Amines, N-coco alkyltrimethylenedi-, acetates

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

publication

Title:

Diethanolamides as Used in Cosmetics; Amended Final Safety Assessment

Author:

Cosmetic Ingredient Safety Review (CIR) panel

Year:

2011

Bibliographic source:

1101 17th Street, NW, Suite 412, Washington DC 20036-4702, United States of America

Report date:

2011

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)

Deviations:

not specified

GLP compliance:

not specified

Remarks:

date of study not specified

Test material

Test material information

Constituent 1

Reference substance name:

Amides, coco, N,N-bis(hydroxyethyl)

EC Number:

271-657-0

EC Name:

Amides, coco, N,N-bis(hydroxyethyl)

Cas Number:

68603-42-9

Molecular formula:

C16H33NO

IUPAC Name:

N,N-Bis(2-hydroxyethyl)dodecanamide

Results and discussion

Effect levels

Remarks on result:

other: Systemic effects attributable to the irritant nature of the test material were reported in two out of three available studies involving dermal application at doses up to 800 mg/kg bw/day.

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Systemic effects attributable to the irritant nature of the test material were reported in two out of three available studies involving dermal application at doses up to 800 mg/kg bw/day.

Executive summary:

Study 1

A shaving cream containing 1.92% cocamide DEA was applied to the intact or abraded skin on the back of 8 New Zealand White (NZW) rabbits. Applications of 500 mg/kg of the test product were made 5x/wk for 4 wks. Dermal irritation was observed at both intact and abraded application sites. No systemic effects attributed to dosing were observed.

Study 2

The repeated-dose dermal toxicity of cocamide DEA (containing 18.2% free diethanolamine by wt) was evaluated using mice. Groups of 10 male and 10 female B6C3F1 mice were dosed with 50, 100, 200, 400, or 800 mg/kg bw cocamide DEA in ethanol (20-320 mg/mL), for 5 exposures/wk, for 14 wks. Vehicle only was applied to the negative control group. All animals survived until study termination. Dermal irritation was observed at the application sites of males and females of the 800 mg/kg dose group. Epidermal and sebaceous gland hyperplasia, parakeratosis, chronic active inflammation, and ulceration were observed; severity generally increased with increased dose. Final mean body weights and mean body weight gains were similar for test and control animals. The absolute liver and kidney weights and relative liver and kidney weights to body weights of males and females of the 800 mg/kg group, relative liver weights to body weights of females of the 400 mg/kg group, and absolute lung weights and relative lung weights to body weights of females of the 800 mg/kg group were significantly greater than for those of the controls. The epididymal spermatozoal concentration was significantly greater in males of the 800 mg/kg dose group.

Study 3

Groups of 20 male and 20 female F344/N rats were dosed dermally with 25, 50, 100, 200, or 400 mg/kg/bw cocamide DEA in ethanol (30-485 mg/ml), 5 exposures/wk, for 14 weeks; 10 rats per group were used for clinical chemistry and hematology evaluation. Vehicle only was applied to the negative control group. All animals survived until study termination. Dermal irritation was observed at the application sites of 2 males and one female of the 100 mg/kg group and in nearly all males and females of the 200 and 400 mg/kg dose groups. Lesions included epidermal and sebaceous gland hyperplasia, parakeratosis, chronic active inflammation, and ulceration; incidence and severity generally increased with increasing dose. Final mean body weights and mean body weight gains of males and females of the 200 and 400 mg groups were significantly less than those of the controls. Kidney weights of females of the 50 mg/kg group were significantly greater than those of the controls. Decreases in epididymal weights in 200 and 400 mg/kg males were attributed to decreased body weights. Changes in some hematology and clinical chemistry parameters were noted and the researchers stated there was an indication of altered lipid metabolism, as evidenced by decreased cholesterol and triglyceride concentrations. The incidences of renal tubule regeneration were greater in females of the 100 dose group, and the incidences and severities were greater in females of the 200 and 400 mg/kg dose groups, as compared to controls.