Dodecan-1-ol, ethoxylated

Endpoint summary

Description of key information

The test material was tested as an aqueous solution and as an ingredient of an aerosol contraceptive formulation containing 20% test chemical to determine if sensitization reactions were produced on group of 7 male guinea pigs.

terile water control, produced a small raised anemic area approximately 7 mm in diameter and 1 mm in height. This reaction was transient and did not last for more than 3 hours. Neither the 0.02% solution of test chemical nor a 0.1% solution of the aerosol formulation containing 20% of test chemical produced direct or delayed sensitization reactions in adult male guinea pigs when injected intracutaneously. Hence the test chemical was considered to be a non-skin sensitizer under the tested conditions.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journal.

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The test material was tested as an aqueous solution and as an ingredient of an aerosol contraceptive formulation containing 20% test chemical to determine if sensitization is produced by the test material on group of seven male guinea pigs.

GLP compliance:

no

Type of study:

Draize test

Justification for non-LLNA method:

Currently no LLNA study is available for assessment. The Non-LLNA Draize test has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.

Species:

guinea pig

Strain:

not specified

Sex:

male

Details on test animals and environmental conditions:

Not specified

Route:

intradermal

Vehicle:

other: Distilled water

Concentration / amount:

First group: a series of ten intracutaneous injections of a 0.02% solution
Second group: a series of ten injections of a 0.1% solution of the formulation were given
Third group: sterile distilled water was injected.

Day(s)/duration:

3 weeks

Adequacy of induction:

not specified

No.:

#1

Route:

intradermal

Vehicle:

other: Distilled water

Concentration / amount:

0.05 ml

Day(s)/duration:

24 hours

Adequacy of challenge:

not specified

No. of animals per dose:

seven guinea pigs/group

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: 24 hours
- Test groups: seven guinea pigs/group
- Control group:
- Site: not specified
- Frequency of applications: every other day, three times each week.
- Duration: 3 weeks
- Concentrations: 0.02% and 0.1%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: after 2 week
- Exposure period: 24 hours
- Test groups: seven guinea pigs/group
- Control group: not specified
- Site: not specified
- Concentrations: 0.05ml
- Evaluation (hr after challenge): after 24 hours

OTHER: Twenty-four hours after each injection, the injection sites were examined and the dimensions and color of the reactions were recorded.

Challenge controls:

not specified

Positive control substance(s):

not specified

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.05ml

No. with + reactions:

0

Total no. in group:

7

Clinical observations:

Neither the 0.02% solution of test chemical nor a 0.1% solution of the aerosol formulation containing 20% of test chemical produced direct or delayed sensitization reactions.

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

other: not sensitizing

Conclusions:

Neither the 0.02% solution of test chemical nor a 0.1% solution of the aerosol formulation containing 20% of test chemical produced direct or delayed sensitization reactions in adult male guinea pigs when injected intracutaneously.
Hence the test chemical was considered to be a non-skin sensitizer under the tested conditions.

Executive summary:

The test material was tested as an aqueous solution and as an ingredient of an aerosol contraceptive formulation containing 20% test chemical to determine if sensitization reactions were produced on group of 7 male guinea pigs.

 

To a group of seven male guinea pigs a series of ten intracutaneous injections of a 0.02% solution of test chemical were administered; to a second group a series of ten injections of a 0.1% solution of the formulation were given; and to a third group (control) sterile distilled water was injected.

 

The sensitizing injections were given every other day, three times each week. The volume of the first dose was 0.05 ml and that of the other nine was 0.1 ml. Two weeks after the tenth sensitizing injection, the guinea pigs received a single challenge injection of 0.05 ml of a freshly prepared solution of the material to which they were sensitized. Twenty-four hours after each injection, the injection sites were examined and the dimensions and color of the reactions were recorded.

 

Intracutaneous injections of all the solutions, including the sterile water control, produced a small raised anemic area approximately 7 mm in diameter and 1 mm in height. This reaction was transient and did not last for more than 3 hours.

 

Further neither the 0.02% solution of test chemical nor a 0.1% solution of the aerosol formulation containing 20% of test chemical produced direct or delayed sensitization reactions in adult male guinea pigs when injected intracutaneously. Hence the test chemical was considered to be a non-skin sensitizer under the tested conditions.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studieshas been investigated for the test chemical to observe the potential for skin sensitization to a greater or lesser extent.Also the predicted data for target chemical using the Danish QSAR database has also been compared with the experimental data.The studies are based on in vivo experiments in guinea pigs, rabbits and human subjects for test chemicalthat have beensummarized as below;

 

In the first study, the test material was tested as an aqueous solution and as an ingredient of an aerosol contraceptive formulation containing 20% test chemical to determine if sensitization is produced by the test material on group of seven male guinea pigs.To a group of seven male guinea pigs a series of ten intracutaneous injections of a 0.02% solution of test chemical were administered; to a second group a series of ten injections of a 0.1% solution of the formulation were given; and to a third group (control) sterile distilled water was injected. The sensitizing injections were given every other day, three times each week. The volume of the first dose was 0.05 ml and that of the other nine was 0.1 ml. Two weeks after the tenth sensitizing injection, the guinea pigs received a single challenge injection of 0.05 ml of a freshly prepared solution of the material to which they were sensitized. Twenty-four hours after each injection, the injection sites were examined and the dimensions and color of the reactions were recorded. Intracutaneous injections of all the solutions, including the sterile water control, produced a small raised anemic area approximately 7 mm in diameter and 1 mm in height. This reaction was transient and did not last for more than 3 hours. Neither the 0.02% solution of test chemical nor a 0.1% solution of the aerosol formulation containing 20% of test chemical produced direct or delayed sensitization reactions in adult male guinea pigs when injected intracutaneously. Hence the test chemical was considered to be a non-skin sensitizer under the tested conditions.

 

Further, three aerosol creams containing 10, 1.5, and 20% of test chemical (preparations 1, 2, and 3, respectively) were evaluated by the repeated patch test procedure described by Draize.Fifty-three subjects (13 adult males and 40 adult females) were tested with a series of nine prechallenge applications. Two subjects who left the area could not be challenged, Challenge patches were thus placed on the arms of 51 volunteers consisting of 12 males and 39 females.Two other widely used commercial contraceptive products were also tested for control purposes: one, foam preparation which contains 8% nonylphenoxypolyethylene ethanol and 0.2% diisobutylphenoxyethoxyethyl dimethyl benzyl ammonium chloride (Control Product 1); and the other, a vaginal cream with a 7-year market history which contains 5% nonylphenoxypolyethoxyethanol as its principal spermicidal agent (Control Product 2).Patches were placed on the anterolateral surfaces of left upper arms of the subjects and the right upper arm for the two control products. Three applications a week (Monday, Wednesday, and Friday) for three consecutive weeks were followed by a challenge application 16 days after the removal of the ninth application. Each product was applied to the same site every time.Patches placed on Monday and Wednesday were removed 24 hours after application; reactions of patch sites were recorded immediately, and again just before placing the next series of patches. The patches that were placed on Friday were removed by the volunteers on Saturday. For the weekend patches, a single reading was taken on the following Monday just before placing the next series of patches. The challenge patches were removed the day following the application, and reactions were read immediately, 24 hours, and 72 hours after removal. Evaluation of skin reactions was carried out according to the procedure described by Draize.None of the 51 subjects challenged with the five preparations tested reacted with edema, vesiculation, eczematization, or pruritus indicative of sensitization.Hence the test chemical was considered to be non –sensitizing to the skin of treated subjects.

 

The above results were supported by the skin sensitization test conducted on rabbits’ skin to assess the skin sensitization potential of test chemical as part of subacute toxicity study. The backs of 12 albino rabbits were depilated with an electric shaver, a circle 6 cm in diameter was marked off into four equal quardants with a dye. The two diagonally situated quadrants were abraded with an instrument having five evenly spaced prongs. One intact and one abraded quadrant received a 1% solution of test chemical while the other two quadrants received no treatment and served as the controls. Applications totaling 5 ml per day were made in three divided doses on each of 10 consecutive days. The doses were impregnated on gauze pads and kept moist during the 6-hour treatment period each day by spraying occasionally with water. After 10 days of treatment, the animals were given a rest for 10 days and then a challenging treatment with the same material was given for 2 successive days. Observations were made daily during the test and 24 hours after completion of the test. The scoring method of Draize et al. (1944) was employed. Weights of the animals at the beginning and end of the experiment did not show any appreciable change. The results indicated that only a slight erythema was produced by the test solution and there was no difference in the degree of erythema between the intact and abraded skin; hence skin sensitization was not observed. Tus on the basis of observed findings, the test chemical can be considered as not sensitizing to the skin of treated rabbits.

 

The overall results were further supported by the predicted Danish QSAR study. According to Danish QSAR database, skin sensitization effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for test chemical. Based on estimation, no Allergic Contact Dermatitis effects were observed when test chemical was exposed to human and guinea pig skin. Hence, the test chemical can be considered as not sensitizing to skin.

 

Based on the available data for key and supporting studies, it can be concluded that test chemical is unable to cause skin sensitization and considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance observed in various studies. From the results obtained from these studies it is concluded that the test chemical is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.