Amines, N-coco alkyltrimethylenedi-, acetates

Endpoint summary

Description of key information

Dermal route: 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.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Reference 1

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

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

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.

Critical effects observed:

no

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.

Reference 2

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

See read-across justification attached in Section 13.

Reason / purpose for cross-reference:

read-across source

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.

Critical effects observed:

no

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available studies involving the dermal administration of an analogue substance (EC 271-657-0] report effects that are considered to be caused by the irritant nature of the test material. Classification for systemic toxicity under the terms ofRegulation (EC) No. 1272/2008 is therefore not appropriate.