Registration Dossier

Administrative data

Description of key information

Modified Draize Technique was employed to determine the concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the test chemical.

No signs of contact sensitization were observed at 0.1% ICC and 30% ACC concentrations. Hence, the test chemical was considered to be non-sensitizing to the skin of albino Hartley guinea pigs.

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 publication.
Qualifier:
according to
Guideline:
other: Modified Draize Technique
Principles of method if other than guideline:
Modified Draize Technique was employed to determine the concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the test chemical
GLP compliance:
not specified
Type of study:
other: Modified Draize Technique
Justification for non-LLNA method:
Currently no LLNA Study is available for assessment.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 350 g
- Housing: Housed in wire mesh cages in pairs of the same sex
- Diet (e.g. ad libitum): Pelleted guinea pig diet, cabbage and hay ad libitum
- Water (e.g. ad libitum): water ad libitum
Route:
intradermal
Vehicle:
other: Yes suitable vehicle was used. (No detailed information )
Concentration / amount:
Induction concentration: 0.1 mL at 2.5 X 0.1(ICC) : 10 guinea pigs
Day(s)/duration:
24 hours
Adequacy of induction:
other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC).
No.:
#1
Route:
intradermal
Vehicle:
other: Yes suitable vehicle was used. (No detailed information )
Concentration / amount:
Challenge concentration: 0.1 mL at 0.1 (ICC) and 30 (ACC): 10 guinea pigs

Day(s)/duration:
24 hours
Adequacy of challenge:
other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC). The highest concentration which caused no irritation was selected as the application challenge concentration (ACC).
No.:
#2
Route:
epicutaneous, open
Vehicle:
other: Yes suitable vehicle was used. (No detailed information )
Concentration / amount:
Rechallenge concentration: 0.1 mL at 0.1(ICC) and 30 (ACC): 10 guinea pigs

Day(s)/duration:
24 hours
Adequacy of challenge:
other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC). The highest concentration which caused no irritation was selected as the application challenge concentration (ACC).
No. of animals per dose:
10 guinea pigs (6 male, 4 females or vice versa)
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE: Intradermal
- No. of exposures:4
- Exposure period: No Data Available
- Test groups:10 guinea pigs
- Control group: No Data Available
- Site: 4 sites, 2 auxillary and 2 inguinal lymph nodes
- Frequency of applications:1
- Duration: No Data Available
- Concentrations: 0.1 mL at 2.5 X 0.1 (ICC)

B. CHALLENGE EXPOSURE: Intradermal and Epicutaneous
- No. of exposures:1
- Day(s) of challenge: Fourteen days later, challenge test was performed
- Exposure period:24 hours
- Test groups:10guinea pigs
- Control group: No Data Available
- Site: onto the shaved flank in a small circular area
- Concentrations: 0.1 mL at 0.1 (ICC) and 30 (ACC).
- Evaluation (hr after challenge):24 hours

C. RECHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge:7 Days Later , rechalleange test was performed.
- Exposure period: No Data Available
- Test groups:10 animal
- Control group: 4 animal (same sex)
- Site: Intradermally and topically on opposite flanks
- Concentrations: 0.1 mL at 0.1 (ICC) and 30 (ACC).
- Evaluation (hr after challenge): No Data Available
-Other:

Observations and scoring –
Each injection reaction was given a total score based on size (2 largest diameters), erythema and oedema. Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale. Reactions were examined under a Philips colour-matching unit with 3 Philips 40 W Actinic Blue 05 fluorescent tubes and 3 Philips 40 W White 35 fluorescent tubes.

Challenge controls:
At each challenge with controls, 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively
Positive control substance(s):
not specified
Positive control results:
No data
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.1 mL at 0.1 (ICC) and 30 (ACC).
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin sensitization was observed.
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
0.1 mL at 0.1 (ICC) and 30 (ACC).
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin sensitization was observed.
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: not sensitising
Conclusions:
No signs of contact sensitization were observed at 0. 1% ICC and 30% ACC concentrations. Hence,the test chemical was considered to be non-sensitizing to the skin of albino Hartley guinea pigs.
Executive summary:

Modified Draize Technique was employed to determine the concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the test chemical.

Hartley strain albino guinea pigs bred were used for the study. Four guinea pigs of same sex were used for the preliminary irritation study and 10 guinea pigs were used for the main sensitization study and 4 previously untreated animals of the same sexwere used as challenge controls.

The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration(ACC) ]

The ICC and ACC for the test chemical was determined to be 0.1% and 30% respectively

In the induction phase, 0.1 ml aliquots of test substance at 2.5 times the ICC were injected intradermally at 4 sites which overlie the 2 auxillary and 2 inguinal lymph nodes. After a rest period of 14 days, each animal was challenged intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC: the topical application was made by spreading 0.1 ml of the test substance onto the shaved flank in a small circular area which was not covered. Twenty-four hours later the reactions were scored and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included. At each challenge with controls, 4 previously untreated animals of the same sex were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively.

 

Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale and individual reactions were considered positive if (a) they were + or greater and (b) there were no erythema reactions in controls.

 

No signs of contact sensitization were observed at 0. 1% ICC and 30% ACC concentrations. Hence, the test chemical was considered to be non-sensitizing to the skin of albino Hartley guinea pigs.

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

In various studies, the test chemical been investigated for potential to cause dermal sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs, humans for the test chemicals. The results are summarized as follows:

 

Modified Draize Technique was employed to determine the concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the test chemical. Hartley strain albino guinea pigs bred were used for the study. Four guinea pigs of same sex were used for the preliminary irritation study and 10 guinea pigs were used for the main sensitization study and 4 previously untreated animals of the same sexwere used as challenge controls. The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration(ACC) ]. The ICC and ACC for the test chemical was determined to be 0.1% and 30% respectively. In the induction phase, 0.1 ml aliquots of test substance at 2.5 times the ICC were injected intradermally at 4 sites which overlie the 2 auxillary and 2 inguinal lymph nodes. After a rest period of 14 days, each animal was challenged intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC: the topical application was made by spreading 0.1 ml of the test substance onto the shaved flank in a small circular area which was not covered. Twenty-four hours later the reactions were scored and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included.At each challenge with controls, 4 previously untreated animals of the same sex were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively. Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale and individual reactions were considered positive if (a) they were + or greater and (b) there were no erythema reactions in controls. No signs of contact sensitization were observed at 0.1% ICC and 30% ACC concentrations. Hence, the test chemical was considered to be non-sensitizing to the skin of albino Hartley guinea pigs.

This is supported by the results of a multicenter study extending over a three year period, dermatitis patients were tested for their sensitivity to fragrance materials. The test chemical was tested in 205 consecutive patients. The test chemical was of high grade quality and provided by Haarmann and Reimer (Germany).It was dissolved in white petrolatum under gentle heating. Patch tests were performed with 1% and 5% test chemical in white petrolatum using Finn Chambers® on Scanpor® applied for two days on the back. Reactions were recorded according to the ICDRG on days 2 and 3 or on days 2 and 4. The test chemical at 5% concentrations produced a questionable/irritant reaction in 1 patient. Hence, it can be considered to be a non sensitizer to human skin.

Skin sensitization effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for the test chemical. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, the test chemical was considered to be not sensitizing.

These results are supported by data from various closely related test chemicals.

Magnusson and Kligman maximization test carried out on female Hartley albino guinea pigs to evaluate the sensitization potential of the test chemical. Backs of nine animals (5 test and 4 controls) were clipped free of hair with an electric hair clipper and an electric shaver. Four-hours after depilation, the animals were induced intradermally with 10% test chemical in 1:1 mixture of Freund’s complete adjuvant (FCA) and physiological saline. Topical induction was carried out with 10% test chemical in FCA. The animals were topically challenged with 5%, 10%, 20%, or 40% test chemical in acetone. Reactions were scored 48 h after challenge. Since there was no evidence of any skin reaction, the test chemical can be considered as non-sensitizing.

The above results are also supported by an open epicutaneous test (OET) conducted to determine the sensitization potential of the test chemical. 0.1 ml aliquot of the test chemical was applied to an 8 cm2 area on the clipped flank skin of 6–8/group Himalayan white spotted guinea pigs weighing 400–500 g. The applications were repeated daily for 21 days on the same skin site. The application site was left uncovered and the reactions were read at 24 h after each application. Challenge was conducted on days 21 and 35 by applying a 0.025 ml aliquot of ionone to skin areas measuring 2 cm2 on the contralateral flank of all test animals as well as 6–8 untreated controls. Reactions were read at 24, 48 and 72 h. The test chemical did not produce any sensitization reactions when applied on to skin and on contralateral flank of guinea pig. Hence, the test chemical was considered to be not sensitizing to skin of Himalayan white-spotted Guinea pig.

The data for the target chemical is supported by the prediction data and data from closely related test chemicals. Considering the details of the studies available, the test chemical is not likely to classify as a skin sensitizer as per the criteria mentioned in CLP regulation.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Considering the details of the studies available, the test chemical is not likely to classify as a skin sensitizer as per the criteria mentioned in CLP regulation.