p,p',p''-tris(dimethylamino)trityl alcohol

Endpoint summary

Description of key information

Skin sensitization:

The skin sensitization potential of test chemical was assessed in various experimental studies conducted on different subjects. Based on the available data for the test chemical and supporting studies, it can be concluded that the test chemical is unable to cause skin sensitization and thus can be considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “not classified”.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

experimental data of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

WoE report is based on 2 skin sensitization studies as- WoE-2 and WoE-3.
Skin sensitization of test chemical was determined by performing patch tests on humans.

GLP compliance:

not specified

Type of study:

other: 2.open epicutaneous test 3.guinea pig maximisation test

Justification for non-LLNA method:

Not specified.

Species:

other: 2.guinea pig 3.guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

2.No data available.

Route:

epicutaneous, open

Vehicle:

propylene glycol

Remarks:

2.

Concentration / amount:

10%

Route:

intradermal and epicutaneous

Vehicle:

other: aqueous solution

Remarks:

3.

Concentration / amount:

Intradermal concentration: 0.1 ml Freund's
complete adjuvant
topical concentration: 25%

Day(s)/duration:

3 weeks

Adequacy of induction:

not specified

Vehicle:

propylene glycol

Remarks:

2.

Concentration / amount:

10,5,2.5 %

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: aqueous solution

Remarks:

3.

Concentration / amount:

25% (0.5ml)

Day(s)/duration:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

2.
10 animals

3.not specified

Details on study design:

2.
Details on study design
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period:48 hour
- Test groups: 10
- Control group: no data
- Site: the left flanks of ten albino guinea pigs were shavedand the test material applied three timesweekly( Monday,Wednesday,Friday)for three consecutiv weeeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area.
- Frequency of applications: three times weekly (Monday, Wednesday Friday) for three consecutive weeks.
- Duration: 3 weeks
- Concentrations:10%

B. CHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge: Two week rest period
- Exposure period: 24 hour
- Test groups: 10
- Control group: No data available.
- Site: right flank of each guinea pig was shaved and test material applied on it.
- Concentrations: 10.0%, 5.0%, and 2.5%
- Evaluation (hr after challenge): 24 hour and 48 hours post-application

Other – The test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale (0 = no reaction, 1 -- slight reaction, 2 = moderate reaction, 3 = severe reaction. A positive reaction was defined as an erythema/edema value during the challenge phase of at least one skin grade higher than during the last induction phase.

3.MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 12 (2 intradermal and 10 topical)
- Exposure period: not specified
- Test groups: no data
- Control group: no data
- Site: no data
- Frequency of applications: no data
- Duration: 3 weeks
- Concentrations: 25%

B. CHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge: after 12 days
- Exposure period: no data
- Test groups: no data
- Control group: no data
- Site: no data
- Concentrations: 25% (0.5ml)
- Evaluation (hr after challenge): no data

Challenge controls:

2.No data available.
3.not specified

Positive control substance(s):

yes

Remarks:

2.DNCB (2,4-dinitrochlorobenze)

Positive control results:

2.The positive DNCB (2,4-dinitrochlorobenze) control at the 0.5% induction /challenge concentration elicited positive response in all animals tested.

Reading:

other: 2. challenge

Hours after challenge:

24

Group:

test chemical

Dose level:

10,5,2.5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No sensitization reaction observed.

Remarks on result:

no indication of skin sensitisation

Reading:

other: 2. challenge

Hours after challenge:

48

Group:

test chemical

Dose level:

10,5,2.5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No sensitization reaction observed.

Remarks on result:

no indication of skin sensitisation

Reading:

other: 3. 1st reading

Group:

test chemical

Dose level:

25% (0.5 ml)

No. with + reactions:

0

Clinical observations:

The chemical did not provoke any sign of sensitization.

Remarks on result:

no indication of skin sensitisation

2.

No indication of skin sensitization observed.

Conclusions:

The test chemical was considered to be not sensitizing to the skin on the basis of summarized studies.

Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical. The studies are as mentioned below:

Skin sensitization test for test chemical was conducted in guinea pig using modified Buehler and Klecak method for open Epicutaneous testing.For the induction phase, the left flanks of 10 albino guinea pigs were shaved and the dye test material applied three times weekly (Monday, Wednesday Friday) for three consecutive weeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area. After a rest period of two weeks. In challenge phase the right flank of each guinea pig was shaved and exposed to three different concentration 10.0%, 5.0%, and 2.5%.Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. No erythema/edema was observed after application of test material .The test result was observed to be negative for the test substance. Therefore test chemical was considered to be non sensitizing to the skin of guinea pig using modified Buehler and Klecak method for open Epicutaneous testing .

The another skin sensitization study of test chemical was conducted on guinea pigs to determine its skin sensitizing potential.The induction involved 10 topical treatments of a 25% aqueous solution and 2 intradermal injections of 0.1 ml Freund's complete adjuvant in a period of 3 weeks.After a rest period of 12 days, animals were challenged with 0.5 mL of the 25% aqueous solution of test chemical and observed for skin reaction.The chemical did not provoke any sign of sensitization as judged from oedema formation and histopathological examination. Also Erythema could not be examined due to the colorant.Thus on the basis of observed effects, the test chemical was considered to be not sensitizing to the skin of guinea pigs.

Based on the above summarized studies for target chemical and its structurally and functionally similar read across substances,it can be concluded that the test chemical is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

Various studies were performed on rabbits to assess the dermal irritation potential of test chemical which have been summarized as follows:

The skin irritation study of test chemical was conducted in Russian breed rabbits. Six rabbits (3 males/3 females) of the Russian breed, weighing 1.5 to 2 kgs, were shaved on the whole back and flanks two days before treatment with an electric clipper. The shaven skin on the left side was slightly scarified immediately before treatment. A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin. The patch was covered with a plastic film 5 x 5 cm, which was fixed, to the body with adhesive tape. The test chemical was applied to each side in quantities of 0.5 g (500mg). Before application a 50 % polyethylene glycol trituration (PEG 400) was made. The gauze patches were removed 24 hours after the application. The reaction of the skin was appraised upon removal and 72 hours after it. The primary irritation index as the measure of the acute skin irritation provoked by the substance was defined as the average of all the ratings found after 24 and 72 hours on the intact and slightly scarified skin. Compounds producing combined averages (primary irritation indexes) of 2 or less are only mildly irritating; whereas those with indexes from 2 to 5 are moderate irritants, and those with scores above 6 are considered severe irritants.

The primary irritation index of test chemical was evaluated to be 0.0 out of maximum score of 8. Since the treated rabbits did not develop any signs of skin irritation, the test chemical was considered to be not irritating to the skin.

In another skin irritation study which was designed and conducted to determine the dermal reaction profile of test chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures.Ten rats (5 male and 5 female) were used for conducting dermal irritation/ corrosion study.The animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Also, the erythema and edema score of rats was calculated as 0. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. Hence, it was concluded that test chemical was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested and Classified as “Category- Not Classified” as per CLP Classification.

All these studies lead to a conclusion that Test chemical is indeed not irritating to skin. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical 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 and its structurally and functionally similar read across substances were observed in various studies. From the results obtained from these studies it is concluded that the chemical is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.