicular cell, adenoma 

Follicular cell, carcinoma 

General Body System 

None 

Genital System 

Epididymis +++++++++++++++++++++++++ 

Preputial gland +++++++++++++++++++++++++ 

Adenoma X 

Carcinoma X 

Prostate +++++++++++++++++++++++++ 

Seminal vesicle +++++++++++++++++++++++++ 

Testes +++++++++++++++++++++++++ 

Bilateral, interstitial cell, adenoma X X X X 

Interstitial cell, adenoma X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 75 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

Number of Days on Study 

6666666666777777777777777 

5677889999001122222222222 

6647780588121999999999999 

Carcass ID Number 

1111111111111111111111111 

4343002424141300112223345 

4882146011320925160253690 

Total 

Tissues/ 

Tumors 

Alimentary System 

Esophagus 

Thymoma malignant, metastatic, thymus 

Intestine large, colon 

Polyp adenomatous

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Mesentery

Oral mucosa

Gingival, squamous cell carcinoma

Pancreas 

Salivary glands 

Stomach, forestomach 

Squamous cell papilloma 

Stomach, glandular 

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

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

X 

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

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

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

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

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

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

+ + 

+ + 

X 

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

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

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

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

50 

1 

50 

1 

50 

50 

50 

49 

50 

50 

6 

2 

1 

50 

50 

50 

1 

50 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma benign X X X 5 

Bilateral, pheochromocytoma benign X 1 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X X X 3 

Parathyroid gland + + + + M + + + + + + + + + + + + + M + M + + + + 45 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pars distalis, adenoma XXX XXXXXXX XXXXX 36 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, adenoma X X X 4 

C-cell, carcinoma X 1 

Follicular cell, adenoma X 1 

Follicular cell, carcinoma X 1 

General Body System 

None 

Genital System 

Epididymis +++++++++++++++++++++++++ 50 

Preputial gland +++++++++++++++++++++++++ 50 

Adenoma 1 

Carcinoma X 2 

Prostate +++++++++++++++++++++++++ 50 

Seminal vesicle +++++++++++++++++++++++++ 50 

Testes +++++++++++++++++++++++++ 50 

Bilateral, interstitial cell, adenoma X X X X XX X X 12 

Interstitial cell, adenoma X X X X X X 7 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

76 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

Number of Days on Study 

3344455555555555566666666 

2827800256666788900222234 

9914558920025926377016720 

Carcass ID Number 

1111111111111111111111111 

2443301210210011402323134 

8761462387973894394775505 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Thymus 

Thymoma malignant

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

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

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

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

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

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

X 

Integumentary System 

Mammary gland 

Carcinoma 

Fibroadenoma

Skin 

Trichoepithelioma

Subcutaneous tissue, fibroma

Subcutaneous tissue, fibrosarcoma

Subcutaneous tissue, skin, site of application, 

fibrosarcoma 

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

X 

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

X 

X 

X 

Musculoskeletal System 

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

Nervous System 

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

Respiratory System 

Lung 

Thymoma malignant, metastatic, thymus

Nose 

Squamous cell carcinoma

Trachea 

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

X 

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

X 

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

Special Senses System 

Eye + + + 

Urinary System 

Kidney 

Thymoma malignant, metastatic, thymus

Renal tubule, adenoma 

Urinary bladder 

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

X 

X 

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

Systemic Lesions 

Multiple organs 

Leukemia mononuclear

Mesothelioma malignant

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

X X X X X 

X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 77 

TABLE A2 

Individual Animal Tumor Pathology of Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

Number of Days on Study 

6666666666777777777777777 

5677889999001122222222222 

6647780588121999999999999 

Carcass ID Number 

1111111111111111111111111 

4343002424141300112223345 

4882146011320925160253690 

Total 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Thymus 

Thymoma malignant 

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

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

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

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

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

M+++++M++++++++++++++++++ 

50 

37 

50 

50 

50 

48 

1 

Integumentary System 

Mammary gland 

Carcinoma

Fibroadenoma 

Skin 

Trichoepithelioma 

Subcutaneous tissue, fibroma 

Subcutaneous tissue, fibrosarcoma 

Subcutaneous tissue, skin, site of application, 

fibrosarcoma

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

X 

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

X 

50 

1 

1 

50 

1 

1 

1 

1 

Musculoskeletal System 

Bone +++++++++++++++++++++++++ 50 

Nervous System 

Brain +++++++++++++++++++++++++ 50 

Respiratory System 

Lung 

Thymoma malignant, metastatic, thymus 

Nose 

Squamous cell carcinoma 

Trachea 

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

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

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

50 

1 

50 

1 

50 

Special Senses System 

Eye + + + + + 8 

Urinary System 

Kidney 

Thymoma malignant, metastatic, thymus 

Renal tubule, adenoma 

Urinary bladder 

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

X X 

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

50 

1 

3 

50 

Systemic Lesions 

Multiple organs 

Leukemia mononuclear

Mesothelioma malignant 

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

X X X XXX X 

50 

12 

1 
78 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Adrenal Medulla: Benign Pheochromocytoma 

Overall ratea 6/50 (12%) 5/50 (10%) 6/50 (12%)
 

Adjusted rateb 18.7% 14.0% 17.1%
 

Terminal ratec 1/8 (13%) 1/12 (8%) 4/11 (36%)
 

First incidence (days) 603 586 607
 

Poly-3 testd P=0.511N P=0.422N P=0.561N
 

Adrenal Medulla: Benign or Malignant Pheochromocytoma 

Overall rate 6/50 (12%) 6/50 (12%) 6/50 (12%)
 

Adjusted rate 18.7% 16.8% 17.1%
 

Terminal rate 1/8 (13%) 1/12 (8%) 4/11 (36%)
 

First incidence (days) 603 586 607
 

Poly-3 test P=0.503N P=0.545N P=0.561N
 

Kidney (Renal Tubule): Adenoma (Single Sections) 

Overall rate 3/50 (6%) 6/50 (12%) 3/50 (6%)
 

Adjusted rate 9.6% 17.1% 8.6%
 

Terminal rate 0/8 (0%) 2/12 (17%) 1/11 (9%)
 

First incidence (days) 593 620 565
 

Poly-3 test P=0.491N P=0.300 P=0.608N
 

Kidney (Renal Tubule): Adenoma (Step Sections) 

Overall rate 8/50 (16%) 8/50 (16%) 8/50 (16%)
 

Adjusted rate 24.6% 22.4% 22.2%
 

Terminal rate 1/8 (13%) 3/12 (25%) 3/11 (27%)
 

First incidence (days) 442 575 389
 

Poly-3 test P=0.472N P=0.530N P=0.524N
 

Kidney (Renal Tubule): Adenoma (Single and Step Sections) 

Overall rate 11/50 (22%) 10/50 (20%) 10/50 (20%)
 

Adjusted rate 32.9% 28.0% 27.4%
 

Terminal rate 1/8 (13%) 4/12 (33%) 4/11 (36%)
 

First incidence (days) 442 575 389
 

Poly-3 test P=0.358N P=0.425N P=0.403N
 

Kidney (Renal Tubule): Adenoma or Carcinoma (Single Sections) 

Overall rate 3/50 (6%) 7/50 (14%) 3/50 (6%)
 

Adjusted rate 9.6% 19.8% 8.6%
 

Terminal rate 0/8 (0%) 2/12 (17%) 1/11 (9%)
 

First incidence (days) 593 620 565
 

Poly-3 test P=0.480N P=0.207 P=0.608N
 

Kidney (Renal Tubule): Adenoma or Carcinoma (Step Sections) 

Overall rate 8/50 (16%) 9/50 (18%) 8/50 (16%)
 

Adjusted rate 24.6% 25.2% 22.2%
 

Terminal rate 1/8 (13%) 3/12 (25%) 3/11 (27%)
 

First incidence (days) 442 575 389
 

Poly-3 test P=0.465N P=0.590 P=0.524N
 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 79 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Kidney (Renal Tubule): Adenoma or Carcinoma (Single and Step Sections) 

Overall rate 11/50 (22%) 11/50 (22%) 10/50 (20%)
 

Adjusted rate 32.9% 30.5% 27.4%
 

Terminal rate 1/8 (13%) 4/12 (33%) 4/11 (36%)
 

First incidence (days) 442 575 389
 

Poly-3 test P=0.354N P=0.520N P=0.403N
 

Mammary Gland: Fibroadenoma or Adenoma 

Overall rate 3/50 (6%) 1/50 (2%) 1/50 (2%)
 

Adjusted rate 9.8% 2.9% 2.9%
 

Terminal rate 2/8 (25%) 0/12 (0%) 0/11 (0%)
 

First incidence (days) 563 670 621
 

Poly-3 test P=0.182N P=0.260N P=0.261N
 

Mammary Gland: Fibroadenoma, Adenoma, or Carcinoma 

Overall rate 3/50 (6%) 2/50 (4%) 2/50 (4%)
 

Adjusted rate 9.8% 5.7% 5.8%
 

Terminal rate 2/8 (25%) 0/12 (0%) 1/11 (9%)
 

First incidence (days) 563 670 621
 

Poly-3 test P=0.367N P=0.442N P=0.445N
 

Pancreatic Islets: Adenoma 

Overall rate 3/50 (6%) 4/50 (8%) 3/50 (6%) 

Adjusted rate 9.7% 11.3% 8.8% 

Terminal rate 0/8 (0%) 2/12 (17%) 3/11 (27%) 

First incidence (days) 607 523 729 (T) 

Poly-3 test P=0.530N P=0.571 P=0.619N 

Pituitary Gland (Pars Distalis): Adenoma 

Overall rate 37/50 (74%) 39/50 (78%) 36/49 (73%)
 

Adjusted rate 80.8% 83.5% 77.6%
 

Terminal rate 5/8 (63%) 8/12 (67%) 6/11 (55%)
 

First incidence (days) 334 444 329
 

Poly-3 test P=0.392N P=0.472 P=0.451N
 

Preputial Gland: Adenoma or Carcinoma 

Overall rate 1/50 (2%) 3/50 (6%) 3/50 (6%) 

Adjusted rate 3.3% 8.5% 8.5% 

Terminal rate 1/8 (13%) 1/12 (8%) 0/11 (0%) 

First incidence (days) 729 (T) 611 552 

Poly-3 test P=0.307 P=0.362 P=0.362 

Skin: Keratoacanthoma 

Overall rate 3/50 (6%) 6/50 (12%) 0/50 (0%) 

Adjusted rate 9.6% 17.0% 0.0% 

Terminal rate 0/8 (0%) 3/12 (25%) 0/11 (0%) e First incidence (days) 467 600 —

Poly-3 test P=0.105N P=0.297 P=0.101N
 
80 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Skin: Squamous Cell Papilloma or Keratoacanthoma 

Overall rate 4/50 (8%) 8/50 (16%) 0/50 (0%)
 

Adjusted rate 12.7% 22.4% 0.0%
 

Terminal rate 1/8 (13%) 4/12 (33%) 0/11 (0%)
 

First incidence (days) 467 600 —
 

Poly-3 test P=0.059N P=0.234 P=0.047N
 

Skin: Squamous Cell Papilloma, Keratoacanthoma, Trichoepithelioma, Basal Cell Adenoma, or Basal Cell Carcinoma 

Overall rate 6/50 (12%) 9/50 (18%) 1/50 (2%)
 

Adjusted rate 18.6% 25.2% 2.9%
 

Terminal rate 2/8 (25%) 4/12 (33%) 0/11 (0%)
 

First incidence (days) 392 600 627
 

Poly-3 test P=0.043N P=0.358 P=0.041N
 

Skin (Subcutaneous Tissue): Fibroma 

Overall rate 3/50 (6%) 3/50 (6%) 1/50 (2%)
 

Adjusted rate 9.7% 8.6% 2.9%
 

Terminal rate 1/8 (13%) 1/12 (8%) 0/11 (0%)
 

First incidence (days) 603 626 485
 

Poly-3 test P=0.197N P=0.608N P=0.261N
 

Skin (Subcutaneous Tissue): Fibroma or Fibrosarcoma 

Overall rate 3/50 (6%) 5/50 (10%) 3/50 (6%)
 

Adjusted rate 9.7% 14.3% 8.4%
 

Terminal rate 1/8 (13%) 2/12 (17%) 0/11 (0%)
 

First incidence (days) 603 626 485
 

Poly-3 test P=0.490N P=0.422 P=0.597N
 

Stomach (Forestomach): Squamous Cell Papilloma 

Overall rate 3/50 (6%) 1/50 (2%) 1/50 (2%)
 

Adjusted rate 9.8% 2.9% 2.9%
 

Terminal rate 1/8 (13%) 1/12 (8%) 0/11 (0%)
 

First incidence (days) 617 729 (T) 552
 

Poly-3 test P=0.181N P=0.261N P=0.259N
 

Testes: Adenoma 

Overall rate 23/50 (46%) 20/50 (40%) 19/50 (38%)
 

Adjusted rate 63.6% 51.8% 50.8%
 

Terminal rate 5/8 (63%) 8/12 (67%) 9/11 (82%)
 

First incidence (days) 467 499 552
 

Poly-3 test P=0.147N P=0.192N P=0.169N
 

Thyroid Gland (C-cell): Adenoma 

Overall rate 3/50 (6%) 4/50 (8%) 4/50 (8%)
 

Adjusted rate 9.7% 11.3% 11.5%
 

Terminal rate 2/8 (25%) 1/12 (8%) 2/11 (18%)
 

First incidence (days) 526 621 579
 

Poly-3 test P=0.498 P=0.578 P=0.569
 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 81 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Thyroid Gland (C-cell): Adenoma or Carcinoma 

Overall rate 3/50 (6%) 4/50 (8%) 5/50 (10%)
 

Adjusted rate 9.7% 11.3% 14.3%
 

Terminal rate 2/8 (25%) 1/12 (8%) 3/11 (27%)
 

First incidence (days) 526 621 579
 

Poly-3 test P=0.353 P=0.578 P=0.424
 

Thyroid Gland (Follicular Cell): Adenoma 

Overall rate 0/50 (0%) 3/50 (6%) 1/50 (2%) 

Adjusted rate 0.0% 8.7% 2.9% 

Terminal rate 0/8 (0%) 3/12 (25%) 1/11 (9%) 

First incidence (days) — 729 (T) 729 (T) 

Poly-3 test P=0.452 P=0.142 P=0.525 

Thyroid Gland (Follicular Cell): Adenoma or Carcinoma 

Overall rate 2/50 (4%) 3/50 (6%) 2/50 (4%)
 

Adjusted rate 6.4% 8.7% 5.8%
 

Terminal rate 0/8 (0%) 3/12 (25%) 1/11 (9%)
 

First incidence (days) 521 729 (T) 701
 

Poly-3 test P=0.553N P=0.547 P=0.661N
 

All Organs: Mononuclear Cell Leukemia 

Overall rate 16/50 (32%) 10/50 (20%) 12/50 (24%)
 

Adjusted rate 45.0% 26.8% 32.3%
 

Terminal rate 3/8 (38%) 3/12 (25%) 3/11 (27%)
 

First incidence (days) 470 529 474
 

Poly-3 test P=0.155N P=0.075N P=0.181N
 

All Organs: Benign Neoplasms 

Overall rate 48/50 (96%) 49/50 (98%) 47/50 (94%)
 

Adjusted rate 99.3% 99.7% 97.5%
 

Terminal rate 8/8 (100%) 12/12 (100%) 11/11 (100%)
 

First incidence (days) 334 444 329
 

Poly-3 test P=0.297N P=0.991 P=0.543N
 

All Organs: Malignant Neoplasms 

Overall rate 25/50 (50%) 20/50 (40%) 21/50 (42%)
 

Adjusted rate 63.5% 51.6% 51.8%
 

Terminal rate 5/8 (63%) 6/12 (50%) 5/11 (46%)
 

First incidence (days) 392 529 389
 

Poly-3 test P=0.158N P=0.182N P=0.186N
 
82 

c 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A3 

Statistical Analysis of Primary Neoplasms in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

All Organs: Benign or Malignant Neoplasms 

Overall rate 49/50 (98%) 49/50 (98%) 49/50 (98%) 

Adjusted rate 100.0% 99.7% 98.4% 

Terminal rate 8/8 (100%) 12/12 (100%) 11/11 (100%) 

First incidence (days) 334 444 329 

Poly-3 test P=0.336N P=1.000N P=0.609N 

(T)Terminal sacrifice 

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for adrenal gland, 

kidney, pancreatic islets, pituitary gland, preputial gland, skin, 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 vehicle control incidence are the P values associated with the trend test. Beneath the dosed group incidence are the P values corresponding to 

pairwise comparisons between the vehicle controls and that dosed 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 a dose group is indicated by N. e Not applicable; no neoplasms in animal group 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 83 

TABLE A4 

Historical Incidence of Renal Tubule Neoplasms in Vehicle Control Male F344/N Ratsa 

Incidence in Controls 

Study Adenoma Carcinoma Adenoma or Carcinoma 

Historical Incidence at Battelle Columbus Laboratories 

Benzethonium Chloride 0/52 0/52 0/52 

Coconut Oil Acid Diethanolamine Condensate 3/50 0/50 3/50 

Diethanolamine 0/50 0/50 0/50 

Lauric Acid Diethanolamine Condensate 0/50 0/50 0/50 

Oleic Acid Diethanolamine Condensate 3/50 1/50 4/50 

Sodium Xylenesulfonate 2/50 0/50 2/50 

Overall Historical Incidence 

Total 8/302 (2.6%) 1/302 (0.3%0 9/302 (3.0%) 

Mean ± standard deviation 2.7% ± 3.0% 0.3% ± 0.8% 3.0% ± 3.5% 

Range 0%-6% 0%-2% 0%-8% 

a Data as of 12 July 2000 
 

84 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 50 mg/kg 100 mg/kg 

Disposition Summary 

Animals initially in study 50 50 50 

Early deaths 

Accidental death 1 

Moribund 28 27 25 

Natural deaths 13 11 14 

Survivors 

Terminal sacrifice 8 12 11 

Animals examined microscopically 50 50 50 

Alimentary System 

Intestine large, colon (50) (50) (50) 

Parasite metazoan 2 (4%) 5 (10%) 1 (2%) 

Intestine large, rectum (50) (50) (50) 

Parasite metazoan 2 (4%) 5 (10%) 

Intestine large, cecum (50) (50) (50) 

Inflammation, chronic active 2 (4%) 

Parasite metazoan 1 (2%) 

Ulcer 1 (2%) 

Intestine small, duodenum (50) (50) (50) 

Epithelium, ulcer 1 (2%) 

Liver (50) (50) (50) 

Basophilic focus 3 (6%) 13 (26%) 3 (6%) 

Clear cell focus 3 (6%) 6 (12%) 2 (4%) 

Eosinophilic focus 1 (2%) 

Fibrosis 1 (2%) 

Hepatodiaphragmatic nodule 9 (18%) 9 (18%) 8 (16%) 

Inflammation, chronic 20 (40%) 25 (50%) 24 (48%) 

Mineralization 1 (2%) 

Vacuolization cytoplasmic 27 (54%) 36 (72%) 33 (66%) 

Bile duct, hyperplasia 47 (94%) 48 (96%) 50 (100%) 

Hepatocyte, degeneration, cystic 8 (16%) 8 (16%) 3 (6%) 

Hepatocyte, necrosis 1 (2%) 3 (6%) 1 (2%) 

Hepatocyte, centrilobular, degeneration 2 (4%) 1 (2%) 

Hepatocyte, centrilobular, necrosis 2 (4%) 1 (2%) 

Portal vein, thrombosis 1 (2%) 

Mesentery (8) (7) (6) 

Accessory spleen 1 (14%) 

Inflammation, chronic active 1 (13%) 1 (14%) 

Fat, necrosis 7 (88%) 3 (43%) 5 (83%) 

Oral mucosa (1) (2) (2) 

Gingival, hyperplasia 1 (50%) 

Gingival, inflammation, chronic active 1 (50%) 1 (50%) 

Pharyngeal, hyperplasia, squamous 1 (50%) 

Pancreas (50) (50) (50) 

Acinus, atrophy 11 (22%) 22 (44%) 25 (50%) 

Artery, inflammation, chronic active 1 (2%) 

Salivary glands (50) (50) (50) 

Duct, cyst 1 (2%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 85 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Alimentary System (continued) 

Stomach, forestomach (50) (50) (50) 

Edema 6 (12%) 5 (10%) 8 (16%) 

Foreign body 1 (2%) 

Inflammation, chronic active 15 (30%) 8 (16%) 14 (28%) 

Mineralization 4 (8%) 2 (4%) 2 (4%) 

Perforation 4 (8%) 2 (4%) 4 (8%) 

Epithelium, hyperplasia 18 (36%) 16 (32%) 18 (36%) 

Epithelium, ulcer 13 (26%) 7 (14%) 13 (26%) 

Stomach, glandular (50) (50) (50) 

Inflammation, chronic active 1 (2%) 2 (4%) 

Mineralization 7 (14%) 6 (12%) 4 (8%) 

Epithelium, erosion 2 (4%) 

Epithelium, ulcer 3 (6%) 

Cardiovascular System 

Blood vessel (50) (50) (50) 

Mineralization 1 (2%) 

Aorta, mineralization 6 (12%) 4 (8%) 4 (8%) 

Pulmonary artery, mineralization 4 (8%) 2 (4%) 

Heart (50) (50) (50) 

Cardiomyopathy, chronic 37 (74%) 43 (86%) 42 (84%) 

Inflammation, suppurative 1 (2%) 

Mineralization 5 (10%) 3 (6%) 4 (8%) 

Atrium, thrombosis 6 (12%) 1 (2%) 1 (2%) 

Endocrine System 

Adrenal cortex (50) (50) (50) 

Accessory adrenal cortical nodule 2 (4%) 1 (2%) 

Atypia cellular 1 (2%) 

Degeneration, cystic 3 (6%) 4 (8%) 3 (6%) 

Degeneration, fatty 36 (72%) 40 (80%) 38 (76%) 

Hyperplasia 13 (26%) 21 (42%) 24 (48%) 

Hypertrophy 2 (4%) 6 (12%) 5 (10%) 

Necrosis 1 (2%) 1 (2%) 

Adrenal medulla (50) (50) (50) 

Hyperplasia 20 (40%) 19 (38%) 16 (32%) 

Islets, pancreatic (50) (50) (50) 

Hyperplasia 1 (2%) 1 (2%) 

Parathyroid gland (48) (46) (45) 

Hyperplasia 14 (29%) 15 (33%) 8 (18%) 

Pituitary gland (50) (50) (49) 

Pigmentation, hematoidin 1 (2%) 

Pars distalis, cyst 16 (32%) 7 (14%) 3 (6%) 

Pars distalis, hyperplasia 13 (26%) 10 (20%) 12 (24%) 

Pars intermedia, cyst 1 (2%) 1 (2%) 

Thyroid gland (50) (50) (50) 

C-cell, hyperplasia 6 (12%) 11 (22%) 11 (22%) 

Follicle, cyst 2 (4%) 
86 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

General Body System 

None 

Genital System 

Coagulating gland (3) 

Inflammation, chronic active 1 (33%) 

Inflammation, suppurative 2 (67%) 

Epididymis (50) (50) (50) 

Mineralization 1 (2%) 

Preputial gland (50) (50) (50) 

Hyperplasia 3 (6%) 1 (2%) 3 (6%) 

Inflammation, chronic active 47 (94%) 46 (92%) 46 (92%) 

Prostate (50) (50) (50) 

Cyst multilocular 9 (18%) 8 (16%) 4 (8%) 

Inflammation, chronic active 46 (92%) 47 (94%) 46 (92%) 

Seminal vesicle (50) (50) (50) 

Dilatation 1 (2%) 

Testes (50) (50) (50) 

Arteriole, inflammation, chronic 9 (18%) 11 (22%) 13 (26%) 

Arteriole, necrosis, fibrinoid 9 (18%) 10 (20%) 13 (26%) 

Bilateral, germinal epithelium, atrophy 1 (2%) 1 (2%) 

Germinal epithelium, atrophy 10 (20%) 15 (30%) 16 (32%) 

Interstitial cell, hyperplasia 12 (24%) 12 (24%) 13 (26%) 

Hematopoietic System 

Bone marrow (50) (50) (50) 

Atrophy 1 (2%) 

Hyperplasia 22 (44%) 22 (44%) 16 (32%) 

Lymph node (35) (30) (37) 

Mediastinal, hyperplasia, lymphoid 1 (3%) 

Mediastinal, pigmentation, hemosiderin 29 (83%) 26 (87%) 33 (89%) 

Lymph node, mandibular (50) (50) (50) 

Ectasia 1 (2%) 

Hyperplasia, plasma cell 1 (2%) 

Lymph node, mesenteric (49) (50) (50) 

Ectasia 1 (2%) 2 (4%) 

Infiltration cellular, histiocyte 1 (2%) 

Spleen (50) (50) (50) 

Fibrosis 6 (12%) 5 (10%) 1 (2%) 

Hematopoietic cell proliferation 1 (2%) 3 (6%) 3 (6%) 

Hyperplasia 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 

Necrosis 1 (2%) 

Red pulp, depletion cellular 2 (4%) 1 (2%) 

Thymus (47) (45) (48) 

Ectopic parathyroid gland 1 (2%) 

Integumentary System 

Mammary gland (48) (49) (50) 

Cyst 2 (4%) 6 (12%) 4 (8%) 

Hyperplasia, cystic 36 (75%) 44 (90%) 43 (86%) 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 87 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Integumentary System (continued) 

Skin (50) (50) (50) 

Cyst epithelial inclusion 1 (2%) 

Inflammation, chronic active 2 (4%) 

Epidermis, hyperkeratosis 1 (2%) 

Epidermis, hyperplasia 1 (2%) 

Epidermis, skin, site of application, hyperkeratosis 36 (72%) 48 (96%) 

Epidermis, skin, site of application, hyperplasia 46 (92%) 50 (100%) 

Epidermis, skin, site of application, parakeratosis 9 (18%) 28 (56%) 

Epidermis, skin, site of application, ulcer 1 (2%) 1 (2%) 

Prepuce, inflammation, chronic active 1 (2%) 

Sebaceous gland, skin, site of application, hyperplasia 45 (90%) 50 (100%) 

Skin, site of application, hemorrhage 1 (2%) 

Skin, site of application, inflammation, chronic active 1 (2%) 2 (4%) 

Musculoskeletal System 

Bone (50) (50) (50) 

Callus 1 (2%) 

Fibrous osteodystrophy 10 (20%) 12 (24%) 6 (12%) 

Nervous System 

Brain (50) (50) (50) 

Hemorrhage 1 (2%) 1 (2%) 1 (2%) 

Mineralization 1 (2%) 

Respiratory System 

Lung (50) (50) (50) 

Fibrosis 1 (2%) 1 (2%) 

Hemorrhage 1 (2%) 

Inflammation, chronic active 2 (4%) 8 (16%) 2 (4%) 

Inflammation, granulomatous 2 (4%) 

Inflammation, suppurative 1 (2%) 

Mineralization 2 (4%) 

Alveolar epithelium, hyperplasia 2 (4%) 4 (8%) 1 (2%) 

Alveolus, infiltration cellular, histiocyte 7 (14%) 13 (26%) 12 (24%) 

Interstitium, mineralization 2 (4%) 4 (8%) 2 (4%) 

Nose (50) (50) (50) 

Inflammation, chronic active 9 (18%) 7 (14%) 10 (20%) 

Inflammation, suppurative 1 (2%) 

Nasolacrimal duct, inflammation, suppurative 2 (4%) 4 (8%) 4 (8%) 

Respiratory epithelium, hyperplasia 9 (18%) 7 (14%) 9 (18%) 

Respiratory epithelium, metaplasia, squamous 3 (6%) 2 (4%) 3 (6%) 

Vein, turbinate, septum, thrombosis 2 (4%) 2 (4%) 
88 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE A5 

Summary of the Incidence of Nonneoplastic Lesions in Male Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Special Senses System 

Eye (2) (3) (8) 

Cornea, inflammation, chronic active 1 (33%) 

Cornea, mineralization 1 (33%) 

Lens, cataract 2 (100%) 2 (67%) 8 (100%) 

Retina, atrophy 2 (100%) 2 (67%) 8 (100%) 

Urinary System 

Kidney (50) (50) (50) 

Accumulation, hyaline droplet 1 (2%) 1 (2%) 

Cyst 8 (16%) 9 (18%) 7 (14%) 

Hydronephrosis 1 (2%) 

Mineralization 3 (6%) 3 (6%) 3 (6%) 

Nephropathy, chronic 49 (98%) 50 (100%) 49 (98%) 

Pigmentation, hemosiderin 43 (86%) 44 (88%) 50 (100%) 

Renal tubule, hyperplasia 13 (26%) 13 (26%) 15 (30%) 

Urinary bladder (50) (50) (50) 

Calculus, gross observation 1 (2%) 

Hemorrhage 1 (2%) 

Inflammation, chronic active 2 (4%) 1 (2%) 

Transitional epithelium, hyperplasia 1 (2%) 1 (2%) 
89 

APPENDIX B
 

SUMMARY OF LESIONS IN FEMALE RATS
 

IN THE 2-YEAR DERMAL STUDY
 

OF COCONUT OIL ACID
 

DIETHANOLAMINE CONDENSATE
 

TABLE B1 Summary of the Incidence of Neoplasms in Female Rats 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ......... 91 
 

TABLE B2 Individual Animal Tumor Pathology of Female Rats 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ......... 94 
 

TABLE B3 Statistical Analysis of Primary Neoplasms in Female Rats 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ........ 106 
 

TABLE B4 Historical Incidence of Renal Tubule Neoplasms
 

in Vehicle Control Female F344/N Rats .................................. 109 
 

TABLE B5 Summary of the Incidence of Nonneoplastic Lesions in Female Rats
 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ........ 110 
 
90 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 
Coconut Oil Acid Diethanolamine Condensate 91 

TABLE B1 

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 50 mg/kg 100 mg/kg 

Disposition Summary 

Animals initially in study 50 50 50 

Early deaths 

Moribund 7 15 10 

Natural deaths 15 11 18 

Survivors 

Died last week of study 1 

Terminal sacrifice 28 24 21 

Animals examined microscopically 50 50 50 

Alimentary System 

Intestine small, duodenum (50) (50) (50) 

Liver (50) (50) (50) 

Hepatocellular adenoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Mesentery (4) (5) (2) 

Oral mucosa (1) (1) (3) 

Gingival, squamous cell carcinoma 1 (33%) 

Pancreas (50) (50) (50) 

Salivary glands (50) (50) (49) 

Stomach, forestomach (50) (50) (50) 

Squamous cell papilloma 1 (2%) 

Squamous cell papilloma, multiple 1 (2%) 

Stomach, glandular (50) (50) (50) 

Cardiovascular System 

Heart (50) (50) (50) 

Endocrine System 

Adrenal cortex (50) (50) (50) 

Adenoma 2 (4%) 

Adrenal medulla (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Pheochromocytoma benign 4 (8%) 

Islets, pancreatic (50) (50) (50) 

Adenoma 1 (2%) 2 (4%) 

Parathyroid gland (42) (46) (45) 

Adenoma 1 (2%) 

Pituitary gland (50) (49) (50) 

Pars distalis, adenoma 27 (54%) 26 (53%) 24 (48%) 

Pars intermedia, adenoma 1 (2%) 

Thyroid gland (50) (50) (50) 

C-cell, adenoma 4 (8%) 3 (6%) 6 (12%) 

C-cell, carcinoma 1 (2%) 2 (4%) 2 (4%) 

Follicular cell, adenoma 2 (4%) 

Follicular cell, carcinoma 1 (2%) 1 (2%) 

General Body System 

None 
92 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B1 

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Genital System 

Clitoral gland (49) (50) (50) 

Adenoma 7 (14%) 5 (10%) 4 (8%) 

Carcinoma 1 (2%) 6 (12%) 2 (4%) 

Bilateral, adenoma 1 (2%) 

Bilateral, carcinoma 1 (2%) 2 (4%) 2 (4%) 

Ovary (50) (50) (50) 

Granulosa-theca tumor malignant 1 (2%) 

Granulosa-theca tumor benign 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Uterus (50) (50) (50) 

Deciduoma benign 1 (2%) 

Leiomyosarcoma 1 (2%) 

Polyp stromal 6 (12%) 6 (12%) 5 (10%) 

Sarcoma stromal 1 (2%) 

Hematopoietic System 

Bone marrow (50) (50) (50) 

Lymph node (41) (36) (36) 

Mediastinal, histiocytic sarcoma 1 (2%) 

Lymph node, mandibular (50) (48) (47) 

Lymph node, mesenteric (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Spleen (50) (50) (50) 

Thymus (47) (50) (49) 

Histiocytic sarcoma 1 (2%) 

Thymoma benign 1 (2%) 

Integumentary System 

Mammary gland (49) (50) (50) 

Adenoma 1 (2%) 

Carcinoma 2 (4%) 1 (2%) 2 (4%) 

Carcinoma, multiple 1 (2%) 

Fibroadenoma 17 (35%) 14 (28%) 3 (6%) 

Fibroadenoma, multiple 1 (2%) 2 (4%) 

Skin (50) (50) (50) 

Squamous cell papilloma, multiple 1 (2%) 

Sebaceous gland, skin, site of application, adenoma 1 (2%) 

Subcutaneous tissue, histiocytic sarcoma 1 (2%) 

Subcutaneous tissue, pinna, melanoma malignant 1 (2%) 

Subcutaneous tissue, skin, site of application,

 fibrosarcoma 1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) 

Femur, osteosarcoma 1 (2%) 

Skeletal muscle (3) (1) 

Histiocytic sarcoma 1 (33%) 

Osteosarcoma, metastatic, bone 1 (33%) 
Coconut Oil Acid Diethanolamine Condensate 93 

TABLE B1 

Summary of the Incidence of Neoplasms in Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Nervous System 

Brain (50) (50) (50) 

Respiratory System 

Lung 

Granulosa-theca tumor malignant, metastatic,

 ovary 

Histiocytic sarcoma 

Osteosarcoma, metastatic, bone 

(50) 

1 (2%) 

1 (2%) 

1 (2%) 

(50) (50) 

Special Senses System 

None 

Urinary System 

Kidney (50) (50) (50) 

Renal tubule, carcinoma 2 (4%) 

Urinary bladder (50) (50) (50) 

Papilloma 1 (2%) 

Transitional epithelium, papilloma 1 (2%) 

Systemic Lesions 

Multiple organsb (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Leukemia mononuclear 10 (20%) 9 (18%) 4 (8%) 

Lymphoma malignant 2 (4%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 48 43 37 

Total primary neoplasms 89 93 65 

Total animals with benign neoplasms 43 39 34 

Total benign neoplasms 69 66 50 

Total animals with malignant neoplasms 19 20 15 

Total malignant neoplasms 20 27 15 

Total animals with metastatic neoplasms 2 

Total metastatic neoplasms 3 

a Number of animals examined microscopically at the site and the number of animals with neoplasm b Number of animals with any tissue examined microscopically 

Primary neoplasms: all neoplasms except metastatic neoplasms c 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

94 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

3455566666666666667777777 

Number of Days on Study 4925801111333568990122222 

2322563389269590788737888 

1111111111111111111111111 

Carcass ID Number 8768985685599597866678667 

0737547129174634845921268 

Alimentary System 

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

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

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

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

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

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

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

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

Histiocytic sarcoma X 

Mesentery + + + 

Oral mucosa 

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

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

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

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

Tooth 

Cardiovascular System 

Blood vessel 

Heart 

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

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

Endocrine System 

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

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

Histiocytic sarcoma X 

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

Adenoma 

Parathyroid gland +++++++++++++++M+++M+++++ 

Adenoma 

Pituitary gland +++++++++++++++++++++++++ 

Pars distalis, adenoma XX XXX XXX XX XXX X 

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

C-cell, adenoma 

C-cell, carcinoma 

Follicular cell, adenoma X 

Follicular cell, carcinoma 

General Body System 

None 

Genital System 

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

Adenoma X 

Carcinoma 

Bilateral, adenoma X 

Bilateral, carcinoma X 

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

Granulosa-theca tumor malignant X 

Histiocytic sarcoma X 

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

Polyp stromal X X 

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

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

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 95 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

7777777777777777777777777 

Number of Days on Study 2222222222222222222222222 

8889999999999999999999999 

1111111111111111111111112 Total 

Carcass ID Number 8995555566677777788899990 Tissues/ 

5282345807801356936901690 Tumors 

Alimentary System 

Esophagus +++++++++++++++++++++++++ 50 

Intestine large, colon +++++++++++++++++++++++++ 50 

Intestine large, rectum +++++++++++++++++++++++++ 50 

Intestine large, cecum +++++++++++++++++++++++++ 50 

Intestine small, duodenum +++++++++++++++++++++++++ 50 

Intestine small, jejunum +++++++++++++++++++++++++ 50 

Intestine small, ileum +++++++++++++++++++++++++ 50 

Liver +++++++++++++++++++++++++ 50 

Histiocytic sarcoma 1 

Mesentery + 4 

Oral mucosa + 1 

Pancreas +++++++++++++++++++++++++ 50 

Salivary glands +++++++++++++++++++++++++ 50 

Stomach, forestomach +++++++++++++++++++++++++ 50 

Stomach, glandular +++++++++++++++++++++++++ 50 

Tooth + 1 

Cardiovascular System 

Blood vessel 

Heart 

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

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

50 

50 

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++ 50 

Adrenal medulla +++++++++++++++++++++++++ 50 

Histiocytic sarcoma 1 

Islets, pancreatic +++++++++++++++++++++++++ 50 

Adenoma X 1 

Parathyroid gland +++++++++M++++M+M++++ MMM+ 42 

Adenoma X 1 

Pituitary gland +++++++++++++++++++++++++ 50 

Pars distalis, adenoma X XX X X XXX XXXX X 27 

Thyroid gland +++++++++++++++++++++++++ 50 

C-cell, adenoma X X X X 4 

C-cell, carcinoma X 1 

Follicular cell, adenoma X 2 

Follicular cell, carcinoma X 1 

General Body System 

None 

Genital System 

Clitoral gland +++++++++++++++++++++++++ 49 

Adenoma X X X X X X 7 

Carcinoma X 1 

Bilateral, adenoma 1 

Bilateral, carcinoma 1 

Ovary +++++++++++++++++++++++++ 50 

Granulosa-theca tumor malignant 1 

Histiocytic sarcoma 1 

Uterus +++++++++++++++++++++++++ 50 

Polyp stromal X X X X 6 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

96 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

3455566666666666667777777 

Number of Days on Study 4925801111333568990122222 

2322563389269590788737888 

1111111111111111111111111 

Carcass ID Number 8768985685599597866678667 

0737547129174634845921268 

Hematopoietic System 

Bone marrow 

Lymph node 

Mediastinal, histiocytic sarcoma

Lymph node, mandibular 

Lymph node, mesenteric 

Histiocytic sarcoma

Spleen 

Thymus 

Histiocytic sarcoma

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

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

X 

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

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

X 

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

++++M++++++++++++M+++M+++ 

X 

Integumentary System 

Mammary gland 

Adenoma 

Carcinoma

Fibroadenoma

Fibroadenoma, multiple

Skin 

Subcutaneous tissue, histiocytic sarcoma

Subcutaneous tissue, pinna, melanoma malignant 

++++++++++++M++++++++++++ 

X 

X X X X X 

X 

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

X 

Musculoskeletal System 

Bone 

Femur, osteosarcoma

Skeletal muscle

Histiocytic sarcoma

Osteosarcoma, metastatic, bone

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

X 

+ ++ 

X 

X 

Nervous System 

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

Respiratory System 

Lung 

Granulosa-theca tumor malignant, 

metastatic, ovary

Histiocytic sarcoma

Osteosarcoma, metastatic, bone

Nose 

Trachea 

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

X 

X 

X 

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

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

Special Senses System 

Eye + + + ++ 

Urinary System 

Kidney 

Urinary bladder 

Transitional epithelium, papilloma

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

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

X 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma

Leukemia mononuclear

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

X 

 X X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 97 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

7777777777777777777777777 

Number of Days on Study 2222222222222222222222222 

8889999999999999999999999 

1111111111111111111111112 Total 

Carcass ID Number 8995555566677777788899990 

5282345807801356936901690 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow 

Lymph node 

Mediastinal, histiocytic sarcoma 

Lymph node, mandibular 

Lymph node, mesenteric 

Histiocytic sarcoma 

Spleen 

Thymus 

Histiocytic sarcoma 

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

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

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

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

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

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

50 

41 

1 

50 

50 

1 

50 

47 

1 

Integumentary System 

Mammary gland 

Adenoma

Carcinoma

Fibroadenoma 

Fibroadenoma, multiple 

Skin 

Subcutaneous tissue, histiocytic sarcoma 

Subcutaneous tissue, pinna, melanoma malignant

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

X 

X 

X X X XX XXXX X X X 

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

X 

49 

1 

2 

17 

1 

50 

1 

1 

Musculoskeletal System 

Bone 

Femur, osteosarcoma 

Skeletal muscle 

Histiocytic sarcoma 

Osteosarcoma, metastatic, bone 

+++++++++++++++++++++++++ 50 

1 

3 

1 

1 

Nervous System 

Brain +++++++++++++++++++++++++ 50 

Respiratory System 

Lung 

Granulosa-theca tumor malignant, 

metastatic, ovary 

Histiocytic sarcoma 

Osteosarcoma, metastatic, bone 

Nose 

Trachea 

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

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

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

50 

1 

1 

1 

50 

50 

Special Senses System 

Eye + 6 

Urinary System 

Kidney 

Urinary bladder 

Transitional epithelium, papilloma 

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

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

50 

50 

1 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Leukemia mononuclear

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

X X X X X 

50 

1 

10 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

98 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 50 mg/kg 

2223344555555556666666777 

Number of Days on Study 2788907133677881357889011 

5102086433288252717992829 

2222222222222222222222222 

Carcass ID Number 2241041101202324044021333 

4385339083875462545906723 

Alimentary System 

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

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

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

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

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

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

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

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

Mesentery + + 

Oral mucosa + 

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

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

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

Squamous cell papilloma, multiple X 

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

Cardiovascular System 

Blood vessel 

Heart 

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

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

Endocrine System 

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

Adenoma 

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

Pheochromocytoma benign X 

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

Parathyroid gland ++++++++++++++++++++M++++ 

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

Pars distalis, adenoma X X X XXX XXXXX XX 

Pars intermedia, adenoma 

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

C-cell, adenoma 

C-cell, carcinoma 

Follicular cell, carcinoma 

General Body System 

None 

Genital System 

Clitoral gland +++++++++++++++++++++++++ 

Adenoma X 

Carcinoma X 

Bilateral, carcinoma 

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

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

Leiomyosarcoma 

Polyp stromal X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 99 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 50 mg/kg 

7777777777777777777777777 

Number of Days on Study 2222222222222222222222222 

2888888899999999999999999 

2222222222222222222222222 Total 

Carcass ID Number 0001122401112233333344445 Tissues/ 

1264729941281701568901670 Tumors 

Alimentary System 

Esophagus +++++++++++++++++++++++++ 50 

Intestine large, colon +++++++++++++++++++++++++ 50 

Intestine large, rectum +++++++++++++++++++++++++ 50 

Intestine large, cecum +++++++++++++++++++++++++ 50 

Intestine small, duodenum +++++++++++++++++++++++++ 50 

Intestine small, jejunum +++++++++++++++++++++++++ 50 

Intestine small, ileum +++++++++++++++++++++++++ 49 

Liver +++++++++++++++++++++++++ 50 

Mesentery + + + 5 

Oral mucosa 1 

Pancreas +++++++++++++++++++++++++ 50 

Salivary glands +++++++++++++++++++++++++ 50 

Stomach, forestomach +++++++++++++++++++++++++ 50 

Squamous cell papilloma, multiple 1 

Stomach, glandular +++++++++++++++++++++++++ 50 

Cardiovascular System 

Blood vessel 

Heart 

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

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

50 

50 

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++ 50 

Adenoma X X 2 

Adrenal medulla +++++++++++++++++++++++++ 50 

Pheochromocytoma benign X X X 4 

Islets, pancreatic +++++++++++++++++++++++++ 50 

Parathyroid gland +++++++++++++++++MM++M+++ 46 

Pituitary gland +++++++++++++++++++++++++ 49 

Pars distalis, adenoma X X XX X XX XXXX XX 26 

Pars intermedia, adenoma X 1 

Thyroid gland +++++++++++++++++++++++++ 50 

C-cell, adenoma X X X 3 

C-cell, carcinoma X X 2 

Follicular cell, carcinoma X 1 

General Body System 

None 

Genital System 

Clitoral gland +++++++++++++++++++++++++ 50 

Adenoma X X X X 5 

Carcinoma X X X X X 6 

Bilateral, carcinoma X X 2 

Ovary +++++++++++++++++++++++++ 50 

Uterus +++++++++++++++++++++++++ 50 

Leiomyosarcoma X 1 

Polyp stromal X X XXX 6 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

100 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 50 mg/kg 

Number of Days on Study 

2223344555555556666666777 

2788907133677881357889011 

5102086433288252717992829 

Carcass ID Number 

2222222222222222222222222 

2241041101202324044021333 

4385339083875462545906723 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Thymus 

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

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

++++++++M++++++++++++++++ 

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

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

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

Integumentary System 

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

Carcinoma 

Carcinoma, multiple 

Fibroadenoma X X X X X X 

Fibroadenoma, multiple 

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

Sebaceous gland, skin, site of application, adenoma X 

Musculoskeletal System 

Bone 

Skeletal muscle

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

+ 

Nervous System 

Brain 

Peripheral nerve

Spinal cord

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

+ 

+ 

Respiratory System 

Lung 

Nose 

Trachea 

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

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

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

Special Senses System 

Eye + 

Urinary System 

Kidney 

Renal tubule, carcinoma

Urinary bladder 

Papilloma 

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

X 

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

Systemic Lesions 

Multiple organs 

Leukemia mononuclear

Lymphoma malignant

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

X X X X 

X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 101 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 50 mg/kg 

7777777777777777777777777 

Number of Days on Study 2222222222222222222222222 

2888888899999999999999999 

2222222222222222222222222 Total 

Carcass ID Number 0001122401112233333344445 Tissues/ 

1264729941281701568901670 Tumors 

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++ 50 

Lymph node +++ + + + ++ ++++++++ + 36 

Lymph node, mandibular ++++++M++++++++++++++++++ 48 

Lymph node, mesenteric +++++++++++++++++++++++++ 50 

Spleen +++++++++++++++++++++++++ 50 

Thymus +++++++++++++++++++++++++ 50 

Integumentary System 

Mammary gland +++++++++++++++++++++++++ 50 

Carcinoma X 1 

Carcinoma, multiple X 1 

Fibroadenoma X X X X XXX X 14 

Fibroadenoma, multiple X X 2 

Skin +++++++++++++++++++++++++ 50 

Sebaceous gland, skin, site of application, adenoma 

1 

Musculoskeletal System 

Bone +++++++++++++++++++++++++ 50 

Skeletal muscle 1 

Nervous System 

Brain +++++++++++++++++++++++++ 50 

Peripheral nerve 1 

Spinal cord 1 

Respiratory System 

Lung +++++++++++++++++++++++++ 50 

Nose +++++++++++++++++++++++++ 50 

Trachea +++++++++++++++++++++++++ 50 

Special Senses System 

Eye + 2 

Urinary System 

Kidney +++++++++++++++++++++++++ 50 

Renal tubule, carcinoma X 2 

Urinary bladder +++++++++++++++++++++++++ 50 

Papilloma X 1 

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++ 50 

Leukemia mononuclear X X X X X 9 

Lymphoma malignant X 2 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

102 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

2233333344555555666666667 

Number of Days on Study 7901777867233458223666780 

1484347769267578069569292 

2222222222222222222222222 

Carcass ID Number 9787587668969798658786659 

3507832747834608276440539 

Alimentary System 

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

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

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

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

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

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

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

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

Hepatocellular adenoma 

Mesentery + 

Oral mucosa + 

Gingival, squamous cell carcinoma 

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

Salivary glands ++++M++++++++++++++++++++ 

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

Squamous cell papilloma 

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

Tongue 

Cardiovascular System 

Blood vessel 

Heart 

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

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

Endocrine System 

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

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

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

Adenoma 

Parathyroid gland ++++++++++M++++++++++MM++ 

Pituitary gland +++++++++++++++++++++++++ 

Pars distalis, adenoma XX X XXXX X X X 

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

C-cell, adenoma X 

C-cell, carcinoma X 

General Body System 

None 

Genital System 

Clitoral gland +++++++++++++++++++++++++ 

Adenoma X 

Carcinoma X 

Bilateral, carcinoma X 

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

Granulosa-theca tumor benign 

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

Deciduoma benign X 

Polyp stromal X X 

Sarcoma stromal X 

Vagina + + 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 103 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

Number of Days on Study 

7777777777777777777777777 

1122222222222222222222222 

5848888888889999999999999 

Carcass ID Number 

2222222222222222222222223 

5555677788995566677889990 

5619913819122416809255670 

Total 

Tissues/ 

Tumors 

Alimentary System 

Esophagus 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Hepatocellular adenoma

Mesentery

Oral mucosa

Gingival, squamous cell carcinoma

Pancreas 

Salivary glands 

Stomach, forestomach 

Squamous cell papilloma

Stomach, glandular 

Tongue

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

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

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

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

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

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

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

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

X 

+ 

+ + 

X 

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

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

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

X 

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

+ 

50 

50 

50 

50 

50 

50 

49 

50 

1 

2 

3 

1 

50 

49 

50 

1 

50 

1 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X X 2 

Parathyroid gland + + + + + + M + + + + + + + + M + + + + + + + + + 45 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pars distalis, adenoma X X X X X X X X X X X X X X 24 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, adenoma X X X X X 6 

C-cell, carcinoma X 2 

General Body System 

None 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma X X X 4 

Carcinoma X 2 

Bilateral, carcinoma X 2 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Granulosa-theca tumor benign X 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Deciduoma benign 1 

Polyp stromal X X X 5 

Sarcoma stromal 1 

Vagina 2 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

104 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

Number of Days on Study 

2233333344555555666666667 

7901777867233458223666780 

1484347769267578069569292 

Carcass ID Number 

2222222222222222222222222 

9787587668969798658786659 

3507832747834608276440539 

Hematopoietic System 

Bone marrow 

Lymph node

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Thymus 

Thymoma benign

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

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

++++M+++M+++++++M++++++++ 

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

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

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

X 

Integumentary System 

Mammary gland 

Carcinoma 

Fibroadenoma

Skin 

Squamous cell papilloma, multiple 

Subcutaneous tissue, skin, site of application, 

fibrosarcoma 

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

X 

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

Musculoskeletal System 

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

Nervous System 

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

Respiratory System 

Lung 

Nose 

Trachea 

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

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

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

Special Senses System 

Eye + + 

Urinary System 

Kidney 

Urinary bladder 

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

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

Systemic Lesions 

Multiple organs 

Leukemia mononuclear

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

X 
 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 105 

TABLE B2 

Individual Animal Tumor Pathology of Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

Number of Days on Study 

7777777777777777777777777 

1122222222222222222222222 

5848888888889999999999999 

Carcass ID Number 

2222222222222222222222223 

5555677788995566677889990 

5619913819122416809255670 

Total 

Tissues/ 

Tumors 

Hematopoietic System 

Bone marrow 

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Thymus 

Thymoma benign 

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

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

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

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

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

+++++++++++M+++++++++++++ 

50 

36 

47 

50 

50 

49 

1 

Integumentary System 

Mammary gland 

Carcinoma

Fibroadenoma

Skin 

Squamous cell papilloma, multiple

Subcutaneous tissue, skin, site of application, 

fibrosarcoma 

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

X X 

X X 

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

X 

X 

50 

2 

3 

50 

1 

1 

Musculoskeletal System 

Bone +++++++++++++++++++++++++ 50 

Nervous System 

Brain +++++++++++++++++++++++++ 50 

Respiratory System 

Lung 

Nose 

Trachea 

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

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

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

50 

50 

50 

Special Senses System 

Eye + + + 5 

Urinary System 

Kidney 

Urinary bladder 

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

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

50 

50 

Systemic Lesions 

Multiple organs 

Leukemia mononuclear

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

X X X 

50 

4 
106 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B3 

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Adrenal Medulla: Benign Pheochromocytoma 

Overall ratea 0/50 (0%) 4/50 (8%) 0/50 (0%) 

Adjusted rateb 0.0% 10.6% 0.0% 

Terminal ratec 0/28 (0%) 3/24 (13%) 0/22 (0%) e First incidence (days) — 677 — f Poly-3 testd P=0.516 P=0.046 —

Clitoral Gland: Adenoma 

Overall rate 8/49 (16%) 5/50 (10%) 4/50 (8%)
 

Adjusted rate 19.1% 13.1% 11.1%
 

Terminal rate 6/28 (21%) 4/24 (17%) 1/22 (5%)
 

First incidence (days) 680 578 669
 

Poly-3 test P=0.200N P=0.338N P=0.259N
 

Clitoral Gland: Carcinoma 

Overall rate 2/49 (4%) 8/50 (16%) 4/50 (8%) 

Adjusted rate 4.8% 21.0% 11.0% 

Terminal rate 1/28 (4%) 7/24 (29%) 2/22 (9%) 

First incidence (days) 669 578 536 

Poly-3 test P=0.197 P=0.029 P=0.272 

Clitoral Gland: Adenoma or Carcinoma 

Overall rate 9/49 (18%) 13/50 (26%) 8/50 (16%)
 

Adjusted rate 21.3% 33.6% 21.8%
 

Terminal rate 6/28 (21%) 11/24 (46%) 3/22 (14%)
 

First incidence (days) 669 578 536
 

Poly-3 test P=0.487 P=0.158 P=0.587 

Kidney: Adenoma or Carcinoma (Step Sections) 

Overall rate 0/50 (0%) 3/50 (6%) 1/50 (2%) 

Adjusted rate 0.0% 8.0% 2.8% 

Terminal rate 0/28 (0%) 3/24 (13%) 1/22 (5%) 

First incidence (days) — 728 (T) 728 (T) 

Poly-3 test P=0.298 P=0.097 P=0.464 

Kidney: Adenoma or Carcinoma (Single and Step Sections) 

Overall rate 0/50 (0%) 4/50 (8%) 1/50 (2%) 

Adjusted rate 0.0% 10.6% 2.8% 

Terminal rate 0/28 (0%) 3/24 (13%) 1/22 (5%) 

First incidence (days) — 719 728 (T) 

Poly-3 test P=0.293 P=0.045 P=0.464 

Mammary Gland: Fibroadenoma 

Overall rate 18/50 (36%) 16/50 (32%) 3/50 (6%)
 

Adjusted rate 41.4% 41.0% 8.4%
 

Terminal rate 13/28 (46%) 9/24 (38%) 2/22 (9%)
 

First incidence (days) 618 578 669
 

Poly-3 test P<0.001N P=0.577N P<0.001N
 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 107 

TABLE B3 

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Mammary Gland: Fibroadenoma or Adenoma 

Overall rate 18/50 (36%) 16/50 (32%) 3/50 (6%) 

Adjusted rate 41.4% 41.0% 8.4% 

Terminal rate 13/28 (46%) 9/24 (38%) 2/22 (9%) 

First incidence (days) 618 578 669 

Poly-3 test P<0.001N P=0.577N P<0.001N 

Mammary Gland: Adenoma or Carcinoma 

Overall rate 3/50 (6%) 2/50 (4%) 2/50 (4%) 

Adjusted rate 7.0% 5.3% 5.6% 

Terminal rate 3/28 (11%) 2/24 (8%) 2/22 (9%) 

First incidence (days) 728 (T) 728 (T) 728 (T) 

Poly-3 test P=0.490N P=0.557N P=0.582N 

Mammary Gland: Fibroadenoma, Adenoma, or Carcinoma 

Overall rate 20/50 (40%) 16/50 (32%) 5/50 (10%) 

Adjusted rate 46.0% 41.0% 14.0% 

Terminal rate 15/28 (54%) 9/24 (38%) 4/22 (18%) 

First incidence (days) 618 578 669 

Poly-3 test P=0.002N P=0.407N P=0.002N 

Pituitary Gland (Pars Distalis): Adenoma 

Overall rate 27/50 (54%) 26/49 (53%) 24/50 (48%) 

Adjusted rate 58.3% 62.2% 60.0% 

Terminal rate 15/28 (54%) 12/24 (50%) 11/22 (50%) 

First incidence (days) 522 382 479 

Poly-3 test P=0.471 P=0.437 P=0.524 

Thyroid Gland (C-cell): Adenoma 

Overall rate 4/50 (8%) 3/50 (6%) 6/50 (12%) 

Adjusted rate 9.4% 8.0% 16.7% 

Terminal rate 4/28 (14%) 3/24 (13%) 5/22 (23%) 

First incidence (days) 728 (T) 728 (T) 626 

Poly-3 test P=0.224 P=0.568N P=0.266 

Thyroid Gland (C-cell): Adenoma or Carcinoma 

Overall rate 5/50 (10%) 5/50 (10%) 8/50 (16%) 

Adjusted rate 11.7% 13.3% 22.1% 

Terminal rate 5/28 (18%) 5/24 (21%) 5/22 (23%) 

First incidence (days) 728 (T) 728 (T) 626 

Poly-3 test P=0.142 P=0.550 P=0.174 

Thyroid Gland (Follicular Cell): Adenoma or Carcinoma 

Overall rate 3/50 (6%) 1/50 (2%) 0/50 (0%) 

Adjusted rate 7.0% 2.7% 0.0% 

Terminal rate 2/28 (7%) 1/24 (4%) 0/22 (0%) 

First incidence (days) 613 728 (T) — 

Poly-3 test P=0.083N P=0.355N P=0.156N 
108 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B3 

Statistical Analysis of Primary Neoplasms in Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Uterus: Stromal Polyp 

Overall rate 6/50 (12%) 6/50 (12%) 5/50 (10%)
 

Adjusted rate 13.8% 15.9% 13.9%
 

Terminal rate 4/28 (14%) 5/24 (21%) 3/22 (14%)
 

First incidence (days) 585 689 665
 

Poly-3 test P=0.553 P=0.521 P=0.622 

Uterus: Stromal Polyp or Stromal Sarcoma 

Overall rate 6/50 (12%) 6/50 (12%) 6/50 (12%)
 

Adjusted rate 13.8% 15.9% 16.4%
 

Terminal rate 4/28 (14%) 5/24 (21%) 3/22 (14%)
 

First incidence (days) 585 689 466
 

Poly-3 test P=0.437 P=0.521 P=0.499 

All Organs: Mononuclear Cell Leukemia 

Overall rate 10/50 (20%) 9/50 (18%) 4/50 (8%)
 

Adjusted rate 22.8% 22.6% 11.2%
 

Terminal rate 5/28 (18%) 5/24 (21%) 3/22 (14%)
 

First incidence (days) 618 280 672
 

Poly-3 test P=0.141N P=0.595N P=0.144N
 

All Organs: Benign Neoplasms 

Overall rate 43/50 (86%) 39/50 (78%) 34/50 (68%)
 

Adjusted rate 89.8% 91.3% 82.8%
 

Terminal rate 26/28 (93%) 23/24 (96%) 19/22 (86%)
 

First incidence (days) 522 382 373
 

Poly-3 test P=0.187N P=0.558 P=0.235N
 

All Organs: Malignant Neoplasms 

Overall rate 19/50 (38%) 20/50 (40%) 15/50 (30%)
 

Adjusted rate 42.4% 48.9% 40.0%
 

Terminal rate 11/28 (39%) 13/24 (54%) 9/22 (41%)
 

First incidence (days) 493 280 466
 

Poly-3 test P=0.497N P=0.347 P=0.505N
 

All Organs: Benign or Malignant Neoplasms 

Overall rate 48/50 (96%) 43/50 (86%) 37/50 (74%)
 

Adjusted rate 97.8% 95.8% 86.9%
 

Terminal rate 27/28 (96%) 24/24 (100%) 19/22 (86%)
 

First incidence (days) 493 280 373
 

Poly-3 test P=0.015N P=0.522N P=0.038N
 

(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, 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 vehicle control incidence are the P values associated with the trend test. Beneath the dosed group incidence are the P values corresponding to 

pairwise comparisons between the vehicle controls and that dosed 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 a dose group is indicated by N. e Not applicable; no neoplasms in animal group f Value of statistic cannot be computed. 

c 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 109 

TABLE B4 

Historical Incidence of Renal Tubule Neoplasms in Vehicle Control Female F344/N Ratsa 

Incidence in Controls 

Study Adenoma Carcinoma Adenoma or Carcinoma 

Historical Incidence at Battelle Columbus Laboratories 

Benzethonium Chloride 

Coconut Oil Acid Diethanolamine Condensate 

Diethanolamine 

Lauric Acid Diethanolamine Condensate 

Oleic Acid Diethanolamine Condensate 

Sodium Xylenesulfonate 

0/51 

0/50 

0/50 

1/50 

0/50 

0/50 

0/51 

0/50 

0/50 

0/50 

0/50 

0/50 

0/51 

0/50 

0/50 

1/50 

0/50 

0/50 

Overall Historical Incidence 

Total 

Mean ± standard deviation 

Range 

1/301 (0.3%) 

0.3% ± 0.8% 

0%-2% 

0/301 (0.0%) 1/301 (0.3%) 

0.3% ± 0.8% 

0%-2% 

a Data as of 12 July 2000 
110 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B5 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 50 mg/kg 100 mg/kg 

Disposition Summary 

Animals initially in study 50 50 50 

Early deaths 

Moribund 7 15 10 

Natural deaths 15 11 18 

Survivors 

Died last week of study 1 

Terminal sacrifice 28 24 21 

Animals examined microscopically 50 50 50 

Alimentary System 

Esophagus (50) (50) (50) 

Perforation 1 (2%) 

Intestine large, colon (50) (50) (50) 

Parasite metazoan 2 (4%) 5 (10%) 1 (2%) 

Intestine large, rectum (50) (50) (50) 

Parasite metazoan 6 (12%) 4 (8%) 6 (12%) 

Intestine large, cecum (50) (50) (50) 

Parasite metazoan 2 (4%) 

Intestine small, duodenum (50) (50) (50) 

Epithelium, ulcer 1 (2%) 

Intestine small, jejunum (50) (50) (50) 

Inflammation, chronic active 1 (2%) 

Intestine small, ileum (50) (49) (49) 

Inflammation, chronic active 1 (2%) 

Liver (50) (50) (50) 

Basophilic focus 31 (62%) 17 (34%) 4 (8%) 

Clear cell focus 5 (10%) 4 (8%) 1 (2%) 

Fibrosis 1 (2%) 

Hematopoietic cell proliferation 1 (2%) 

Hepatodiaphragmatic nodule 10 (20%) 11 (22%) 14 (28%) 

Inflammation, chronic 29 (58%) 26 (52%) 13 (26%) 

Mixed cell focus 1 (2%) 2 (4%) 

Pigmentation, hemosiderin 1 (2%) 

Vacuolization cytoplasmic 23 (46%) 20 (40%) 22 (44%) 

Bile duct, hyperplasia 26 (52%) 21 (42%) 16 (32%) 

Hepatocyte, degeneration, cystic 1 (2%) 

Hepatocyte, hyperplasia, adenomatous 1 (2%) 1 (2%) 

Hepatocyte, necrosis 1 (2%) 2 (4%) 

Hepatocyte, centrilobular, degeneration 2 (4%) 1 (2%) 2 (4%) 

Hepatocyte, centrilobular, necrosis 1 (2%) 

Serosa, necrosis, fibrinoid 1 (2%) 

Mesentery (4) (5) (2) 

Fat, inflammation, chronic active 1 (50%) 

Fat, necrosis 3 (75%) 4 (80%) 1 (50%) 

Oral mucosa (1) (1) (3) 

Gingival, hyperplasia, squamous 1 (100%) 

Gingival, inflammation, chronic active 1 (33%) 

Pharyngeal, hyperplasia, squamous 1 (100%) 1 (33%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 111 

TABLE B5 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Alimentary System (continued) 

Pancreas (50) (50) (50) 

Inflammation, granulomatous 1 (2%) 

Acinus, atrophy 19 (38%) 13 (26%) 11 (22%) 

Stomach, forestomach (50) (50) (50) 

Edema 1 (2%) 1 (2%) 2 (4%) 

Inflammation, chronic active 1 (2%) 3 (6%) 10 (20%) 

Mineralization 1 (2%) 

Epithelium, hyperplasia 2 (4%) 5 (10%) 13 (26%) 

Epithelium, ulcer 1 (2%) 3 (6%) 11 (22%) 

Stomach, glandular (50) (50) (50) 

Mineralization 1 (2%) 1 (2%) 

Epithelium, erosion 1 (2%) 1 (2%) 

Epithelium, hyperplasia 1 (2%) 

Epithelium, ulcer 1 (2%) 

Glands, hyperplasia 1 (2%) 

Tongue (1) 

Hyperplasia, squamous 1 (100%) 

Tooth (1) 

Inflammation, chronic active 1 (100%) 

Cardiovascular System 

Blood vessel (50) (50) (50) 

Aorta, mineralization 1 (2%) 1 (2%) 

Pulmonary artery, mineralization 1 (2%) 

Heart (50) (50) (50) 

Cardiomyopathy, chronic 22 (44%) 16 (32%) 14 (28%) 

Inflammation, chronic active 1 (2%) 

Mineralization 1 (2%) 1 (2%) 

Atrium, thrombosis 1 (2%) 3 (6%) 

Endocrine System 

Adrenal cortex (50) (50) (50) 

Accessory adrenal cortical nodule 1 (2%) 

Atrophy 1 (2%) 

Degeneration, cystic 8 (16%) 6 (12%) 8 (16%) 

Degeneration, fatty 22 (44%) 14 (28%) 16 (32%) 

Fibrosis 1 (2%) 

Hyperplasia 22 (44%) 14 (28%) 11 (22%) 

Hypertrophy 10 (20%) 3 (6%) 7 (14%) 

Necrosis 1 (2%) 

Adrenal medulla (50) (50) (50) 

Hyperplasia 1 (2%) 2 (4%) 3 (6%) 

Parathyroid gland (42) (46) (45) 

Hyperplasia 1 (2%) 3 (7%) 

Pituitary gland (50) (49) (50) 

Pars distalis, cyst 23 (46%) 27 (55%) 17 (34%) 

Pars distalis, hyperplasia 20 (40%) 19 (39%) 19 (38%) 

Pars intermedia, cyst 1 (2%) 2 (4%) 2 (4%) 

Thyroid gland (50) (50) (50) 

Ectopic thymus 1 (2%) 

C-cell, hyperplasia 17 (34%) 7 (14%) 7 (14%) 
112 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B5 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

General Body System 

None 

Genital System 

Clitoral gland (49) (50) (50) 

Hyperplasia 4 (8%) 1 (2%) 3 (6%) 

Inflammation, chronic active 6 (12%) 6 (12%) 8 (16%) 

Bilateral, duct, cyst 1 (2%) 

Duct, cyst 2 (4%) 1 (2%) 1 (2%) 

Ovary (50) (50) (50) 

Cyst 7 (14%) 8 (16%) 8 (16%) 

Uterus (50) (50) (50) 

Dysplasia 1 (2%) 

Inflammation, suppurative 1 (2%) 

Endometrium, hyperplasia, cystic 1 (2%) 

Vagina (2) 

Inflammation, suppurative 1 (50%) 

Hematopoietic System 

Bone marrow (50) (50) (50) 

Atrophy 1 (2%) 

Hyperplasia 12 (24%) 14 (28%) 10 (20%) 

Lymph node (41) (36) (36) 

Pigmentation, hemosiderin 1 (2%) 

Inguinal, ectasia 1 (2%) 

Mediastinal, congestion 1 (3%) 

Mediastinal, pigmentation, hemosiderin 38 (93%) 35 (97%) 34 (94%) 

Lymph node, mandibular (50) (48) (47) 

Pigmentation, hemosiderin 1 (2%) 

Spleen (50) (50) (50) 

Congestion 1 (2%) 

Fibrosis 1 (2%) 

Hematopoietic cell proliferation 3 (6%) 4 (8%) 1 (2%) 

Necrosis 1 (2%) 

Pigmentation, hemosiderin 1 (2%) 

Capsule, fibrosis 1 (2%) 

Capsule, inflammation, granulomatous 1 (2%) 

Integumentary System 

Mammary gland (49) (50) (50) 

Cyst 3 (6%) 

Hyperplasia, cystic 44 (90%) 40 (80%) 40 (80%) 

Skin (50) (50) (50) 

Cyst epithelial inclusion 2 (4%) 

Inflammation, chronic active 1 (2%) 2 (4%) 

Inflammation, suppurative 1 (2%) 

Epidermis, hyperplasia 1 (2%) 

Epidermis, skin, site of application,

 hyperkeratosis 3 (6%) 45 (90%) 47 (94%) 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 113 

TABLE B5 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Integumentary System (continued) 

Skin (continued) (50) (50) (50) 

Epidermis, skin, site of application,

 hyperplasia 3 (6%) 46 (92%) 50 (100%) 

Epidermis, skin, site of application,

 parakeratosis 1 (2%) 11 (22%) 23 (46%) 

Epidermis, skin, site of application, ulcer 2 (4%) 9 (18%) 

Sebaceous gland, skin, site of application,

 hyperplasia 2 (4%) 46 (92%) 49 (98%) 

Skin, site of application, inflammation,

 chronic active 3 (6%) 6 (12%) 

Musculoskeletal System 

Bone (50) (50) (50) 

Fibrous osteodystrophy 2 (4%) 2 (4%) 

Osteopetrosis 2 (4%) 2 (4%) 

Skeletal muscle (3) (1) 

Inflammation, chronic active 1 (33%) 

Nervous System 

Brain (50) (50) (50) 

Hemorrhage 1 (2%) 1 (2%) 

Spinal cord (1) 

Hemorrhage 1 (100%) 

Respiratory System 

Lung (50) (50) (50) 

Congestion 1 (2%) 

Hemorrhage 1 (2%) 

Inflammation, chronic active 7 (14%) 16 (32%) 9 (18%) 

Inflammation, granulomatous 3 (6%) 1 (2%) 1 (2%) 

Metaplasia, osseous 1 (2%) 

Alveolar epithelium, hyperplasia 2 (4%) 1 (2%) 3 (6%) 

Alveolus, infiltration cellular, histiocyte 22 (44%) 24 (48%) 28 (56%) 

Mediastinum, necrosis 1 (2%) 

Nose (50) (50) (50) 

Inflammation, chronic active 1 (2%) 4 (8%) 3 (6%) 

Nasolacrimal duct, inflammation, suppurative 4 (8%) 3 (6%) 3 (6%) 

Respiratory epithelium, hyperplasia 1 (2%) 4 (8%) 3 (6%) 

Respiratory epithelium, metaplasia, squamous 1 (2%) 2 (4%) 

Vein, turbinate, septum, thrombosis 1 (2%) 

Special Senses System 

Eye (6) (2) (5) 

Anterior chamber, cornea, iris, synechia 1 (17%) 

Bilateral, inflammation, suppurative 1 (20%) 

Cornea, inflammation, chronic 1 (17%) 

Lens, cataract 5 (83%) 1 (50%) 4 (80%) 

Retina, atrophy 3 (50%) 1 (50%) 3 (60%) 
114 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE B5 

Summary of the Incidence of Nonneoplastic Lesions in Female Rats in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 50 mg/kg 100 mg/kg 

Urinary System 

Kidney (50) (50) (50) 

Accumulation, hyaline droplet 2 (4%) 

Cyst 2 (4%) 1 (2%) 

Mineralization 50 (100%) 45 (90%) 47 (94%) 

Nephropathy, chronic 47 (94%) 46 (92%) 46 (92%) 

Pigmentation, hemosiderin 48 (96%) 46 (92%) 47 (94%) 

Renal tubule, hyperplasia 2 (4%) 8 (16%) 15 (30%) 

Urinary bladder (50) (50) (50) 

Transitional epithelium, hyperplasia 1 (2%) 2 (4%) 
115 

APPENDIX C 

SUMMARY OF LESIONS IN MALE MICE 

IN THE 2-YEAR DERMAL STUDY 

OF COCONUT OIL ACID 

DIETHANOLAMINE CONDENSATE 

TABLE C1 

TABLE C2 

TABLE C3 

TABLE C4a 

TABLE C4b 

TABLE C5 

Summary of the Incidence of Neoplasms in Male Mice 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ....... 

Individual Animal Tumor Pathology of Male Mice 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ....... 

Statistical Analysis of Primary Neoplasms in Male Mice 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ....... 

Historical Incidence of Liver Neoplasms in Vehicle Control Male B6C3F1 Mice . . . . . . 

Historical Incidence of Renal Tubule Neoplasms 

in Vehicle Control Male B6C3F1 Mice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ....... 

116 

120 

138 

141 

141 

142 
 

116 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C1 

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 100 mg/kg 200 mg/kg 

Disposition Summary 

Animals initially in study 50 50 50 

Early deaths 

Moribund 5 7 7 

Natural deaths 4 6 7 

Survivors 

Terminal sacrifice 41 37 36 

Animals examined microscopically 50 50 50 

Alimentary System 

Intestine large, colon (50) (50) (50) 

Intestine large, cecum (50) (50) (50) 

Intestine small, duodenum (49) (50) (50) 

Hepatoblastoma, metastatic, liver 1 (2%) 

Intestine small, jejunum (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Liver (50) (50) (50) 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 (2%) 

Hemangioma 1 (2%) 

Hemangiosarcoma 1 (2%) 2 (4%) 

Hemangiosarcoma, multiple 1 (2%) 1 (2%) 

Hemangiosarcoma, metastatic, spleen 1 (2%) 1 (2%) 

Hepatoblastoma 1 (2%) 10 (20%) 

Hepatoblastoma, multiple 1 (2%) 

Hepatocellular carcinoma 7 (14%) 10 (20%) 12 (24%) 

Hepatocellular carcinoma, multiple 5 (10%) 2 (4%) 8 (16%) 

Hepatocellular adenoma 11 (22%) 11 (22%) 4 (8%) 

Hepatocellular adenoma, multiple 11 (22%) 24 (48%) 41 (82%) 

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

Mast cell tumor malignant, metastatic, skin 1 (2%) 

Mesentery (3) (3) (4) 

Hepatoblastoma, metastatic, liver 1 (33%) 

Hepatoblastoma, metastatic, pancreas 1 (25%) 

Histiocytic sarcoma 1 (33%) 1 (33%) 

Oral mucosa (1) 

Gingival, squamous cell carcinoma 1 (100%) 

Pancreas (50) (50) (50) 

Hepatoblastoma, metastatic, liver 1 (2%) 

Hepatoblastoma, metastatic, pancreas 1 (2%) 

Salivary glands (50) (50) (50) 

Stomach, forestomach (50) (50) (50) 

Hemangioma 1 (2%) 

Squamous cell papilloma 2 (4%) 

Stomach, glandular (50) (50) (50) 

Hepatoblastoma, metastatic, liver 1 (2%) 

Histiocytic sarcoma 1 (2%) 
 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 117 

TABLE C1 

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Cardiovascular System 

Heart (50) (50) (50) 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 (2%) 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Endocrine System 

Adrenal cortex (50) (50) (50) 

Islets, pancreatic (50) (50) (50) 

Adenoma 1 (2%) 1 (2%) 

Pituitary gland (45) (47) (49) 

Pars distalis, adenoma 1 (2%) 

Pars intermedia, adenoma 1 (2%) 

Thyroid gland (50) (50) (50) 

Follicular cell, adenoma 1 (2%) 

General Body System 

None 

Genital System 

Ductus deferens (1) 

Epididymis (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Preputial gland (49) (50) (50) 

Prostate (50) (50) (50) 

Seminal vesicle (50) (49) (50) 

Hemangiosarcoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Testes (50) (50) (50) 

Interstitial cell, adenoma 1 (2%) 1 (2%) 

Hematopoietic System 

Bone marrow (50) (50) (50) 

Hemangiosarcoma, metastatic, liver 1 (2%) 

Hemangiosarcoma, metastatic, spleen 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Lymph node (2) (5) (1) 

Lumbar, alveolar/bronchiolar carcinoma,

 metastatic, lung 1 (20%) 

Mediastinal, alveolar/bronchiolar carcinoma,

 metastatic, lung 1 (20%) 

Mediastinal, histiocytic sarcoma 1 (20%) 

Lymph node, mandibular (47) (45) (44) 

Lymph node, mesenteric (46) (48) (47) 

Hepatoblastoma, metastatic, liver 1 (2%) 

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

Spleen (50) (50) (50) 

Hemangiosarcoma 3 (6%) 1 (2%) 

Hepatoblastoma, metastatic, liver 1 (2%) 

Thymus (43) (44) (41) 

Histiocytic sarcoma 1 (2%) 
118 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C1 

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Integumentary System 

Skin (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Melanoma malignant 1 (2%) 

Skin, site of application, mast cell tumor malignant 1 (2%) 

Subcutaneous tissue, hemangiosarcoma 1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) 

Vertebra, osteosarcoma 1 (2%) 

Skeletal muscle (1) (3) 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 (100%) 

Hepatoblastoma, metastatic, pancreas 1 (33%) 

Nervous System 

Brain (50) (50) (50) 

Respiratory System 

Lung (50) (50) (50) 

Alveolar/bronchiolar adenoma 10 (20%) 7 (14%) 6 (12%) 

Alveolar/bronchiolar adenoma, multiple 1 (2%) 3 (6%) 1 (2%) 

Alveolar/bronchiolar carcinoma 3 (6%) 2 (4%) 1 (2%) 

Alveolar/bronchiolar carcinoma, multiple 1 (2%) 5 (10%) 2 (4%) 

Hepatoblastoma, metastatic, liver 1 (2%) 3 (6%) 

Hepatoblastoma, metastatic, pancreas 1 (2%) 

Hepatocellular carcinoma, metastatic, liver 6 (12%) 2 (4%) 4 (8%) 

Histiocytic sarcoma 2 (4%) 

Mediastinum, alveolar/bronchiolar carcinoma,

 metastatic, lung 1 (2%) 

Serosa, alveolar/bronchiolar carcinoma,

 metastatic, lung 1 (2%) 

Nose (50) (50) (50) 

Special Senses System 

Eye (1) (2) (1) 

Sarcoma 1 (100%) 

Harderian gland (3) (3) (6) 

Adenoma 2 (67%) 

Carcinoma 2 (67%) 3 (50%) 

Bilateral, carcinoma 1 (33%) 1 (17%) 

Urinary System 

Kidney (50) (50) (50) 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 (2%) 

Hepatoblastoma, metastatic, liver 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Mast cell tumor malignant, metastatic, skin 1 (2%) 

Renal tubule, adenoma 1 (2%) 1 (2%) 7 (14%) 

Renal tubule, carcinoma 2 (4%) 

Urinary bladder (50) (50) (50) 
119 

c 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C1 

Summary of the Incidence of Neoplasms in Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Systemic Lesions 

Multiple organsb (50) (50) (50) 

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

Lymphoma malignant 2 (4%) 3 (6%) 3 (6%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 35 45 50 

Total primary neoplasms 65 80 113 

Total animals with benign neoplasms 26 39 47 

Total benign neoplasms 38 49 65 

Total animals with malignant neoplasms 22 28 35 

Total malignant neoplasms 27 31 48 

Total animals with metastatic neoplasms 9 3 12 

Total metastatic neoplasms 17 9 16 

a Number of animals examined microscopically at the site and the number of animals with neoplasm b Number of animals with any tissue examined microscopically 

Primary neoplasms: all neoplasms except metastatic neoplasms 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

120 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

Number of Days on Study 

4456666677777777777777777 

2981146702222222222222222 

0042854307777788888888889 

Carcass ID Number 

0000000000000000000000000 

5000230330112201112233440 

0296007155182612677948573 

Alimentary System 

Esophagus 

Gallbladder 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Hepatoblastoma, metastatic, liver

Intestine small, jejunum 

Histiocytic sarcoma

Intestine small, ileum 

Liver 

Hemangiosarcoma

Hemangiosarcoma, multiple 

Hemangiosarcoma, metastatic, spleen

Hepatoblastoma, multiple

Hepatocellular carcinoma

Hepatocellular carcinoma, multiple

Hepatocellular adenoma

Hepatocellular adenoma, multiple

Histiocytic sarcoma

Mesentery

Hepatoblastoma, metastatic, liver

Histiocytic sarcoma

Pancreas 

Hepatoblastoma, metastatic, liver

Salivary glands 

Stomach, forestomach 

Stomach, glandular 

Hepatoblastoma, metastatic, liver

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

+++++++++++++++M+M+++++++ 

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

++++++++++++++M++++++++++ 

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

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

X 

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

X 

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

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

X 

X 

X 

X 

X X X 

X X X X X 

 X X X X X X X 

X X X 

X 

+ + 

X 

X 

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

X 

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

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

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

X 

Cardiovascular System 

Blood vessel +++++++++++++++++++++++++ 

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

Endocrine System 

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

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

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

Adenoma X 

Parathyroid gland ++M++MM++++++++++M+++++++ 

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

Pars intermedia, adenoma 

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

General Body System 

None 

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

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

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 121 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

Number of Days on Study 

7777777777777777777777777 

2222222222222222222222222 

9999999999999999999999999 

Carcass ID Number 

0000000000000000000000000 

0011111222223333344444444 

4803459134582367901234689 

Total 

Tissues/ 

Tumors 

Alimentary System 

Esophagus 

Gallbladder 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Hepatoblastoma, metastatic, liver 

Intestine small, jejunum 

Histiocytic sarcoma 

Intestine small, ileum 

Liver 

Hemangiosarcoma 

Hemangiosarcoma, multiple 

Hemangiosarcoma, metastatic, spleen 

Hepatoblastoma, multiple 

Hepatocellular carcinoma

Hepatocellular carcinoma, multiple 

Hepatocellular adenoma

Hepatocellular adenoma, multiple

Histiocytic sarcoma 

Mesentery

Hepatoblastoma, metastatic, liver 

Histiocytic sarcoma 

Pancreas 

Hepatoblastoma, metastatic, liver 

Salivary glands 

Stomach, forestomach 

Stomach, glandular 

Hepatoblastoma, metastatic, liver 

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

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

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

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

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

+ M +++++++++++++++++++++++ 

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

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

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

X X X X 

X X X X 

X XXX X XXX 

+ 

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

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

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

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

50 

48 

50 

49 

50 

49 

1 

50 

1 

50 

50 

1 

1 

1 

1 

7 

5 

11 

11 

1 

3 

1 

1 

50 

1 

50 

50 

50 

1 

Cardiovascular System 

Blood vessel + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Heart + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma 1 

Parathyroid gland + + + + + + + + + + + + + + M + + + M + + + + M + 43 

Pituitary gland + + M M + + + + + M + + + + + + + + + + + + + + + 45 

Pars intermedia, adenoma X 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

122 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

4456666677777777777777777 

Number of Days on Study 2981146702222222222222222 

0042854307777788888888889 

0000000000000000000000000 

Carcass ID Number 5000230330112201112233440 

0296007155182612677948573 

Genital System 

Epididymis +++++++++++++++++++++++++ 

Preputial gland +++++++++++++++++++++++++ 

Prostate +++++++++++++++++++++++++ 

Seminal vesicle +++++++++++++++++++++++++ 

Histiocytic sarcoma X 

Testes +++++++++++++++++++++++++ 

Hematopoietic System 

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

Hemangiosarcoma, metastatic, liver X 

Hemangiosarcoma, metastatic, spleen X 

Lymph node + 

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

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

Hepatoblastoma, metastatic, liver X 

Histiocytic sarcoma X 

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

Hemangiosarcoma X X 

Hepatoblastoma, metastatic, liver X 

Thymus M++++++M+++++M+++++++M+++ 

Integumentary System 

Mammary gland MMMMMMMMMMMM+MMMMMMMMMMMM 

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

Subcutaneous tissue, hemangiosarcoma X 

Musculoskeletal System 

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

Nervous System 

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

Respiratory System 

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

Alveolar/bronchiolar adenoma X X X X 

Alveolar/bronchiolar adenoma, multiple 

Alveolar/bronchiolar carcinoma X X 

Alveolar/bronchiolar carcinoma, multiple 

Hepatoblastoma, metastatic, liver X 

Hepatocellular carcinoma, metastatic, liver XXX X X 

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

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

Special Senses System 

Eye 

Sarcoma 

Harderian gland ++ 

Adenoma X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 123 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle 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 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 

9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

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 0 0 1 1 1 1 1 2 2 2 2 2 3 3 3 3 3 4 4 4 4 4 4 4 4 

4 8 0 3 4 5 9 1 3 4 5 8 2 3 6 7 9 0 1 2 3 4 6 8 9 

Tissues/ 

Tumors 

Genital System 

Epididymis 

Preputial gland 

Prostate 

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

+++++M+++++++++++++++++++ 

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

50 

49 

50 

Seminal vesicle +++++++++++++++++++++++++ 50 

Histiocytic sarcoma 

Testes +++++++++++++++++++++++++ 

1 

50 

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++ 50 

Hemangiosarcoma, metastatic, liver 

Hemangiosarcoma, metastatic, spleen 

Lymph node

Lymph node, mandibular 

Lymph node, mesenteric 

Hepatoblastoma, metastatic, liver 

Histiocytic sarcoma 

Spleen 

Hemangiosarcoma

Hepatoblastoma, metastatic, liver 

Thymus 

+ 

+ ++++++M+++++++++++++++++ 

+ M +++++++++++++++++++++++ 

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

X 

++++++++++++M++MM++++++++ 

1 

1 

2 

47 

46 

1 

1 

50 

3 

1 

43 

Integumentary System 

Mammary gland 

Skin 

MMMMMMMMMMMMMMMMMMMMMMMMM 

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

1 

50 

Subcutaneous tissue, hemangiosarcoma 1 

Musculoskeletal System 

Bone +++++++++++++++++++++++++ 50 

Nervous System 

Brain +++++++++++++++++++++++++ 50 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar adenoma, multiple

Alveolar/bronchiolar carcinoma

Alveolar/bronchiolar carcinoma, multiple

Hepatoblastoma, metastatic, liver 

Hepatocellular carcinoma, metastatic, liver

Nose 

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

X X X X X X 

X 

X 

X 

X 

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

50 

10 

1 

3 

1 

1 

6 

50 

Trachea +++++++++++++++++++++++++ 50 

Special Senses System 

Eye

Sarcoma

 + 

X 

1 

1 

Harderian gland 

Adenoma 

+ M 3 

2 
 

 

 

 

 

 

124 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

4456666677777777777777777 

Number of Days on Study 2981146702222222222222222 

0042854307777788888888889 

0000000000000000000000000 

Carcass ID Number 5000230330112201112233440 

0296007155182612677948573 

Urinary System 

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

Hepatoblastoma, metastatic, liver X 

Renal tubule, adenoma X 

Ureter + 

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

Systemic Lesions 

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

Histiocytic sarcoma X 

Lymphoma malignant X 
 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 125 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

7777777777777777777777777 

Number of Days on Study 2222222222222222222222222 

9999999999999999999999999 

0000000000000000000000000 Total 

Carcass ID Number 0011111222223333344444444 Tissues/ 

4803459134582367901234689 Tumors 

Urinary System 

Kidney +++++++++++++++++++++++++ 50 

Hepatoblastoma, metastatic, liver 1 

Renal tubule, adenoma 1 

Ureter 1 

Urinary bladder +++++++++++++++++++++++++ 50 

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++ 50 

Histiocytic sarcoma 1 

Lymphoma malignant X 2 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

126 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

Number of Days on Study 

3 3 4 5 5 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 

0 5 5 0 7 1 4 5 5 5 9 9 1 2 2 2 2 2 2 2 2 2 2 2 2 

4 6 4 7 6 7 5 2 3 3 2 6 1 7 7 7 7 7 7 7 7 7 7 7 8 

Carcass ID Number 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 

8 8 7 6 6 9 8 7 5 8 9 7 8 5 5 6 6 6 7 7 8 8 9 0 5 

6 5 0 3 7 9 9 6 1 8 5 2 2 5 9 0 1 5 1 8 3 4 8 0 2 

Alimentary System 

Esophagus 

Gallbladder 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Alveolar/bronchiolar carcinoma, metastatic, lung

Hemangiosarcoma

Hepatoblastoma

Hepatocellular carcinoma

Hepatocellular carcinoma, multiple

Hepatocellular adenoma

Hepatocellular adenoma, multiple

Histiocytic sarcoma

Mesentery

Histiocytic sarcoma

Oral mucosa 

Gingival, squamous cell carcinoma 

Pancreas 

Salivary glands 

Stomach, forestomach 

Stomach, glandular 

Histiocytic sarcoma

Tooth

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

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

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

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

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

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

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

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

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

X 

X 

X 

X X X X X X 

X X 

XXXXXX 

X XX XX XXX XXX 

X X 

+ 

X 

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

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

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

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

X 

+ 

Cardiovascular System 

Blood vessel 

Heart 

Alveolar/bronchiolar carcinoma, metastatic, lung

Histiocytic sarcoma

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

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

X 

X 

Endocrine System 

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

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

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

Adenoma X 

Parathyroid gland +M+M++MMMMM +++++++++M++++ 

Pituitary gland +++++++++++++++++++++++MM 

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

Follicular cell, adenoma X 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 127 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

Number of Days on Study 

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 

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 

8 8 8 8 8 8 8 8 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

Carcass ID Number 

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 

5 6 6 6 7 9 9 9 5 5 5 5 6 6 7 7 7 7 8 8 8 9 9 9 9 

4 6 8 9 7 2 3 4 3 6 7 8 2 4 3 4 5 9 0 1 7 0 1 6 7 

Total 

Tissues/ 

Tumors 

Alimentary System 

Esophagus 

Gallbladder 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Alveolar/bronchiolar carcinoma, metastatic, lung 

Hemangiosarcoma

Hepatoblastoma 

Hepatocellular carcinoma 

Hepatocellular carcinoma, multiple 

Hepatocellular adenoma

Hepatocellular adenoma, multiple 

Histiocytic sarcoma 

Mesentery

Histiocytic sarcoma 

Oral mucosa

Gingival, squamous cell carcinoma

Pancreas 

Salivary glands 

Stomach, forestomach 

Stomach, glandular 

Histiocytic sarcoma 

Tooth 

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

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

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

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

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

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

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

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

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

X 

X X X X 

X X X X X 

X X X X X X X X X X X X X 

+ + 

+ 

X 

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

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

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

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

50 

50 

50 

50 

50 

50 

50 

50 

50 

1 

2 

1 

10 

2 

11 

24 

2 

3 

1 

1 

1 

50 

50 

50 

50 

1 

1 

Cardiovascular System 

Blood vessel 

Heart 

Alveolar/bronchiolar carcinoma, metastatic, lung 

Histiocytic sarcoma 

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

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

50 

50 

1 

1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma 1 

Parathyroid gland + + M + + + + M + + + + M + + M + + + + + + + + + 38 

Pituitary gland + + + + + + + + + + + + + M + + + + + + + + + + + 47 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Follicular cell, adenoma 1 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

128 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

3 3 4 5 5 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 0 5 5 0 7 1 4 5 5 5 9 9 1 2 2 2 2 2 2 2 2 2 2 2 2 

4 6 4 7 6 7 5 2 3 3 2 6 1 7 7 7 7 7 7 7 7 7 7 7 8 

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 

Carcass ID Number 8 8 7 6 6 9 8 7 5 8 9 7 8 5 5 6 6 6 7 7 8 8 9 0 5 

6 5 0 3 7 9 9 6 1 8 5 2 2 5 9 0 1 5 1 8 3 4 8 0 2 

Genital System 

Ductus deferens + 

Epididymis +++++++++++++++++++++++++ 

Histiocytic sarcoma X 

Preputial gland +++++++++++++++++++++++++ 

Prostate +++++++++++++++++++++++++ 

Seminal vesicle ++++++ ++++++++++++++++++ 

Testes +++++++++++++++++++++++++ 

Interstitial cell, adenoma 

Hematopoietic System 

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

Histiocytic sarcoma X 

Lymph node + + + + 

Lumbar, alveolar/bronchiolar carcinoma, 

metastatic, lung X 

Mediastinal, alveolar/bronchiolar carcinoma, 

metastatic, lung X 

Mediastinal, histiocytic sarcoma X 

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

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

Histiocytic sarcoma X 

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

Thymus +++++++M++M+++++M+++++MM+ 

Histiocytic sarcoma X 

Integumentary System 

Mammary gland MMMMMMMMMMMMMMMMMMMMMMMMM 

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

Histiocytic sarcoma X 

Musculoskeletal System 

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

Skeletal muscle + 

Alveolar/bronchiolar carcinoma, metastatic, lung X 

Nervous System 

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

Respiratory System 

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

Alveolar/bronchiolar adenoma X X X X 

Alveolar/bronchiolar adenoma, multiple X 

Alveolar/bronchiolar carcinoma X 

Alveolar/bronchiolar carcinoma, multiple X X 

Hepatocellular carcinoma, metastatic, liver 

Histiocytic sarcoma X X 

Serosa, alveolar/bronchiolar carcinoma, 

metastatic, lung X 

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

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

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 129 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

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 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 

8 8 8 8 8 8 8 8 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

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 5 6 6 6 7 9 9 9 5 5 5 5 6 6 7 7 7 7 8 8 8 9 9 9 9 Tissues/ 

4 6 8 9 7 2 3 4 3 6 7 8 2 4 3 4 5 9 0 1 7 0 1 6 7 Tumors 

Genital System 

Ductus deferens 1 

Epididymis +++++++++++++++++++++++++ 50 

Histiocytic sarcoma 1 

Preputial gland +++++++++++++++++++++++++ 50 

Prostate +++++++++++++++++++++++++ 50 

Seminal vesicle +++++++++++++++++++++++++ 49 

Testes +++++++++++++++++++++++++ 50 

Interstitial cell, adenoma X 1 

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++ 50 

Histiocytic sarcoma 1 

Lymph node + 5 

Lumbar, alveolar/bronchiolar carcinoma, 

metastatic, lung 1 

Mediastinal, alveolar/bronchiolar carcinoma, 

metastatic, lung 1 

Mediastinal, histiocytic sarcoma 1 

Lymph node, mandibular + ++++++++++M++++++++++++M 45 

Lymph node, mesenteric + ++++++++++++++++++++++++ 48 

Histiocytic sarcoma 1 

Spleen +++++++++++++++++++++++++ 50 

Thymus +++++++++++++++M+++++++++ 44 

Histiocytic sarcoma 1 

Integumentary System 

Mammary gland MMMMMMMMMMMMMMMMMMMMMMMMM 

Skin +++++++++++++++++++++++++ 50 

Histiocytic sarcoma 1 

Musculoskeletal System 

Bone +++++++++++++++++++++++++ 50 

Skeletal muscle 1 

Alveolar/bronchiolar carcinoma, metastatic, lung 1 

Nervous System 

Brain +++++++++++++++++++++++++ 50 

Respiratory System 

Lung +++++++++++++++++++++++++ 50 

Alveolar/bronchiolar adenoma X X X 7 

Alveolar/bronchiolar adenoma, multiple X X 3 

Alveolar/bronchiolar carcinoma X 2 

Alveolar/bronchiolar carcinoma, multiple X X X 5 

Hepatocellular carcinoma, metastatic, liver X X 2 

Histiocytic sarcoma 2 

Serosa, alveolar/bronchiolar carcinoma, 

metastatic, lung 1 

Nose +++++++++++++++++++++++++ 50 

Trachea +++++++++++++++++++++++++ 50 
 

 

 

 

 

 

 

 

 

 

 

130 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

3345566666667777777777777 

Number of Days on Study 0550714555991222222222222 

4647675233261777777777778 

0000000000000000000000010 

Carcass ID Number 8876698758978556667788905 

6503799618522590151834802 

Special Senses System 

Eye 

Harderian gland + 

Carcinoma X 

Bilateral, carcinoma 

Urinary System 

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

Alveolar/bronchiolar carcinoma, metastatic, lung X 

Histiocytic sarcoma X 

Renal tubule, adenoma X 

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

Systemic Lesions 

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

Histiocytic sarcoma X X 

Lymphoma malignant X X 
 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 131 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

7777777777777777777777777 

Number of Days on Study 2222222222222222222222222 

8888888899999999999999999 

0000000000000000000000000 Total 

Carcass ID Number 5666799955556677778889999 

4689723436782434590170167 

Tissues/ 

Tumors 

Special Senses System 

Eye

Harderian gland

Carcinoma

Bilateral, carcinoma

 +

 +

 X 

+ 

+ 

X 

2 

3 

2 

1 

Urinary System 

Kidney 

Alveolar/bronchiolar carcinoma, metastatic, lung 

Histiocytic sarcoma 

Renal tubule, adenoma 

Urinary bladder 

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

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

50 

1 

1 

1 

50 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Lymphoma malignant

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

X 

50 

2 

3 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

132 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

Number of Days on Study 

4 4 5 5 5 5 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

0 5 0 5 9 9 3 6 6 9 9 1 1 2 2 2 2 2 2 2 2 2 2 2 2 

1 6 5 5 5 7 0 2 7 2 2 0 3 2 7 7 7 7 7 7 7 7 7 7 8 

Carcass ID Number 

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 

2 1 2 4 2 3 1 4 2 1 5 2 0 4 1 1 1 1 2 2 3 3 3 3 0 

5 0 2 6 7 2 8 5 0 9 0 4 7 1 1 2 3 7 3 9 0 1 3 4 2 

Alimentary System 

Esophagus 

Gallbladder 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Hemangioma 

Hemangiosarcoma, multiple

Hemangiosarcoma, metastatic, spleen 

Hepatoblastoma

Hepatocellular carcinoma 

Hepatocellular carcinoma, multiple

Hepatocellular adenoma 

Hepatocellular adenoma, multiple 

Mast cell tumor malignant, metastatic, skin 

Mesentery

Hepatoblastoma, metastatic, pancreas 

Pancreas 

Hepatoblastoma, metastatic, pancreas 

Salivary glands 

Stomach, forestomach 

Hemangioma 

Squamous cell papilloma

Stomach, glandular 

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

+++++++++++++++++++++M+++ 

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

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

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

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

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

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

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

X 

X X X X X 

X X X 

X X X X X 

X X X X 

X X XXXXX X X XXX XXXXX 

+ 

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

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

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

X 

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

Cardiovascular System 

Blood vessel 

Heart 

Alveolar/bronchiolar carcinoma, metastatic, lung 

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

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

Endocrine System 

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

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

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

Parathyroid gland +M++++++M+++++++MM+M++++M 

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

Pars distalis, adenoma X 

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

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 133 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

Number of Days on Study 

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 

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 

8 8 8 8 8 8 8 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

Carcass ID Number 

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 

0 0 1 3 3 3 4 0 0 0 0 0 1 1 2 2 2 3 3 4 4 4 4 4 4 

3 5 4 5 7 9 0 1 4 6 8 9 5 6 1 6 8 6 8 2 3 4 7 8 9 

Total 

Tissues/ 

Tumors 

Alimentary System 

Esophagus 

Gallbladder 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Hemangioma

Hemangiosarcoma, multiple 

Hemangiosarcoma, metastatic, spleen

Hepatoblastoma 

Hepatocellular carcinoma 

Hepatocellular carcinoma, multiple

Hepatocellular adenoma 

Hepatocellular adenoma, multiple 

Mast cell tumor malignant, metastatic, skin 

Mesentery 

Hepatoblastoma, metastatic, pancreas 

Pancreas 

Hepatoblastoma, metastatic, pancreas 

Salivary glands 

Stomach, forestomach 

Hemangioma

Squamous cell papilloma

Stomach, glandular 

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

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

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

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

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

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

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

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

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

X 

X 

X X X X X 

X XX XXX X XX 

X X X 

XXXXXXXXXXXXXXXXXXXXXXXX 

X 

+ + + 

X 

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

X 

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

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

X 

X 

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

50 

49 

50 

50 

50 

50 

50 

50 

50 

1 

1 

1 

10 

12 

8 

4 

41 

1 

4 

1 

50 

1 

50 

50 

1 

2 

50 

Cardiovascular System 

Blood vessel 

Heart 

Alveolar/bronchiolar carcinoma, metastatic, lung

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

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

X 

50 

50 

1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Parathyroid gland + + + + + + + M + M + + + + + M + + M + + + + + + 40 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Pars distalis, adenoma 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

134 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

4 4 5 5 5 5 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 

Number of Days on Study 0 5 0 5 9 9 3 6 6 9 9 1 1 2 2 2 2 2 2 2 2 2 2 2 2 

1 6 5 5 5 7 0 2 7 2 2 0 3 2 7 7 7 7 7 7 7 7 7 7 8 

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 2 1 2 4 2 3 1 4 2 1 5 2 0 4 1 1 1 1 2 2 3 3 3 3 0 

5 0 2 6 7 2 8 5 0 9 0 4 7 1 1 2 3 7 3 9 0 1 3 4 2 

Genital System 

Epididymis 

Penis

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

+ 

Preputial gland 

Prostate 

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

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

Seminal vesicle +++++++++++++++++++++++++ 

Hemangiosarcoma

Testes 

X 

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

Interstitial cell, adenoma X 

Hematopoietic System 

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

Lymph node

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Hemangiosarcoma 

Thymus 

+ 

+ M ++++++++++M++MM+++M++++ 

+ M ++++++++M++++++++++++++ 

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

M++++M+M++M+++++++M+M++++ 

Integumentary System 

Mammary gland 

Skin 

MMMMMMMMMMMMMMMM+MMMMMMMM 

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

Melanoma malignant 

Skin, site of application,

 mast cell tumor malignant 

Musculoskeletal System 

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

Vertebra, osteosarcoma

Skeletal muscle

 X 

+ 

Hepatoblastoma, metastatic, pancreas 

Nervous System 

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

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar adenoma, multiple

Alveolar/bronchiolar carcinoma 

Alveolar/bronchiolar carcinoma, multiple

Hepatoblastoma, metastatic, liver

Hepatoblastoma, metastatic, pancreas 

Hepatocellular carcinoma, metastatic, liver 

Mediastinum, alveolar/bronchiolar carcinoma, 

metastatic, lung

Nose 

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

 X X X 

X 

X X 

X X 

X X X 

X 

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

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

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 135 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

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 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 

8 8 8 8 8 8 8 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 

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 3 3 3 4 0 0 0 0 0 1 1 2 2 2 3 3 4 4 4 4 4 4 

3 5 4 5 7 9 0 1 4 6 8 9 5 6 1 6 8 6 8 2 3 4 7 8 9 

Tissues/ 

Tumors 

Genital System 

Epididymis 

Penis 

+++++++++++++++++++++++++ 50 

1 

Preputial gland 

Prostate 

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

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

50 

50 

Seminal vesicle +++++++++++++++++++++++++ 50 

Hemangiosarcoma 

Testes +++++++++++++++++++++++++ 

1 

50 

Interstitial cell, adenoma 1 

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++ 50 

Lymph node 

Lymph node, mandibular 

Lymph node, mesenteric 

Spleen 

Hemangiosarcoma

Thymus 

+ +++M++++++++++++++++++++ 

+ +++++++++++++++M++++++++ 

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

X 

+++++++++M++++++++MM+++++ 

1 

44 

47 

50 

1 

41 

Integumentary System 

Mammary gland 

Skin 

MM+MMMMMMMMMMMMMMMMMMMMMM

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

2 

50 

Melanoma malignant

Skin, site of application, 

mast cell tumor malignant 

X 

X 

1 

1 

Musculoskeletal System 

Bone +++++++++++++++++++++++++ 50 

Vertebra, osteosarcoma 

Skeletal muscle + + 

1 

3 

Hepatoblastoma, metastatic, pancreas X 1 

Nervous System 

Brain +++++++++++++++++++++++++ 50 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar adenoma, multiple 

Alveolar/bronchiolar carcinoma

Alveolar/bronchiolar carcinoma, multiple 

Hepatoblastoma, metastatic, liver

Hepatoblastoma, metastatic, pancreas 

Hepatocellular carcinoma, metastatic, liver

Mediastinum, alveolar/bronchiolar carcinoma, 

metastatic, lung 

Nose 

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

X X X 

X 

X 

X 

X 

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

50 

6 

1 

1 

2 

3 

1 

4 

1 

50 

Trachea +++++++++++++++++++++++++ 50 
 

 

 

 

 

 

 

 

 

 

136 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

4455556666677777777777777 

Number of Days on Study 0505993669911222222222222 

1655570272203277777777778 

1111111111111111111111111 

Carcass ID Number 2124231421520411112233330 

5026728509047112373901342 

Special Senses System 

Eye + 

Harderian gland + + + + 

Carcinoma X X 

Bilateral, carcinoma X 

Urinary System 

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

Mast cell tumor malignant, metastatic, skin 

Renal tubule, adenoma X X X X 

Renal tubule, carcinoma 

Ureter + 

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

Systemic Lesions 

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

Lymphoma malignant X X 
 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 137 

TABLE C2 

Individual Animal Tumor Pathology of Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

Number of Days on Study 

7777777777777777777777777 

2222222222222222222222222 

8888888999999999999999999 

Carcass ID Number 

1111111111111111111111111 

0013334000001122233444444 

3545790146895616868234789 

Total 

Tissues/ 

Tumors 

Special Senses System 

Eye 

Harderian gland

Carcinoma

Bilateral, carcinoma 

+

 X 

+ 

1 

6 

3 

1 

Urinary System 

Kidney 

Mast cell tumor malignant, metastatic, skin 

Renal tubule, adenoma

Renal tubule, carcinoma

Ureter 

Urinary bladder 

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

X 

X X X 

X X 

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

50 

1 

7 

2 

1 

50 

Systemic Lesions 

Multiple organs 

Lymphoma malignant

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

X 

50 

3 
138 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C3 

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Harderian Gland: Carcinoma 

Overall ratea 0/50 (0%) 3/50 (6%) 4/50 (8%) 

Adjusted rateb 0.0% 6.8% 8.8% 

Terminal ratec 0/41 (0%) 3/37 (8%) 1/36 (3%) e First incidence (days) — 727 (T) 630 

Poly-3 testd P=0.045 P=0.111 P=0.058 

Harderian Gland: Adenoma or Carcinoma 

Overall rate 2/50 (4%) 3/50 (6%) 4/50 (8%) 

Adjusted rate 4.3% 6.8% 8.8% 

Terminal rate 2/41 (5%) 3/37 (8%) 1/36 (3%) 

First incidence (days) 727 (T) 727 (T) 630 

Poly-3 test P=0.258 P=0.480 P=0.329 

Kidney (Renal Tubule): Adenoma 

Overall rate 1/50 (2%) 1/50 (2%) 7/50 (14%)
 

Adjusted rate 2.2% 2.3% 15.3%
 

Terminal rate 1/41 (2%) 1/37 (3%) 4/36 (11%)
 

First incidence (days) 727 (T) 727 (T) 597
 

Poly-3 test P=0.009 P=0.751 P=0.029
 

Kidney (Renal Tubule): Adenoma or Carcinoma 

Overall rate 1/50 (2%) 1/50 (2%) 9/50 (18%)
 

Adjusted rate 2.2% 2.3% 19.6%
 

Terminal rate 1/41 (2%) 1/37 (3%) 6/36 (17%)
 

First incidence (days) 727 (T) 727 (T) 597
 

Poly-3 test P<0.001 P=0.751 P=0.007
 

Liver: Hepatocellular Adenoma 

Overall rate 22/50 (44%) 35/50 (70%) 45/50 (90%)
 

Adjusted rate 46.2% 75.4% 91.4%
 

Terminal rate 18/41 (44%) 29/37 (78%) 34/36 (94%)
 

First incidence (days) 612 507 401
 

Poly-3 test P<0.001 P=0.002 P<0.001
 

Liver: Hepatocellular Carcinoma 

Overall rate 12/50 (24%) 12/50 (24%) 20/50 (40%)
 

Adjusted rate 25.4% 26.2% 43.0%
 

Terminal rate 9/41 (22%) 7/37 (19%) 15/36 (42%)
 

First incidence (days) 584 576 456
 

Poly-3 test P=0.041 P=0.561 P=0.055
 

Liver: Hepatocellular Adenoma or Carcinoma 

Overall rate 28/50 (56%) 39/50 (78%) 47/50 (94%)
 

Adjusted rate 58.0% 82.4% 95.3%
 

Terminal rate 22/41 (54%) 30/37 (81%) 34/36 (94%)
 

First incidence (days) 584 507 401
 

Poly-3 test P<0.001 P=0.007 P<0.001
 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 139 

TABLE C3 

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Liver: Hepatoblastoma 

Overall rate 1/50 (2%) 1/50 (2%) 10/50 (20%)
 

Adjusted rate 2.1% 2.2% 22.1%
 

Terminal rate 0/41 (0%) 0/37 (0%) 8/36 (22%)
 

First incidence (days) 664 507 692
 

Poly-3 test P<0.001 P=0.753 P=0.003
 

Liver: Hepatocellular Carcinoma or Hepatoblastoma 

Overall rate 13/50 (26%) 13/50 (26%) 25/50 (50%)
 

Adjusted rate 27.4% 28.0% 53.7%
 

Terminal rate 9/41 (22%) 7/37 (19%) 19/36 (53%)
 

First incidence (days) 584 507 456
 

Poly-3 test P=0.005 P=0.567 P=0.007
 

Liver: Hepatocellular Adenoma, Hepatocellular Carcinoma, or Hepatoblastoma 

Overall rate 29/50 (58%) 39/50 (78%) 49/50 (98%)
 

Adjusted rate 59.8% 82.4% 99.3%
 

Terminal rate 22/41 (54%) 30/37 (81%) 36/36 (100%)
 

First incidence (days) 584 507 401
 

Poly-3 test P<0.001 P=0.011 P<0.001
 

Lung: Alveolar/bronchiolar Adenoma 

Overall rate 11/50 (22%) 10/50 (20%) 7/50 (14%)
 

Adjusted rate 23.7% 22.3% 15.3%
 

Terminal rate 11/41 (27%) 8/37 (22%) 5/36 (14%)
 

First incidence (days) 727 (T) 645 630
 

Poly-3 test P=0.193N P=0.535N P=0.226N
 

Lung: Alveolar/bronchiolar Carcinoma 

Overall rate 4/50 (8%) 7/50 (14%) 3/50 (6%)
 

Adjusted rate 8.6% 15.6% 6.6%
 

Terminal rate 4/41 (10%) 5/37 (14%) 2/36 (6%)
 

First incidence (days) 727 (T) 653 667
 

Poly-3 test P=0.451N P=0.243 P=0.513N
 

Lung: Alveolar/bronchiolar Adenoma or Carcinoma 

Overall rate 15/50 (30%) 17/50 (34%) 9/50 (18%)
 

Adjusted rate 32.3% 37.4% 19.6%
 

Terminal rate 15/41 (37%) 13/37 (35%) 6/36 (17%)
 

First incidence (days) 727 (T) 645 630
 

Poly-3 test P=0.110N P=0.385 P=0.122N
 

Spleen: Hemangiosarcoma 

Overall rate 3/50 (6%) 0/50 (0%) 1/50 (2%) 

Adjusted rate 6.5% 0.0% 2.2% 

Terminal rate 3/41 (7%) 0/37 (0%) 1/36 (3%) 

First incidence (days) 727 (T) — 727 (T) 

Poly-3 test P=0.180N P=0.127N P=0.316N 
140 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C3 

Statistical Analysis of Primary Neoplasms in Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

All Organs: Hemangiosarcoma 

Overall rate 6/50 (12%) 2/50 (4%) 3/50 (6%)
 

Adjusted rate 12.5% 4.5% 6.6%
 

Terminal rate 4/41 (10%) 2/37 (5%) 2/36 (6%)
 

First incidence (days) 420 727 (T) 555
 

Poly-3 test P=0.184N P=0.159N P=0.267N
 

All Organs: Hemangioma or Hemangiosarcoma 

Overall rate 6/50 (12%) 2/50 (4%) 5/50 (10%)
 

Adjusted rate 12.5% 4.5% 11.0%
 

Terminal rate 4/41 (10%) 2/37 (5%) 4/36 (11%)
 

First incidence (days) 420 727 (T) 555
 

Poly-3 test P=0.454N P=0.159N P=0.534N
 

All Organs: Malignant Lymphoma 

Overall rate 2/50 (4%) 3/50 (6%) 3/50 (6%) 

Adjusted rate 4.3% 6.6% 6.6% 

Terminal rate 1/41 (2%) 1/37 (3%) 2/36 (6%) 

First incidence (days) 612 304 505 

Poly-3 test P=0.402 P=0.489 P=0.490 

All Organs: Benign Neoplasms 

Overall rate 26/50 (52%) 39/50 (78%) 47/50 (94%)
 

Adjusted rate 54.7% 83.6% 95.3%
 

Terminal rate 22/41 (54%) 31/37 (84%) 35/36 (97%)
 

First incidence (days) 612 507 401
 

Poly-3 test P<0.001 P<0.001 P<0.001
 

All Organs: Malignant Neoplasms 

Overall rate 22/50 (44%) 28/50 (56%) 35/50 (70%)
 

Adjusted rate 44.3% 57.0% 71.7%
 

Terminal rate 14/41 (34%) 16/37 (43%) 24/36 (67%)
 

First incidence (days) 420 304 456
 

Poly-3 test P=0.003 P=0.143 P=0.004
 

All Organs: Benign or Malignant Neoplasms 

Overall rate 35/50 (70%) 45/50 (90%) 50/50 (100%)
 

Adjusted rate 70.0% 91.6% 100.0%
 

Terminal rate 26/41 (63%) 33/37 (89%) 36/36 (100%)
 

First incidence (days) 420 304 401
 

Poly-3 test P<0.001 P=0.005 P<0.001
 

(T)Terminal sacrifice 

a Number of neoplasm-bearing animals/number of animals examined. Denominator is number of animals examined microscopically for kidney, liver, lung, 

and spleen; 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 vehicle control incidence are the P values associated with the trend test. Beneath the dosed group incidence are the P values corresponding to 

pairwise comparisons between the vehicle controls and that dosed 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 a dose group is indicated by N. e Not applicable; no neoplasms in animal group 

c 
 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 141 

TABLE C4a 

Historical Incidence of Liver Neoplasms in Vehicle Control Male B6C3F1 Micea 

Incidence in Controls 

Study Hepatocellular Hepatocellular Hepatoblastoma Hepatocellular Adenoma, 

Adenoma Carcinoma Hepatocellular Carcinoma,

 or Hepatoblastoma 

Historical Incidence at Battelle Columbus Laboratories 

Benzethonium Chloride 24/50 10/50 0/50 29/50 

Coconut Oil Acid Diethanolamine Condensate 22/50 12/50 1/50 29/50 

Diethanolamine 31/50 12/50 0/50 39/50 

Lauric Acid Diethanolamine Condensate 19/50 11/50 0/50 28/50 

Oleic Acid Diethanolamine Condensate 22/49 9/49 0/49 29/49 

Overall Historical Incidence 

Total 118/249 (47.4%) 54/249 (21.7%) 1/249 (0.4%) 154/249 (61.8%) 

Mean ± standard deviation 47.4% ± 8.9% 21.7% ± 2.5% 0.4% ± 0.9% 61.8% ± 9.1% 

Range 38%-62% 18%-24% 0%-2% 56%-78% 

a Data as of 12 July 2000. Vehicle controls from the sodium xylenesulfonate study were excluded because liver neoplasms were associated with hepatitis due 

to Helicobacter hepaticus infection. 

TABLE C4b 

Historical Incidence of Renal Tubule Neoplasms in Vehicle Control Male B6C3F1 Micea 

Incidence in Controls 

Study Adenoma Carcinoma Adenoma or Carcinoma 

Historical Incidence at Battelle Columbus Laboratories 

Benzethonium Chloride 0/50 0/50 0/50 

Coconut Oil Acid Diethanolamine Condensate 1/50 0/50 1/50 

Diethanolamine 1/50 2/50 3/50 

Lauric Acid Diethanolamine Condensate 0/50 0/50 0/50 

Oleic Acid Diethanolamine Condensate 0/49 0/49 0/49 

Sodium Xylenesulfonate 0/50 0/50 0/50 

Overall Historical Incidence 

Total 2/299 (0.7%) 2/299 (0.7%) 4/299 (1.3%) 

Mean ± standard deviation 0.7% ± 1.0% 0.7% ± 1.6% 1.3% ± 2.4% 

Range 0%-2% 0%-4% 0%-6% 

a Data as of 12 July 2000 
142 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C5 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 100 mg/kg 200 mg/kg 

Disposition Summary 

Animals initially in study 50 50 50 

Early deaths 

Moribund 5 7 7 

Natural deaths 4 6 7 

Survivors 

Terminal sacrifice 41 37 36 

Animals examined microscopically 50 50 50 

Alimentary System 

Intestine small, duodenum (49) (50) (50) 

Ulcer 1 (2%) 

Intestine small, jejunum (50) (50) (50) 

Inflammation 1 (2%) 

Lymphatic, hyperplasia 1 (2%) 

Liver (50) (50) (50) 

Angiectasis 1 (2%) 

Basophilic focus 3 (6%) 

Clear cell focus 8 (16%) 8 (16%) 4 (8%) 

Degeneration, cystic 1 (2%) 

Eosinophilic focus 20 (40%) 29 (58%) 31 (62%) 

Hematopoietic cell proliferation 1 (2%) 1 (2%) 

Mixed cell focus 6 (12%) 7 (14%) 6 (12%) 

Necrosis 1 (2%) 3 (6%) 2 (4%) 

Bile duct, hyperplasia 1 (2%) 

Mesentery (3) (3) (4) 

Artery, inflammation 1 (25%) 

Fat, necrosis 1 (33%) 1 (33%) 2 (50%) 

Pancreas (50) (50) (50) 

Atrophy 2 (4%) 2 (4%) 5 (10%) 

Hypertrophy, focal 1 (2%) 

Inflammation, granulomatous 1 (2%) 

Duct, cyst 1 (2%) 1 (2%) 

Duct, hyperplasia 1 (2%) 

Salivary glands (50) (50) (50) 

Inflammation 1 (2%) 

Inflammation, granulomatous 1 (2%) 

Stomach, forestomach (50) (50) (50) 

Hyperplasia, focal 1 (2%) 1 (2%) 

Ulcer 1 (2%) 

Stomach, glandular (50) (50) (50) 

Dysplasia 1 (2%) 

Erosion 1 (2%) 

Hyperplasia 1 (2%) 

Inflammation, granulomatous 1 (2%) 

Tooth (1) 

Inflammation 1 (100%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 143 

TABLE C5 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Cardiovascular System 

Blood vessel (50) (50) (50) 

Aorta, inflammation 1 (2%) 

Heart (50) (50) (50) 

Degeneration 3 (6%) 

Artery, inflammation 1 (2%) 

Atrium, thrombosis 1 (2%) 

Coronary artery, thrombosis 1 (2%) 

Endocrine System 

Adrenal cortex (50) (50) (50) 

Angiectasis 1 (2%) 

Hyperplasia 3 (6%) 6 (12%) 3 (6%) 

Hypertrophy 28 (56%) 30 (60%) 26 (52%) 

Necrosis 1 (2%) 

Capsule, hyperplasia 8 (16%) 15 (30%) 11 (22%) 

Adrenal medulla (50) (50) (50) 

Hyperplasia 2 (4%) 2 (4%) 

Isets, pancreatic (50) (50) (50) 

Hyperplasia 21 (12%) 23 (46%) 21 (42%) 

Pituitary gland (45) (47) (49) 

Cyst 2 (4%) 3 (6%) 

Pars distalis, hyperplasia 4 (9%) 2 (4%) 4 (8%) 

Pars intermedia, hyperplasia 1 (2%) 1 (2%) 

Thyroid gland (50) (50) (50) 

Follicular cell, hyperplasia 11 (22%) 20 (40%) 23 (46%) 

General Body System 

None 

Genital System 

Epididymis (50) (50) (50) 

Granuloma sperm 2 (4%) 1 (2%) 2 (4%) 

Penis (1) 

Congestion 1 (100%) 

Preputial Gland (49) (50) (50) 

Cyst 21 (43%) 21 (42%) 14 (28%) 

Inflammation 1 (2%) 1 (2%) 

Prostate (50) (50) (50) 

Inflammation 1 (2%) 1 (2%) 

Seminal vesicle (50) (49) (50) 

Inflammation, granulomatous 1 (2%) 

Testes (50) (50) (50) 

Atrophy 2 (4%) 2 (4%) 1 (2%) 

Mineralization 1 (2%) 

Interstitial cell, hyperplasia 1 (2%) 
 

 

 

144 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE C5 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Hematopoietic System 

Bone marrow (50) (50) (50) 

Hyperplasia 10 (20%) 10 (20%) 19 (38%) 

Lymph node, mandibular (47) (45) (44) 

Hematopoietic cell proliferation 1 (2%) 

Lymph node, mesenteric (46) (48) (47) 

Angiectasis 1 (2%) 1 (2%) 1 (2%) 

Atrophy 2 (4%) 

Hematopoietic cell proliferation 2 (4%) 2 (4%) 3 (6%) 

Hemorrhage 1 (2%) 

Hyperplasia, lymphoid 1 (2%) 2 (4%) 

Inflammation, granulomatous 1 (2%) 

Spleen (50) (50) (50) 

Angiectasis 1 (2%) 

Fibrosis 1 (2%) 

Hematopoietic cell proliferation 25 (50%) 23 (46%) 30 (60%) 

Thymus (43) (44) (41) 

Atrophy 13 (30%) 13 (30%) 14 (34%) 

Integumentary System 

Skin (50) (50) (50) 

Control, edema 1 (2%) 

Control, infiltration cellular, mast cell 1 (2%) 

Epidermis, skin, site of application, hyperplasia 5 (10%) 47 (94%) 50 (100%) 

Lymphatic, angiectasis 1 (2%) 

Sebaceous gland, skin, site of application, hyperplasia 44 (88%) 49 (98%) 

Skin, site of application, hyperkeratosis 24 (48%) 23 (46%) 

Skin, site of application, inflammation 2 (4%) 2 (4%) 2 (4%) 

Skin, site of application, parakeratosis 1 (2%) 4 (8%) 5 (10%) 

Skin, site of application, ulcer 1 (2%) 7 (14%) 

Musculoskeletal System 

Bone (50) (50) (50) 

Hyperostosis 1 (2%) 

Nervous System 

Brain (50) (50) (50) 

Neuron, necrosis 1 (2%) 

Respiratory System 

Lung (50) (50) (50) 

Inflammation 1 (2%) 1 (2%) 

Inflammation, granulomatous 1 (2%) 

Pigmentation, hemosiderin 1 (2%) 

Alveolar epithelium, hyperplasia 4 (8%) 4 (8%) 1 (2%) 

Nose (50) (50) (50) 

Inflammation 1 (2%) 1 (2%) 

Nasolacrimal duct, inflammation 1 (2%) 1 (2%) 
 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 145 

TABLE C5 

Summary of the Incidence of Nonneoplastic Lesions in Male Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Special Senses System 

Eye (1) (2) (1) 

Cornea, inflammation 2 (100%) 1 (100%) 

Harderian gland (3) (3) (6) 

Hyperplasia 1 (33%) 1 (17%) 

Urinary System 

Kidney (50) (50) (50) 

Accumulation, hyaline droplet 1 (2%) 1 (2%) 

Cyst 12 (24%) 16 (32%) 11 (22%) 

Inflammation, granulomatous 1 (2%) 

Inflammation, suppurative 1 (2%) 

Nephropathy 47 (94%) 49 (98%) 50 (100%) 

Pigmentation, hemosiderin 3 (6%) 

Artery, inflammation 2 (4%) 1 (2%) 

Renal tubule, hyperplasia 1 (2%) 2 (4%) 

Ureter (1) (1) 

Inflammation, granulomatous 1 (100%) 

Urinary bladder (50) (50) (50) 

Inflammation 1 (2%) 

Inflammation, granulomatous 1 (2%) 
146 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 
147 

APPENDIX D 

SUMMARY OF LESIONS IN FEMALE MICE 

IN THE 2-YEAR DERMAL STUDY 

OF COCONUT OIL ACID 

DIETHANOLAMINE CONDENSATE 

TABLE D1 

TABLE D2 

TABLE D3 

TABLE D4 

TABLE D5 

Summary of the Incidence of Neoplasms in Female Mice 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ....... 

Individual Animal Tumor Pathology of Female Mice 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ....... 

Statistical Analysis of Primary Neoplasms in Female Mice 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ....... 

Historical Incidence of Liver Neoplasms 

in Vehicle Control Female B6C3F1 Mice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice 

in the 2-Year Dermal Study of Coconut Oil Acid Diethanolamine Condensate ....... 

148 

152 

170 

173 

174 
 

 

 

 

148 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 100 mg/kg 200 mg/kg 

Disposition Summary 

Animals initially in study 50 50 50 

Early deaths 

Moribund 11 11 15 

Natural deaths 4 3 9 

Survivors 

Died last week of study 1 

Terminal sacrifice 35 35 26 

Animals examined microscopically 50 50 50 

Alimentary System 

Gallbladder (49) (48) (50) 

Intestine large, rectum (50) (50) (50) 

Intestine small, duodenum (50) (50) (50) 

Leiomyosarcoma, metastatic, intestine small, jejunum 1 (2%) 

Polyp adenomatous 1 (2%) 

Intestine small, jejunum (49) (50) (50) 

Carcinoma 1 (2%) 

Leiomyosarcoma 1 (2%) 

Liver (50) (50) (50) 

Carcinoma, metastatic, harderian gland 1 (2%) 

Carcinoma, metastatic, thyroid gland 1 (2%) 

Hemangiosarcoma, multiple 1 (2%) 

Hepatoblastoma 1 (2%) 2 (4%) 

Hepatoblastoma, multiple 1 (2%) 

Hepatocellular carcinoma 1 (2%) 17 (34%) 16 (32%) 

Hepatocellular carcinoma, multiple 2 (4%) 4 (8%) 16 (32%) 

Hepatocellular adenoma 8 (16%) 5 (10%) 5 (10%) 

Hepatocellular adenoma, multiple 24 (48%) 39 (78%) 38 (76%) 

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

Leiomyosarcoma, metastatic, intestine small, jejunum 1 (2%) 

Mesentery (12) (9) (8) 

Leiomyosarcoma, metastatic, intestine small, jejunum 1 (11%) 

Pancreas (50) (50) (50) 

Hemangioma 1 (2%) 

Leiomyosarcoma, metastatic, intestine small, jejunum 1 (2%) 

Salivary glands (50) (50) (50) 

Stomach, forestomach (50) (50) (50) 

Squamous cell papilloma 1 (2%) 2 (4%) 1 (2%) 

Stomach, glandular (50) (50) (50) 

Tongue (1) 

Squamous cell carcinoma 1 (100%) 

Cardiovascular System 

Heart (50) (50) (50) 

Carcinoma, metastatic, thyroid gland 1 (2%) 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 149 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Endocrine System 

Adrenal cortex (50) (50) (50) 

Adenoma 1 (2%) 

Adrenal medulla (50) (50) (50) 

Pheochromocytoma malignant 1 (2%) 

Pheochromocytoma complex 1 (2%) 

Pheochromocytoma benign 2 (4%) 1 (2%) 

Islets, pancreatic (50) (50) (50) 

Adenoma 1 (2%) 1 (2%) 

Pituitary gland (48) (50) (49) 

Pars distalis, adenoma 5 (10%) 2 (4%) 1 (2%) 

Pars distalis, carcinoma 1 (2%) 1 (2%) 

Pars intermedia, adenoma 1 (2%) 1 (2%) 

Thyroid gland (50) (50) (50) 

C-cell, carcinoma 1 (2%) 

Follicular cell, adenoma 2 (4%) 5 (10%) 3 (6%) 

General Body System 

None 

Genital System 

Clitoral gland (48) (49) (47) 

Carcinoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Ovary (50) (50) (50) 

Cystadenoma 3 (6%) 1 (2%) 

Granulosa cell tumor malignant 1 (2%) 

Hemangioma 1 (2%) 

Hemangiosarcoma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Luteoma 1 (2%) 

Teratoma benign 1 (2%) 

Teratoma malignant 1 (2%) 

Uterus (50) (50) (50) 

Hemangioma 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Leiomyosarcoma 1 (2%) 

Polyp stromal 1 (2%) 2 (4%) 2 (4%) 

Vagina (1) 

Histiocytic sarcoma 1 (100%) 

Hematopoietic System 

Bone marrow (50) (50) (50) 

Hemangiosarcoma 1 (2%) 

Hemangiosarcoma, metastatic, ovary 1 (2%) 

Histiocytic sarcoma 1 (2%) 
150 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Hematopoietic System (continued) 

Lymph node (7) (3) (6) 

Bronchial, histiocytic sarcoma 1 (33%) 

Inguinal, fibrosarcoma, metastatic, skin 1 (14%) 

Lumbar, histiocytic sarcoma 1 (17%) 

Mediastinal, alveolar/bronchiolar carcinoma,

 metastatic, lung 1 (17%) 

Mediastinal, carcinoma, metastatic, thyroid gland 1 (14%) 

Mediastinal, hepatoblastoma, metastatic, liver 1 (33%) 

Mediastinal, histiocytic sarcoma 1 (33%) 1 (17%) 

Pancreatic, carcinoma, metastatic, thyroid gland 1 (14%) 

Lymph node, mandibular (49) (47) (49) 

Carcinoma, metastatic, thyroid gland 1 (2%) 

Histiocytic sarcoma 1 (2%) 

Lymph node, mesenteric (48) (50) (49) 

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

Leiomyosarcoma, metastatic, intestine small, jejunum 1 (2%) 

Spleen (50) (50) (50) 

Histiocytic sarcoma 1 (2%) 

Leiomyosarcoma, metastatic, intestine small, jejunum 1 (2%) 

Thymus (47) (40) (41) 

Leiomyosarcoma, metastatic, intestine small, jejunum 1 (3%) 

Integumentary System 

Mammary gland (48) (49) (50) 

Carcinoma 1 (2%) 1 (2%) 

Skin (50) (50) (50) 

Melanoma benign 1 (2%) 

Melanoma malignant 1 (2%) 

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

Subcutaneous tissue, fibrous histiocytoma 1 (2%) 

Subcutaneous tissue, melanoma benign 1 (2%) 1 (2%) 

Subcutaneous tissue, control, sarcoma 1 (2%) 

Musculoskeletal System 

None 

Nervous System 

Brain (50) (50) (50) 

Carcinoma, metastatic, pituitary gland 1 (2%) 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 151 

TABLE D1 

Summary of the Incidence of Neoplasms in Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Respiratory System 

Lung (50) (50) (50) 

Alveolar/bronchiolar adenoma 1 (2%) 3 (6%) 

Alveolar/bronchiolar adenoma, multiple 1 (2%) 1 (2%) 

Alveolar/bronchiolar carcinoma 1 (2%) 1 (2%) 

Carcinoma, metastatic, harderian gland 1 (2%) 2 (4%) 

Carcinoma, metastatic, thyroid gland 1 (2%) 

Hepatoblastoma, metastatic, liver 1 (2%) 1 (2%) 

Hepatocellular carcinoma, metastatic, liver 2 (4%) 3 (6%) 9 (18%) 

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

Mediastinum, leiomyosarcoma, metastatic,

 intestine small, jejunum 1 (2%) 

Nose (50) (50) (49) 

Carcinoma, metastatic, harderian gland 1 (2%) 1 (2%) 

Special Senses System 

Eye (1) (2) (1) 

Carcinoma, metastatic, harderian gland 1 (50%) 

Harderian gland (1) (2) (1) 

Carcinoma 1 (100%) 2 (100%) 1 (100%) 

Urinary System 

Kidney (50) (50) (50) 

Hepatoblastoma, metastatic, liver 1 (2%) 

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

Leiomyosarcoma, metastatic, intestine small, jejunum 1 (2%) 

Renal tubule, adenoma 1 (2%) 

Urinary bladder (50) (50) (50) 

Hemangioma 1 (2%) 

Systemic Lesions 

Multiple organsb (50) (50) (50) 

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

Lymphoma malignant 13 (26%) 5 (10%) 7 (14%) 

Neoplasm Summary 

Total animals with primary neoplasmsc 47 48 50 

Total primary neoplasms 78 104 110 

Total animals with benign neoplasms 39 45 45 

Total benign neoplasms 53 66 56 

Total animals with malignant neoplasms 23 30 41 

Total malignant neoplasms 25 38 54 

Total animals with metastatic neoplasms 5 8 11 

Total metastatic neoplasms 11 21 12 

a Number of animals examined microscopically at the site and the number of animals with neoplasm b Number of animals with any tissue examined microscopically 

Primary neoplasms: all neoplasms except metastatic neoplasms c 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

152 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

Number of Days on Study 

4455566666777777777777777 

2706816788001122222222222 

9968974917123969999999999 

Carcass ID Number 

1111121111111111111111111 

8885907795985685555666666 

7698004369305531234124689 

Alimentary System 

Esophagus 

Gallbladder 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Carcinoma, metastatic, thyroid gland

Hemangiosarcoma, multiple

Hepatocellular carcinoma

Hepatocellular carcinoma, multiple

Hepatocellular adenoma

Hepatocellular adenoma, multiple

Histiocytic sarcoma

Mesentery

Pancreas 

Salivary glands 

Stomach, forestomach 

Squamous cell papilloma 

Stomach, glandular 

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

+++++++++++++++++++++++M+ 

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

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

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

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

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

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

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

X 

X 

X 

X 

X X X X 

XX X X XXXX X 

X 

+++ + + 

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

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

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

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

Cardiovascular System 

Blood vessel 

Heart 

Carcinoma, metastatic, thyroid gland

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

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

X 

Endocrine System 

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

Adenoma X 

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

Pheochromocytoma benign X 

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

Parathyroid gland +MMMM+M ++++++++++++MM+M++ 

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

Pars distalis, adenoma X X X 

Pars distalis, carcinoma X 

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

C-cell, carcinoma X 

Follicular cell, adenoma X 

General Body System 

None 

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

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

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 153 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

Number of Days on Study 

7777777777777777777777777 

2222222222222333333333333 

9999999999999000000000000 

Carcass ID Number 

1111111111111111111111111 

7777778899999556667788899 

0156895812789670372712445 

Total 

Tissues/ 

Tumors 

Alimentary System 

Esophagus 

Gallbladder 

Intestine large, colon 

Intestine large, rectum 

Intestine large, cecum 

Intestine small, duodenum 

Intestine small, jejunum 

Intestine small, ileum 

Liver 

Carcinoma, metastatic, thyroid gland 

Hemangiosarcoma, multiple 

Hepatocellular carcinoma 

Hepatocellular carcinoma, multiple

Hepatocellular adenoma

Hepatocellular adenoma, multiple 

Histiocytic sarcoma 

Mesentery

Pancreas 

Salivary glands 

Stomach, forestomach 

Squamous cell papilloma

Stomach, glandular 

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

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

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

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

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

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

+++++++++++++++++++M+++++ 

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

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

X 

X X X X 

XX XXXXXX XX XXXXX 

+ + + + + ++ 

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

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

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

X 

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

50 

49 

50 

50 

50 

50 

49 

50 

50 

1 

1 

1 

2 

8 

24 

1 

12 

50 

50 

50 

1 

50 

Cardiovascular System 

Blood vessel 

Heart 

Carcinoma, metastatic, thyroid gland 

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

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

50 

50 

1 

Endocrine System 

Adrenal cortex + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Adenoma 1 

Adrenal medulla + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Pheochromocytoma benign X 2 

Islets, pancreatic + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Parathyroid gland M + + + + + + M + + M + + + + M + + + + + M + + + 37 

Pituitary gland + + + + + + + + + + + + + + + + + + + + + + + + M 48 

Pars distalis, adenoma X X 5 

Pars distalis, carcinoma 1 

Thyroid gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

C-cell, carcinoma 1 

Follicular cell, adenoma X 2 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

154 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

4455566666777777777777777 

Number of Days on Study 2706816788001122222222222 

9968974917123969999999999 

1111121111111111111111111 

Carcass ID Number 8885907795985685555666666 

7698004369305531234124689 

Genital System 

Clitoral gland 

Ovary 

Cystadenoma

Luteoma 

++++++MM+++++++++++++++++ 

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

X 

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

Hemangioma 

Leiomyosarcoma

Polyp stromal X 

X 

Hematopoietic System 

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

Lymph node

Inguinal, fibrosarcoma, metastatic, skin 

Mediastinal, carcinoma, metastatic, 

thyroid gland

Pancreatic, carcinoma, metastatic, 

thyroid gland

Lymph node, mandibular 

Carcinoma, metastatic, thyroid gland

Lymph node, mesenteric 

Spleen 

Thymus 

 + + + 

X 

X 

+ M +++++++++++++++++++++++ 

X 

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

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

+++++++++++++M+++++++++++ 

Integumentary System 

Mammary gland 

Carcinoma 

++++++++++M+++++M++++++++ 

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

Subcutaneous tissue, fibrosarcoma 

Subcutaneous tissue, melanoma benign 

Subcutaneous tissue, control, sarcoma X 

Musculoskeletal System 

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

Nervous System 

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

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar adenoma, multiple 

Carcinoma, metastatic, harderian gland 

Carcinoma, metastatic, thyroid gland

Hepatocellular carcinoma, metastatic, liver

Nose 

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

X 

X 

X 

X X 

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

Carcinoma, metastatic, harderian gland 

Trachea 

X 

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

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 155 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

7777777777777777777777777 

Number of Days on Study 2222222222222333333333333 

9999999999999000000000000 

1111111111111111111111111 Total 

Carcass ID Number 7777778899999556667788899 

0156895812789670372712445 

Tissues/ 

Tumors 

Genital System 

Clitoral gland 

Ovary 

Cystadenoma

Luteoma

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

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

X X 

X 

48 

50 

3 

1 

Uterus +++++++++++++++++++++++++ 50 

Hemangioma

Leiomyosarcoma 

Polyp stromal 

X 1 

1 

1 

Hematopoietic System 

Bone marrow +++++++++++++++++++++++++ 50 

Lymph node

Inguinal, fibrosarcoma, metastatic, skin

Mediastinal, carcinoma, metastatic, 

thyroid gland 

Pancreatic, carcinoma, metastatic, 

thyroid gland 

Lymph node, mandibular 

Carcinoma, metastatic, thyroid gland 

Lymph node, mesenteric 

Spleen 

Thymus 

+ + + + 

X 

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

+++++M+++M+++++++++++++++ 

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

+++++++++++++++++++M++M++ 

7 

1 

1 

1 

49 

1 

48 

50 

47 

Integumentary System 

Mammary gland 

Carcinoma

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

X 

48 

1 

Skin +++++++++++++++++++++++++ 50 

Subcutaneous tissue, fibrosarcoma

Subcutaneous tissue, melanoma benign

Subcutaneous tissue, control, sarcoma 

X 

X 1 

1 

1 

Musculoskeletal System 

Bone +++++++++++++++++++++++++ 50 

Nervous System 

Brain +++++++++++++++++++++++++ 50 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma 

Alveolar/bronchiolar adenoma, multiple 

Carcinoma, metastatic, harderian gland 

Carcinoma, metastatic, thyroid gland 

Hepatocellular carcinoma, metastatic, liver 

Nose 

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

X 

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

50 

1 

1 

1 

1 

2 

50 

Carcinoma, metastatic, harderian gland 

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

1 

50 
 

 

 

 

 

156 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

4455566666777777777777777 

Number of Days on Study 2706816788001122222222222 

9968974917123969999999999 

1111121111111111111111111 

Carcass ID Number 8885907795985685555666666 

7698004369305531234124689 

Special Senses System 

Eye + 

Harderian gland + 

Carcinoma X 

Urinary System 

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

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

Hemangioma 

Systemic Lesions 

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

Histiocytic sarcoma X 

Lymphoma malignant X X X X X X X 
 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 157 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: Vehicle Control 

7777777777777777777777777 

Number of Days on Study 2222222222222333333333333 

9999999999999000000000000 

1111111111

Carcass ID Number 7777778899

0156895812

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Total 

9 9 9 5 5 6 6 6 7 7 8 8 8 9 9 Tissues/ 

7 8 9 6 7 0 3 7 2 7 1 2 4 4 5 Tumors 

Special Senses System 

Eye 1 

Harderian gland 1 

Carcinoma 1 

Urinary System 

Kidney 

Urinary bladder 

Hemangioma

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

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

X 

50 

50 

1 

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Lymphoma malignant 

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

XXXX X X 

50 

1 

13 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

158 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

4555566666666677777777777 

Number of Days on Study 7566811124478922222222222 

3317416894980199999999999 

2222222222222222222222222 

Carcass ID Number 4034010133211200000112222 

9713438245694912359560123 

Alimentary System 

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

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

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

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

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

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

Leiomyosarcoma, metastatic, 

intestine small, jejunum X 

Polyp adenomatous 

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

Carcinoma 

Leiomyosarcoma X 

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

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

Carcinoma, metastatic, harderian gland X 

Hepatoblastoma X 

Hepatocellular carcinoma X X X X X 

Hepatocellular carcinoma, multiple X X 

Hepatocellular adenoma X X X X 

Hepatocellular adenoma, multiple XXX XXX XXXXXXXXXXX XX 

Histiocytic sarcoma 

Leiomyosarcoma, metastatic, 

intestine small, jejunum X 

Mesentery + +++ 

Leiomyosarcoma, metastatic, 

intestine small, jejunum X 

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

Hemangioma X 

Leiomyosarcoma, metastatic, 

intestine small, jejunum X 

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

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

Squamous cell papilloma X 

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

Tooth 

Cardiovascular System 

Blood vessel +++++++++++++++++++++++++ 

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

Endocrine System 

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

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

Pheochromocytoma benign 

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

Adenoma X 

Parathyroid gland M++MM++++++++M+++++++++++ 

Pituitary gland +++++++++++++++++++++++++ 

Pars distalis, adenoma 

Pars distalis, carcinoma X 

Pars intermedia, adenoma 

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

Follicular cell, adenoma X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 159 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

7777777777777777777777777 

Number of Days on Study 2222222222233333333333333 

9999999999900000000000000 

2222222222222222222222222 Total 

Carcass ID Number 2222344444501111333333444 Tissues/ 

4578004568060178236789127 Tumors 

Alimentary System 

Esophagus +++++++++++++++++++++++++ 50 

Gallbladder +++++++++M++++++++++M++++ 48 

Intestine large, colon +++++++++++++++++++++++++ 50 

Intestine large, rectum +++++++++++++++++++++++++ 50 

Intestine large, cecum +++++++++++++++++++++++++ 50 

Intestine small, duodenum +++++++++++++++++++++++++ 50 

Leiomyosarcoma, metastatic, 

intestine small, jejunum 1 

Polyp adenomatous X 1 

Intestine small, jejunum +++++++++++++++++++++++++ 50 

Carcinoma X 1 

Leiomyosarcoma 1 

Intestine small, ileum +++++++++++++++++++++++++ 50 

Liver +++++++++++++++++++++++++ 50 

Carcinoma, metastatic, harderian gland 1 

Hepatoblastoma 1 

Hepatocellular carcinoma XX X X XX XX XX X X 17 

Hepatocellular carcinoma, multiple X X 4 

Hepatocellular adenoma X 5 

Hepatocellular adenoma, multiple X X X X XXXXXXXXXXX XXXXX 39 

Histiocytic sarcoma X 1 

Leiomyosarcoma, metastatic, 

intestine small, jejunum 1 

Mesentery + + + + + 9 

Leiomyosarcoma, metastatic, 

intestine small, jejunum 1 

Pancreas +++++++++++++++++++++++++ 50 

Hemangioma 1 

Leiomyosarcoma, metastatic, 

intestine small, jejunum 1 

Salivary glands +++++++++++++++++++++++++ 50 

Stomach, forestomach +++++++++++++++++++++++++ 50 

Squamous cell papilloma X 2 

Stomach, glandular +++++++++++++++++++++++++ 50 

Tooth + 1 

Cardiovascular System 

Blood vessel +++++++++++++++++++++++++ 50 

Heart +++++++++++++++++++++++++ 50 

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++ 50 

Adrenal medulla +++++++++++++++++++++++++ 50 

Pheochromocytoma benign X 1 

Islets, pancreatic +++++++++++++++++++++++++ 50 

Adenoma 1 

Parathyroid gland ++++++M++MM++++++++M+++++ 42 

Pituitary gland +++++++++++++++++++++++++ 50 

Pars distalis, adenoma X X 2 

Pars distalis, carcinoma 1 

Pars intermedia, adenoma X 1 

Thyroid gland +++++++++++++++++++++++++ 50 

Follicular cell, adenoma X 5 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

160 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

4555566666666677777777777 

Number of Days on Study 7566811124478922222222222 

3317416894980199999999999 

2222222222222222222222222 

Carcass ID Number 4034010133211200000112222 

9713438245694912359560123 

General Body System 

None 

Genital System 

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

Carcinoma X 

Histiocytic sarcoma 

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

Granulosa cell tumor malignant 

Hemangioma 

Histiocytic sarcoma 

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

Polyp stromal X X 

Vagina 

Histiocytic sarcoma 

Hematopoietic System 

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

Histiocytic sarcoma 

Lymph node + + 

Bronchial, histiocytic sarcoma 

Mediastinal, hepatoblastoma, 

metastatic, liver X 

Mediastinal, histiocytic sarcoma 

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

Histiocytic sarcoma 

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

Histiocytic sarcoma 

Leiomyosarcoma, metastatic, 

intestine small, jejunum X 

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

Histiocytic sarcoma 

Leiomyosarcoma, metastatic, 

intestine small, jejunum X 

Thymus +++++M+MM++M+++M+++++++++ 

Leiomyosarcoma, metastatic, 

intestine small, jejunum X 

Integumentary System 

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

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

Subcutaneous tissue, fibrous histiocytoma X 

Subcutaneous tissue, melanoma benign 

Musculoskeletal System 

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

Nervous System 

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

Carcinoma, metastatic, pituitary gland X 

Peripheral nerve + 

Spinal cord + 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 161 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

7777777777777777777777777 

Number of Days on Study 2222222222233333333333333 

9999999999900000000000000 

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 2 2 2 2 3 4 4 4 4 4 5 0 1 1 1 1 3 3 3 3 3 3 4 4 4 Tissues/ 

4 5 7 8 0 0 4 5 6 8 0 6 0 1 7 8 2 3 6 7 8 9 1 2 7 Tumors 

General Body System 

None 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Carcinoma 1 

Histiocytic sarcoma X 1 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Granulosa cell tumor malignant X 1 

Hemangioma X 1 

Histiocytic sarcoma X 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Polyp stromal 2 

Vagina + 1 

Histiocytic sarcoma X 1 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma X 1 

Lymph node + 3 

Bronchial, histiocytic sarcoma X 1 

Mediastinal, hepatoblastoma, 

metastatic, liver 1 

Mediastinal, histiocytic sarcoma X 1 

Lymph node, mandibular + + + + M + + + + + + + + + + + + + + + + + + + + 47 

Histiocytic sarcoma X 1 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma X 1 

Leiomyosarcoma, metastatic, 

intestine small, jejunum 1 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma X 1 

Leiomyosarcoma, metastatic, 

intestine small, jejunum 1 

Thymus + + + M + M + M + + + + + + + + + + + + + + + M M 40 

Leiomyosarcoma, metastatic, 

intestine small, jejunum 1 

Integumentary System 

Mammary gland + + + + + + + M + + + + + + + + + + + + + + + + + 49 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Subcutaneous tissue, fibrous histiocytoma 1 

Subcutaneous tissue, melanoma benign X 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma, metastatic, pituitary gland 1 

Peripheral nerve 1 

Spinal cord 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

162 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

4555566666666677777777777 

Number of Days on Study 7566811124478922222222222 

3317416894980199999999999 

2222222222222222222222222 

Carcass ID Number 4034010133211200000112222 

9713438245694912359560123 

Respiratory System 

Lung 

Alveolar/bronchiolar adenoma

Alveolar/bronchiolar adenoma, multiple 

Alveolar/bronchiolar carcinoma 

Carcinoma, metastatic, harderian gland

Hepatoblastoma, metastatic, liver

Hepatocellular carcinoma, metastatic, liver

Histiocytic sarcoma 

Mediastinum, leiomyosarcoma, 

metastatic, intestine small, jejunum 

Nose 

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

X 

X X 

X 

X 

X 

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

Carcinoma, metastatic, harderian gland

Trachea 

X 

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

Special Senses System 

Eye

Carcinoma, metastatic, harderian gland

Harderian gland

Carcinoma

 +

 X 

+

 X

 + 

+ 

X 

Urinary System 

Kidney 

Hepatoblastoma, metastatic, liver

Histiocytic sarcoma 

Leiomyosarcoma, metastatic, 

intestine small, jejunum 

Urinary bladder 

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

X 

X 

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

Systemic Lesions 

Multiple organs 

Histiocytic sarcoma 

Lymphoma malignant

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

X X X X 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 163 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 100 mg/kg 

7777777777777777777777777 

Number of Days on Study 2222222222233333333333333 

9999999999900000000000000 

2222222222222222222222222 Total 

Carcass ID Number 2222344444501111333333444 Tissues/ 

4578004568060178236789127 Tumors 

Respiratory System 

Lung +++++++++++++++++++++++++ 50 

Alveolar/bronchiolar adenoma X X 3 

Alveolar/bronchiolar adenoma, multiple X 1 

Alveolar/bronchiolar carcinoma X 1 

Carcinoma, metastatic, harderian gland 2 

Hepatoblastoma, metastatic, liver 1 

Hepatocellular carcinoma, metastatic, liver X X 3 

Histiocytic sarcoma X 1 

Mediastinum, leiomyosarcoma, 

metastatic, intestine small, jejunum 1 

Nose +++++++++++++++++++++++++ 50 

Carcinoma, metastatic, harderian gland 1 

Trachea +++++++++++++++++++++++++ 50 

Special Senses System 

Eye 2 

Carcinoma, metastatic, harderian gland 1 

Harderian gland 2 

Carcinoma 2 

Urinary System 

Kidney +++++++++++++++++++++++++ 50 

Hepatoblastoma, metastatic, liver 1 

Histiocytic sarcoma X 1 

Leiomyosarcoma, metastatic, 

intestine small, jejunum 1 

Urinary bladder +++++++++++++++++++++++++ 50 

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++ 50 

Histiocytic sarcoma X X 2 

Lymphoma malignant X 5 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

164 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

0345555566666666666777777 

Number of Days on Study 9620566811233455667001222 

8626247000102933152121289 

2222222222222222222322222 

Carcass ID Number 5569557769858879666089775 

1507281023796388467000623 

Alimentary System 

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

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

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

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

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

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

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

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

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

Hepatoblastoma X X 

Hepatoblastoma, multiple 

Hepatocellular carcinoma X X X XXXX X 

Hepatocellular carcinoma, multiple X X X X X X X 

Hepatocellular adenoma X X X X 

Hepatocellular adenoma, multiple X XXXXXXXXX XX X X X 

Histiocytic sarcoma X 

Mesentery + + 
 

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

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

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

Squamous cell papilloma 

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

Tongue + 

Squamous cell carcinoma X 

Cardiovascular System 

Blood vessel 

Heart 

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

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

Endocrine System 

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

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

Pheochromocytoma malignant 

Pheochromocytoma complex X 

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

Adenoma X 

Parathyroid gland M++++++++++++MM+M++++++++ 

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

Pars distalis, adenoma 

Pars intermedia, adenoma X 

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

Follicular cell, adenoma 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 165 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

7777777777777777777777777 

Number of Days on Study 2222222222222222233333333 

9999999999999999900000000 

2222222222222222222222222 Total 

Carcass ID Number 5556666778888999967778899 Tissues/ 

4671389791259145953454826 Tumors 

Alimentary System 

Esophagus +++++++++++++++++++++++++ 50 

Gallbladder +++++++++++++++++++++++++ 50 

Intestine large, colon +++++++++++++++++++++++++ 50 

Intestine large, rectum +++++++++++++++++++++++++ 50 

Intestine large, cecum +++++++++++++++++++++++++ 50 

Intestine small, duodenum +++++++++++++++++++++++++ 50 

Intestine small, jejunum +++++++++++++++++++++++++ 50 

Intestine small, ileum +++++++++++++++++++++++++ 50 

Liver +++++++++++++++++++++++++ 50 

Hepatoblastoma 2 

Hepatoblastoma, multiple X 1 

Hepatocellular carcinoma X X X X X X X X 16 

Hepatocellular carcinoma, multiple XXX X XXX XX 16 

Hepatocellular adenoma X 5 

Hepatocellular adenoma, multiple XXXXXXXXXXXXXXXXXXX XXXX 38 

Histiocytic sarcoma 1 

Mesentery ++ + + ++ 8 

Pancreas +++++++++++++++++++++++++ 50 

Salivary glands +++++++++++++++++++++++++ 50 

Stomach, forestomach +++++++++++++++++++++++++ 50 

Squamous cell papilloma X 1 

Stomach, glandular +++++++++++++++++++++++++ 50 

Tongue 1 

Squamous cell carcinoma 1 

Cardiovascular System 

Blood vessel 

Heart 

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

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

50 

50 

Endocrine System 

Adrenal cortex +++++++++++++++++++++++++ 50 

Adrenal medulla +++++++++++++++++++++++++ 50 

Pheochromocytoma malignant X 1 

Pheochromocytoma complex 1 

Islets, pancreatic +++++++++++++++++++++++++ 50 

Adenoma 1 

Parathyroid gland M++++++M+++++++M+++++++++ 43 

Pituitary gland +++++++++++++++++++++++++ 49 

Pars distalis, adenoma X 1 

Pars intermedia, adenoma 1 

Thyroid gland +++++++++++++++++++++++++ 50 

Follicular cell, adenoma X X X 3 

General Body System 

None 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

166 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

0345555566666666666777777 

Number of Days on Study 9620566811233455667001222 

8626247000102933152121289 

2222222222222222222322222 

Carcass ID Number 5569557769858879666089775 

1507281023796388467000623 

Genital System 

Clitoral gland +++++M++++++++MM+++++++++ 

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

Cystadenoma 

Hemangiosarcoma X 

Teratoma benign X 

Teratoma malignant X 

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

Histiocytic sarcoma X 

Polyp stromal 

Hematopoietic System 

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

Hemangiosarcoma 

Hemangiosarcoma, metastatic, ovary X 

Lymph node + + + + + 

Lumbar, histiocytic sarcoma X 

Mediastinal, alveolar/bronchiolar carcinoma, 

metastatic, lung X 

Mediastinal, histiocytic sarcoma X 

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

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

Histiocytic sarcoma X 

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

Thymus +++M+++++++M++++ MMMM +++M+ 

Integumentary System 

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

Carcinoma 

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

Melanoma benign 

Melanoma malignant X 

Subcutaneous tissue, fibrosarcoma X 

Musculoskeletal System 

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

Nervous System 

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

Peripheral nerve + 

Spinal cord + 

Respiratory System 

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

Alveolar/bronchiolar carcinoma X 

Hepatoblastoma, metastatic, liver X 

Hepatocellular carcinoma, metastatic, liver X X X X X 

Histiocytic sarcoma X 

Nose ++++++++++++++++++++++++M 

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

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 167 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

7777777777777777777777777 

Number of Days on Study 2222222222222222233333333 

9999999999999999900000000 

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 5 5 5 6 6 6 6 7 7 8 8 8 8 9 9 9 9 6 7 7 7 8 8 9 9 Tissues/ 

4 6 7 1 3 8 9 7 9 1 2 5 9 1 4 5 9 5 3 4 5 4 8 2 6 Tumors 

Genital System 

Clitoral gland + + + + + + + + + + + + + + + + + + + + + + + + + 47 

Ovary + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Cystadenoma X 1 

Hemangiosarcoma 1 

Teratoma benign 1 

Teratoma malignant 1 

Uterus + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Histiocytic sarcoma 1 

Polyp stromal X X 2 

Hematopoietic System 

Bone marrow + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Hemangiosarcoma X 1 

Hemangiosarcoma, metastatic, ovary 1 

Lymph node + 6 

Lumbar, histiocytic sarcoma 1 

Mediastinal, alveolar/bronchiolar carcinoma, 

metastatic, lung 1 

Mediastinal, histiocytic sarcoma 1 

Lymph node, mandibular + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Lymph node, mesenteric + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Histiocytic sarcoma 1 

Spleen + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Thymus + + + + + + + + M + + + + M + + + + + + + + + + + 41 

Integumentary System 

Mammary gland + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Carcinoma X 1 

Skin + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Melanoma benign X 1 

Melanoma malignant 1 

Subcutaneous tissue, fibrosarcoma 1 

Musculoskeletal System 

Bone + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Nervous System 

Brain + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Peripheral nerve 1 

Spinal cord 1 

Respiratory System 

Lung + + + + + + + + + + + + + + + + + + + + + + + + + 50 

Alveolar/bronchiolar carcinoma 1 

Hepatoblastoma, metastatic, liver 1 

Hepatocellular carcinoma, metastatic liver X X X X 9 

Histiocytic sarcoma 1 

Nose + + + + + + + + + + + + + + + + + + + + + + + + + 49 

Trachea + + + + + + + + + + + + + + + + + + + + + + + + + 50 
 

 

 

 

 

 

 

168 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

Number of Days on Study 

0345555566666666666777777 

9620566811233455667001222 

8626247000102933152121289 

Carcass ID Number 

2222222222222222222322222 

5569557769858879666089775 

1507281023796388467000623 

Special Senses System 

Eye 

Harderian gland 

Carcinoma 

Urinary System 

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

Histiocytic sarcoma X 

Renal tubule, adenoma X 

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

Systemic Lesions 

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

Histiocytic sarcoma X 

Lymphoma malignant X X X 
 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 169 

TABLE D2 

Individual Animal Tumor Pathology of Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate: 200 mg/kg 

7777777777777777777777777 

Number of Days on Study 2222222222222222233333333 

9999999999999999900000000 

2222222222222222222222222 Total 

Carcass ID Number 5556666778888999967778899 Tissues/ 

4671389791259145953454826 Tumors 

Special Senses System 

Eye + 1 

Harderian gland + 1 

Carcinoma X 1 

Urinary System 

Kidney +++++++++++++++++++++++++ 50 

Histiocytic sarcoma 1 

Renal tubule, adenoma 1 

Urinary bladder +++++++++++++++++++++++++ 50 

Systemic Lesions 

Multiple organs +++++++++++++++++++++++++ 50 

Histiocytic sarcoma 1 

Lymphoma malignant X X X X 7 
170 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D3 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Liver: Hepatocellular Adenoma 

Overall ratea 32/50 (64%) 44/50 (88%) 43/50 (86%)
 

Adjusted rateb 69.0% 90.3% 90.7%
 

Terminal ratec 26/35 (74%) 32/36 (89%) 25/26 (96%)
 

First incidence (days) 568 561 366
 

Poly-3 testd P=0.002 P=0.006 P=0.005
 

Liver: Hepatocellular Carcinoma 

Overall rate 3/50 (6%) 21/50 (42%) 32/50 (64%)
 

Adjusted rate 6.6% 45.8% 70.4%
 

Terminal rate 1/35 (3%) 17/36 (47%) 18/26 (69%)
 

First incidence (days) 681 584 366
 

Poly-3 test P<0.001 P<0.001 P<0.001
 

Liver: Hepatocellular Adenoma or Carcinoma 

Overall rate 33/50 (66%) 46/50 (92%) 48/50 (96%)
 

Adjusted rate 70.9% 94.4% 99.0%
 

Terminal rate 26/35 (74%) 34/36 (94%) 26/26 (100%)
 

First incidence (days) 568 561 366
 

Poly-3 test P<0.001 P<0.001 P<0.001
 

Liver: Hepatoblastoma 

Overall rate 0/50 (0%) 1/50 (2%) 3/50 (6%) 

Adjusted rate 0.0% 2.2% 7.3% 

Terminal rate 0/35 (0%) 0/36 (0%) 1/26 (4%) e First incidence (days) — 629 567 

Poly-3 test P=0.054 P=0.498 P=0.103 

Liver: Hepatocellular Carcinoma or Hepatoblastoma 

Overall rate 3/50 (6%) 21/50 (42%) 33/50 (66%)
 

Adjusted rate 6.6% 45.8% 71.8%
 

Terminal rate 1/35 (3%) 17/36 (47%) 18/26 (69%)
 

First incidence (days) 681 584 366
 

Poly-3 test P<0.001 P<0.001 P<0.001
 

Liver: Hepatocellular Adenoma, Hepatocellular Carcinoma, or Hepatoblastoma 

Overall rate 33/50 (66%) 46/50 (92%) 48/50 (96%)
 

Adjusted rate 70.9% 94.4% 99.0%
 

Terminal rate 26/35 (74%) 34/36 (94%) 26/26 (100%)
 

First incidence (days) 568 561 366
 

Poly-3 test P<0.001 P<0.001 P<0.001
 

Lung: Alveolar/bronchiolar Adenoma 

Overall rate 2/50 (4%) 4/50 (8%) 0/50 (0%)
 

Adjusted rate 4.4% 9.0% 0.0%
 

Terminal rate 2/35 (6%) 3/36 (8%) 0/26 (0%)
 

First incidence (days) 729 (T) 691 —
 

Poly-3 test P=0.277N P=0.330 P=0.262N
 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 171 

TABLE D3 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Lung: Alveolar/bronchiolar Adenoma or Carcinoma 

Overall rate 2/50 (4%) 5/50 (10%) 1/50 (2%)
 

Adjusted rate 4.4% 11.2% 2.4%
 

Terminal rate 2/35 (6%) 4/36 (11%) 0/26 (0%)
 

First incidence (days) 729 (T) 691 506
 

Poly-3 test P=0.477N P=0.209 P=0.531N
 

Ovary: Cystadenoma 

Overall rate 3/50 (6%) 0/50 (0%) 1/50 (2%) 

Adjusted rate 6.6% 0.0% 2.5% 

Terminal rate 2/35 (6%) 0/36 (0%) 1/26 (4%) 

First incidence (days) 664 — 729 (T) 

Poly-3 test P=0.191N P=0.123N P=0.346N 

Pituitary Gland (Pars Distalis): Adenoma 

Overall rate 5/48 (10%) 2/50 (4%) 1/49 (2%) 

Adjusted rate 11.3% 4.5% 2.5% 

Terminal rate 4/34 (12%) 2/36 (6%) 1/26 (4%) 

First incidence (days) 568 729 (T) 729 (T) 

Poly-3 test P=0.073N P=0.214N P=0.128N 

Pituitary Gland (Pars Distalis): Adenoma or Carcinoma 

Overall rate 6/48 (13%) 3/50 (6%) 1/49 (2%) 

Adjusted rate 13.4% 6.7% 2.5% 

Terminal rate 4/34 (12%) 2/36 (6%) 1/26 (4%) 

First incidence (days) 506 616 729 (T) 

Poly-3 test P=0.048N P=0.242N P=0.078N 

Thyroid Gland (Follicular Cell): Adenoma 

Overall rate 2/50 (4%) 5/50 (10%) 3/50 (6%) 

Adjusted rate 4.4% 11.2% 7.4% 

Terminal rate 2/35 (6%) 4/36 (11%) 3/26 (12%) 

First incidence (days) 729 (T) 649 729 (T) 

Poly-3 test P=0.357 P=0.211 P=0.451 

All Organs: Hemangioma or Hemangiosarcoma 

Overall rate 3/50 (6%) 2/50 (4%) 2/50 (4%)
 

Adjusted rate 6.6% 4.5% 4.9%
 

Terminal rate 3/35 (9%) 2/36 (6%) 1/26 (4%)
 

First incidence (days) 729 (T) 729 (T) 610
 

Poly-3 test P=0.449N P=0.509N P=0.544N
 

All Organs: Malignant Lymphoma 

Overall rate 13/50 (26%) 5/50 (10%) 7/50 (14%)
 

Adjusted rate 28.1% 10.9% 16.8%
 

Terminal rate 8/35 (23%) 1/36 (3%) 4/26 (15%)
 

First incidence (days) 589 584 564
 

Poly-3 test P=0.094N P=0.033N P=0.158N
 
172 

c 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D3 

Statistical Analysis of Primary Neoplasms in Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

All Organs: Benign Neoplasms 

Overall rate 39/50 (78%) 45/50 (90%) 45/50 (90%)
 

Adjusted rate 83.1% 92.4% 94.9%
 

Terminal rate 30/35 (86%) 33/36 (92%) 26/26 (100%)
 

First incidence (days) 568 561 366
 

Poly-3 test P=0.029 P=0.126 P=0.048
 

All Organs: Malignant Neoplasms 

Overall rate 23/50 (46%) 30/50 (60%) 41/50 (82%)
 

Adjusted rate 47.4% 61.8% 84.6%
 

Terminal rate 12/35 (34%) 20/36 (56%) 20/26 (77%)
 

First incidence (days) 429 473 98
 

Poly-3 test P<0.001 P=0.109 P<0.001
 

All Organs: Benign or Malignant Neoplasms 

Overall rate 47/50 (94%) 48/50 (96%) 50/50 (100%)
 

Adjusted rate 95.4% 97.1% 100.0%
 

Terminal rate 33/35 (94%) 35/36 (97%) 26/26 (100%)
 

First incidence (days) 429 473 98
 

Poly-3 test P=0.109 P=0.533 P=0.180 

(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 vehicle control incidence are the P values associated with the trend test. Beneath the dosed group incidence are the P values corresponding to 

pairwise comparisons between the vehicle controls and that dosed 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 a dose group is indicated by N. e Not applicable; no neoplasms in animal group 
 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 173 

TABLE D4 

Historical Incidence of Liver Neoplasms in Vehicle Control Female B6C3F1 Micea 

Incidence in Controls 

Study Hepatocellular Hepatocellular Hepatoblastoma Hepatocellular Adenoma, 

Adenoma Carcinoma Hepatocellular Carcinoma, 

Hepatoblastoma 

Historical Incidence at Battelle Columbus Laboratories 

Benzethonium Chloride 20/52 12/52 0/52 27/52 

Coconut Oil Acid Diethanolamine Condensate 32/50 3/50 0/50 33/50 

Diethanolamine 32/50 5/50 0/50 33/50 

Lauric Acid Diethanolamine Condensate 23/50 10/50 0/50 28/50 

Oleic Acid Diethanolamine Condensate 26/50 5/50 1/50 28/50 

Overall Historical Incidence 

Total 133/252 (52.8%) 35/252 (13.9%) 1/252 (0.4%) 149/252 (59.1%) 

Mean ± standard deviation 52.8% ± 11.4% 13.9% ± 7.3% 0.4% ± 0.9% 59.1% ± 6.4% 

Range 38%-64% 6%-23% 0%-2% 52%-66% 

a Data as of 12 July 2000. Vehicle controls from the sodium xylenesulfonate study were excluded because liver neoplasms were associated with hepatitis due 

to Helicobacter hepaticus infection. 
 

 

 

 

 

 

 

 

 

174 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D5 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 100 mg/kg 200 mg/kg 

Disposition Summary 

Animals initially in study 50 50 50 

Early deaths 

Moribund 11 11 15 

Natural deaths 4 3 9 

Survivors 

Died last week of study 1 

Terminal sacrifice 35 35 26 

Animals examined microscopically 50 50 50 

Alimentary System 

Esophagus (50) (50) (50) 

Inflammation 1 (2%) 

Intestine large, rectum (50) (50) (50) 

Hemorrhage 1 (2%) 

Intestine small, duodenum (50) (50) (50) 

Erosion 2 (4%) 

Ulcer 1 (2%) 1 (2%) 

Intestine small, jejunum (49) (50) (50) 

Hyperplasia, lymphoid 1 (2%) 2 (4%) 

Inflammation 1 (2%) 

Ulcer 1 (2%) 

Mucosa, hyperplasia 1 (2%) 

Liver (50) (50) (50) 

Angiectasis 1 (2%) 1 (2%) 

Basophilic focus 2 (4%) 

Clear cell focus 2 (4%) 2 (4%) 2 (4%) 

Eosinophilic focus 18 (36%) 25 (50%) 24 (48%) 

Fibrosis 2 (4%) 1 (2%) 

Inflammation, suppurative 1 (2%) 

Mixed cell focus 1 (2%) 5 (10%) 

Necrosis 2 (4%) 5 (10%) 8 (16%) 

Bile duct, hyperplasia 1 (2%) 1 (2%) 

Mesentery (12) (9) (8) 

Fat, inflammation 2 (17%) 

Fat, necrosis 9 (75%) 8 (89%) 7 (88%) 

Pancreas (50) (50) (50) 

Atrophy 1 (2%) 4 (8%) 1 (2%) 

Hypertrophy 1 (2%) 

Hypertrophy, focal 3 (6%) 1 (2%) 1 (2%) 

Duct, cyst 2 (4%) 1 (2%) 

Stomach, forestomach (50) (50) (50) 

Erosion 1 (2%) 1 (2%) 

Hyperplasia, focal 2 (4%) 2 (4%) 1 (2%) 

Inflammation 1 (2%) 

Ulcer 1 (2%) 

Stomach, glandular (50) (50) (50) 

Erosion 1 (2%) 2 (4%) 

Inflammation 2 (4%) 

Mineralization 2 (4%) 1 (2%) 1 (2%) 

Ulcer 1 (2%) 

Tooth (1) 

Inflammation 1 (100%) 

a Number of animals examined microscopically at the site and the number of animals with lesion 
 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 175 

TABLE D5 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Cardiovascular System 

Heart (50) (50) (50) 

Infiltration cellular, mononuclear cell 1 (2%) 

Mineralization 1 (2%) 1 (2%) 1 (2%) 

Artery, inflammation 1 (2%) 

Endocrine System 

Adrenal cortex (50) (50) (50) 

Hematopoietic cell proliferation 1 (2%) 

Hyperplasia 1 (2%) 1 (2%) 

Hypertrophy 1 (2%) 

Vacuolization cytoplasmic 1 (2%) 

Capsule, hyperplasia 2 (4%) 

Adrenal medulla (50) (50) (50) 

Hyperplasia 2 (4%) 1 (2%) 2 (4%) 

Islets, pancreatic (50) (50) (50) 

Hyperplasia 1 (2%) 2 (4%) 

Parathyroid gland (37) (42) (43) 

Cyst 1 (3%) 

Hyperplasia, focal 1 (2%) 

Pituitary gland (48) (50) (49) 

Angiectasis 1 (2%) 

Pars distalis, hyperplasia 28 (58%) 31 (62%) 27 (55%) 

Pars intermedia, hyperplasia 1 (2%) 1 (2%) 

Thyroid gland (50) (50) (50) 

Follicular cell, hyperplasia 27 (54%) 36 (72%) 33 (66%) 

General Body System 

None 

Genital System 

Clitoral gland (48) (49) (47) 

Inflammation 1 (2%) 

Ovary (50) (50) (50) 

Angiectasis 2 (4%) 

Cyst 15 (30%) 14 (28%) 15 (30%) 

Hemorrhage 2 (4%) 2 (4%) 

Mineralization 1 (2%) 

Granulosa cell, hyperplasia 1 (2%) 1 (2%) 

Uterus (50) (50) (50) 

Decidual reaction 1 (2%) 

Hyperplasia 37 (74%) 26 (52%) 22 (44%) 

Inflammation, suppurative 1 (2%) 

Thrombosis 1 (2%) 1 (2%) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

176 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE D5 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Hematopoietic System 

Bone marrow (50) (50) (50) 

Hyperplasia 7 (14%) 10 (20%) 19 (38%) 

Myelofibrosis 21 (42%) 21 (42%) 19 (38%) 

Lymph node (7) (3) (6) 

Inguinal, hematopoietic cell proliferation 1 (17%) 

Mediastinal, hematopoietic cell proliferation 1 (17%) 

Renal, hematopoietic cell proliferation 1 (17%) 

Lymph node, mandibular (49) (47) (49) 

Hematopoietic cell proliferation 2 (4%) 

Hyperplasia, lymphoid 1 (2%) 

Hyperplasia, plasma cell 1 (2%) 

Lymph node, mesenteric (48) (50) (49) 

Angiectasis 1 (2%) 2 (4%) 

Hematopoietic cell proliferation 1 (2%) 2 (4%) 

Hyperplasia, lymphoid 1 (2%) 

Hyperplasia, plasma cell 1 (2%) 

Inflammation 1 (2%) 

Spleen (50) (50) (50) 

Accessory spleen 1 (2%) 

Hematopoietic cell proliferation 33 (66%) 33 (66%) 36 (72%) 

Lymphoid follicle, hyperplasia 1 (2%) 5 (10%) 

Thymus (47) (40) (41) 

Atrophy 7 (15%) 4 (10%) 8 (20%) 

Hyperplasia, lymphoid 1 (2%) 2 (5%) 1 (2%) 

Integumentary System 

Skin (50) (50) (50) 

Control, edema 1 (2%) 

Control, hyperkeratosis 1 (2%) 

Control, inflammation 3 (6%) 

Control, parakeratosis 1 (2%) 

Epidermis, control, hyperplasia 1 (2%) 

Epidermis, skin, site of application, hyperplasia 9 (18%) 47 (94%) 50 (100%) 

Sebaceous gland, skin, site of application, hyperplasia 42 (84%) 48 (96%) 

Skin, site of application, hyperkeratosis 5 (10%) 30 (60%) 40 (80%) 

Skin, site of application, inflammation 3 (6%) 2 (4%) 11 (22%) 

Skin, site of application, parakeratosis 3 (6%) 4 (8%) 16 (32%) 

Skin, site of application, ulcer 1 (2%) 3 (6%) 

Subcutaneous tissue, control, hemorrhage 1 (2%) 

Musculoskeletal System 

Bone (50) (50) (50) 

Osteomalacia 1 (2%) 

Joint, inflammation, chronic 1 (2%) 

Nervous System 

Brain (50) (50) (50) 

Cyst epithelial inclusion 1 (2%) 

Neuron, necrosis 2 (4%) 3 (6%) 
 

 

 

 

 

 

 

 

 

 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 177 

TABLE D5 

Summary of the Incidence of Nonneoplastic Lesions in Female Mice in the 2-Year Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 100 mg/kg 200 mg/kg 

Respiratory System 

Lung (50) (50) (50) 

Inflammation 2 (4%) 1 (2%) 

Alveolar epithelium, hyperplasia 1 (2%) 1 (2%) 2 (4%) 

Nose (50) (50) (49) 

Inflammation 1 (2%) 2 (4%) 

Nasolacrimal duct, inflammation 1 (2%) 

Special Senses System 

Eye (1) (2) (1) 

Degeneration 1 (50%) 

Cornea, inflammation 1 (100%) 1 (100%) 

Urinary System 

Kidney (50) (50) (50) 

Accumulation, hyaline droplet 2 (4%) 1 (2%) 

Cyst 1 (2%) 

Hydronephrosis 1 (2%) 1 (2%) 1 (2%) 

Mineralization 2 (4%) 

Nephropathy 27 (54%) 24 (48%) 15 (30%) 

Pigmentation, hemosiderin 1 (2%) 2 (4%) 

Pigmentation, hemoglobin 1 (2%) 

Glomerulus, thrombosis 1 (2%) 

Renal tubule, degeneration 1 (2%) 

Renal tubule, hyperplasia 2 (4%) 1 (2%) 

Urinary bladder (50) (50) (50) 

Inflammation 1 (2%) 

Transitional epithelium, hyperplasia 1 (2%) 
178 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 
179 

APPENDIX E
 

GENETIC TOXICOLOGY
 

SALMONELLA TYPHIMURIUM MUTAGENICITY TEST PROTOCOL . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180 
 

MOUSE LYMPHOMA MUTAGENICITY TEST PROTOCOL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180 
 

CHINESE HAMSTER OVARY CELL CYTOGENETICS PROTOCOLS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 
 

MOUSE PERIPHERAL BLOOD MICRONUCLEUS TEST PROTOCOL . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 
 

RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 
 

TABLE E1 Mutagenicity of Coconut Oil Acid Diethanolamine Condensate 

in Salmonella typhimurium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 
 

TABLE E2 Induction of Trifluorothymidine Resistance in L5178Y Mouse Lymphoma Cells
 

by Coconut Oil Acid Diethanolamine Condensate . . . . . . . . . . . . . . . . . . . . . . . . . . . 185 
 

TABLE E3 Induction of Sister Chromatid Exchanges in Chinese Hamster Ovary Cells
 

by Coconut Oil Acid Diethanolamine Condensate . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 
 

TABLE E4 Induction of Chromosomal Aberrations in Chinese Hamster Ovary Cells 

by Coconut Oil Acid Diethanolamine Condensate . . . . . . . . . . . . . . . . . . . . . . . . . . . 193 
 

TABLE E5 Frequency of Micronuclei in Mouse Peripheral Blood Erythrocytes
 

Following Dermal Application of Coconut Oil Acid Diethanolamine Condensate 

for 14 Weeks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 
 
180 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

GENETIC TOXICOLOGY 

SALMONELLA TYPHIMURIUM MUTAGENICITY TEST PROTOCOL 

Testing was performed as reported by Zeiger et al. (1988). Coconut oil acid diethanolamine condensate 

was sent to the laboratory as a coded aliquot from Radian Corporation (Austin, TX). It was incubated with 

the Salmonella typhimurium tester strains TA97, TA98, TA100, and TA1535 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 

coconut oil acid diethanolamine condensate. The high dose was limited by toxicity. 

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. 

MOUSE LYMPHOMA MUTAGENICITY TEST PROTOCOL 

The experimental protocol is presented in detail by Myhr et al. (1985). Coconut oil acid diethanolamine 

condensate was supplied as a coded aliquot by Radian Corporation. The high dose of coconut oil acid 

diethanolamine condensate was determined by toxicity. L5178Y mouse lymphoma cells were maintained at 

37E C as suspension cultures in supplemented Fischer’s medium; normal cycling time was approximately 

10 hours. To reduce the number of spontaneously occurring cells resistant to trifluorothymidine (TFT), 

subcultures were exposed to medium containing thymidine, hypoxanthine, methotrexate, and glycine for 

1 day; to medium containing thymidine, hypoxanthine, and glycine for 1 day; and to normal medium for 

3 to 5 days. For cloning, the horse serum content was increased and Noble agar was added. 

All treatment levels within an experiment, including concurrent positive and solvent controls, were 

replicated. Treated cultures contained 6 × 106

 cells in 10 mL medium. This volume included the S9 

fraction in those experiments performed with metabolic activation. Incubation with coconut oil acid 

diethanolamine condensate continued for 4 hours, at which time the medium plus coconut oil acid 

diethanolamine condensate was removed, and the cells were resuspended in fresh medium and incubated for 

an additional 2 days to express the mutant phenotype. Cell density was monitored so that log phase growth 

was maintained. After the 48-hour expression period, cells were plated in medium and soft agar 

supplemented with TFT for selection of TFT-resistant cells, and cells were plated in nonselective medium 

and soft agar to determine cloning efficiency. Plates were incubated at 37E C in 5% CO2 for 10 to 12 days. 

The test was initially performed without S9. Because a clearly positive response was not obtained, the test 

was repeated with freshly prepared S9 from the livers of Aroclor 1254-induced male Fischer 344 rats. 

Minimum criteria for accepting an experiment as valid and a detailed description of the statistical analysis 

and data evaluation are presented by Caspary et al. (1988). All data were evaluated statistically for trend 

and peak responses. Both responses had to be significant (P#0.05) for coconut oil acid diethanolamine 

condensate to be considered positive, i.e., capable of inducing TFT resistance. A single significant 
 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 181 

response led to a “questionable” conclusion, and the absence of both a trend and peak response resulted in a 

“negative” call. 

CHINESE HAMSTER OVARY CELL CYTOGENETICS PROTOCOLS 

Testing was performed as reported by Galloway et al. (1987). Coconut oil acid diethanolamine condensate 

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 bromodeoxyuridinesubstituted DNA. Each test consisted of concurrent solvent and positive controls and of at least three doses 

of coconut oil acid diethanolamine condensate; 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 

coconut oil acid diethanolamine condensate in supplemented McCoy’s 5A medium. Bromodeoxyuridine 

(BrdU) was added 2 hours after culture initiation. After 26 hours, the medium containing coconut oil acid 

diethanolamine condensate 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 coconut oil acid 

diethanolamine condensate, serum-free medium, and S9 for 2 hours. The medium was then removed and 

replaced with medium containing serum and BrdU and no coconut oil acid diethanolamine condensate. 

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. 

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 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 coconut oil acid diethanolamine condensate 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 coconut oil acid diethanolamine condensate 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). 
182 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

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 PERIPHERAL BLOOD MICRONUCLEUS TEST PROTOCOL 

A detailed discussion of this assay is presented by MacGregor et al., (1990). At the end of the 14-week 

dermal study, peripheral blood samples were obtained from male and female mice, and smears were 

immediately prepared and fixed in absolute methanol. The methanol-fixed slides were stained with acridine 

orange and coded. Slides were scanned to determine the frequency of micronuclei in 

2,000 normochromatic erythrocytes (NCEs) in each of five animals per dose group. 

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 NCEs was analyzed 

by a statistical software package that tested for increasing trend over dose groups with a one-tailed CochranArmitage trend test, followed by pairwise comparisons between each dose group and the control group 

(ILS, 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. 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 magnitudes of those 

effects. 

RESULTS 

Results of in vitro assays for genotoxicity with coconut oil acid diethanolamine condensate were uniformly 

negative. It did not induce mutations in Salmonella typhimurium strain TA97, TA98, TA100, or TA1535, 

with or without S9 metabolic activation (Zeiger et al., 1988; Table E1). The highest concentration was 

limited to 200 μg/plate by toxicity. No increase in mutant L5178Y mouse lymphoma cell colonies was 

observed after exposure to coconut oil acid diethanolamine condensate, with or without S9 (Table E2). A 

single positive response noted at 8 nL/mL in the second trial conducted without S9 was not reproducible, 

and the test results overall were considered to be negative. In tests for induction of chromosomal damage, 

no increases in the frequencies of SCEs (Table E3) or Abs (Table E4) were observed in cultured CHO cells 

after incubation with coconut oil acid diethanolamine condensate, with or without S9. 

In contrast to the negative results obtained in in vitro assays, positive results were obtained in a 14-week 

dermal study conducted with coconut oil acid diethanolamine condensate in male and female mice. At the 

end of 14 weeks, significant increases in the frequencies of micronucleated NCEs were seen in peripheral 

blood of both male and female mice (Table E5). Statistical analysis of the data showed positive trends for 

both data sets as well as significantly elevated micronucleus frequencies at the highest dose tested 

(800 mg/kg) in male and female mice. 
 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 183 

TABLE E1 

Mutagenicity of Coconut Oil Acid Diethanolamine Condensate in Salmonella typhimuriuma 

Revertants/plateb 

Strain Dose

(μg/plate) Trial 1 

 -S9

Trial 2 

 +hamster S9

10% 30% 10% 

 +rat S9 

30% 

TA100 0.0 

0.1 

0.3 

1.0 

3.3 

6.7 

10.0 

33.0 

100.0 

200.0 

118 ± 4.3 

101 ± 1.5 

111 ± 3.8 

91 ± 5.0 

97 ± 5.8 

91 ± 3.0 

171 ± 7.2 

170 ± 8.5 

144 ± 12.2 

131 ± 6.8 

125 ± 5.2 

133 ± 3.5 

101 ± 2.9 

87 ± 3.1 

85 ± 5.8 

88 ± 10.8 

68 ± 3.5 

41 ± 3.9c 

145 ± 9.2 

160 ± 2.5 

152 ± 5.5 

163 ± 3.2 

172 ± 5.7 

130 ± 3.8 

103 ± 4.1 

86 ± 7.5 

90 ± 4.6 

86 ± 7.8 

82 ± 3.7 

22 ± 5.2c 

168 ± 10.5 

163 ± 17.9 

151 ± 11.8 

162 ± 6.6 

166 ± 2.5 

128 ± 6.6 

Trial summary 

Positive controld Negative 

1,302 ± 33.1 

Negative 

314 ± 8.2 

Negative 

1,286 ± 23.1 

Negative 

372 ± 10.2 

Negative 

2,232 ± 41.5 

Negative 

564 ± 29.3 

TA1535 0.0 

0.1 

0.3 

1.0 

3.3 

6.7 

10.0 

33.0 

100.0 

200.0 

31 ± 4.4 

31 ± 0.6 

25 ± 1.0 

32 ± 2.1 

28 ± 3.7 

25 ± 1.5c 

46 ± 6.2 

51 ± 2.3 

47 ± 5.2 

39 ± 2.9 

43 ± 2.8 

37 ± 3.5 

13 ± 1.5 

11 ± 3.2 

10 ± 3.0 

9 ± 1.0 

9 ± 1.5 

8 ± 0.7 

34 ± 1.2 

34 ± 4.2 

40 ± 3.8 

35 ± 3.2 

39 ± 0.9 

33 ± 3.7 

14 ± 1.8 

13 ± 2.6 

8 ± 1.3 

9 ± 1.9 

9 ± 1.5 

4 ± 0.9 

40 ± 2.8 

31 ± 3.8 

35 ± 2.0 

42 ± 2.1 

36 ± 2.8 

29 ± 5.3 

Trial summary 

Positive control 

Negative 

876 ± 38.5 

Negative 

123 ± 9.8 

Negative 

82 ± 4.6 

Negative 

102 ± 5.0 

Negative 

104 ± 8.3 

Negative 

116 ± 9.4 
 

184 

c 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE E1 

Mutagenicity of Coconut Oil Acid Diethanolamine Condensate in Salmonella typhimurium 

Revertants/plate 

Strain Dose -S9 +hamster S9 +rat S9 

(μg/plate) Trial 1 Trial 2 10% 30% 30% 10% 30% 

TA97 0.0 104 ± 4.4 81 ± 1.5 103 ± 9.0 217 ± 17.7 108 ± 3.0 72 ± 4.9 219 ± 6.8 

0.1 100 ± 1.7 90 ± 0.9 

0.3 115 ± 9.2 90 ± 2.5 

1.0 114 ± 0.7 91 ± 8.0 

3.3 115 ± 11.5 100 ± 6.8 104 ± 3.2 194 ± 5.9 101 ± 1.5 81 ± 2.3 201 ± 8.7 

6.7 112 ± 7.9 73 ± 7.5 

10.0	 99 ± 8.4 174 ± 1.7 108 ± 3.8 72 ± 14.2 216 ± 9.1 

33.0	 98 ± 2.9 204 ± 8.8 101 ± 12.9 68 ± 1.3 255 ± 2.3 

100.0	 87 ± 5.4c 214 ± 2.3 104 ± 9.0 24 ± 5.4 225 ± 10.7 

200.0	 2 ± 0.7c 231 ± 17.3 115 ± 4.3 3 ± 0.3 172 ± 2.3 

Trial summary Negative Negative Negative Negative Negative Negative Negative 

Positive control 909 ± 27.3 181 ± 7.5 768 ± 19.1 277 ± 6.2 238 ± 11.9 1,156 ± 15.3 460 ± 9.2 

TA98 0.0 22 ± 2.6 31 ± 2.6 37 ± 2.9 43 ± 1.2	 33 ± 1.8 36 ± 1.2 

0.1 18 ± 2.3 27 ± 1.9 

0.3 16 ± 1.9 21 ± 0.3 

1.0 16 ± 4.5 23 ± 3.2 

3.3 18 ± 5.0 26 ± 3.3 37 ± 2.3 38 ± 3.8	 36 ± 4.1 40 ± 1.2 

6.7 21 ± 4.4 20 ± 2.4 

10.0	 30 ± 2.0 39 ± 3.5 32 ± 1.8 40 ± 5.8 

33.0	 29 ± 2.0 43 ± 1.9 26 ± 2.7 36 ± 3.2 

100.0	 37 ± 5.3 43 ± 2.7 30 ± 1.0 43 ± 4.4 

200.0	 31 ± 6.0 49 ± 6.8 32 ± 2.8 44 ± 3.3 

Trial summary Negative Negative Negative Negative Negative Negative 

Positive control 1,981 ± 74.7 171 ± 12.0 777 ± 21.0 103 ± 8.0 1,159 ± 50.0 194 ± 9.6 

a Study was performed at Microbiological Associates, Inc. The detailed protocol and these data are presented by Zeiger et al. (1988). 

0.0 μg/plate was the solvent control. b Revertants are presented as mean ± standard error from three plates. 

Slight toxicity d	 The positive controls in the absence of metabolic activation were sodium azide (TA100 and TA1535), 9-aminoacridine (TA97), and 

4-nitro-o-phenylenediamine (TA98). The positive control for metabolic activation with all strains was 2-aminoanthracene. 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 185 

TABLE E2 

Induction of Trifluorothymidine Resistance in L5178Y Mouse Lymphoma Cells 

by Coconut Oil Acid Diethanolamine Condensatea 

Compound Concentration 

Cloning 

Efficiency 

(%) 

Relative 

Total Growth 

(%) 

Mutant Count Mutant 

Fractionb 

Average 

Mutant 

Fraction 

-S9 

Trial 1 

Ethanolc (nL/mL) 72 81 134 62 

Methyl methanesulfonated

 (μg/mL) 

5 33 38 644 654 

60 60 704 390 

49 39 769 525 523* 

Coconut oil acid diethanolamine condensate (nL/mL) 

0 74 94 103 47 

76 101 108 47 

64 123 83 44 50 

1.25 83 90 118 47 

63 67 95 50 49 

Lethal 

2.5 53 65 72 46 

77 77 114 49 

75 74 128 57 50 

5 61 63 81 44 

57 47 97 57 

70 54 114 55 52 

6 69 53 126 61 

64 46 99 52 

70 46 89 42 52 

10 61 84 113 62 

54 9 135 84 

72 15 139 65 70 

12 Lethal 

Lethal 

Lethal 
186 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE E2 

Induction of Trifluorothymidine Resistance in L5178Y Mouse Lymphoma Cells 

by Coconut Oil Acid Diethanolamine Condensate 

Compound Concentration 

Cloning 

Efficiency 

(%) 

Relative 

Total Growth 

(%) 

Mutant Count Mutant 

Fraction 

Average 

Mutant 

Fraction 

-S9 (continued) 

Trial 2 

Ethanol (nL/mL) 93 94 45 16 

Methyl methanesulfonate (μg/mL) 

5 119 101 271 76 

90 72 213 79 

89 77 182 68 74* 

Coconut oil acid diethanolamine condensate (nL/mL) 

0 92 91 62 22 

115 110 60 17 

108 106 38 12 17 

4 91 90 48 18 

96 113 42 15 

100 99 61 20 18 

5 85 87 49 19 

101 89 52 17 

75 69 47 21 19 

6 91 76 72 26 

90 99 53 20 

93 82 44 16 21 

8 74 63 82 37 

78 65 61 26 

86 73 54 21 28* 

10 92 50 82 30 

114 64 70 21 

100 58 74 25 25 

12 75 50 65 29 

99 27 54 18 

77 45 68 30 26 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 187 

TABLE E2 

Induction of Trifluorothymidine Resistance in L5178Y Mouse Lymphoma Cells 

by Coconut Oil Acid Diethanolamine Condensate 

Compound Concentration 

Cloning 

Efficiency 

(%) 

Relative 

Total Growth 

(%) 

Mutant Count Mutant 

Fraction 

Average 

Mutant 

Fraction 

-S9 (continued) 

Trial 3 

Ethanol (nL/mL) 92 66 119 43 

Methyl methanesulfonate (μg/mL) 

5 51 33 868 564 

43 27 574 445 

93 52 698 252 420* 

Coconut oil acid diethanolamine condensate (nL/mL) 

0 115 74 91 26 

111 125 73 22 

114 135 85 25 29 

1.5 102 113 77 25 

116 200 87 25 

103 135 93 30 27 

3 87 113 108 41 

98 114 96 33 

114 126 99 29 34 

6 112 92 86 26 

83 84 110 44 

92 83 104 38 36 

8 115 37 116 34 

108 45 178 55 

111 34 83 25 38 

10 101 25 85 28 

107 76 109 34 

94 20 87 31 31 

12 90 15 115 43 

103 36 114 37 40 

Lethal 

15 Lethal 

Lethal 
188 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE E2 

Induction of Trifluorothymidine Resistance in L5178Y Mouse Lymphoma Cells 

by Coconut Oil Acid Diethanolamine Condensate 

Compound Concentration 

Cloning 

Efficiency 

(%) 

Relative 

Total Growth 

(%) 

Mutant Count Mutant 

Fraction 

Average 

Mutant 

Fraction 

+S9 

Trial 1 

Ethanol (nL/mL) 84 76 138 55 

Methyl cholanthrened

 (μg/mL) 

2.5 66 57 781 392 

60 68 680 377 

80 45 822 344 371* 

Coconut oil acid diethanolamine condensate (nL/mL) 

0 83 93 136 54 

71 102 179 84 

102 129 111 36 57 

1.25 58 73 137 79 

73 89 148 68 

50 97 116 77 75 

2.5 78 117 134 57 

74 117 138 62 

83 105 141 56 59 

5 91 135 61 22 

69 107 92 45 33 

Lethal 

10 54 14 126 78 

92 27 121 44 61 

15 Lethal 

Lethal 

Lethal 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 189 

TABLE E2 

Induction of Trifluorothymidine Resistance in L5178Y Mouse Lymphoma Cells 

by Coconut Oil Acid Diethanolamine Condensate 

Compound Concentration 

Cloning 

Efficiency 

(%) 

Relative 

Total Growth 

(%) 

Mutant Count Mutant 

Fraction 

Average 

Mutant 

Fraction 

+S9 (continued) 

Trial 2 

Ethanol (nL/mL) 78 117 119 51 

Methyl cholanthrene (μg/mL) 

2.5 45 18 613 456 

39 15 626 542 

51 26 570 376 458* 

Coconut oil acid diethanolamine condensate (nL/mL) 

0 91 106 183 67 

85 78 144 56 

82 99 141 58 58 

4 88 137 184 70 

95 121 215 75 

103 144 206 67 71 

5 75 143 157 70 

76 123 166 73 

80 140 141 59 67 

6 72 113 181 84 

67 73 141 70 

83 131 170 69 74 

8 76 92 186 82 

96 89 215 75 

108 118 182 56 71 

10 105 81 194 62 

83 81 202 81 

75 79 137 61 68 

12 93 83 166 60 

81 88 147 60 

78 65 189 81 67 
190 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE E2 

Induction of Trifluorothymidine Resistance in L5178Y Mouse Lymphoma Cells 

by Coconut Oil Acid Diethanolamine Condensate 

Compound Concentration 

Cloning 

Efficiency 

(%) 

Relative 

Total Growth 

(%) 

Mutant Count Mutant 

Fraction 

Average 

Mutant 

Fraction 

+S9 (continued) 

Trial 3 

Ethanol (nL/mL) 104 140 116 37 

Methyl cholanthrene (μg/mL) 

2.5 100 76 578 194

 105 69 605 192 

90 73 457 169 185* 

Coconut oil acid diethanolamine condensate (nL/mL) 

0 88 98 113 43 

103 48 60 19 

98 114 102 35 34 

6 105 116 127 40 

95 109 155 55 

73 85 106 48 48 

8 71 84 101 48 

96 115 143 50 

107 111 101 32 43 

10 95 85 117 41 

98 88 99 34 

105 127 123 39 38 

12 102 105 121 40 

105 85 97 31 

90 117 98 36 36 

15 87 45 101 39 

97 63 108 37 

91 47 137 50 42 

20 107 135 97 30 

93 131 118 42 

104 92 110 35 36 
191 

c 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE E2 

Induction of Trifluorothymidine Resistance in L5178Y Mouse Lymphoma Cells 

by Coconut Oil Acid Diethanolamine Condensate 

Cloning	 Relative Average Mutant Compound Concentration Efficiency Total Growth Mutant Count	 Mutant Fraction (%)	 (%) Fraction 

+S9 (continued) 

Trial 4 

Ethanol (nL/mL)	 82 145 147 60 

Methyl cholanthrene (μg/mL) 

2.5	 60 44 442 246 

60 25 598 330 

84 69 447 177 251* 

Coconut oil acid diethanolamine condensate (nL/mL) 

0	 71 32 146 68 

78 126 129 55 

77	 96 101 44 57 

5	 66 113 113 57 

67	 78 86 43 

65	 89 93 48 49 

10 79 100 153 65 

72	 88 150 70 

62	 94 137 74 69 

15 66 100 100 51 

79 103 147 62 

66 108 115 58 57 

20 67 76 117 58 

58	 74 114 66 

58	 89 115 66 63 

30 57 78 93 55 

72	 95 122 57 

53	 38 91 57 56 

40 62 18 128 69 

63	 17 136 72 70 

Lethal 

50 Lethal 

Lethal 

Lethal 

*	 Positive response (P#0.05) versus the solvent control a Study was performed at Litton Bionetics, Inc. The detailed protocol is presented by Myhr et al. (1985). b	 Mutant fraction (MF) (frequency) is a ratio of the mutant count to the cloning efficiency, divided by 3 (to arrive at MF/106

 cells treated). 

Solvent control 

d Positive control 
192 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE E3 

Induction of Sister Chromatid Exchanges in Chinese Hamster Ovary Cells 

by Coconut Oil Acid Diethanolamine Condensatea 

Relative Change Concen- Total Total SCEs/ Total SCEs/ Hrs of SCEs/ Compound tration Cells Chromo- Chromo- SCEs	 Cell in BrdU Chromosomeb 

(μg/mL) Scored somes	 some (%) 

-S9 

Summary: Negative 

Solvent control	 50 1,048 397 0.37 7.9 26.0 

Mitomycin-Cc	 0.0005 50 1,048 557 0.53 11.1 26.0 40.30 

0.0050 10 210 231 1.10 23.1 26.0 190.38 

Coconut oil acid diethanolamine condensate 

0.5 50 1,050 341 0.32 6.8 26.0 –14.27 

1.6 50 1,050 392 0.37 7.8 26.0 –1.45 

5.0 50 1,049 393 0.37 7.9 26.0 –1.10 

16.0 50	 1,048 375 0.35 7.5 26.0 –5.54 

P=0.446d 

+S9 

Trial 1 

Summary: Weakly positive 

Solvent control	 50 1,053 355 0.33 7.1 26.0 

Cyclophosphamidec	 0.1 50 1,049 522 0.49 10.4 26.0 47.60 

0.6 10 210 269 1.28 26.9 26.0 279.96 

Coconut oil acid diethanolamine condensate 

0.5 50 1,048 407 0.38 8.1 26.0 15.19 

5.0 50 1,049 435 0.41 8.7 26.0 23.00* 

16.0 50	 1,045 408 0.39 8.2 26.0 15.81 

P=0.010 

Trial 2 

Summary: Negative 

Solvent control	 50 1,048 455 0.43 9.1 26.0 

Cyclophosphamide	 0.1 50 1,050 569 0.54 11.4 26.0 24.82 

0.6 10 209 212 1.01 21.2 26.0 133.64 

Coconut oil acid diethanolamine condensate 

5 50 1,050 423 0.40 8.5 26.0 –7.21 

10 50 1,049 473 0.45 9.5 26.0 3.86 

16 50 1,049 373 0.35 7.5 26.0 –18.10 

30 50 1,050 359 0.34 7.2 26.0 –21.25 

P=1.000 

*	 Positive response (P$20% increase over solvent control) a Study was performed at Environmental Health Research and Testing. The detailed protocol is presented by Galloway et al. (1987). 

SCE=sister chromatid exchange; BrdU=bromodeoxyuridine b	 SCEs/chromosome in treated cells versus SCEs/chromosome in solvent control cells 

Positive control 

d	 Significance of SCEs/chromosome tested by the linear regression trend test versus log of the dose 

c 
193 

c 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE E4 

Induction of Chromosomal Aberrations in Chinese Hamster Ovary Cells 

by Coconut Oil Acid Diethanolamine Condensatea 

Concentration Total Cells Number of	 Cells with Compound	 Aberrations/Cell (μg/mL) Scored Aberrations	 Aberrations (%) 

-S9 

Harvest time: 12 hours 

Summary: Negative 

Solvent control	 200 2 0.01 1.0 

Mitomycin-Cb	 0.0625 200 35 0.18 16.5 

0.2500 50 26 0.52 32.0 

Coconut oil acid diethanolamine condensate 

16 200 3 0.02 1.5 

30 200 3 0.02 1.5 

50 200 5 0.03 2.5 

P=0.134c 

+S9 

Harvest time: 13 hours 

Summary: Negative 

Solvent control	 200 2 0.01 1.0 

Cyclophosphamideb	 2.5 200 39 0.20 17.5 

7.5	 50 24 0.48 38.0 

Coconut oil acid diethanolamine condensate 

16 200 5 0.03 2.5 

30 200 4 0.02 2.0 

50 200 4 0.02 2.0 

P=0.280 

a Study was performed at Environmental Health Research and Testing. The detailed protocol is presented by Galloway et al. (1987). b Positive control
 

Significance of percent cells with aberrations tested by the linear regression trend test versus log of the dose
 
194 

c 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE E5 

Frequency of Micronuclei in Mouse Peripheral Blood Erythrocytes Following Dermal Application 

of Coconut Oil Acid Diethanolamine Condensate for 14 Weeksa 

Number of Compound Dose (mg/kg) Mice Micronucleated NCEs/1,000 NCEsb 

Male 

Ethanolc 5 1.60 ± 0.40 

Coconut oil acid diethanolamine condensate 

50 5 2.30 ± 0.25 

100 5 2.90 ± 0.43 

200 5 3.00 ± 0.61 

400 5 2.70 ± 0.20 

800 5 3.50 ± 0.42* 

P=0.015d 

Female 

Ethanolc 5 1.40 ± 0.10 

Coconut oil acid diethanolamine condensate 

50 5 1.70 ± 0.25 

100 5 2.20 ± 0.25 

200 5 2.30 ± 0.41 

400 5 2.10 ± 0.37 

800 5 3.40 ± 0.19* 

P=0.001 

* Significantly different from vehicle control (P#0.005) a Study was performed at Environmental Health Research and Testing, Inc. NCE=normochromatic erythrocyte b Mean ± standard error 

Vehicle control 

d Significance of micronucleated NCEs/1,000 NCEs tested by the one-tailed trend test; significant at P#0.025 (ILS, 1990) 
195 

APPENDIX F
 

HEMATOLOGY AND CLINICAL CHEMISTRY
 

RESULTS
 

TABLE F1	 Hematology and Clinical Chemistry Data for Rats in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate . . . . . . . . . . . . . . . . . . . . . . . . . . . 196 
196 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE F1 

Hematology and Clinical Chemistry Data for Rats in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 25 mg/kg 50 mg/kg 100 mg/kg 200 mg/kg 400 mg/kg 

Male 

Hematology 

n 

Day 4 10 8 7 10 9 9 

Day 24 10 10 9 7 10 10 

Week 14 10 10 10 10 10 10 

Hematocrit (%) 

Day 4 46.2 ± 0.6 44.1 ± 0.5 43.4 ± 0.5** 44.7 ± 0.5 45.6 ± 0.8 44.2 ± 0.5 

Day 24 51.1 ± 0.8 50.0 ± 0.6 49.5 ± 0.7 50.3 ± 0.7 49.8 ± 0.8 48.0 ± 0.8** 

Week 14 47.5 ± 0.5 49.2 ± 0.4 48.4 ± 0.4 49.5 ± 0.5 46.7 ± 0.4 44.8 ± 0.5* 

Hemoglobin (g/dL) 

Day 4 16.1 ± 0.2 15.4 ± 0.2 15.2 ± 0.1* 15.4 ± 0.1 15.9 ± 0.2 15.5 ± 0.2 

Day 24 17.5 ± 0.2 17.4 ± 0.1 17.2 ± 0.2 17.3 ± 0.2 17.4 ± 0.2 16.9 ± 0.2 

Week 14 15.9 ± 0.1 16.5 ± 0.1 16.3 ± 0.1 16.5 ± 0.1 15.6 ± 0.1 14.9 ± 0.1* 

Erythrocytes (106

/μL) 

Day 4 7.41 ± 0.12 7.03 ± 0.10 6.99 ± 0.10 7.13 ± 0.08 7.33 ± 0.14 7.10 ± 0.07 

Day 24 8.63 ± 0.14 8.51 ± 0.10 8.45 ± 0.13 8.57 ± 0.14 8.56 ± 0.12 8.24 ± 0.14 

Week 14 8.61 ± 0.11 9.06 ± 0.07* 8.83 ± 0.08 9.19 ± 0.10** 8.76 ± 0.09 8.45 ± 0.12 

Reticulocytes (106

/μL) 

Day 4 0.24 ± 0.01 0.22 ± 0.01 0.19 ± 0.01* 0.21 ± 0.01* 0.23 ± 0.02 0.17 ± 0.01** 

Day 24 0.17 ± 0.01 0.17 ± 0.01 0.16 ± 0.01 0.17 ± 0.01 0.17 ± 0.01 0.17 ± 0.01 

Week 14 0.18 ± 0.01 0.17 ± 0.01 0.16 ± 0.01 0.17 ± 0.01 0.15 ± 0.01 0.15 ± 0.01 

Nucleated erythrocytes (103

/μL) 

Day 4 0.04 ± 0.02 0.09 ± 0.04 0.01 ± 0.01 0.09 ± 0.02 0.07 ± 0.04 0.04 ± 0.02 

Day 24 0.01 ± 0.01 0.01 ± 0.01 0.01 ± 0.01 0.01 ± 0.01 0.01 ± 0.01 0.02 ± 0.01 

Week 14 0.02 ± 0.01 0.03 ± 0.02 0.05 ± 0.02 0.06 ± 0.02 0.04 ± 0.02 0.01 ± 0.01 

Mean cell volume (fL) 

Day 4 62.4 ± 0.3 62.8 ± 0.3 62.1 ± 0.3 62.7 ± 0.2 62.3 ± 0.3 62.2 ± 0.3 

Day 24 59.2 ± 0.4 58.7 ± 0.2 58.6 ± 0.1 58.6 ± 0.2 58.2 ± 0.2 58.3 ± 0.3 

Week 14 55.2 ± 0.3 54.3 ± 0.1** 54.8 ± 0.3 53.8 ± 0.2** 53.3 ± 0.3** 53.0 ± 0.2** 

Mean cell hemoglobin (pg) 

Day 4 21.7 ± 0.2 21.9 ± 0.2 21.8 ± 0.1 21.5 ± 0.1 21.6 ± 0.1 21.9 ± 0.1 

Day 24 20.3 ± 0.1 20.5 ± 0.1 20.4 ± 0.1 20.2 ± 0.2 20.3 ± 0.1 20.5 ± 0.1 

Week 14 18.4 ± 0.2 18.3 ± 0.1 18.5 ± 0.1 18.0 ± 0.1* 17.8 ± 0.1** 17.7 ± 0.1** 

Mean cell hemoglobin concentration (g/dL) 

Day 4 34.8 ± 0.2 34.9 ± 0.2 35.1 ± 0.2 34.4 ± 0.2 34.8 ± 0.2 35.2 ± 0.2 

Day 24 34.3 ± 0.3 34.9 ± 0.2 34.8 ± 0.2 34.5 ± 0.3 35.0 ± 0.2 35.2 ± 0.2* 

Week 14 33.4 ± 0.2 33.6 ± 0.2 33.7 ± 0.2 33.4 ± 0.3 33.5 ± 0.2 33.4 ± 0.2 

Platelets (103

/μL) 

Day 4 1,052.0 ± 21.2 1,016.0 ± 16.7 984.1 ± 34.8 1,020.9 ± 21.8 1,033.7 ± 34.7 964.0 ± 20.8 

Day 24 808.0 ± 21.7 806.2 ± 14.2 770.2 ± 12.3 783.9 ± 8.0 776.7 ± 14.2 768.5 ± 16.1 

Week 14 731.7 ± 15.9 711.8 ± 15.4 701.4 ± 19.1 672.1 ± 15.2 744.6 ± 39.0 729.5 ± 21.4 

Leukocytes (103

/μL) 

Day 4 11.47 ± 0.96 11.35 ± 0.77 10.74 ± 0.77 10.63 ± 0.41 11.26 ± 0.99 11.70 ± 0.17 

Day 24 10.81 ± 0.70 10.51 ± 0.63 10.19 ± 0.95 9.60 ± 0.89 10.87 ± 0.76 10.42 ± 0.85 

Week 14 7.93 ± 0.44 8.04 ± 0.44 7.59 ± 0.21 7.57 ± 0.38 8.11 ± 0.73 8.96 ± 0.78 

Segmented neutrophils (103

/μL) 

Day 4 1.35 ± 0.13 1.36 ± 0.11 1.16 ± 0.18 1.12 ± 0.10 1.41 ± 0.17 1.79 ± 0.25 

Day 24 1.19 ± 0.10 1.27 ± 0.15 1.06 ± 0.12 1.01 ± 0.13 1.18 ± 0.11 1.19 ± 0.11 

Week 14 1.16 ± 0.10 1.26 ± 0.11 1.00 ± 0.07 1.08 ± 0.14 1.38 ± 0.18 1.94 ± 0.21* 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 197 

TABLE F1 

Hematology and Clinical Chemistry Data for Rats in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 25 mg/kg 50 mg/kg 100 mg/kg 200 mg/kg 400 mg/kg 

Male (continued) 

Hematology (continued) 

n 

Day 4 10 8 7 10 9 9 

Day 24 10 10 9 7 10 10 

Week 14 10 10 10 10 10 10 

Lymphocytes (103

/μL) 

Day 4 9.99 ± 0.84 9.81 ± 0.70 9.46 ± 0.76 9.37 ± 0.39 9.74 ± 0.96 9.76 ± 0.31 

Day 24 9.46 ± 0.66 9.08 ± 0.52 8.92 ± 0.85 8.40 ± 0.80 9.52 ± 0.66 8.96 ± 0.73 

Week 14 6.66 ± 0.38 6.70 ± 0.40 6.50 ± 0.23 6.35 ± 0.29 6.60 ± 0.53 6.77 ± 0.63 

Monocytes (103

/μL) 

Day 4 0.04 ± 0.03 0.10 ± 0.02 0.07 ± 0.04 0.06 ± 0.02 0.07 ± 0.02 0.08 ± 0.02 

Day 24 0.09 ± 0.02 0.12 ± 0.04 0.07 ± 0.03 0.16 ± 0.05 0.17 ± 0.05 0.11 ± 0.03 

Week 14 0.03 ± 0.02 0.02 ± 0.01 0.00 ± 0.00 0.05 ± 0.02 0.03 ± 0.02 0.02 ± 0.01 

Eosinophils (103

/μL) 

Day 4 0.09 ± 0.03 0.09 ± 0.03 0.04 ± 0.03 0.06 ± 0.02 0.03 ± 0.02 0.07 ± 0.02 

Day 24 0.06 ± 0.02 0.04 ± 0.02 0.07 ± 0.03 0.04 ± 0.02 0.01 ± 0.01 0.13 ± 0.04 

Week 14 0.09 ± 0.03 0.07 ± 0.03 0.10 ± 0.03 0.13 ± 0.03 0.14 ± 0.03 0.24 ± 0.06 

Clinical Chemistry 

n 

Day 4 10 10 10 10 10 10 

Day 24 10 10 9 10 10 10 

Week 14 10 10 10 10 10 10 

Urea nitrogen (mg/dL) 

Day 4 23.7 ± 0.5 22.3 ± 0.7 23.0 ± 0.6 23.2 ± 0.6 23.0 ± 0.7 22.8 ± 0.2 

Day 24 25.3 ± 0.4 23.5 ± 0.8 25.7 ± 0.5 25.4 ± 0.8 25.6 ± 0.8 25.2 ± 0.7 

Week 14 23.8 ± 0.4 23.2 ± 0.2 23.4 ± 0.4 24.2 ± 0.5 23.5 ± 0.7 24.2 ± 0.4 

Creatinine (mg/dL) 

Day 4 0.91 ± 0.02 0.87 ± 0.02 0.80 ± 0.03* 0.86 ± 0.02 0.85 ± 0.03 0.82 ± 0.01* 

Day 24 

Week 14 

0.82 ± 0.02 

0.64 ± 0.02 

0.78 ± 0.02 

0.60 ± 0.00 

0.78 ± 0.01 

0.62 ± 0.01 

0.81 ± 0.02 

0.64 ± 0.02b 

0.78 ± 0.02 

0.63 ± 0.02b 

0.78 ± 0.01 

0.61 ± 0.02 

Total protein (g/dL) 

Day 4 6.7 ± 0.1 6.5 ± 0.1 6.4 ± 0.1 6.6 ± 0.1 6.8 ± 0.1 6.4 ± 0.1 

Day 24 

Week 14 

7.5 ± 0.2 

7.0 ± 0.1 

7.4 ± 0.1 

7.2 ± 0.1 

7.2 ± 0.2 

7.0 ± 0.0 

7.6 ± 0.1 

7.2 ± 0.1 

7.2 ± 0.1 

7.1 ± 0.1b 

7.3 ± 0.2 

7.1 ± 0.1 

Albumin (g/dL) 

Day 4 4.8 ± 0.1 4.6 ± 0.1 4.6 ± 0.1 4.7 ± 0.1 4.8 ± 0.1 4.6 ± 0.1 

Day 24 

Week 14 

5.3 ± 0.1 

4.8 ± 0.0 

5.2 ± 0.1 

5.0 ± 0.0* 

5.1 ± 0.1 

4.9 ± 0.0 

5.4 ± 0.1 

5.1 ± 0.1** 

5.2 ± 0.1 

5.0 ± 0.1**b 

5.3 ± 0.1 

5.1 ± 0.0** 

Cholesterol (mg/dL) 

Day 4 100 ± 3 94 ± 2 95 ± 3 99 ± 3 96 ± 2 86 ± 2** 

Day 24 94 ± 2 93 ± 2 90 ± 2 90 ± 4 82 ± 2** 77 ± 3** 

Week 14 102 ± 3 99 ± 3 95 ± 3 97 ± 3 87 ± 2** 74 ± 2** 

Triglycerides (mg/dL) 

Day 4 

Day 24 

249 ± 16 

328 ± 25 

227 ± 11 

334 ± 30 

228 ± 15 

363 ± 15 

241 ± 10 

267 ± 32 

255 ± 20 

340 ± 27 

220 ± 15 

258 ± 24b 

Week 14 340 ± 17 319 ± 26 384 ± 18 367 ± 21 261 ± 24* 174 ± 11** 
198 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE F1 

Hematology and Clinical Chemistry Data for Rats in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 25 mg/kg 50 mg/kg 100 mg/kg 200 mg/kg 400 mg/kg 

Male (continued) 

Clinical Chemistry (continued) 

n 

Day 4 10 10 10 10 10 10 

Day 24 10 10 9 10 10 10 

Week 14 10 10 10 10 10 10 

Alanine aminotransferase (IU/L) 

Day 4 53 ± 2 48 ± 2 49 ± 3 50 ± 1 53 ± 3 49 ± 1 

Day 24 58 ± 2 50 ± 1 54 ± 2 56 ± 6 49 ± 1* 55 ± 3 

Week 14 48 ± 2 50 ± 2 54 ± 2* 58 ± 3* 57 ± 5* 70 ± 4** 

Alkaline phosphatase (IU/L) 

Day 4 1,639 ± 30 1,591 ± 38 1,549 ± 29 1,599 ± 26 1,582 ± 44 1,524 ± 48 

Day 24 1,230 ± 34 1,127 ± 22 1,145 ± 21 1,156 ± 27 1,097 ± 25* 1,161 ± 31 

Week 14 553 ± 10 566 ± 16 585 ± 11 554 ± 12 509 ± 44 617 ± 12** 

Sorbitol dehydrogenase (IU/L) 

Day 4 19 ± 2 19 ± 1 19 ± 3 20 ± 2 21 ± 2 19 ± 1 

Day 24 

Week 14 

25 ± 2 

23 ± 1 

21 ± 2 

21 ± 1 

21 ± 2 

24 ± 1 

23 ± 3 

22 ± 2b 

18 ± 1* 

21 ± 1 

20 ± 1 

19 ± 1 

Bile salts (μm/L) 

Day 4 54.9 ± 8.9 61.8 ± 8.3 44.2 ± 5.5 57.3 ± 9.4 49.8 ± 4.3 46.4 ± 14.2 

Day 24 37.1 ± 4.1 42.7 ± 5.9 40.2 ± 4.8 52.3 ± 9.0 41.0 ± 5.1 44.5 ± 8.1 

Week 14 19.9 ± 0.5 19.6 ± 1.3 21.7 ± 1.4 21.4 ± 0.6 20.5 ± 0.5 20.3 ± 1.2 

Female 

n 10 10 10 10 10 10 

Hematology 

Hematocrit (%) 

Day 4 47.8 ± 0.5 49.0 ± 0.7 47.2 ± 0.8 48.2 ± 1.4 48.3 ± 0.5 47.2 ± 0.5 

Day 24 49.0 ± 0.5 49.5 ± 0.6 49.8 ± 0.8 48.4 ± 0.7 47.1 ± 0.7 46.7 ± 0.4* 

Week 14 47.5 ± 0.5 47.9 ± 0.5 46.8 ± 0.3 45.5 ± 0.6* 43.1 ± 1.2** 42.2 ± 0.6** 

Hemoglobin (g/dL) 

Day 4 16.2 ± 0.2 16.5 ± 0.2 16.1 ± 0.2 16.4 ± 0.4 16.3 ± 0.2 16.1 ± 0.2 

Day 24 16.7 ± 0.1 17.0 ± 0.2 17.0 ± 0.2 16.7 ± 0.2 16.4 ± 0.2 16.3 ± 0.1 

Week 14 15.9 ± 0.2 16.2 ± 0.1 15.9 ± 0.1 15.4 ± 0.2* 14.5 ± 0.4** 14.2 ± 0.2** 

Erythrocytes (106

/μL) 

Day 4 7.41 ± 0.09 7.65 ± 0.13 7.40 ± 0.13 7.53 ± 0.20 7.53 ± 0.09 7.31 ± 0.08 

Day 24 7.84 ± 0.08 7.96 ± 0.10 8.11 ± 0.11 7.85 ± 0.11 7.68 ± 0.11 7.63 ± 0.07 

Week 14 7.99 ± 0.10 8.08 ± 0.08 7.97 ± 0.04 7.77 ± 0.09 7.43 ± 0.18** 7.38 ± 0.09** 

Reticulocytes (106

/μL) 

Day 4 0.31 ± 0.02 0.30 ± 0.02 0.27 ± 0.02 0.30 ± 0.03 0.32 ± 0.03 0.32 ± 0.02 

Day 24 0.12 ± 0.01 0.12 ± 0.01 0.12 ± 0.01 0.13 ± 0.01 0.13 ± 0.01 0.11 ± 0.01 

Week 14 0.10 ± 0.01 0.10 ± 0.01 0.08 ± 0.01 0.08 ± 0.01 0.11 ± 0.03 0.09 ± 0.01 

Nucleated erythrocytes (103

/μL) 

Day 4 0.02 ± 0.01 0.04 ± 0.02 0.11 ± 0.04 0.11 ± 0.03 0.05 ± 0.02 0.06 ± 0.03 

Day 24 

Week 14 

0.00 ± 0.00 

0.00 ± 0.00b 

0.00 ± 0.00 

0.05 ± 0.02 

0.00 ± 0.00 

0.03 ± 0.02 

0.00 ± 0.00 

0.00 ± 0.00 

0.00 ± 0.00 

0.03 ± 0.02 

0.00 ± 0.00 

0.05 ± 0.02 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 199 

TABLE F1 

Hematology and Clinical Chemistry Data for Rats in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 25 mg/kg 50 mg/kg 100 mg/kg 200 mg/kg 400 mg/kg 

Female (continued) 

n 10 10 10 10 10 10 

Hematology (continued) 

Mean cell volume (fL) 

Day 4 64.6 ± 0.3 64.1 ± 0.2 63.8 ± 0.4 64.0 ± 0.2 64.2 ± 0.2 64.6 ± 0.2 

Day 24 62.5 ± 0.2 62.2 ± 0.3 61.4 ± 0.4* 61.7 ± 0.3* 61.3 ± 0.2** 61.2 ± 0.4** 

Week 14 59.5 ± 0.2 59.3 ± 0.2 58.7 ± 0.3* 58.5 ± 0.2** 58.0 ± 0.3** 57.1 ± 0.2** 

Mean cell hemoglobin (pg) 

Day 4 21.9 ± 0.0 21.7 ± 0.2 21.8 ± 0.1 21.8 ± 0.1 21.7 ± 0.1 22.0 ± 0.1 

Day 24 21.3 ± 0.1 21.4 ± 0.1 21.0 ± 0.2 21.3 ± 0.2 21.4 ± 0.1 21.4 ± 0.2 

Week 14 19.9 ± 0.1 20.0 ± 0.1 19.9 ± 0.1 19.8 ± 0.1 19.6 ± 0.2 19.3 ± 0.1** 

Mean cell hemoglobin concentration (g/dL) 

Day 4 33.8 ± 0.2 33.8 ± 0.3 34.1 ± 0.2 34.0 ± 0.3 33.8 ± 0.2 34.0 ± 0.2 

Day 24 34.1 ± 0.2 34.4 ± 0.2 34.2 ± 0.2 34.5 ± 0.3 34.8 ± 0.2* 34.9 ± 0.2** 

Week 14 33.6 ± 0.2 33.8 ± 0.2 33.9 ± 0.1 33.8 ± 0.1 33.7 ± 0.2 33.8 ± 0.2 

Platelets (103

/μL) 

Day 4 917.6 ± 13.8 963.2 ± 20.7 911.8 ± 16.6 950.8 ± 18.6 962.6 ± 11.9 935.7 ± 16.9 

Day 24 718.1 ± 10.3 750.9 ± 12.4 720.8 ± 13.7 760.6 ± 12.3 735.9 ± 21.9 704.9 ± 15.5 

Week 14 719.5 ± 53.7 628.0 ± 14.3 676.1 ± 19.3 675.4 ± 12.2 651.2 ± 17.4 697.8 ± 80.9 

Leukocytes (103

/μL) 

Day 4 10.80 ± 0.40 9.94 ± 0.62 10.03 ± 0.48 9.87 ± 0.38 10.09 ± 0.63 11.32 ± 0.58 

Day 24 

Week 14 

6.47 ± 0.32 

7.02 ± 0.40b 

7.25 ± 0.60 

7.16 ± 0.38 

7.55 ± 0.58 

6.80 ± 0.23 

7.35 ± 0.58 

6.75 ± 0.35 

7.77 ± 0.43* 

7.29 ± 0.28 

8.58 ± 0.60** 

8.19 ± 0.65 

Segmented neutrophils (103

/μL) 

Day 4 1.21 ± 0.12 0.92 ± 0.09 1.01 ± 0.12 1.21 ± 0.22 1.03 ± 0.19 1.55 ± 0.18 

Day 24 

Week 14 

0.75 ± 0.09 

1.02 ± 0.08b 

0.75 ± 0.07 

0.93 ± 0.10 

0.60 ± 0.06 

0.86 ± 0.08 

0.72 ± 0.07 

0.80 ± 0.10 

0.88 ± 0.12 

1.40 ± 0.15 

1.36 ± 0.20** 

1.90 ± 0.30** 

Lymphocytes (103

/μL) 

Day 4 9.32 ± 0.36 8.76 ± 0.55 8.82 ± 0.40 8.51 ± 0.35 8.74 ± 0.50 9.56 ± 0.51 

Day 24 

Week 14 

5.56 ± 0.31 

5.87 ± 0.34b 

6.29 ± 0.55 

6.11 ± 0.32 

6.81 ± 0.52 

5.85 ± 0.22 

6.49 ± 0.54 

5.86 ± 0.28 

6.67 ± 0.33 

5.68 ± 0.23 

6.95 ± 0.44 

6.08 ± 0.39 

Monocytes (103

/μL) 

Day 4 0.17 ± 0.05 0.21 ± 0.05 0.18 ± 0.04 0.12 ± 0.03 0.22 ± 0.06 0.09 ± 0.03 

Day 24 

Week 14 

0.08 ± 0.03 

0.09 ± 0.03b 

0.10 ± 0.02 

0.07 ± 0.02 

0.12 ± 0.04 

0.07 ± 0.02 

0.08 ± 0.02 

0.08 ± 0.03 

0.15 ± 0.04 

0.04 ± 0.02 

0.18 ± 0.04 

0.02 ± 0.01 

Eosinophils (103

/μL) 

Day 4 0.07 ± 0.03 0.04 ± 0.02 0.04 ± 0.02 0.06 ± 0.03 0.11 ± 0.04 0.12 ± 0.04 

Day 24 

Week 14 

0.08 ± 0.02 

0.08 ± 0.03b 

0.10 ± 0.03 

0.05 ± 0.02 

0.02 ± 0.01 

0.07 ± 0.02 

0.07 ± 0.02 

0.06 ± 0.03 

0.06 ± 0.02 

0.16 ± 0.05 

0.11 ± 0.03 

0.25 ± 0.04** 

Clinical Chemistry 

Urea nitrogen (mg/dL) 

Day 4 23.5 ± 0.9 24.8 ± 0.8 23.8 ± 1.0 22.6 ± 0.9 22.3 ± 0.6 23.2 ± 0.7 

Day 24 25.2 ± 0.7 25.5 ± 0.4 25.9 ± 0.6 26.5 ± 0.4 27.1 ± 0.4* 30.4 ± 0.7** 

Week 14 23.8 ± 0.5 26.2 ± 0.6* 24.9 ± 0.6 23.0 ± 0.4 27.0 ± 1.1** 30.0 ± 0.7** 

Creatinine (mg/dL) 

Day 4 0.79 ± 0.01 0.75 ± 0.02 0.70 ± 0.02* 0.72 ± 0.04 0.71 ± 0.03 0.74 ± 0.03 

Day 24 0.69 ± 0.02 0.71 ± 0.02 0.73 ± 0.02 0.69 ± 0.03 0.69 ± 0.02 0.75 ± 0.02 

Week 14 0.62 ± 0.01 0.63 ± 0.02 0.66 ± 0.03 0.61 ± 0.01 0.63 ± 0.04 0.64 ± 0.02 
200 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE F1 

Hematology and Clinical Chemistry Data for Rats in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensate 

Vehicle Control 25 mg/kg 50 mg/kg 100 mg/kg 200 mg/kg 400 mg/kg 

Female (continued) 

n 10 10 10 10 10 10 

Clinical Chemistry (continued) 

Total protein (g/dL) 

Day 4 6.4 ± 0.1 6.5 ± 0.1 6.1 ± 0.1 6.3 ± 0.1 6.3 ± 0.1 6.3 ± 0.1 

Day 24 6.3 ± 0.1 6.3 ± 0.2 6.2 ± 0.1 6.3 ± 0.1 6.3 ± 0.1 6.7 ± 0.1 

Week 14 6.5 ± 0.1 6.6 ± 0.1 6.7 ± 0.1 6.8 ± 0.1 6.9 ± 0.1** 7.1 ± 0.1** 

Albumin (g/dL) 

Day 4 4.6 ± 0.1 4.7 ± 0.1 4.4 ± 0.1 4.6 ± 0.1 4.6 ± 0.1 4.6 ± 0.0 

Day 24 4.5 ± 0.1 4.6 ± 0.1 4.6 ± 0.1 4.7 ± 0.1 4.8 ± 0.1 5.3 ± 0.1** 

Week 14 4.6 ± 0.0 4.8 ± 0.1* 4.8 ± 0.0** 5.0 ± 0.1** 5.2 ± 0.1** 5.4 ± 0.1** 

Cholesterol (mg/dL) 

Day 4 109 ± 3 110 ± 4 102 ± 3 110 ± 4 103 ± 3 94 ± 3** 

Day 24 95 ± 2 91 ± 3 84 ± 2** 80 ± 3** 71 ± 2** 64 ± 2** 

Week 14 100 ± 3 94 ± 3 92 ± 3 79 ± 2** 75 ± 4** 66 ± 2** 

Triglycerides (mg/dL) 

Day 4 177 ± 12 183 ± 12 178 ± 15 211 ± 15 173 ± 16 193 ± 14 

Day 24 147 ± 17 140 ± 25 174 ± 22 152 ± 20 146 ± 21 141 ± 17 

Week 14 115 ± 13 178 ± 21 174 ± 19 131 ± 20 143 ± 15 126 ± 22 

Alanine aminotransferase (IU/L) 

Day 4 45 ± 1 48 ± 2 47 ± 1 51 ± 3 50 ± 1 46 ± 2 

Day 24 37 ± 2 38 ± 1 37 ± 2 36 ± 1 35 ± 2 40 ± 1 

Week 14 56 ± 5 53 ± 5 64 ± 7 60 ± 7 58 ± 4 56 ± 6 

Alkaline phosphatase (IU/L) 

Day 4 1,361 ± 41 1,426 ± 20 1,359 ± 29 1,421 ± 48 1,351 ± 38 1,325 ± 23 

Day 24 893 ± 26 921 ± 46 876 ± 33 884 ± 28 854 ± 23 929 ± 26 

Week 14 524 ± 30 579 ± 20 549 ± 16 506 ± 16 530 ± 16 592 ± 22 

Sorbitol dehydrogenase (IU/L) 

Day 4 13 ± 2 16 ± 3 16 ± 1 19 ± 4 17 ± 2 16 ± 2 

Day 24 19 ± 1 20 ± 2 23 ± 3 20 ± 2 20 ± 2 25 ± 2 

Week 14 21 ± 1 24 ± 1 26 ± 3 28 ± 4 25 ± 2 24 ± 2 

Bile salts (μm/L) 

Day 4 38.2 ± 7.5 38.6 ± 9.0 41.5 ± 6.1 43.2 ± 6.7 36.9 ± 4.4 34.6 ± 7.8 

Day 24 

Week 14 

30.9 ± 6.8 

25.8 ± 2.3 

25.7 ± 3.4 

31.5 ± 6.2 

33.3 ± 4.8 

31.9 ± 6.4 

27.4 ± 3.4 

25.2 ± 3.6 

36.5 ± 6.3 

25.7 ± 3.4b 

23.6 ± 4.2 

23.5 ± 1.3 

* Significantly different (P#0.05) from the vehicle 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 
201 

APPENDIX G 

ORGAN WEIGHTS AND 

ORGAN-WEIGHT-TO-BODY-WEIGHT RATIOS 

TABLE G1 

TABLE G2 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats 

in the 14-Week Dermal Study of Coconut Oil Acid Diethanolamine Condensate ...... 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice 

in the 14-Week Dermal Study of Coconut Oil Acid Diethanolamine Condensate ...... 

202 

203 
202 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE G1 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Rats in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle 

Control 25 mg/kg 50 mg/kg 100 mg/kg 200 mg/kg 400 mg/kg 

n 10 10 10 10 10 10 

Male 

Necropsy body wt 362 ± 6 351 ± 7 345 ± 5 343 ± 11 321 ± 7** 284 ± 9** 

Heart 

Absolute 1.128 ± 0.033 1.109 ± 0.035 1.068 ± 0.026 1.079 ± 0.030 1.065 ± 0.034 0.999 ± 0.025** 

Relative 3.12 ± 0.09 3.16 ± 0.07 3.09 ± 0.05 3.15 ± 0.06 3.32 ± 0.06* 3.53 ± 0.04** 

R. Kidney 

Absolute 1.423 ± 0.019 1.401 ± 0.029 1.419 ± 0.029 1.474 ± 0.038 1.475 ± 0.032 1.434 ± 0.030 

Relative 3.93 ± 0.03 4.00 ± 0.05 4.11 ± 0.04* 4.30 ± 0.06** 4.61 ± 0.06** 5.07 ± 0.08** 

Liver 

Absolute 16.831 ± 0.417 16.186 ± 0.450 16.063 ± 0.335 16.337 ± 0.612 15.689 ± 0.539 14.021 ± 0.519** 

Relative 46.47 ± 0.86 46.17 ± 0.91 46.53 ± 0.85 47.54 ± 0.66 48.89 ± 1.13 49.31 ± 0.43* 

Lung 

Absolute 1.862 ± 0.076 1.766 ± 0.082 1.592 ± 0.057* 1.859 ± 0.068 1.719 ± 0.060 1.560 ± 0.067* 

Relative 5.16 ± 0.23 5.02 ± 0.17 4.61 ± 0.17 5.42 ± 0.12 5.36 ± 0.12 5.50 ± 0.18 

R. Testis 

Absolute 1.529 ± 0.007 1.500 ± 0.015 1.538 ± 0.014 1.461 ± 0.069 1.494 ± 0.017 1.485 ± 0.022 

Relative 4.23 ± 0.07 4.29 ± 0.08 4.46 ± 0.04 4.24 ± 0.12 4.67 ± 0.08** 5.26 ± 0.10** 

Thymus 

Absolute 0.359 ± 0.011 0.349 ± 0.017 0.343 ± 0.013 0.346 ± 0.025 0.313 ± 0.008 0.257 ± 0.016** 

Relative 0.99 ± 0.03 1.00 ± 0.05 0.99 ± 0.04 1.00 ± 0.05 0.98 ± 0.03 0.90 ± 0.04 

Female 

Necropsy body wt 192 ± 3 198 ± 4 192 ± 4 194 ± 6 182 ± 3 172 ± 4** 

Heart 

Absolute 0.727 ± 0.023 0.736 ± 0.020 0.716 ± 0.017 0.719 ± 0.019 0.747 ± 0.023 0.715 ± 0.018 

Relative 3.79 ± 0.09 3.72 ± 0.07 3.73 ± 0.05 3.72 ± 0.11 4.11 ± 0.11* 4.17 ± 0.08** 

R. Kidney 

Absolute 0.792 ± 0.016 0.848 ± 0.020* 0.884 ± 0.017** 0.941 ± 0.015** 0.985 ± 0.015** 1.006 ± 0.027** 

Relative 4.13 ± 0.06 4.29 ± 0.05 4.61 ± 0.07** 4.88 ± 0.15** 5.43 ± 0.08** 5.86 ± 0.10** 

Liver 

Absolute 7.712 ± 0.263 7.813 ± 0.238 7.639 ± 0.151 8.057 ± 0.174 8.007 ± 0.089 8.452 ± 0.247 

Relative 40.19 ± 1.16 39.50 ± 0.60 39.85 ± 0.70 41.64 ± 0.55 44.17 ± 0.46** 49.27 ± 1.16** 

Lung 

Absolute 1.297 ± 0.028 1.282 ± 0.055 1.367 ± 0.042 1.282 ± 0.047 1.185 ± 0.032 1.112 ± 0.037** 

Relative 6.76 ± 0.08 6.50 ± 0.29 7.13 ± 0.23 6.67 ± 0.34 6.55 ± 0.21 6.51 ± 0.28 

Thymus 

Absolute 0.246 ± 0.009 0.252 ± 0.011 0.259 ± 0.006 0.271 ± 0.011 0.225 ± 0.008 0.204 ± 0.003** 

Relative 1.28 ± 0.04 1.28 ± 0.05 1.35 ± 0.04 1.40 ± 0.05 1.24 ± 0.04 1.19 ± 0.03 

* Significantly different (P#0.05) from the vehicle 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). 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 203 

TABLE G2 

Organ Weights and Organ-Weight-to-Body-Weight Ratios for Mice in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle 

Control 50 mg/kg 100 mg/kg 200 mg/kg 400 mg/kg 800 mg/kg 

n 10 10 10 10 10 10 

Male 

Necropsy body wt 38.8 ± 1.3 37.3 ± 0.6 37.0 ± 0.9 37.8 ± 1.1 38.6 ± 1.3 38.1 ± 1.3 

Heart 

Absolute 0.197 ± 0.008 0.182 ± 0.004 0.190 ± 0.007 0.190 ± 0.004 0.195 ± 0.006 0.197 ± 0.005 

Relative 5.10 ± 0.21 4.88 ± 0.11 5.12 ± 0.11 5.06 ± 0.17 5.11 ± 0.22 5.21 ± 0.19 

R. Kidney 

Absolute 0.367 ± 0.008 0.369 ± 0.007 0.364 ± 0.010 0.381 ± 0.011 0.395 ± 0.009 0.424 ± 0.013** 

Relative 9.51 ± 0.17 9.87 ± 0.15 9.84 ± 0.20 10.16 ± 0.39 10.30 ± 0.27* 11.16 ± 0.27** 

Liver 

Absolute 1.963 ± 0.075 1.887 ± 0.055 0.048 ± 0.002 1.950 ± 0.039 2.088 ± 0.068 2.156 ± 0.075* 

Relative 50.65 ± 1.04 50.49 ± 1.02 1.29 ± 0.04 51.73 ± 0.68 54.23 ± 1.09** 56.67 ± 0.85** 

Lung 

Absolute 0.236 ± 0.011 0.231 ± 0.007 0.244 ± 0.006 0.251 ± 0.012 0.249 ± 0.009 0.239 ± 0.009 

Relative 6.12 ± 0.29 6.21 ± 0.21 6.62 ± 0.21 6.65 ± 0.25 6.49 ± 0.23 6.34 ± 0.28 

R. Testis 

Absolute 0.122 ± 0.002 0.122 ± 0.002 0.122 ± 0.002 0.122 ± 0.002 0.122 ± 0.004 0.122 ± 0.002 

Relative 3.16 ± 0.06 3.26 ± 0.06 3.30 ± 0.07 3.25 ± 0.07 3.19 ± 0.11 3.23 ± 0.08 

Thymus 

Absolute 0.047 ± 0.004 0.045 ± 0.003 0.048 ± 0.002 0.046 ± 0.002 0.048 ± 0.003 0.047 ± 0.003 

Relative 1.20 ± 0.09 1.21 ± 0.08 1.29 ± 0.04 1.22 ± 0.07 1.24 ± 0.05 1.23 ± 0.05 

Female 

Necropsy body wt 31.5 ± 0.8 32.4 ± 0.8 32.9 ± 1.0 29.8 ± 0.4 31.2 ± 0.3 30.1 ± 0.5 

Heart 

Absolute 0.154 ± 0.004 0.156 ± 0.005 0.147 ± 0.004 0.161 ± 0.006 0.158 ± 0.006 0.157 ± 0.004 

Relative 4.94 ± 0.20 4.82 ± 0.18 4.51 ± 0.15 5.40 ± 0.22 5.05 ± 0.18 5.23 ± 0.13 

R. Kidney 

Absolute 0.237 ± 0.006 0.246 ± 0.004 0.248 ± 0.005 0.239 ± 0.005 0.248 ± 0.006 0.258 ± 0.003* 

Relative 7.56 ± 0.19 7.61 ± 0.13 7.58 ± 0.20 8.01 ± 0.18 7.95 ± 0.14 8.59 ± 0.15** 

Liver 

Absolute 1.602 ± 0.048 1.674 ± 0.032 1.690 ± 0.046 1.659 ± 0.040 1.808 ± 0.040** 1.866 ± 0.047** 

Relative 51.07 ± 1.60 51.74 ± 0.87 51.76 ± 1.75 55.58 ± 1.10* 58.00 ± 1.15** 61.98 ± 0.96** 

Lung 

Absolute 0.208 ± 0.006 0.222 ± 0.008 0.237 ± 0.011 0.216 ± 0.006 0.231 ± 0.010 0.246 ± 0.013** 

Relative 6.61 ± 0.14 6.86 ± 0.22 7.24 ± 0.36 7.26 ± 0.22 7.41 ± 0.34 8.16 ± 0.42** 

Thymus 

Absolute 0.058 ± 0.003 0.062 ± 0.004 0.059 ± 0.002 0.057 ± 0.003 0.055 ± 0.001 0.053 ± 0.002 

Relative 1.84 ± 0.10 1.91 ± 0.10 1.81 ± 0.10 1.91 ± 0.09 1.77 ± 0.05 1.77 ± 0.05 

* Significantly different (P#0.05) from the vehicle 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). 
204 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 
205 

APPENDIX H 

REPRODUCTIVE TISSUE EVALUATIONS 

AND ESTROUS CYCLE CHARACTERIZATION 

TABLE H1 Summary of Reproductive Tissue Evaluations for Male Rats 

in the 14-Week Dermal Study of Coconut Oil Acid Diethanolamine Condensate ...... 206 

TABLE H2 Summary of Estrous Cycle Characterization for Female Rats 

in the 14-Week Dermal Study of Coconut Oil Acid Diethanolamine Condensate ...... 206 

TABLE H3 Summary of Reproductive Tissue Evaluations for Male Mice 

in the 14-Week Dermal Study of Coconut Oil Acid Diethanolamine Condensate ...... 207 

TABLE H4 Summary of Estrous Cycle Characterization for Female Mice 

in the 14-Week Dermal Study of Coconut Oil Acid Diethanolamine Condensate ...... 207 
206 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE H1 

Summary of Reproductive Tissue Evaluations for Male Rats in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 100 mg/kg 200 mg/kg 400 mg/kg 

n 10 9 10 10 

Weights (g) 

Necropsy body wt 362 ± 6 343 ± 11b 321 ± 7** 284 ± 9** 

L. cauda epididymis 0.1559 ± 0.0056 0.1550 ± 0.0055 0.1520 ± 0.0032 0.1470 ± 0.0039 

L. epididymis 0.4655 ± 0.0087 0.4533 ± 0.0059 0.4400 ± 0.0052* 0.4250 ± 0.0081** 

L. testis 1.5943 ± 0.0220 1.6001 ± 0.0204 1.5605 ± 0.0244 1.5499 ± 0.0213 

Spermatid measurements 

Spermatid heads (107

/g testis) 9.68 ± 0.18 9.03 ± 0.18 9.36 ± 0.26 9.74 ± 0.24 

Spermatid heads (107

/testis) 15.42 ± 0.34 14.45 ± 0.35 14.56 ± 0.25 15.08 ± 0.38 

Spermatid count

 (mean/10-4 mL suspension) 77.10 ± 1.71 72.25 ± 1.75 72.80 ± 1.23 75.38 ± 1.89 

Epididymal spermatozoal measurements 

Motility (%) 68.45 ± 1.02 65.68 ± 1.40 68.59 ± 2.12 67.29 ± 1.39 

Concentration

 (106

/g cauda epididymal tissue) 1,084 ± 49 1,065 ± 37 1,109 ± 60 1,111 ± 54 

* Significantly different (P#0.05) from the vehicle control group by Williams’ test 

** P#0.01 a Data are presented as mean ± standard error. Differences from the vehicle control group are not significant by Dunnett’s test (left 

cauda epididymis and left testis weights) or Dunn’s test (spermatid and epididymal spermatozoal measurements). b n=10 

TABLE H2 

Summary of Estrous Cycle Characterization for Female Rats in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 100 mg/kg 200 mg/kg 400 mg/kg 

n 10 10 10 10 

Necropsy body wt (g) 

Estrous cycle length (days) 

192 ± 3 

5.00 ± 0.00 

194 ± 6 

5.00 ± 0.00 

182 ± 3 

5.00 ± 0.00b 

172 ± 4** 

5.06 ± 0.06b 

Estrous stages (% of cycle) 

Diestrus 39.2 38.3 35.8 47.5 

Proestrus 10.8 19.2 15.8 13.3 

Estrus 30.8 25.8 29.2 20.0 

Metestrus 19.2 16.7 19.2 19.2 

** Significantly different (P#0.01) from the vehicle control group by Williams’ test a Necropsy body weight and estrous cycle length data are presented as mean ± standard error. Differences from the vehicle control group 

for estrous cycle length are not significant by Dunn’s test. By multivariate analysis of variance, dosed females do not differ significantly 

from the vehicle control females in the relative length of time spent in the estrous stages. b Estrous cycle was longer than 12 days or unclear in 1 of 10 animals. 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 207 

TABLE H3 

Summary of Reproductive Tissue Evaluations for Male Mice in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 200 mg/kg 400 mg/kg 800 mg/kg 

n 10 10 10 10 

Weights (g) 

Necropsy body wt 38.8 ± 1.3 37.8 ± 1.1 38.6 ± 1.3 38.1 ± 1.3 

L. cauda epididymis 0.0147 ± 0.0007 0.0150 ± 0.0008 0.0142 ± 0.0006 0.0165 ± 0.0005 

L. epididymis 0.0433 ± 0.0007 0.0432 ± 0.0008 0.0431 ± 0.0014 0.0440 ± 0.0016 

L. testis 0.1178 ± 0.0025 0.1173 ± 0.0027 0.1157 ± 0.0041 0.1191 ± 0.0016 

Spermatid measurements 

Spermatid heads (107

/g testis) 22.31 ± 0.49 22.77 ± 0.56 22.04 ±0.59 21.47 ± 0.51 

Spermatid heads (107

/testis) 2.63 ± 0.09 2.66 ± 0.04 2.54 ± 0.09 2.56 ± 0.06 

Spermatid count

 (mean/10-4 mL suspension) 82.18 ± 2.72 83.13 ± 1.38 79.40 ± 2.97 79.85 ± 2.01 

Epididymal spermatozoal parameters 

Motility (%) 64.21 ± 1.42 66.57 ± 0.58 69.97 ± 1.96 67.02 ± 1.36 

Concentration 

 (106

/g cauda epididymal tissue) 1,664 ± 121 1,981 ± 224 1,977 ± 131 2,289 ± 111* 

* Significantly different (P#0.05) from the vehicle control group by Dunn’s test a Data are presented as mean ± standard error. Differences from the vehicle control group are not significant by Dunnett’s test (body and 

tissue weights) or Dunn’s test (spermatid and epididymal spermatozoal motility). 

TABLE H4 

Summary of Estrous Cycle Characterization for Female Mice in the 14-Week Dermal Study 

of Coconut Oil Acid Diethanolamine Condensatea 

Vehicle Control 200 mg/kg 400 mg/kg 800 mg/kg 

n 10 10 10 10 

Necropsy body wt (g) 31.5 ± 0.7 29.8 ± 0.4 31.2 ± 0.3 30.1 ± 0.5 

Estrous cycle length (days) 4.30 ± 0.13 4.70 ± 0.39 4.25 ± 0.13 4.35 ± 0.15 

Estrous stages (% of cycle) 

Diestrus 26.7 24.2 30.0 25.8 

Proestrus 22.5 21.7 19.2 21.7 

Estrus 28.3 32.5 27.5 29.2 

Metestrus 22.5 21.7 23.3 23.3 

a Necropsy body weight and estrous cycle length data are presented as mean ± standard error. Differences from the vehicle control group 

are not significant by Dunnett’s test (body weights) or Dunn’s test (estrous cycle length). By multivariate analysis of variance, dosed 

females do not differ significantly from the vehicle control females in the relative length of time spent in the estrous stages. 
 

208 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 
209 

APPENDIX I
 

CHEMICAL CHARACTERIZATION
 

AND DOSE FORMULATION STUDIES
 

PROCUREMENT AND CHARACTERIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210 
 

PREPARATION AND ANALYSIS OF DOSE FORMULATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 
 

FIGURE I1 Infrared Absorption Spectrum of Coconut Oil Acid Diethanolamine Condensate . . . . . . 212 
 

FIGURE I2 Nuclear Magnetic Resonance Spectrum
 

of Coconut Oil Acid Diethanolamine Condensate . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 
 

TABLE I1 Preparation and Storage of Dose Formulations in the Dermal Studies
 

of Coconut Oil Acid Diethanolamine Condensate . . . . . . . . . . . . . . . . . . . . . . . . . . . 214 
 

TABLE I2 Results of Analyses of Dose Formulations Administered to Rats and Mice
 

in the 14-Week Dermal Studies of Coconut Oil Acid Diethanolamine Condensate . . . . . 215 
 

TABLE I3 Results of Analyses of Dose Formulations Administered to Rats and Mice
 

in the 2-Year Dermal Studies of Coconut Oil Acid Diethanolamine Condensate . . . . . . . 217 
 
210 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

CHEMICAL CHARACTERIZATION 

AND DOSE FORMULATION STUDIES 

PROCUREMENT AND CHARACTERIZATION 

Coconut Oil Acid Diethanolamine Condensate 

Coconut oil acid diethanolamine condensate was obtained from Henkel Corporation (Mauldin, SC) in one 

lot (1G01742286), which was used during the 14-week and 2-year studies. Identity and purity analyses 

were conducted by the study laboratory. Stability studies were performed by the analytical chemistry 

laboratory, Midwest Research Institute (Kansas City, MO). Reports on analyses performed in support of 

the coconut oil acid diethanolamine condensate studies are on file at the National Institute of Environmental 

Health Sciences. 

The chemical, a viscous yellow liquid, was identified as coconut oil acid diethanolamine condensate by 

infrared and nuclear magnetic resonance (NMR) spectroscopy. The spectra were consistent with those 

expected for the proposed compounds in the structure of coconut oil acid diethanolamine condensate and 

with those of a previously analyzed lot (D542578C0) not used in the current studies (MRI, 1978). The 

infrared spectrum contained an additional absorbance, characteristic of amine salts; the NMR spectrum 

indicated the presence of unreacted diethanolamine and some unsaturated salts. The infrared and nuclear 

magnetic spectra are presented in Figures I1 and I2. 

The purity of lot 1G01742286 was determined by high-performance liquid chromatography (HPLC) and 

nitrosamine quantitation. HPLC was performed with a Phenomenex Ultracarb 5 ODS (30) column using 

ultraviolet detection (230 nm) and two solvent systems: A) methanol and water (80:20) and B) methanol. 

The flow rate was 0.5 mL/minute. ThermedeTec, Inc. (Woburn, MA), analyzed polar and nonpolar 

nitrosamines by HPLC with a thermo-energy analyzer. 

HPLC indicated one major peak and 15 smaller peaks with areas of 0.5% or greater relative to the major 

peak area. Lot 1G01742286 was composed primarily of diethanolamides of coconut oil acids, with 

unreacted diethanolamine, alkanolamides of unsaturated acids, and amine salts of the acids. The polar 

nitrosamine, N-nitrosodiethanolamine, was detected at a concentration of 219 ppb, which was considered 

consistent with the anticipated composition of commercial coconut oil acid diethanolamine condensate. No 

nonpolar nitrosamines were detected (detection limits: 10 ppb for volatile nitrosamines or 80 ppb for 

nonvolatile nitrosamines). Based on calculations using the amine value provided by the manufacturer, the 

unreacted diethanolamine content was estimated at 18.2%. 

Stability studies of the bulk chemical were performed by the analytical chemistry laboratory on 

lot DS42578C0 using nonaqueous titration of amine function of diethanolamine with perchloric acid. 

Coconut oil acid diethanolamine condensate showed some instability when stored in glass tubes for 2 weeks 

at 60E C. Stability was monitored during the 14-week and 2-year studies using HPLC. No degradation of 

the bulk chemical was detected. To ensure stability, the bulk chemical was stored at room temperature, 

protected from light, in amber glass bottles sealed with Teflon®-lined caps. 

Ethanol 

Ethanol (95%) was obtained from Aaper Alcohol and Chemical Company (Shelbyville, KY) in 14 lots. The 

purity of the 95% ethanol used in these studies was monitored at the beginning and end of the 14-week 

studies and every 2 to 4 months during the 2-year studies using gas chromatography with a flame ionization 

detector. The column system used a 60/80 Carbopack B/1% SP-1000 glass column with a nitrogen carrier 

gas at a flow rate of 20 mL/minute. The oven temperature program was set at 80E C for 4 minutes and 

then increased to 220E C at a rate of 10E C/minute. USP/NF ethanol reference standards were analyzed 

concomitantly. Purity of the bulk chemical ranged from 96.6% to 103.4% relative to that of the reference 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 211 

standard, except for one sample taken during the 2-year studies which measured 109.6%. This was
 

considered to be a spurious result because analysis of the same material approximately 2 months later
 

indicated a relative purity of 101.1%. 

PREPARATION AND ANALYSIS OF DOSE FORMULATIONS 

The dose formulations were prepared every 3 weeks by mixing coconut oil acid diethanolamine condensate 

and 95% ethanol to give the required concentration (Table I1). The dose formulations were stored at room 

temperature, protected from light, in amber glass bottles for up to 28 days. 

Stability studies of the 10 mg/mL dose formulation were performed by the study laboratory using HPLC. 

When stored in sealed glass containers and protected from ultraviolet light, the stability of the dose 

formulations was confirmed for at least 28 days between -20E C and room temperature. When open to air 

and light, the stability of coconut oil acid diethanolamine condensate was confirmed for 3 hours; however, a 

narrow-mouth bottle was suggested for storage during dose administration to decrease evaporation of the 

ethanol. 

Periodic analyses of the dose formulations of coconut oil acid diethanolamine condensate were conducted at 

the study laboratory using HPLC. For the 14-week studies, dose formulations from the beginning, middle, 

and end of the studies were analyzed (Table I2). During the 2-year studies, dose formulations were 

analyzed approximately every 2 months (Table I3). During the 14-week studies, 13 of 15 dose formulations 

for rats and all 15 dose formulations for mice were within 10% of the target concentrations; two dose 

formulations for rats were 111% and 117% of the target concentrations. These dose formulations were 

remixed, and the remixes were determined to be within 10% of the target concentrations. All 48 dose 

formulations analyzed and used during the 2-year studies were within 10% of the target concentrations. In 

addition to dose formulation analysis prior to dosing, samples collected after dosing (animal room samples) 

were analyzed periodically. All animal room samples analyzed during the 14-week studies were within 

10% of the target concentration. For the 2-year studies, 14 of 16 were within 10% of target concentration; 

two samples were 112% and 116% of target concentrations, apparently due to evaporation of the 95% 

ethanol from improperly sealed dosing bottles. 
2 1 2 C o c o nut Oil Acid Diethanolamine Condensat e, NTP TR 479
 

F i g u re I1 

I n f ra red Absorption Spectrum of Coconut Oil Acid Diethanolamine Condensat e 
C o c o nut Oil Acid Diethanolamine Condensat e, NTP TR 479 2 1 3
 

F i g u re I2 

N u clear Magnetic Resonance Spectrum of Coconut Oil Acid Diethanolamine Condensat e 
214 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE I1 

Preparation and Storage of Dose Formulations in the Dermal Studies 

of Coconut Oil Acid Diethanolamine Condensate 

14-Week Studies 2-Year Studies 

Preparation 

A weighed amount of coconut oil acid diethanolamine 

condensate was diluted to volume with 95% ethanol, and then 

the solution was thoroughly mixed by shaking. Doses were 

prepared every 3 weeks. 

Chemical Lot Number 

1G01742286 

Maximum Storage Time 

28 days 

Storage Conditions 

Stored protected from light in amber glass bottles at room 

temperature 

Study Laboratory 

Battelle Columbus Laboratories 

(Columbus, OH) 

A weighed amount of coconut oil acid diethanolamine 

condensate was diluted with 95% ethanol. The mixture was 

stirred or sonicated and allowed to cool to room temperature. 

Additional 95% ethanol was added to obtain the final volume, 

and the solution was mixed by shaking. Doses were prepared 

every 3 weeks. 

Same as 14-week studies 

Same as 14-week studies 

Same as 14-week studies 

Battelle Columbus Laboratories 

(Columbus, OH) 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 215 

TABLE I2 

Results of Analyses of Dose Formulations Administered to Rats and Mice in the 14-Week Dermal Studies 

of Coconut Oil Acid Diethanolamine Condensate 

Target Determined Difference 

Date Prepared Date Analyzed Concentration Concentrationa from Target 

(mg/mL) (mg/mL) (%) 

Rats 

3 February 1992 4 February 1992 30 31.2 +4 

61 63.3 +4 

121 129 +7 

243 240 !1 

485 534 +10 

5 March 1992b 30	 30.2 +1 

61 62.3 +2 

121 128 +6 

243 233 !4 

485 490 +1 

16 March 1992 16-17 March 1992 30 29.0 !3 

61 58.9 !3 

121 120 !1 

243 241 !1 

485 485 0 

13-15 April 1992b 30	 30.1 0 

61 61.9 +1 

121 121 0 

243 241 !1 

485 488 +1 

27 April 1992 1&4 May 1992 30 30.2 +1 

61 61.9 +1 

121 120 !1 

243 270 +11 

485 568 +17 

4 May 1992 5-6 May 1992c	 243 234 !4 

485 464 !4 

18-20 May 1992b 30	 30.2 +1 

61 63.2 +4 

121 122 +1 

243 249 +2 

485 513 +6 
 

216 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE I2 

Results of Analyses of Dose Formulations Administered to Rats and Mice in the 14-Week Dermal Studies 

of Coconut Oil Acid Diethanolamine Condensate 

Target Determined Difference 

Date Prepared Date Analyzed Concentration Concentration from Target 

(mg/mL) (mg/mL) (%) 

Mice 

3 February 1992 4 February 1992 20 20.7 +4 

40 42.6 +7 

80 83.0 +4 

160 164 +3 

320 320 0 

5 March 1992b 20 20.4 +2 

40 40.0 0 

80 82.9 +4 

160 162 +1 

320 324 +1 

16 March 1992 16-17 March 1992 20 21.2 +6 

40 38.8 !3 

80 79.0 !1 

160 157 !2 

320 313 !2 

13-15 April 1992b 20 19.8 !1 

40 40.6 +2 

80 82.0 +3 

160 160 0 

320 315 !2 

27 April 1992 1&4 May 1992 20 20.4 +2 

40 40.5 +1 

80 80.9 +1 

160 161 +1 

320 340 +6 

18-20 May 1992b 20 19.9 0 

40 41.7 +4 

80 83.1 +4 

160 165 +3 

320 316 !1 

a Results of duplicate analyses. For rats, dosing volumes ranged from 117 to 285 μL (males) and 95 to 161 μL (females); 

30 mg/mL=25 mg/kg; 61 mg/mL=50 mg/kg; 121 mg/mL=100 mg/kg; 243 mg/mL=200 mg/kg; and 485 mg/mL=400 mg/kg. For 

mice, dosing volumes ranged from 62 to 94 μL (males) and 51 to 82 μL (females); 20 mg/mL=50 mg/kg; 40 mg/mL=100 mg/kg; 

80 mg/mL=200 mg/kg; 160 mg/mL=400 mg/kg; and 320 mg/mL=800 mg/kg. b	 Animal room samples 

Results of remix c 
Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 217 

TABLE I3 

Results of Analyses of Dose Formulations Administered to Rats and Mice in the 2-Year Dermal Studies 

of Coconut Oil Acid Diethanolamine Condensate 

Target Determined Difference 

Date Prepared Date Analyzed Concentration Concentrationa from Target 

(mg/mL) (mg/mL) (%) 

Rats 

11 January 1993 12-13 January 1993 85 82.5 !3 

170 156 !8 

11 January 1993b 11 February 1993 85 95.5 +12 

170 185 +9 

15 March 1993 15-16 March 1993 85 87.1 +2 

170 175 +3 

17 May 1993 18-19 May 1993 85 85.7 +1 

170 169 !1 

19 July 1993 20-24 July 1993 85 87.4 +3 

170 163 !4 

19 July 1993b 16-17 August 1993 85 90.3 +6 

170 170 0 

20 September 1993 20-21 September 1993 85 85.1 0 

170 173 +2 

22 November 1993 22-23 November 1993 85 86.2 +1 

170 172 +1 

24 January 1994 26-27 January 1994 85 85.4 0 

170 173 +2 

24 January 1994b 23-24 February 1994 85 84.2 !1 

170 168 !1 

28 March 1994 28-29 March 1994 85 89.9 +6 

170 182 +7 

1 June 1994 1-2 June 1994 85 84.8 0 

170 169 !1 

2 August 1994 2 August 1994 85 91.0 +7 

170 185 +9 

2 August 1994b 7-8 September 1994 85 88.2 +4 

170 171 +1 

3 October 1994 4-5 October 1994 85 86.2 +1 

170 175 +3 

5 December 1994 6-7 December 1994 85 85.2 0 

170 172 +1 
218 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE I3 

Results of Analyses of Dose Formulations Administered to Rats and Mice in the 2-Year Dermal Studies 

of Coconut Oil Acid Diethanolamine Condensate 

Target Determined Difference 

Date Prepared Date Analyzed Concentration Concentration from Target 

(mg/mL) (mg/mL) (%) 

Mice 

11 January 1993 12-13 January 1993 50 48.3 !3 

100 96.8 !3 

11 January 1993b 11 February 1993 50 54.1 +8 

100 116 +16 

15 March 1993 15-16 March 1993 50 47.9 !4 

100 103 +3 

17 May 1993 18-19 May 1993 50 51.0 +2 

100 101 +1 

19 July 1993 20-24 July 1993 50 46.9 !6 

100 98.8 !1 

19 July 1993b 16-17 August 1993 50 50.5 +1 

100 97.0 !3 

20 September 1993 20-21 September 1993 50 51.1 +2 

100 104 +4 

22 November 1993 22-23 November 1993 50 50.5 +1 

100 103 +3 

24 January 1994 26-27 January 1994 50 49.9 0 

100 102 +2 

24 January 1994b 23-24 February 1994 50 49.9 0 

100 103 +3 

28 March 1994 28-29 March 1994 50 52.9 +6 

100 109 +9 

1 June 1994 1-2 June 1994 50 50.4 +1 

100 102 +2 

2 August 1994 2 August 1994 50 52.5 +5 

100 107 +7 

2 August 1994b 7-8 September 1994 50 52.9 +6 

100 104 +4 

3 October 1994 4-5 October 1994 50 51.2 +2 

100 103 +3 

5 December 1994 6-7 December 1994 50 50.3 +1 

100 102 +2 

a Results of duplicate analyses. For rats, dosing volumes ranged from 76 to 274 μL (males) and 62 to 179 μL (females); 

85 mg/mL=50 mg/kg and 170 mg/mL=100 mg/kg. For mice, dosing volumes ranged from 48 to 107 μL (males) and 40 to 114 μL 

(females); 50 mg/mL=100 mg/kg and 100 mg/mL=200 mg/kg. b Animal room samples 
219 

APPENDIX J 

INGREDIENTS, NUTRIENT COMPOSITION, 

AND CONTAMINANT LEVELS 

IN NIH-07 RAT AND MOUSE RATION 

TABLE J1 

TABLE J2 

TABLE J3 

TABLE J4 

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 . . . . . . . . . . . . . . . . . . . . . . . 

220 

220 

221 

222 
 

 

220 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE J1 

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 J2 

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 
 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 221 

TABLE J3 

Nutrient Composition of NIH-07 Rat and Mouse Ration 

Mean ± Standard 

Nutrient Deviation Range Number of Samples

 Protein (% by weight) 22.92 ± 0.50 22.1 – 23.9 25

 Crude fat (% by weight) 5.33 ± 0.15 5.00 – 5.60 25

 Crude fiber (% by weight) 3.13 ± 0.29 2.60 – 4.00 25

 Ash (% by weight) 6.25 ± 0.18 5.72 – 6.64 25 

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) 6,785 ± 499 6,160 – 8,800 25

 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) 16.33 ± 2.42 13.0 – 24.0 24

 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 B12 (ppb) 41.6 ± 18.6 10.6 – 65.0 12

 Choline (ppm) 2,955 ± 382 2,300 – 3,430 11 

Minerals

 Calcium (%) 1.15 ± 0.06 1.03 – 1.33 25

 Phosphorus (%) 0.88 ± 0.02 0.84 – 0.93 25

 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 
 

 

 

 

 

 

 

 

222 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

TABLE J4 

Contaminant Levels in NIH-07 Rat and Mouse Rationa 

Mean ± Standard 

Deviationb Range Number of Samples 

Contaminants

 Arsenic (ppm) 0.51 ± 0.15 0.10 – 0.70 25

 Cadmium (ppm) 0.04 ± 0.01 0.04 – 0.06 25

 Lead (ppm) 0.24 ± 0.06 0.20 – 0.40 25

 Mercury (ppm) <0.02 25

 Selenium (ppm) 0.35 ± 0.10 0.10 – 0.50 25

 Aflatoxins (ppb) <5.0 25

 Nitrate nitrogen (ppm)c 7.82 ± 2.44 3.0 – 14.0 25

25

 Nitrite nitrogen (ppm)c 1.19 ± 0.91 0.20 – 3.50 25

 BHA (ppm)d 2.18 ± 4.13 0.40 – 20.0 

 BHT (ppm)d 1.78 ± 1.07 0.40 – 5.00 25

 Aerobic plate count (CFU/g) 131,880 ± 133,954 28,000 – 460,000 25

 Coliform (MPN/g) 17 ± 43.0 3 – 210 25
 

Escherichia coli (MPN/g) 5 ± 3.4 3 – 10 25
 

Salmonella (MPN/g) Negative 25

 Total nitrosoamines (ppb)e 12.12 ± 4.05 4.0 – 23.0 25
 

N-Nitrosodimethylamine (ppb)e 10.20 ± 4.00 3.0 – 21.0 25
 

N-Nitrosopyrrolidine (ppb)e 1.92 ± 1.16 1.0 – 6.0 25
 

"-BHC <0.01 25
 

$-BHC <0.02 25
 

(-BHC <0.01 25
 

*-BHC <0.01 25

 Heptachlor <0.01 25

 Aldrin <0.01 25

 Heptachlor epoxide <0.01 25

 DDE <0.01 25

 DDD <0.01 25

 DDT <0.01 25

 HCB <0.01 25

 Mirex <0.01 25

 Methoxychlor <0.05 25

 Dieldrin <0.01 25

 Endrin <0.01 25

 Telodrin <0.01 25

 Chlordane <0.05 25

 Toxaphene <0.10 25

 Estimated PCBs <0.20 25

 Ronnel <0.01 25

 Ethion <0.02 25

 Trithion <0.05 25

 Diazinon <0.10 25

 Methyl parathion <0.02 25

 Ethyl parathion <0.02 25

 Malathion 0.10 ± 0.07 0.02 – 0.30 25

 Endosulfan I <0.01 25

 Endosulfan II <0.01 25

Pesticides (ppm)
 

 Endosulfan sulfate <0.03 25
 

a CFU=colony-forming units; MPN=most probable number; BHC=hexachlorocyclohexane or benzene hexachloride b For values less than the limit of detection, the detection limit is given as the mean. 

Sources of contamination: alfalfa, grains, and fish meal d Sources of contamination: soy oil and fish meal e All values were corrected for percent recovery. 

c 
223 

APPENDIX K 

SENTINEL ANIMAL PROGRAM 

METHODS 

RESULTS 

............................................................. 

............................................................. 

224 

226 
 

 

224 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

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) 

 RCV/SDA (rat coronavirus/

 sialodacryoadenitis virus) 

Sendai 

Study termination

Study termination

Study termination 

Hemagglutination Inhibition

 H-1 (Toolan’s H-1 virus) 

 KRV (Kilham rat virus) 

Study termination

Study termination 

2-Year Study 

ELISA 

Mycoplasma arthritidis 

Mycoplasma pulmonis 

 PVM 

 RCV/SDA 

Sendai 

12 months and study termination 

12 months and study termination

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination 

Hemagglutination Inhibition

 H-1 

KRV 

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination 
 

 

Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 225 

Method and Test 

MICE 

14-Week Study 

ELISA

 Ectromelia virus 

 EDIM (epizootic diarrhea of infant mice) 

 GDVII (mouse encephalomyelitis virus) 

 LCM (lymphocytic choriomeningitis virus) 

 Mouse adenoma virus-FL 

 MHV (mouse hepatitis virus) 

 PVM 

 Reovirus 3 

Sendai 

Immunofluorescence Assay

 EDIM 

Hemagglutination Inhibition

 K (papovavirus) 

 MVM (minute virus of mice) 

 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

 Mouse adenoma virus-FL 

 Reovirus 3 

LCM 

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

Study termination 

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination 

Study termination 

Study termination

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination 

18 months

18 months

Study termination 

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination

1, 6, 12, and 18 months, study termination 
226 Coconut Oil Acid Diethanolamine Condensate, NTP TR 479 

RESULTS 

At the end of the 2-year studies, 6 of 10 rats and 8 of 10 mice evaluated had positive titers to M. arthritidis. 

Further evaluation of samples positive for M. arthritidis by immunoblot and Western blot procedures 

indicated that the positive titers may have been due to cross reaction with antibodies of nonpathogenic 

Mycoplasma or other agents. There were no clinical findings or histopathologic changes of M. arthritidis 

infection in animals with positive titers. Accordingly, M. arthritidis-positive titers were considered false 

positives. 
National Toxicology Program Technical Reports
 

Printed as of January 2001
 

The Environmental Health Information Service (EHIS) maintains the library of NTP Technical Reports in electronic and print format. 


To gain access to these reports, contact EHIS online at http://ehis.niehs.nih.gov or call 800-315-3010 or 919-541-3841.
 

Chemical 

Acetaminophen 

Acetonitrile 

Agar 

Allyl Glycidyl Ether 

Allyl Isothiocyanate 

Allyl Isovalerate 

1-Amino-2,4-Dibromoanthraquinone 

2-Amino-4-Nitrophenol 

2-Amino-5-Nitrophenol 

11-Aminoundecanoic Acid 

dl-Amphetamine Sulfate 

Ampicillin Trihydrate 

Anthraquinone 

Asbestos, Amosite (Hamsters) 

Asbestos, Amosite (Rats) 

Asbestos, Chrysotile (Hamsters) 

Asbestos, Chrysotile (Rats) 

Asbestos, Crocidolite 

Asbestos, Tremolite 

L-Ascorbic Acid 

AZT and AZT/"-Interferon A/D 

Barium Chloride Dihydrate 

Benzaldehyde 

Benzene 

Benzethonium Chloride 

Benzofuran 

Benzyl Acetate (Gavage) 

Benzyl Acetate (Feed) 

Benzyl Alcohol 

o-Benzyl-p-Chlorophenol (Gavage) 

o-Benzyl-p-Chlorophenol (Mouse Skin) 

2-Biphenylamine Hydrochloride 

2,2-Bis(Bromomethyl)-1,3-Propanediol 

Bis(2-Chloro-1-Methylethyl) Ether 

Bisphenol A 

Boric Acid 

Bromodichloromethane 

Bromoethane 

1,3-Butadiene 

1,3-Butadiene 

t-Butyl Alcohol 

Butyl Benzyl Phthalate 

Butyl Benzyl Phthalate 

N-Butyl Chloride 

t-Butylhydroquinone 

(-Butyrolactone 

Caprolactam 

d-Carvone 

Chlorinated and Chloraminated Water 

Chlorendic Acid 

Chlorinated Paraffins: C23, 43% Chlorine 

Chlorinated Paraffins: C12, 60% Chlorine 

Chlorinated Trisodium Phosphate 

2-Chloroacetophenone 

p-Chloroaniline Hydrochloride 

CS2 

Chlorobenzene 

Chlorodibromomethane 

Chloroethane 

2-Chloroethanol 

3-Chloro-2-Methylpropene 

Chloroprene 

1-Chloro-2-Propanol 

Chlorpheniramine Maleate 

TR No. 

394
 

447
 

230
 

376
 

234
 

253
 

383
 

339
 

334
 

216
 

387
 

318
 

494
 

249
 

279
 

246
 

295
 

280
 

277
 

247
 

469
 

432
 

378
 

289
 

438
 

370
 

250
 

431
 

343
 

424
 

444
 

233
 

452
 

239
 

215
 

324
 

321
 

363
 

288
 

434
 

436
 

213
 

458
 

312
 

459
 

406
 

214
 

381
 

392
 

304
 

305
 

308
 

294
 

379
 

351
 

377
 

261
 

282
 

346
 

275
 

300
 

467
 

477
 

317
 

Chemical TR No. 

C.I. Acid Orange 3 335
 

C.I. Acid Orange 10 211
 

C.I. Acid Red 14 220
 

C.I. Acid Red 114 405
 

C.I. Basic Red 9 Monohydrochloride 285
 

C.I. Direct Blue 15 397
 

C.I. Direct Blue 218 430
 

C.I. Disperse Blue 1 299
 

C.I. Disperse Yellow 3 222
 

C.I. Pigment Red 3 407
 

C.I. Pigment Red 23 411
 

C.I. Solvent Yellow 14 226
 

Cobalt Sulfate Heptahydrate 471
 

Coconut Oil Acid Diethanolamine Condensate 479
 

Codeine 455
 

Comparative Initiation/Promotion Studies (Mouse Skin) 441
 

Corn Oil, Safflower Oil, and Tricaprylin 426
 

Coumarin 422
 

Cytembena 207
 

D&C Red No. 9 225
 

D&C Yellow No. 11 463
 

Decabromodiphenyl Oxide 309
 

Diallyl Phthalate (Mice) 242
 

Diallyl Phthalate (Rats) 284
 

4,4 ́-Diamino-2,2 ́-Stilbenedisulfonic Acid, Disodium Salt 412
 

2,4-Diaminophenol Dihydrochloride 401
 

1,2-Dibromo-3-Chloropropane 206
 

1,2-Dibromoethane 210
 

2,3-Dibromo-1-Propanol 400
 

1,2-Dichlorobenzene (o-Dichlorobenzene) 255
 

1,4-Dichlorobenzene (p-Dichlorobenzene) 319
 

2,4-Dichlorophenol 353
 

2,6-Dichloro-p-Phenylenediamine 219
 

1,2-Dichloropropane 263
 

1,3-Dichloropropene (Telone II) 269
 

Dichlorvos 342
 

Dietary Restriction 460
 

Diethanolamine 478
 

Di(2-Ethylhexyl) Adipate 212
 

Di(2-Ethylhexyl) Phthalate 217
 

Diethyl Phthalate 429
 

Diglycidyl Resorcinol Ether 257
 

3,4-Dihydrocoumarin 423
 

1,2-Dihydro-2,2,4-Trimethylquinoline (Monomer) 456
 

Dimethoxane 354
 

3,3 ́-Dimethoxybenzidine Dihydrochloride 372
 

N,N-Dimethylaniline 360
 

3,3 ́-Dimethylbenzidine Dihydrochloride 390
 

Dimethyl Hydrogen Phosphite 287
 

Dimethyl Methylphosphonate 323
 

Dimethyl Morpholinophosphoramidate 298
 

Dimethylvinyl Chloride 316
 

Diphenhydramine Hydrochloride 355
 

5,5-Diphenylhydantoin 404
 

Emodin 493
 

Ephedrine Sulfate 307
 

Epinephrine Hydrochloride 380
 

1,2-Epoxybutane 329
 

Erythromycin Stearate 338
 

Ethyl Acrylate 259
 

Ethylbenzene 466
 

Ethylene Glycol 413
 

Ethylene Glycol Monobutyl Ether 484
 

Ethylene Oxide 326
 
Chemical TR No. Chemical TR No. 

Ethylene Thiourea 

Eugenol 

FD&C Yellow No. 6 

Furan 

Furfural 

Furfuryl Alcohol 

Furosemide 

Gallium Arsenide 

Geranyl Acetate 

Glutaraldehyde 

Glycidol 

Guar Gum 

Gum Arabic 

HC Blue 1 

HC Blue 2 

HC Red 3 

HC Yellow 4 

Hexachlorocyclopentadiene 

Hexachloroethane 

4-Hexylresorcinol 

Hydrochlorothiazide 

Hydroquinone 

8-Hydroxyquinoline 

Iodinated Glycerol 

Isobutene 

Isobutyl Nitrite 

Isobutyraldehyde 

Isophorone 

Isoprene 

Lauric Acid Diethanolamine Condensate 

d-Limonene 

Locust Bean Gum 

60-Hz Magnetic Fields 

Magnetic Field Promotion 

Malonaldehyde, Sodium Salt 

Manganese Sulfate Monohydrate 

D-Mannitol 

Marine Diesel Fuel and JP-5 Navy Fuel 

Melamine 

2-Mercaptobenzothiazole 

Mercuric Chloride 

8-Methoxypsoralen 

"-Methylbenzyl Alcohol 

Methyl Bromide 

Methyl Carbamate 

Methyldopa Sesquihydrate 

Methylene Chloride 

4,4 ́-Methylenedianiline Dihydrochloride 

Methyleugenol 

Methyl Methacrylate 

N-Methylolacrylamide 

Methylphenidate Hydrochloride 

Mirex 

Molybdenum Trioxide 

Monochloroacetic Acid 

Monuron 

Nalidixic Acid 

Naphthalene (Mice) 

Naphthalene (Rats) 

Nickel (II) Oxide 

Nickel Sulfate Hexahydrate 

Nickel Subsulfide 

p-Nitroaniline 

o-Nitroanisole 

p-Nitrobenzoic Acid 

Nitrofurantoin 

Nitrofurazone 

Nitromethane 

p-Nitrophenol 

Ochratoxin A 

388
 

223
 

208
 

402
 

382
 

482
 

356
 

492
 

252
 

490
 

374
 

229
 

227
 

271
 

293
 

281
 

419
 

437
 

361
 

330
 

357
 

366
 

276
 

340
 

487
 

448
 

472
 

291
 

486
 

480
 

347
 

221
 

488
 

489
 

331
 

428
 

236
 

310
 

245
 

332
 

408
 

359
 

369
 

385
 

328
 

348
 

306
 

248
 

491
 

314
 

352
 

439
 

313
 

462
 

396
 

266
 

368
 

410
 

500
 

451
 

454
 

453
 

418
 

416
 

442
 

341
 

337
 

461
 

417
 

358
 

Oleic Acid Diethanolamine Condensate 481
 

Oxazepam (Mice) 443
 

Oxazepam (Rats) 468
 

Oxymetholone 485
 

Oxytetracycline Hydrochloride 315
 

Ozone and Ozone/NNK 440
 

Penicillin VK 336
 

Pentachloroanisole 414
 

Pentachloroethane 232
 

Pentachloronitrobenzene 325
 

Pentachlorophenol, Purified 483
 

Pentachlorophenol, Technical Grade 349
 

Pentaerythritol Tetranitrate 365
 

Phenolphthalein 465
 

Phenylbutazone 367
 

Phenylephrine Hydrochloride 322
 

N-Phenyl-2-Naphthylamine 333
 

o-Phenylphenol 301
 

Polybrominated Biphenyl Mixture (Firemaster FF-1) (Gavage) 244
 

Polybrominated Biphenyl Mixture (Firemaster FF-1) (Feed) 398
 

Polysorbate 80 (Glycol) 415
 

Polyvinyl Alcohol 474
 

Primidone 476
 

Probenecid 395
 

Promethazine Hydrochloride 425
 

Propylene 272
 

1,2-Propylene Oxide 267
 

Propyl Gallate 240
 

Pyridine 470
 

Quercetin 409
 

Resorcinol 403
 

Rhodamine 6G 364
 

Rotenone 320
 

Roxarsone 345
 

Salicylazosulfapyridine 457
 

Scopolamine Hydrobromide Trihydrate 445
 

Sodium Azide 389
 

Sodium Fluoride 393
 

Sodium Nitrite 495
 

Sodium Xylenesulfonate 464
 

Stannous Chloride 231
 

Succinic Anhydride 373
 

Talc 421
 

Tara Gum 224
 

2,3,7,8-Tetrachlorodibenzo-p-Dioxin (Dermal) 201
 

2,3,7,8-Tetrachlorodibenzo-p-Dioxin (Gavage) 209
 

1,1,1,2-Tetrachloroethane 237
 

Tetrachloroethylene 311
 

Tetracycline Hydrochloride 344
 

Tetrafluoroethylene 450
 

1-Trans-Delta9-Tetrahydrocannabinol 446
 

Tetrahydrofuran 475
 

Tetrakis(Hydroxymethyl)Phosphonium Sulfate 296
 

Tetrakis(Hydroxymethyl)Phosphonium Chloride 296
 

Tetranitromethane 386
 

Theophylline 473
 

4,4-Thiobis(6-t-Butyl-m-Cresol) 435
 

Titanocene Dichloride 399
 

Toluene 371
 

2,4- & 2,6-Toluene Diisocyanate 251
 

o-Toluidine Hydrochloride 153
 

Triamterene 420
 

Tribromomethane 350
 

Trichloroethylene 243
 

Trichloroethylene 273
 

1,2,3-Trichloropropane 384
 

Tricresyl Phosphate 433
 

Triethanolamine 449
 

Tris(2-Chloroethyl) Phosphate 391
 

Tris(2-Ethylhexyl) Phosphate 274
 
Chemical TR No. Chemical TR No. 

Turmeric Oleoresin (Curcumin) 427 Xylenes (Mixed) 327 

4-Vinylcyclohexene 303 2,6-Xylidine 278 

4-Vinyl-1-Cyclohexene Diepoxide 362 Zearalenone 235 

Vinylidene Chloride 228 Ziram 238 

Vinyl Toluene 375