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Diss Factsheets

Administrative data

Description of key information

Skin sensitisation (WoE), guinea pig: not sensitising (RA from CAS 131459-39-7 and CAS 67762-53-2 and (QSAR) prediction)

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:
weight of evidence
Study period:
14 Dec 1998 - 31 Jan 1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (Limited documentation of induction and test substance; only 4 control animals due to sacrifice of one animal at day 21, challenge was done open and not occlusive)
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Magnussen and Kligmann Method
Deviations:
yes
Remarks:
Limited documentation of induction and test substance; only 4 control animals due to sacrifice of one animal at day 21, challenge was done open and not occlusive
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
yes
Remarks:
Limited documentation of induction and test substance; only 4 control animals due to sacrifice of one animal at day 21, challenge was done open and not occlusive
GLP compliance:
yes (incl. QA statement)
Remarks:
The Department of Health of the Government of the United Kingdom
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was performed in 1999 when the OECD Guideline 406 adopted in 1992 was the current version. According to this guideline "the Guinea Pig Maximisation Test (GPMT) [...] and the non-adjuvant Buehler Test are given preference over other methods".
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Staffordshire, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 340 g - 421 g
- Housing: individually housed in solid floor polypropylene cages furnished with woodflakes
- Diet: Guinea Pig FD1 Diet, Special Diets Services Limited, Witham, Essex, UK), ad libitum
- Water: ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 44 - 57
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
Induction: Intradermal induction 25%, epicutaneous induction 100%
Route:
epicutaneous, open
Vehicle:
arachis oil
Concentration / amount:
Challenge: 100% and 75% (v/v) in arachis oil
No. of animals per dose:
10 (test groups)
4 (control group; initially 5, but 1 animal was sacrificed on Day 21)
Details on study design:
RANGE FINDING TESTS: Yes

Intradermal: Four concentrations of the test substance were investigated (1%, 5%, 10% and 25%) in a total of 4 guinea pigs. Each animal received four injections of 0.1 ml (only one concentration) and the skin reaction was assessed 24 h, 48 h, 72 h and 7 d afterwards according to Draize.
Topical: Two animals were pre-treated with an intradermal injection of FCA 17 days prior to test material administration.
Animals were administered four different concentrations (25%, 50%, 75% and 100%) of the test substance. Treatment was for 24 h under occlusive conditions and skin reaction was observed for dermal irritation 24 and 48 h afterwards.

MAIN STUDY
A. INDUCTION EXPOSURE
No further data available due to a loss of one page of the study report
- Concentrations: Intradermal induction: 25%, Topical induction: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 after topical induction
- Exposure period: 24 h
- Test groups: 1
- Control group: 1
- Site: Left (75%) and right (100%) flank
- Concentrations: 75% and 100%
- Evaluation (hr after challenge): 24 and 48 h after removal of the patches
Positive control substance(s):
yes
Remarks:
PEG 400 70:30 in Acetone
Positive control results:
In the range of the historical controls
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
4
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: 4.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
4
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: 4.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0.

One control animal was sacrificed on Day 21 due to respiratory problems. The absence of this animal was considered not to affect the purpose or integrity of the study. No skin reactions were noted at the challenge sites of the test or control animals at 24 h or 48 h observations. Body weight gain of the test group was comparable to those observed in the control group animals.

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (no analytical purity reported)
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted in 1992
Deviations:
yes
Remarks:
analytical purity not reported
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was performed in 1999 when the OECD Guideline 406 adopted in 1992 was the current version. According to this guideline "the Guinea Pig Maximisation Test (GPMT) [...] and the non-adjuvant Buehler Test are given preference over other methods".
Species:
guinea pig
Strain:
other: Albino Guinea Pigs
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Convance Research Products Inc., Denver, Pennsylvania; USA
- Age at study initiation: approximately 4 - 7 weeks at dosing (range-finding study; intradermal); approximately 9 - 12 weeks (rang-finding study; topical); approximately 5-7 weeks at first dose (sensitisation study)
- Weight at study initiation: 376 - 428 g
- Housing: individually housed in suspended, stainless steel cages with wire mesh bottoms
- Diet: certified Guinea Pig Diet, No. 5026, ad libitum
- Water: automatic watering system (Municipal water supply), ad libitum
- Acclimation period: 8 days (range-finding animals); 14 days (sensitization animals)

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
Induction: 5% (intradermal), 100% (epicutaneous)
Day(s)/duration:
Days 1-8
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
Challenge: 100% and 50%
Day(s)/duration:
Day 22
No. of animals per dose:
5 (controls), 10 (in test groups)
Details on study design:
RANGE FINDING TESTS:
Intradermal:
Two animals were administered intradermal injections (2 injection / animal) of a 5% v/v concentration of test substance in propylene glycol, one on either side of the spinal column. The concentration tested did not produce extensive tissue damage or severe systemic toxicity.
Topical:
4 animals were tested at 4 different concentrations (25, 50, 75% v/v; 100%) per animal (one concentration/site), two on either side of the spinal column. 24 h and 48 h after removal of the patches no signs of erythema and edema were observed for at any of the concentration tested.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and
- Test group:
Intradermal (3 pairs of injections)
Injection 1: a 1:1 mixture (v/v) FCA/ water
Injection 2: test substance in propylene glycol
Injection 3: test substance in a 1:1 mixture (v/v) FCA/water
Epicutaneous: test substance in propylene glycol
- Control group:
Intradermal (3 pairs of injections)
Injection 1: a 1:1 mixture (v/v) FCA/ water
Injection 2: propylene glycol
Injection 3: propylene glycol at 50% (v/v) in a 1:1 mixture (v/v) FCA/water
Epicutaneous: propylene glycol
- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 1-8
- Concentrations: Intradermal 5%, epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 24 h
- Test groups: test substance
- Control group: test substance
- Site: both flanks (two concentrations were applied for a total of two sites per animal)
- Concentrations: 100% and 50%
- Evaluation (hr after challenge): 24 and 48 h after patch removal
Positive control substance(s):
yes
Remarks:
hexylcinnamic aldehyde (HCA)
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons).
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons)..
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons)
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons).
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons)
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons).
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons)
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons).
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
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
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose for cross-reference:
read-across source
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Staffordshire, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 340 g - 421 g
- Housing: individually housed in solid floor polypropylene cages furnished with woodflakes
- Diet: Guinea Pig FD1 Diet, Special Diets Services Limited, Witham, Essex, UK), ad libitum
- Water: ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 44 - 57
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
Induction: Intradermal induction 25%, epicutaneous induction 100%
Route:
epicutaneous, open
Vehicle:
arachis oil
Concentration / amount:
Challenge: 100% and 75% (v/v) in arachis oil
No. of animals per dose:
10 (test groups)
4 (control group; initially 5, but 1 animal was sacrificed on Day 21)
Details on study design:
RANGE FINDING TESTS: Yes

Intradermal: Four concentrations of the test substance were investigated (1%, 5%, 10% and 25%) in a total of 4 guinea pigs. Each animal received four injections of 0.1 ml (only one concentration) and the skin reaction was assessed 24 h, 48 h, 72 h and 7 d afterwards according to Draize.
Topical: Two animals were pre-treated with an intradermal injection of FCA 17 days prior to test material administration.
Animals were administered four different concentrations (25%, 50%, 75% and 100%) of the test substance. Treatment was for 24 h under occlusive conditions and skin reaction was observed for dermal irritation 24 and 48 h afterwards.

MAIN STUDY
A. INDUCTION EXPOSURE
No further data available due to a loss of one page of the study report
- Concentrations: Intradermal induction: 25%, Topical induction: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 after topical induction
- Exposure period: 24 h
- Test groups: 1
- Control group: 1
- Site: Left (75%) and right (100%) flank
- Concentrations: 75% and 100%
- Evaluation (hr after challenge): 24 and 48 h after removal of the patches
Positive control substance(s):
yes
Remarks:
PEG 400 70:30 in Acetone
Positive control results:
In the range of the historical controls
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
4
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: 4.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
4
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: 4.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0.

One control animal was sacrificed on Day 21 due to respiratory problems. The absence of this animal was considered not to affect the purpose or integrity of the study. No skin reactions were noted at the challenge sites of the test or control animals at 24 h or 48 h observations. Body weight gain of the test group was comparable to those observed in the control group animals.

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
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
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose for cross-reference:
read-across source
Species:
guinea pig
Strain:
other: Albino Guinea Pigs
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Convance Research Products Inc., Denver, Pennsylvania; USA
- Age at study initiation: approximately 4 - 7 weeks at dosing (range-finding study; intradermal); approximately 9 - 12 weeks (rang-finding study; topical); approximately 5-7 weeks at first dose (sensitisation study)
- Weight at study initiation: 376 - 428 g
- Housing: individually housed in suspended, stainless steel cages with wire mesh bottoms
- Diet: certified Guinea Pig Diet, No. 5026, ad libitum
- Water: automatic watering system (Municipal water supply), ad libitum
- Acclimation period: 8 days (range-finding animals); 14 days (sensitization animals)

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
Induction: 5% (intradermal), 100% (epicutaneous)
Day(s)/duration:
Days 1-8
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
Challenge: 100% and 50%
Day(s)/duration:
Day 22
No. of animals per dose:
5 (controls), 10 (in test groups)
Details on study design:
RANGE FINDING TESTS:
Intradermal:
Two animals were administered intradermal injections (2 injection / animal) of a 5% v/v concentration of test substance in propylene glycol, one on either side of the spinal column. The concentration tested did not produce extensive tissue damage or severe systemic toxicity.
Topical:
4 animals were tested at 4 different concentrations (25, 50, 75% v/v; 100%) per animal (one concentration/site), two on either side of the spinal column. 24 h and 48 h after removal of the patches no signs of erythema and edema were observed for at any of the concentration tested.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and
- Test group:
Intradermal (3 pairs of injections)
Injection 1: a 1:1 mixture (v/v) FCA/ water
Injection 2: test substance in propylene glycol
Injection 3: test substance in a 1:1 mixture (v/v) FCA/water
Epicutaneous: test substance in propylene glycol
- Control group:
Intradermal (3 pairs of injections)
Injection 1: a 1:1 mixture (v/v) FCA/ water
Injection 2: propylene glycol
Injection 3: propylene glycol at 50% (v/v) in a 1:1 mixture (v/v) FCA/water
Epicutaneous: propylene glycol
- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 1-8
- Concentrations: Intradermal 5%, epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 24 h
- Test groups: test substance
- Control group: test substance
- Site: both flanks (two concentrations were applied for a total of two sites per animal)
- Concentrations: 100% and 50%
- Evaluation (hr after challenge): 24 and 48 h after patch removal

Positive control substance(s):
yes
Remarks:
hexylcinnamic aldehyde (HCA)
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons).
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons)..
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons)
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons).
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons)
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons).
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons)
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons).
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
Endpoint:
skin sensitisation, other
Remarks:
QSAR prediction
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Validated QSAR model
Justification for type of information:
The OECD QSAR Toolbox v3.3.5 is a Quantitative Structure-Activity Relationship model that was developed by the Laboratory of Mathematical Chemistry, Bourgas, Bulgaria (http://toolbox.oasis-lmc.org). It contains several different databases with data on chemicals. The model was used to predict the skin sensitisation potential of the test substance in the database 'Protein binding alerts for skin sensitisation by OASIS v1.3'.
Principles of method if other than guideline:
Prediction based on OECD QSAR Toolbox v3.3.5 QSAR prediction of the skin sensitisation properties of the test substance. The presence of protein binding alerts that may indicate a skin sensitising potential is assessed.
GLP compliance:
no
Reading:
other: QSAR prediction
Group:
other: not applicable
Dose level:
not applicable
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
skin sensitisation prediction as protein binding potential: negative

The predicted skin sensitisation potential of the test substance as protein binding potential was modelled in the OECD QSAR Toolbox v3.3.5.The test substance falls within the model applicability domain for the database OASIS v1.3.No alerts were found. Therefore, the test substance is not expected to exhibit skin sensitising properties.

Smiles or other identifiers used for Tetraesters of pentaerythritol with heptanoic acid and 3,5,5-trimethylhexanoic acid as input for the model:

- O=C(CCCCCC)OCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COC(=O)CCCCCC

- O=C(CC(C)CC(C)(C)C)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CCCCCC)COC(=O)CCCCCC

- O=C(CC(C)CC(C)(C)C)OCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COC(=O)CCCCCC

- O=C(CC(C)CC(C)(C)C)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CCCCCC)COC(=O)CC(C)CC(C)(C)C

Interpretation of results:
study cannot be used for classification
Conclusions:
The test material is not predicted to have skin sensitising potential.
Endpoint:
skin sensitisation, other
Remarks:
QSAR prediction
Type of information:
other: (Q)SAR (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Validated QSAR model
Justification for type of information:
The OECD QSAR Toolbox v3.3.5 is a Quantitative Structure-Activity Relationship model that was developed by the Laboratory of Mathematical Chemistry, Bourgas, Bulgaria (http://toolbox.oasis-lmc.org). It contains several different databases with data on chemicals. The model was used to predict the skin sensitisation potential of the analogue substances in the database 'Protein binding alerts for skin sensitisation by OASIS v1.3'.

Principles of method if other than guideline:
Prediction based on OECD QSAR Toolbox v3.3.5 QSAR prediction of the skin sensitisation properties of the analogue substances. The presence of protein binding alerts that may indicate a skin sensitising potential is assessed.
GLP compliance:
no
Reading:
other: QSAR prediction
Group:
other: not applicable
Dose level:
not applicable
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
skin sensitisation prediction as protein binding potential: negative

The predicted skin sensitisation potential of the analogue substances as protein binding potential was modelled in the OECD QSAR Toolbox v3.3.5.The read-across substances fall within the model applicability domain for the database OASIS v1.3. No alerts were found. Therefore, the analogue substances are not expected to exhibit skin sensitising properties.

Smiles or other identifiers of the analogue substances used as input for the model:

Carboxylic acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2)

- O=C(OCC(COC(=O)CCCC)(COC(=O)CCCC)COC(=O)CCCC)CCCC

-O=C(OCC(COC(=O)CCCCCCCC)(COC(=O)CCCCCCCC)COC(=O)CCCCCCCC)CCCCCCCC

 

Isononanoic acid, mixed esters with 2-methylbutanoic acid, 3-methylbutanoic acid, pentaerythritol and valeric acid (CAS 146289-36-3)

- =C(CCCCCC(C)C)OCC(COC(=O)CCCCCC(C)C)(COC(=O)CCCCCC(C)C)COC(=O)CCCCCC(C)C

- O=C(OCC(COC(=O)C(C)CC)(COC(=O)C(C)CC)COC(=O)C(C)CC)C(C)CC

- O=C(CC(C)C)OCC(COC(=O)CC(C)C)(COC(=O)CC(C)C)COC(=O)CC(C)C

- O=C(OCC(COC(=O)CCCC)(COC(=O)CCCC)COC(=O)CCCC)CCCC

 

Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7)

- O=C(OCC(COC(=O)CCCC)(COC(=O)CCCC)COC(=O)CCCC)CCCC

- =C(OCC(COC(=O)CCCCCCCCC)(COC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC)CCCCCCCCC

 

Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9)

- O=C(OCC(COC(=O)CCCC)(COC(=O)CCCC)COC(=O)CCCC)CCCC

- O=C(OCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COC(=O)CCCCCC)CCCCCC

- =C(OCC(COC(=O)CCCCCCCCC)(COC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC)CCCCCCCCC

 

3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol (CAS 131459-39-7)

- O=C(CC(C)CC(C)(C)C)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CC(C)CC(C)(C)C

 

2,2-bis[[(1-oxopentyl)oxy]methyl]propane-1,3-diyl divalerate (C5 tetraester with PE) (CAS 15834-04-5)

- O=C(OCC(COC(=O)CCCC)(COC(=O)CCCC)COC(=O)CCCC)CCCC

 

TMP ester of C8/C10 fatty acids (ESIS: Decanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol octanoate) (CAS 11138-60-6)

- O=C(OCC(CC)(COC(=O)CCCCCCC)COC(=O)CCCCCCC)CCCCCCC

- O=C(OCC(CC)(COC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC)CCCCCCCCC

 

Isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2)

- CC(C)(CC)CCCC(=O)OCCCCCCCCCCCCCCCC

- CC(C)(CC)CCCC(=O)OCCCCCCCCCCCCCCCCCC
Interpretation of results:
study cannot be used for classification
Conclusions:
The analogue substances are not predicted to have skin sensitising potential.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Justification for read-across

There are no data available on skin sensitisation of Tetraesters of pentaerythritol with heptanoic acid and 3,5,5-trimethylhexanoic acid. In order to fulfil the standard information requirements set out in Annex VII, 8.3., in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted. In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across) “to avoid the need to test every substance for every endpoint”. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

 

Skin sensitisation

CAS 131459-39-7

The skin sensitising properties of 3,5,5-trimethylhexanoic acid mixed tetraesters with PE and valeric acid (CAS 131459-39-7) were tested in a study performed equivalent or similar to OECD TG 406 under GLP conditions using the Guinea pig maximization test (GPMT, Allen, 1999e). The GPMT test was performed on initially 15 male Dunkin-Hartley guinea pigs 1/5 control group animals was sacrificed on Day 21 due to respiratory problems). For the intradermal and epicutaneous inductions the initial test item concentration was 25% (v/v in arachis oil) and 100%, respectively, whereas a 75% and 100% (v/v in arachis oil) formulation of the test item was selected for the challenge exposure. At the beginning of the induction exposure 10 test animals and 5 control animals were either intradermally treated with 25% of the test substance or vehicle (Day 0), followed by a topical induction (100% or vehicle, type of coverage not reported). 14 days after topical induction all animals were challenged with the test substance at a concentration of 75% and 100%. Skin reactions of all animals were evaluated 24 and 48 hours after challenge exposure (after removal of the patch). No skin reactions were noted at the challenge sites of the test or control animals at the 24 h or 48 h observations time points. Body weight gain of the test group was comparable to those observed in the control group animals. Periodic reliability checks had been performed 2 times a year with 10 test and 5 control animals using 2-mercaptobenzothiazole as positive control substance confirming the sensititvity of the used animal strain. Thus, under the conditions of the test, the test substance revealed no skin sensitising properties.

 

CAS 67762-53-2

The skin sensitising properties of Carboxylic acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) were tested in a study performed equivalent or similar to OECD TG 406 using the Guinea pig maximization test (GPMT, Zolyniene, 1999d). The GPMT test was performed on initially 15 male Albino Guinea pigs (one animal was sacrificed on Day 10 at the end of topical induction exposure, due to dosing trauma (humane reasons)). For the intradermal and epicutaneous inductions the initial test item concentration was 5% (v/v in propylene glycol) and 100%, respectively, whereas a 50% and 100% (v/v in propylene glycol) formulation of the test item was selected for the challenge exposure. At the beginning of the induction exposure 10 test animals and 5 control animals were either intradermally treated with 5% of the test substance or vehicle (Day 0), followed by a topical induction (100% or vehicle) under occlusive conditions one week later. On Day 22 all animals were challenged with the test substance at a concentration of 50% and 100%. Skin reactions of all animals were evaluated 24 and 48 hours after challenge exposure (after removal of the patch). No skin reactions were noted at the challenge sites of the test or control animals at the 24 h or 48 h observations time points. Body weight gain of the test group was comparable to those observed in the control group animals. Periodic reliability checks had been performed in a recent study with 10 test animals using hexylcinnamic aldehyde as positive control substance confirming the sensititvity of the used animal strain. Thus, under the conditions of the test, the test substance revealed no skin sensitising properties.

In addition, QSAR predictions based on the OECD QSAR Toolbox v3.3.5 were performed with main constituents of the target and analogue substances (Szymoszek, A., 2016). The predicted skin sensitisation potential based on protein binding potential was modelled in the OECD QSAR Toolbox v3.3.5 No alerts for protein binding were found according to Protein binding by OASIS v1.3, Protein binding by OECD and Protein binding alerts for skin sensitisation v1.3. Based on these results, especially considering the results of the skin sensitising relevant profiler, OASIS v1.3 (endpoint specific), the target and analogue substances are not expected to exhibit skin sensitising properties.

 

Overall conclusion on skin sensitisation

The available experimental data did not indicate a sensitising potential of the structural analogue substances. The QSAR predictions performed with the target and analogue substances revealed no alerts for protein binding indicative of skin sensitising properties in the OASIS v1.3 database. Thus, Tetraesters of pentaerythritol with heptanoic acid and 3,5,5-trimethylhexanoic acid is not considered to be a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

Based on the analogue read-across approach, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.