National Toxicology Program

National Toxicology Program
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Abstract for TR-481 - Oleic Acid DiethanolamineCondensate (CASRN 93-83-4)

Toxicology and Carcinogenesis Studies of Oleic Acid Diethanolamine Condensate (CAS No. 93-83-4) in F344/N Rats and B6C3F1 Mice (Dermal Studies)

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Chemical Formula: C22H43 NO3

Oleic acid diethanolamine condensate is widely used as an emollient, thickener, and foam stabilizer present in cosmetic formulations of bath additives, shampoos, conditioners, lipsticks, and hair dyes. Male and female F344/N rats and B6C3F1 mice received dermal applications of diethanolamine in 95% ethanol for 13 weeks or 2 years. Genetic toxicology studies were performed in Salmonella typhimurium and L5178Y mouse lymphoma cells.

13-WEEK STUDY IN RATS

Groups of 10 male and 10 female rats were admin istered 0, 25, 50, 100, 200, or 400 mg oleic acid diethanolamine condensate/kg body weight in ethanol dermally for 13 weeks. All male and female rats survived until the end of the study. The final mean body weights and body weight gains of 200 and 400 mg/kg males and the mean body weight gain of 400 mg/kg females were significantly less than those of the vehicle controls. The only chemical-related clinical finding was irritation of the skin at the site of application in most males administered 100 mg/kg or greater and in all females administered 50 mg/kg or greater. Segmented neutrophil counts were increased relative to the vehicle controls in the 400 mg/kg male group on days 5 and 19, in the 200 mg/kg female group on day 19 and at week 13, and in the 400 mg/kg female group on days 5 and 19 and at week 13. Alkaline phosphatase concentrations were significantly increased in the 200 mg/kg male group on day 19, the 200 mg/kg female group at week 13, and in the 400 mg/kg groups of males and females at week 13. Kidney weights of 200 and 400 mg/kg females were significantly greater than those of the vehicle controls. Lesions of the skin at the site of application included epidermal hyperplasia, parakeratosis, chronic active dermal inflammation, suppurative epidermal inflammation, and sebaceous gland hypertrophy in dosed rats. The severities of these lesions generally increased with increasing dose.

13-WEEK STUDY IN MICE

Groups of 10 male and 10 female mice were admin istered 0, 50, 100, 200, 400, or 800 mg oleic acid diethanolamine condensate/kg body weight in ethanol dermally for 13 weeks. All male and female mice except one 800 mg/kg male survived until the end of the study. Final mean body weights and body weight gains of 800 mg/kg males and females and 400 mg/kg females were significantly less than those of the vehicle controls. Clinical findings in dosed mice included irritation of the skin at the site of application. Irritation occurred in all surviving dosed males and in most females administered 100 mg/kg or greater and progressed to ulcer in one 800 mg/kg male. The heart weights of 400 and 800 mg/kg males and females and 200 mg/kg females and the kidney weights of 50, 100, and 400 mg/kg males were significantly greater than those of the vehicle controls. Relative to the vehicle controls, the liver weights were increased in all dosed groups. Lesions of the skin at the site of application in dosed mice included epidermal hyperplasia, parakeratosis, suppurative epidermal inflammation, chronic active dermal inflammation, sebaceous gland hypertrophy, and ulcer. The severities of these lesions generally increased with increasing dose.

2-YEAR STUDY IN RATS

Groups of 50 male and 50 female rats were administered 0, 50, or 100 mg oleic acid diethanolamine condensate/kg body weight in ethanol dermally for 2 years.

Survival, Body Weights, and Clinical Findings
Survival of dosed male and female rats was similar to that of the vehicle control groups. Mean body weights of 100 mg/kg males were slightly less than those of the vehicle controls throughout most of the study. Mean body weights of 100 mg/kg females were less than those of the vehicle controls beginning at week 24. The only significant treatment-related clinical finding was mild to moderate irritation of the skin at the site of application in dosed males and females.

Pathology Findings
The predominant effects of oleic acid diethanolamine condensate administration were minimal to moderate nonneoplastic lesions of the skin at the site of application in dosed rats. These lesions included epidermal hyperplasia, sebaceous gland hyperplasia, hyperkeratosis, parakeratosis, chronic active dermal inflammation, and ulcer.

2-YEAR STUDY IN MICE

Groups of 55 male and 55 female mice were administered 0, 15, or 30 mg oleic acid diethanolamine condensate/kg body weight in ethanol dermally for 2 years. Five animals from each group were evaluated at 3 months for gross lesions and skin histopathology.

Survival, Body Weights, and Clinical Findings
Survival of dosed male and female mice was similar to that of the vehicle control groups. Mean body weights of dosed males and of 15 mg/kg females were similar to those of the vehicle controls throughout the study. Mean body weights of 30 mg/kg females were less than those of the vehicle controls from week 76 until the end of the study. The only significant treatment-related clinical finding was irritation of the skin at the site of application in 30 mg/kg males.

Pathology Findings
The incidences of epidermal hyperplasia, sebaceous gland hyperplasia, and chronic active inflammation of the dermis in all dosed groups were significantly increased relative to the vehicle controls at 3 months and at 2 years. The increased incidences of hyperkeratosis in dosed males at 3 months and in dosed males and females at 2 years, of parakeratosis in 30 mg/kg males at 3 months and 2 years, and of ulcer in 30 mg/kg males and exudate in 30 mg/kg males and females at 2 years were also attributed to chem ical administration.

GENETIC TOXICOLOGY

Oleic acid diethanolamine condensate was not mutagenic in S. typhimurium strain TA97, TA98, TA100, or TA1535, with or without S9 metabolic activation enzymes. In addition, it did not induce mutations in mouse L5178Y lymphoma cells treated with or without S9.

CONCLUSIONS

Under the conditions of these 2-year dermal studies, there was no evidence of carcinogenic activity of oleic acid diethanolamine condensate in male or female F344/N rats administered 50 or 100 mg/kg or in male or female B6C3F1 mice administered 15 or 30 mg/kg. Dermal administration of oleic acid diethanolamine condensate to male and female rats was associated with epidermal hyperplasia, sebaceous gland hyper plasia, hyperkeratosis, parakeratosis, chronic active inflammation of the dermis, and ulceration of the skin at the site of application. Dermal administration of oleic acid diethanolamine condensate to mice was associated with epidermal hyperplasia, sebaceous gland hyperplasia, hyperkeratosis, chronic active inflammation of the dermis, and exudate of the skin at the site of application in males and females and parakeratosis and ulcer of the skin at the site of application in males.

Synonyms: Diethanolamine oleate; diethanolammonium oleate; (Z)-9-octadecenoic acid, compound with 2,2.-imnobis(ethanol) (1:1); oleamide diethanolamine
 

 

Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies of
Oleic Acid Diethanolamine Condensate

 

Male
F344/N Rats
Female
F344/N Rats
Male
B6C3F1 Mice
Female
B6C3F1 Mice
Doses in ethanol by dermal application

0, 50, or 100 mg/kg

0, 50, or 100 mg/kg

0, 15, or 30 mg/kg

0, 15, or 30 mg/kg

Body weights

100 mg/kg group slightly less than vehicle control group

100 mg/kg group less than vehicle control group

Dosed groups similar to vehicle control group

30 mg/kg group less than vehicle control group

Survival rates

8/50, 10/50, 14/50

15/50, 18/50, 14/50

41/49, 35/50, 34/50

34/50, 30/50, 35/50

Nonneoplastic effects Skin (site of application): epidermal hyperplasia (0/50, 49/50, 47/50); sebaceous gland, hyperplasia (1/50, 45/50, 45/50); hyperkeratosis (0/50, 44/50, 40/50); parakeratosis (0/50, 10/50, 11/50); chronic active dermal inflammation (0/50, 48/50, 41/50); ulcer (0/50, 7/50, 6/50) Skin (site of application): epidermal hyperplasia (3/50, 50/50, 50/50); sebaceous gland, hyperplasia (2/50, 48/50, 49/50); hyperkeratosis (1/50, 38/50, 31/50); parakeratosis (2/50, 27/50, 43/50); chronic active dermal inflammation (2/50, 44/50, 48/50); ulcer (3/50, 20/50, 36/50) Skin (site of application): epidermal hyperplasia (1/49, 40/50, 47/50); sebaceous gland hyperplasia (1/49, 21/50, 34/50); hyperkeratosis (1/49, 38/50, 37/50); parakeratosis (0/49, 2/50, 8/50); chronic active dermal inflammation (0/49, 34/50, 50/50); ulcer (0/49, 0/50, 7/50); exudate (1/49, 3/50, 9/50) Skin (site of application): epidermal hyperplasia (0/50, 43/50, 50/50); sebaceous gland hyperplasia (0/50, 39/50, 46/50); hyperkeratosis (0/50, 36/50, 42/50); chronic active dermal inflammation (0/50, 40/50, 49/50); exudate (0/50, 0/50, 6/50)
Neoplastic effects

None

None

None

None

Level of evidence of carcinogenic activity

No evidence

No evidence

No evidence

No evidence


Genetic Toxicology
Assay Results
Salmonella typhimurium gene mutations:

Negative with and without S9 in strains TA97, TA98, TA100, and TA1535

Mouse lymphoma gene mutations:

Negative with and without S9

Report Date: July 1999

Pathology Tables, Survival and Growth Curves from NTP 2-year Studies

Target Organs and Incidences for 2-year Studies


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