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Description of key information

Draize test was performed to evaluate the dermal sensitization potential of the test chemical.

200 normal human volunteers aged between 21 -50 years were used for the study.

The test chemical was not a contact sensitizer when 1.5% test chemical in aqueous soap suspension was used for induction. Hence, the test chemical was considered for not sensitizing to skin

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:
other: Draize test
Principles of method if other than guideline:
Draize test was performed to evaluate the dermal sensitization potential of the test chemical
GLP compliance:
not specified
Type of study:
Draize test
Justification for non-LLNA method:
The Guinea Pig Maximization Test (GPMT) 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:
other: Human
Strain:
other: Not applicable
Sex:
male
Details on test animals and environmental conditions:
- Age at study initiation: 21-50 years, The test subjects were approximately 82%Caucasian, 13% Negro and 5% American Indian (Mexican). This test, like other predictive sensitization tests, is derived from Jadassohn's diagnostic patch test introduced around the turn of the century.
Route:
epicutaneous, occlusive
Vehicle:
other: aqueous soap suspension
Concentration / amount:
0.5 g of 1.5% test chemical in aqueous soap suspension
Day(s)/duration:
10 epicutaneous application; 48 or 72 hours
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: aqueous soap suspension
Concentration / amount:
1.5% test chemical in aqueous soap suspension
Day(s)/duration:
72 hours
Adequacy of challenge:
not specified
No. of animals per dose:
200 male volunteers
Details on study design:
Details on study design
RANGE FINDING TESTS:no data available
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: 48 to 72 hrs
- Test groups: 31
- Control group:no data
- Site: upper lateral portion of the arm
- Frequency of applications: 10 epicutaneous applications were administered successively to the same site for induction
- Duration: 48 to 72 hrs
- Concentrations:1. 5% test chemical in aqueous soap suspension

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: after 2 weeks of induction
- Exposure period: 72 hrs
- Test groups:31
- Control group: no data
- Site: upper lateral portion of the arm
- Concentrations: 5% test chemical in petrolatum
- Evaluation (hr after challenge): 72 hrs

OTHER: Skin reactions were assigned four grades of intensity: 1 = erythema; 2 = erythema snd
induration; 3 =vesiculation;and 4 =bulla formation.
Challenge controls:
not specified
Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
88
Clinical observations:
No evidence of skin sensitization in the 88 volunteers tested.
Remarks on result:
no indication of skin sensitisation

Response of human subjects tested with the test chemical in aqueous soap suspension (Draize procedure)

Induction

%

Challenge

%

Sensitized

Fraction

%

1.5

1.5

0/200

0

 

Interpretation of results:
other: not sensitizing
Conclusions:
The test chemical was not a contact sensitizer when 1.5% test chemical in aqueous soap suspension was used for induction. Hence, the test chemical was considered for not sensitizing to skin
Executive summary:

Draize test was performed to evaluate the dermal sensitization potential of the test chemical.

200 normal human volunteers aged between 21 -50 years were used for the study. 0.5 g of 1.5% test chemical was applied to the upper lateral portion of the arm, covered with an occlusive patch, and removed after 48 or 72 hours.10 epicutaneous applications were administered successively to the same site for induction. After a rest period of 2 weeks, the challenge patch was applied for 72 hours, the reactions were read. Skin reactions were assigned four grades of intensity: 1 = erythema; 2

= erythema snd induration; 3 =vesiculation;and 4 =bulla formation.

The test chemical was not a contact sensitizer when 1.5% test chemical in aqueous soap suspension was used for induction. Hence, the test chemical was considered for not sensitizing to skin

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Various studies have been reviewed to ascertain the potential of the test chemical to cause dermal sensitization in living organisms. These include in vivo experimental studies performed on guinea pigs as well as humans for the test chemical. The results are summarized as follows:

Draize test was performed to evaluate the dermal sensitization potential of the test chemical.

200 normal human volunteers aged between 21 -50 years were used for the study. 0.5 g of 1.5% test chemical was applied to the upper lateral portion of the arm, covered with an occlusive patch, and removed after 48 or 72 hours.10 epicutaneous applications were administered successively to the same site for induction. After a rest period of 2 weeks, the challenge patch was applied for 72 hours, the reactions were read. Skin reactions were assigned four grades of intensity: 1 = erythema; 2 = erythema snd induration; 3 =vesiculation;and 4 =bulla formation.

The test chemical was not a contact sensitizer when 1.5% test chemical in aqueous soap suspension was used for induction. Hence, the test chemical was considered for not sensitizing to skin

This is supported by a Modified Draize test conducted on normal male human paid subjects to assess the skin sensitization potential of test chemical. A single concentration (9%) of test chemical was applied to the upper lateral portion of the arm of 185 male subjects. Material was applied to the same skin site three times weekly and remained in place either 48 hours (during the week) or 72 hours over the weekend. Each individual was given a total of 10 applications. The induction period (3½ weeks) was followed by a rest phase (2 weeks) and then a challenge patch of 9% test chemical was applied for a final 72h contact period and graded at 96 hours.

No positive responses were observed in the 185 test subjects following induction and subsequent challenge with 9% test chemical. Hence the test material was considered to be not sensitizing to the skin of treated subjects.

These results are supported by a study where Human subjects were used to evaluate the skin sensitization potential of the test chemical using Modified Draize test.

1.5% and 10% test chemical in petrolatum was applied to the upper portion of the arm of male test subjects(200, 88) and covered with an occlusive patch (Johnson & Johnson Square Band Aid ®, without perforations) for 48 or 72 hours. Usually, 10 epicutaneous applications were administered successively at the same site for induction. Following a rest period of approximately 2 weeks, the challenge patch(1.5% and 10%) was applied and allowed to remain for 72 hours, after which the reaction was read. Challenge was always done with a non-irritant concentration of the test material. Skin reactions were assigned four grades of intensity: 1 = erythema; 2 = erythema and induration; 3= vesiculation; 4= bulla formation.

The test chemical failed to cause any signs of dermal sensitization in 200, 88 when tested at 1.5%, 10% in petrolatum respectively. Hence the test chemical was considered as not sensitizing to the skin of human.

Also, Shelanski Repeated Insult Patch Test Method was used to determine the allergic contact sensitization potential of test chemical upon human skin.

Fifty human volunteers were treated on the back with 15 semi-occlusive patches containing approximately 50 mg of undiluted test chemical for 24 hours. The patches were then removed and the sites examined for skin irritation reactions. After a 24 hours rest, the patches were reapplied for 24 hours and the sites examined on removal. After a two week rest period, a final 24 hour challenge application of 50 mg undiluted test substance was made. All applications were made to the same site on the skin of each subject.

There were no observed reactions on any of the fifty human test subjects, to either of the 15 primary applications or the challenge applications.

From the results obtained in the study it was concluded that the test chemical was neither primary irritant, nor a skin sensitizer to any of the fifty subjects tested.

The above results are supported by a study which reports of a screening programme with dermatitis patients to evaluate the response of sensitive subgroups to test chemical.

Members of the International Contact Dermatitis Research group included 1% test chemical in petrolatum in their routine test battery for 6 months. Such routine series are used in defining the etiology of suspected allergic contact dermatitis cases.

All positive reactions were to be retested with a second patch to verify the results of the initial patch. Patients reacting in the repeat patch test, if any, were to be instructed to apply a test chemical use-dilution sample (1.5% test chemical in bar soap) twice daily to their cubital fossa for a week. These patients were to be re-examined at that time. Over 2200 dermatitis patients were patch tested with 1% test chemical when tested with the standard series.

A single patient reacted, and the reaction was reproducible on repeat patch testing. Product-use testing of this individual was negative after 21 days of use.

The overall frequency of response was so low that the test chemical was considered to be not sensitizing to the skin of treated volunteers.

These results are further supported by a Patch test performed to determine the degree of sensitization potential of the test chemical.

179 patients suspected of cosmetic allergy were patch tested with a series of 16 fragrances an-d 9 preservatives. For patch testing, 10% test chemical was dissolved in petrolatum and applied on the patients. Silver patch testes (van der Bend bv, The Netherlands) were used. Reactions were read after 48 and 72 hours, and scored according to Internationally accepted criteria. 1 of 179 patients tested gave a positive reaction to the test chemical.

Hence, the test chemical can be considered to be not sensitizing to skin.

These patch tests are again supported by a series of patch tests performed on human volunteers to ascertain the dermal sensitization potential of the test chemical.

114 human volunteers were treated with patches of a 10% w/v aqueous solution of bar soap containing 1.2% test chemical under patches.

The patches were applied on the back under semi-occlusive conditions, for 24 hours, three times a week at the same skin site, for 3 weeks during the induction period. After a 10 -14 day rest period, a final 24 hour challenge application of the test material was made and read after 48 and 72 hours

At challenge there was no evidence of skin sensitization in any of the 101 human subjects who completed the test. Hence, the test chemical can be considered to be not sensitizing to skin.

All the patch test results are also lent support by a Magnusson-Kligman guinea pig maximisation test performed to evaluate the dermal sensitization potential of the test chemical in guinea pigs. The study was performed in accordance with OECD 406 Guidelines. The test chemical was formulated as a suspension with Cremophor EL® (2% v/v) in physiological saline solution.

The study included a treatment group with 20 male animals and 2 control groups of 10 guinea pigs each. In the induction phase, the treatment group was injected (0.1 ml) in a row on each side of the vertebral column on day zero in duplicate with: 1:1 mixture Freund’s complete adjuvant (FCA) and physiological saline solution; 5% test substance formulated with Cremophor solution and 5% test substance in a 1:1 mixture FCA. The animals in the control groups were treated in the same way, except that the formulations for injections 2 and 3 contained a corresponding amount of Cremophor solution instead of the test substance. A week later, a patch containing 0.5 mL of a 50% solution of the test substance was placed over the injection area for 48 hours in the treatment group. The control groups were treated in the same manner but with 0.5 mL Cremophor solution instead of the test substance. Three weeks after the induction phase, the back and the flanks of the treated and the control animals were shaved and an occlusive ‘challenge’ patch containing a 50% test substance formulation as a suspension with Cremophor EL® (2% v/v) in physiological saline solution (or Cremophor EL® (2% v/v) in physiological saline solution in case of the control group) was applied to the left flank of the animals for 24hours. 48 hours and 72 hours after challenge, any observed skin reactions were recorded according to the Magnusson-Kligman grading scale.

The test chemical failed to cause skin sensitization in guinea pigs. Hence, the test chemical was considered to be not sensitizing to skin.

Based on the available in vivo results, the test chemical indeed lacks the potential to cause sensitization to skin. Hence, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations to the criteria of CLP Regulation, the 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

Based on the available in vivo results, the test chemical indeed lacks the potential to cause sensitization to skin. Hence, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations to the criteria of CLP Regulation, the test chemical can be classified under the category “Not Classified”.