Registration Dossier

Administrative data

Description of key information

Hostapon SLG is not skin sensitizing based on the read-across to Hostapon SG:

Hostapon SG was investigated for its skin sensitization property according to the OECD 406 (M&K). Hostapon SG is not skin sensitizing.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed prior to the establishment of LLNA.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 282 – 388 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 guinea pig breeding / maintenance diet, ad libidum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 2008-09-18 to 2008-10-13


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Route:
intradermal
Vehicle:
water
Concentration / amount:
5 % / 0.1 ml
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
50% /0.3 ml
Day(s)/duration:
24h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
5% /0.2 mL
Day(s)/duration:
24h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
5 control animals (males)
10 treated animals (males)
Details on study design:
RANGE FINDING TESTS:
A: Intradermal injections:
Four intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline (day 1) (shaved neck of one guinea pig)
Five days later: Four intradermal injections (0.1 mL/site) at concentrations of H = 15 %, I = 10 % and J = 5 % of the test item in purified water (clipped flank of the same guinea pig)
Dermal reactions assessed 24 hrs later.

B: Epidermal applications:
Four intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline (day 1) (shaved necks of two guinea pigs)
Five days later: Epidermal application with the test item at K = 15 %, L = 10 %, M = 5 % and N = 3 % in purified water (shaved flanks of the same two guinea pigs)
Dermal reactions assessed 24 and 48 hrs after removal of the bandage.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal / epicutaneously)
- Exposure period: injected / 48 h occlusive
- Site: scapular region (clipped free of hair)
- Frequency of applications: 1 / 1
- Duration: 0 - 8 days
- Concentrations:
1st application: 5% intradermal; 2nd application: 50% epicutaneous

B.
CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
-Exposure period: 24 hrs
- Site: left flank (test item); right flank: vehicle (clipped free of hair)
- Concentrations: 5% occlusive epicutaneous
- Evaluation (hr after challenge): 24 and 48 hrs
Positive control substance(s):
yes
Remarks:
ALPHA-HEXYLCINNAMALDEHYDE
Positive control results:
Discrete/patchy to moderate/confluent erythema with or without scaling was observed in nine out of ten test animals at the 24- and 48-hour reading after the challenge treatment with ALPHA-HEXYLCINNAMALDEHYDE at 1 % in PEG 300 (left shoulder). Five test animals showed discrete/patchy erythema at the 24-hour reading after treatment with ALPHAHEXYLCINNAMALDEHYDE at 0.1 % in PEG 300 (left flank). No skin effect was observed in the control group.
Based on the above mentioned findings in an adjuvant sensitization test (M&K-test) in guinea pigs and in accordance to Commission Directive 2001/59/EC, ALPHAHEXYLCINNAMALDEHYDE has to be classified and labelled as a skin sensitizer.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

 

Skin reactions in the intradermal pretest

Animal No.

Concentration (%)

Reactions

671, male

75

Moderate and confluent erythema

Oedema and necrosis

50

Moderate and confluent erythema

Oedema and necrosis

25

Moderate and confluent erythema

Oedema and necrosis

689, male

15

Moderate and confluent erythema

Necrosis

10

Moderate and confluent erythema

Necrosis

5

Discrete/patch erythema

 

Skin reactions in the intradermal pretest

Animal No.

Concentration (%)

Reactions after removal of badange

24h

28h

672, male

100

Intense erythema and swelling;

Fissures

Moderate and confluent erythema;

Scaling

75

Intense erythema and swelling;

Fissure

Moderate and confluent erythema;

Scaling

50

Moderate and confluent erythema

Moderate and confluent erythema;

Scaling

25

Discrete/patchy erythema

 

No visible change

 

673, male

100

Intense erythema and swelling;

Fissures

Moderate and confluent erythema;

Scaling

75

Intense erythema and swelling;

Fissures

Moderate and confluent erythema;

Scaling

50

Discrete/patchy erythema

 

No visible change

 

25

Discrete/patchy erythema

 

Discrete/patchy erythema

 

690, male

15

Discrete/patchy erythema

 

No visible change

 

10

No visible change

 

No visible change

 

5

No visible change

 

No visible change

 

3

No visible change

 

No visible change

 

691, male

15

Discrete/patchy erythema

 

No visible change

 

10

Discrete/patchy erythema

 

No visible change

 

5

No visible change

 

No visible change

 

3

No visible change

 

No visible change

 

 

 

Skin reactions after epidermal induction of with test item treated animals

Animal No.

Reactions after removal of badange

24h

48h

679

Discrete/patchy erythema

Discrete/patchy erythema

680

Discrete/patchy erythema

Discrete/patchy erythema

681

Discrete/patchy erythema

No visible change

682

Discrete/patchy erythema

Discrete/patchy erythema

683

Discrete/patchy erythema

Discrete/patchy erythema

684

Discrete/patchy erythema

Discrete/patchy erythema

685

Discrete/patchy erythema

No visible change

686

Discrete/patchy erythema

Discrete/patchy erythema

687

Moderate and confluent erythema

Discrete/patchy erythema

688

Discrete/patchy erythema

Discrete/patchy erythema

 

 

Skin reactions after epidermal challenge of with test item treated animals

Animal No.

Reactions after removal of badange

24h

48h

679

No visible change

No visible change

680

No visible change

No visible change

681

No visible change

No visible change

682

No visible change

No visible change

683

No visible change

No visible change

684

No visible change

No visible change

685

No visible change

No visible change

686

No visible change

No visible change

687

No visible change

No visible change

688

No visible change

No visible change

Interpretation of results:
GHS criteria not met
Conclusions:
Hostapon SG was investigated for its skin isensitization property according to the Guideline OECD 406 (M&K). It is not skin sensitizing.
Executive summary:

Hostapon SG was investigated for its skin sensitization property according to the OECD 406 (M&K). As for induction, ten male guinea pigs were treated intradermally at concentration of 5% in water and one week later epidermally at concentration of 50 % in water. Five control animals were treated with vehicle only. Two weeks after the epidermal induction, all animals were epidermally challenged at concentration of 5%. None of the animals responded. Hostapon SG is not skin sensitizing.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Justification is provided in Chapter 13.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed prior to the establishment of LLNA.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 282 – 388 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 guinea pig breeding / maintenance diet, ad libidum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 2008-09-18 to 2008-10-13


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Route:
intradermal
Vehicle:
water
Concentration / amount:
5 % / 0.1 ml
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
50% /0.3 ml
Day(s)/duration:
24h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
5% /0.2 mL
Day(s)/duration:
24h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
5 control animals (males)
10 treated animals (males)
Details on study design:
RANGE FINDING TESTS:
A: Intradermal injections:
Four intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline (day 1) (shaved neck of one guinea pig)
Five days later: Four intradermal injections (0.1 mL/site) at concentrations of H = 15 %, I = 10 % and J = 5 % of the test item in purified water (clipped flank of the same guinea pig)
Dermal reactions assessed 24 hrs later.

B: Epidermal applications:
Four intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline (day 1) (shaved necks of two guinea pigs)
Five days later: Epidermal application with the test item at K = 15 %, L = 10 %, M = 5 % and N = 3 % in purified water (shaved flanks of the same two guinea pigs)
Dermal reactions assessed 24 and 48 hrs after removal of the bandage.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal / epicutaneously)
- Exposure period: injected / 48 h occlusive
- Site: scapular region (clipped free of hair)
- Frequency of applications: 1 / 1
- Duration: 0 - 8 days
- Concentrations:
1st application: 5% intradermal; 2nd application: 50% epicutaneous

B.
CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
-Exposure period: 24 hrs
- Site: left flank (test item); right flank: vehicle (clipped free of hair)
- Concentrations: 5% occlusive epicutaneous
- Evaluation (hr after challenge): 24 and 48 hrs
Positive control substance(s):
yes
Remarks:
ALPHA-HEXYLCINNAMALDEHYDE
Positive control results:
Discrete/patchy to moderate/confluent erythema with or without scaling was observed in nine out of ten test animals at the 24- and 48-hour reading after the challenge treatment with ALPHA-HEXYLCINNAMALDEHYDE at 1 % in PEG 300 (left shoulder). Five test animals showed discrete/patchy erythema at the 24-hour reading after treatment with ALPHAHEXYLCINNAMALDEHYDE at 0.1 % in PEG 300 (left flank). No skin effect was observed in the control group.
Based on the above mentioned findings in an adjuvant sensitization test (M&K-test) in guinea pigs and in accordance to Commission Directive 2001/59/EC, ALPHAHEXYLCINNAMALDEHYDE has to be classified and labelled as a skin sensitizer.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

 

Skin reactions in the intradermal pretest

Animal No.

Concentration (%)

Reactions

671, male

75

Moderate and confluent erythema

Oedema and necrosis

50

Moderate and confluent erythema

Oedema and necrosis

25

Moderate and confluent erythema

Oedema and necrosis

689, male

15

Moderate and confluent erythema

Necrosis

10

Moderate and confluent erythema

Necrosis

5

Discrete/patch erythema

 

Skin reactions in the intradermal pretest

Animal No.

Concentration (%)

Reactions after removal of badange

24h

28h

672, male

100

Intense erythema and swelling;

Fissures

Moderate and confluent erythema;

Scaling

75

Intense erythema and swelling;

Fissure

Moderate and confluent erythema;

Scaling

50

Moderate and confluent erythema

Moderate and confluent erythema;

Scaling

25

Discrete/patchy erythema

 

No visible change

 

673, male

100

Intense erythema and swelling;

Fissures

Moderate and confluent erythema;

Scaling

75

Intense erythema and swelling;

Fissures

Moderate and confluent erythema;

Scaling

50

Discrete/patchy erythema

 

No visible change

 

25

Discrete/patchy erythema

 

Discrete/patchy erythema

 

690, male

15

Discrete/patchy erythema

 

No visible change

 

10

No visible change

 

No visible change

 

5

No visible change

 

No visible change

 

3

No visible change

 

No visible change

 

691, male

15

Discrete/patchy erythema

 

No visible change

 

10

Discrete/patchy erythema

 

No visible change

 

5

No visible change

 

No visible change

 

3

No visible change

 

No visible change

 

 

 

Skin reactions after epidermal induction of with test item treated animals

Animal No.

Reactions after removal of badange

24h

48h

679

Discrete/patchy erythema

Discrete/patchy erythema

680

Discrete/patchy erythema

Discrete/patchy erythema

681

Discrete/patchy erythema

No visible change

682

Discrete/patchy erythema

Discrete/patchy erythema

683

Discrete/patchy erythema

Discrete/patchy erythema

684

Discrete/patchy erythema

Discrete/patchy erythema

685

Discrete/patchy erythema

No visible change

686

Discrete/patchy erythema

Discrete/patchy erythema

687

Moderate and confluent erythema

Discrete/patchy erythema

688

Discrete/patchy erythema

Discrete/patchy erythema

 

 

Skin reactions after epidermal challenge of with test item treated animals

Animal No.

Reactions after removal of badange

24h

48h

679

No visible change

No visible change

680

No visible change

No visible change

681

No visible change

No visible change

682

No visible change

No visible change

683

No visible change

No visible change

684

No visible change

No visible change

685

No visible change

No visible change

686

No visible change

No visible change

687

No visible change

No visible change

688

No visible change

No visible change

Interpretation of results:
GHS criteria not met
Conclusions:
Not skin sensitizing
Executive summary:

Hostapon SLG is assessed for its skin sensization property via read-across to Hostapon SG.

Hostapon SG was investigated for its skin sensitization property according to the OECD 406 (M&K). As for induction, ten male guinea pigs were treated intradermally at concentration of 5% in water and one week later epidermally at concentration of 50 % in water. Five control animals were treated with vehicle only. Two weeks after the epidermal induction, all animals were epidermally challenged at concentration of 5%. None of the animals responded. Hostapon SG is not skin sensitizing

Likewise, Hostapon SLG is not skin sensitizing.

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

Justification for classification or non-classification

Hostapon SLG is assessed based on the read-across to Hostapon SG.

Hostapon SG was investigated for its skin sensitization property according to the OECD 406 (M&K). Hostapon SG is not skin sensitizing.

No classification is assigned to Hostapon SLG.