Amides, vegetable-oil, N,N-bis(hydroxyethyl)

Endpoint summary

Description of key information

Lauramide DEA CAS N. 120 -40 -1 SUBCHRONIC TOXICITY ORAL

The subchronic oral toxicity of Lauramide DEA was studied in SPF rats. Fifteen

male and 15 female rats per group were fed for 90 days diets containing 0

(controls), 0.1, 0.5, 1 .O, or 2.0% Lauramide DEA.Two male rats in the 1.0 % dietary

group developed bronchopneumonia and were killed on Days 23 and 58,

respectively. No other deaths occurred in any group during the test period.

Growth was normal in the 0.1% group, slightly reduced in the 0.5% group, and

moderately reduced in those animals consuming 1.0 or 2.0% Lauramide DEA.

Growth retardation was associated with reduced food intake, at and above the

0.5% level. Hematological values were normal except for lower hemoglobin,

hematocrit, and red blood cell count values in the rats fed 1 .O and 2.0% Lauramide

DEA. Serum glutamic oxaloacetate transaminase activities were increased

in animals fed diets of 0.5, 1 .O, and 2.0% Lauramide DEA. Bone marrow cytological

values, renal function tests, and gross and microscopic findings of test animals

were comparable to controls. The no-effect dose was 0.1% Lauramide DEA

(equivalent to 50 mglkg per day) in the diet of rats for 90 days.‘46’

 

Groups of 20 male and 20 female Wistar rats were fed diets containing 0, 25,

80, or 250 mglkg per day Lauramide DEA for 13 weeks. All test animals were

comparable to controls in general health, body weight and feed consumption,

hematological values at 6 and 12 weeks, mortality (no deaths in any group),

organ weights, and gross and microscopic findings. There were no differences

between control and test group values of blood urea nitrogen, serum activities of

glutamic oxalacetic transaminase and lactic dehydrogenase, or urinalysis (specific

gravity, pH, albumin, glucose, and sediment) at either 6 or 12 weeks. A

transient increase in blood glucose concentration at 6 weeks was observed

when the male animals were consuming 250 mglkg per day Lauramide DEA. The

no-effect dose for rats was 250 mg/kg per day.c4”

COCAMIDE DEA CAS 68603 -42 -9 Sub Chronic Toxicity Dermal

A study was conducted to evaluate the subchronic toxic effects of structurally similar 'amides, C8 -18 (even-numbered) and C18 -unsatd., N,N-bis(hydroxyethyl)' (i.e.,coconut oil acid diethanolamine condensate)when administered by dermal route in F344/N rats. The study was performed in compliance with Food and Drug Administration Good Laboratory Practice Regulations (21 CFR, Part 58).

Groups of 10 male and 10 female rats were administered 0, 25, 50, 100, 200, or 400 mg/kg bw/d of the test substancein ethanol by dermal application 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 bw/d 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 bw/d malesand females. Hematological changes include minimal microcytic anemia at the end of the treatment period.Decreases in cholesterol and triglyceride concentrations were observed in the higher group rats (i.e.,≥.100 mg/kg bw/d)

Histopathological lesions of the skin at the site of application included epidermalhyperplasia, sebaceous gland hyperplasia, chronic active inflammation, parakeratosis, and ulcer. Theincidences and severities of these skin lesions generally increased with increasing dose in males andfemales. The incidences of epidermal hyperplasia in all dosed groups of males and in females administered 50 mg/kg bw/d or greater were significantly greater than those in the vehicle controls. The incidences of renal tubule regeneration in 100, 200, and 400 mg/kg bw/d females were significantly greater than the vehicle control incidence, and the severities in 200 and 400 mg/kg bw/d females were increased.

 

Under the test conditions, the No Observed Adverse Effect Level (NOAEL) for systemic effects of the test substance can be considered to be 50 mg/kg bw/d and the LOAEL for local effects at 25 mg/kg bw/d.

COCAMIDE DEA CAS 68603 -42 -9 Chronic Toxicity Dermal

A two-year dermal study was conducted in F344/N rats to evaluate the carcinogenic potential of 'amides, C8-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl)' (in the form ofcoconut oil acid diethanolamine condensate).

 

 Doses studied include 0, 50, or 100 mg/kg bw/d test substance (0, 85, or 170 mg/mL in ethanol). 50 male/female test animals were used in each group. 5 exposures per week were given for 104 wk. The animals were observed twice daily, body weights and clinical findings were recorded periodically. Necropsy was performed on all animals and complete histopathology was performed.

 

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 the study. The only chemical-related clinical finding was irritation of the skin at the site of application in 100 mg/kg bw/d females. There were marginal increases in the incidences of renal tubule adenoma or carcinoma (combined) in 50 mg/kg bw/d females. The severity of nephropathy increased with increasing dose in female rats.

 

 Non neoplastic 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 bw/d group.

 

 Under the test conditions, there was no evidence of carcinogenic activity of the test substance in male rats administered 50 or 100 mg/kg bw/d. There was an equivocal evidence of carcinogenic activity in female rats based on a marginal increase in the incidences of renal tubule neoplasms. However, the absence of an increase in neoplasms in the 100 mg/kg bw/d group in the presence of increased hyperplasia makes the association with chemical exposure uncertain.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

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