Alcohols, C12-14

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

other: published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Materials and methods

Study type:

medical monitoring

Endpoint addressed:

skin irritation / corrosion

skin sensitisation

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Type: other: allergic skin reaction in man

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hexadecan-1-ol

EC Number:

253-149-0

EC Name:

Hexadecan-1-ol

Cas Number:

36653-82-4

Molecular formula:

C16H34O

IUPAC Name:

hexadecan-1-ol

Details on test material:

Cetearyl Alcohol (CAS No. 8005-44-5) is, Cetyl Alcohol (CAS No, 36653-82-4) , Isostearyl Alcohol (CAS No. 27458-93-l and 41744-75-6) , Myristyl Alcohol(CAS No. 112-72-I) , and Behenyl Alcohol (CAS No. 661-l 9-8).

Method

Type of population:

general

Ethical approval:

not specified

Details on study design:

The authors report the results of patch testing with aliphatic alcohols in 1664 consecutive patients at a dermatological clinic. Patch testing with cetyl alcohol (30% in vaseline) resulted in 2 positive reactions an incidence of 0.12%.

Results and discussion

Results:

Skin Irritation
Cetyl Alcohol
The skin irritation potential of Cetyl Alcohol (100.0%) was evaluated in 20 subjects (18-65 years old). One-tenth milliliter of the test substance was applied via an occlusive patch to the volar surface of the forearm of each subject; each patch remained for 24 or 48 h. Skin reactions were scored 2 and 24 h after patch removal according to the scale 0.5 (barely perceptible irritation) to 4.0 (severe irritation). No erythematous reactions were elicited by the test substance (112) (Table 12) .The same finding was reported in a similar study of Cetyl Alcohol (113) (Table 12).


A topical tolerance study involving an 11.5% Cetyl Alcohol cream base was conducted with 80 male subjects, ranging in age from 21 to 52 years and in weight from 120 to 220 pounds (62) (Table 12). The 80 subjects were assigned at random to eight treatment groups of 10 each. The cream base was applied (gentle rubbing) to the left forearm (700 mg/202 cm2 area) in four groups and to the left lower facial region (250 mg/202 cm2 area), including the left side of the lips, in the other four groups. The preparations were applied five times daily (every 3 hours) for 10 days. One subject had erythema, folliculitis, and pustule formation (forearm site).

A formulation containing 6.0% Cetyl Alcohol was tested for its skin irritation potential in 20 subjects according to the protocol stated above. The product did not induce skin irritation (114) (Table 12). In another study, the skin irritation potential of a cream containing 6.0% Cetyl Alcohol was evaluated in 12 female subjects (18-60 years old). An occlusive patch containing 0.3 ml of the product was applied to the back of each subject. Patches were removed 23 h after application, and sites were bathed immediately. Reactions were scored 1 h after patch removal. The product was applied to the same test site for 21 consecutive days. The grading scale for cumulative irritation ranged from 0 to 630 (primary irritation). The total irritation score (all panelists) for the 21 applications was 418, indicating mild cumulative irritation(115) (Table 12).

The skin irritation potential of a cream containing 5.0% Cetyl Alcohol was evaluated in 9 female subjects (30-65 years old). A closed patch containing the product (amount sufficient to cover patch) was applied to the back of each subject. Patches were removed 23 h after application, and sites were bathed immediately. Reactions were scored 1 h after patch removal. The product was applied to the same site for 21 consecutive days. The grading scale for cumulative irritation ranged from 0 to 630 (primary irritation). The total irritation score (9
subjects) was 1, interpreted as no evidence of cumulative irritation. The product was classified as a mild material (116) (Table 12). In another study (same protocol), 0.2-0.3 ml of a cream containing 4.0% Cetyl Alcohol was applied to 12 male and female subjects (10- > 60 years old) via semiocclusive patches. The total irritation score (12 subjects) was 211, and the product was classified as a slight irritant(117) (Table 12). .

A lipstick product containing 4.0% Cetyl Alcohol was applied to the face and lips of 52 subjects over a period of 4 weeks. The detailed experimental procedure was not stated. Reactions were graded according to the scale by Wilkinson et al.: 1 (weak nonvesicular reaction) to 3 (bullous or ulcerative reaction). None of the subjects had signs of skin irritation(118) (Table 12)..

The irritation potential of a hair conditioner containing 3.25% Cetyl Alcohol was evaluated in 75 female subjects (15-30 years old) during a 30-day home use study. Subjects were instructed to shampoo and condition their hair daily. Scalp irritation was evaluated by a dermatologist before the beginning of the study and after 2 and 4 weeks of product use according to the scale 0 to 4 (erythema and excoriations). There were no significant irritation reactions that were attributed to 4 weeks of use of the conditioner (119) (Table 12).In another study, two conditioners containing 3.25% Cetyl Alcohol were applied to the back of each of 15 adult subjects (21-65 years old). Each patch (0.2 ml of product) was removed after 24 h, and sites were then scored according to the scale 0 to 4 (intense erythema, edema, and vesicles). Fresh applications were then made to the same sites, and scoring occurred 24 h after patch removal. Patches applied on Friday were removed on the following Monday. This procedure was repeated for a total of 21 days. A cumulative score of less than 90 was interpreted as an insignificant level of irritation. Cumulative scores ranging from 91 to 180 were interpreted as very mild irritation. A cumulative (21 days) irritation score of 95 was reported for one of the products and 80 for the other (120) (Table 12)..

In three separate studies, three different products containing 2.0% Cetyl Alcohol were tested according to the protocol stated immediately above. In one of the studies, 0.3 ml of a lotion was applied to 9 subjects (18->60 years old) via closed patches. The total irritation score (9 subjects) was 9, interpreted as essentially no evidence of cumulative irritation. The product was classified as a mild material(121) (Table 12). In the second study, approximately 0.2 ml of a cream was applied to 11 female subjects (18-59 years old) via closed patches. The total irritation score was 105, indicating that the product was slightly irritating(122) (Table 12).. In the third study, 0.2 ml of a cream was applied to 11 male and female subjects (l8- >60 years old) via closed patches. A total irritation score of 55 was reported, indicating evidence of a slight potential for very mild cumulative irritation(123) (Table 12)..


Skin irritation and sensitization

The skin irritation and sensitization potential of a product containing 8.4% Cetyl Alcohol was evaluated in 110 female subjects. The product was applied to the upper back of each subject, and sites were covered with a patch plaster. Patches remained in place for 48 h, after which sites were scored according to the scale 0 to 3 (vesiculation with edema). This procedure was repeated 10 times. Fourteen days after scoring of the tenth application site, a challenge patch was applied to each subject and removed after 48 h; sites were scored after patch removal. The product did not induce primary irritation or sensitization(131) (Table 12).


A moisturizing cream containing 6.36% Cetyl Alcohol was applied to the backs of 229 male and female subjects via occlusive patches. Patches remained for 24 h, after which reactions were scored according to the scale: 0 to 4 (intense erythema with edema and vesicles). The product was applied to the same site for a total of 10 induction applications. After a 2-week nontreatment period, the product was again applied to each subject (first challenge). Challenge patches remained for 48 h, after which sites were scored. One week later, challenge
patches were reapplied; sites were scored 48 and 72 h postapplication. The product did not induce irritation or sensitization in any of the subjects(132) (Table 12).

Any other information on results incl. tables

 Cetearyl, Cetyl, Isostearyl, Myristyl, and Behenyl Alcohols are long-chain aliphatic alcohols that are, at most, only slightly toxic when administered orally at doses of 5 g/kg and greater. In acute dermal toxicity studies (rabbits), doses of up to 2.6 g/kg of Cetyl Alcohol and 2.0 g/kg of a product containing 0.8% Myristyl Alcohol were both practically nontoxic. Mild irritation was observed when a cream containing 3.0% Cetearyl Alcohol was applied to the skin of New Zealand albino rabbits. Cetyl Alcohol (50.0% in petrolatum) applied to abraded and intact skin of albino rabbits produced minimal to slight skin irritation. Cetyl Alcohol was considered to be practically nonirritating when instilled into the eyes of albino rabbits. An aerosol antiperspirant containing 3.0% Myristyl Alcohol induced mild to moderate irritation; a moisturizing lotion containing 0.8% Myristyl Alcohol was nonirritating to rabbit eyes. Corneal irritation was reported following an ocular test using a 5.0% Isostearyl Alcohol antiperspirant. Conjunctival irritation was observed 2 and 6 h after instillation of 1.0% Behenyl Alcohol. Isostearyl Alcohol (5.0% in propylene glycol) and an antiperspirant containing 5.0% Isostearyl Alcohol were not sensitizers in guinea pigs. Cetyl Alcohol was not mutagenic in Salmonella typhimurium LT2 mutant strains in the spot test.

Clinical skin irritation and sensitization studies of product formulations containing up to 8.4% Cetyl Alcohol produced no evidence of irritation or sensitization.

Moisturizing lotions containing 0.8% Myristyl Alcohol were nonirritating to human skin, and moisturizers containing 0.25% Myristyl Alcohol were neither irritants nor sensitizers.

No signs of skin irritation or sensitization were observed in humans following the dermal application of 25% Isostearyl Alcohol. In a human skin sensitization study of a cream containing 3.0% Cetearyl Alcohol, none of the subjects had positive reactions. An analysis of the data and comparison with data from other toxicity studies on long-chain aliphatic alcohols is presented.

Based on the available data included in this report, it is concluded that Cetearyl Alcohol, Cetyl Alcohol, Isostearyl Alcohol, Myristyl Alcohol, and Behenyl Alcohol are safe as cosmetic ingredients in the present practices of use.

Applicant's summary and conclusion

Conclusions:

Clinical skin irritation and sensitization studies of product formulations containing 8.4%, 6.36%, 6.0%, 4.0%, 3.3%, 3.25%, 3.0%, 2.85%, 2.0%, and 1.0%
Cetyl Alcohol produced no substantial evidence of irritation or sensitization.
Based on the available data included in this report, it is concluded that Cetearyl Alcohol, Cetyl Alcohol, Isostearyl Alcohol, Myristyl Alcohol, and Behenyl Alcohol are safe as cosmetic ingredients in the present practices of use.