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Description of key information

Skin sensitisation

C10-12 isoalkanes (<2% aromatics), C11-C14 n-alkanes (<2% aromatics) and C10-C13 (<2% aromatics) were not dermal sensitizers using a Magnusson and Kligman Guinea-Pig Maximization test (OECD TG 406).

Respiratory sensitisation

No data

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:
1983/05/10-1983/06/06
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: According or similar to OECD Guideline 406. GLP
Justification for type of information:
The justification for read across is provided as an attachment in IUCLID Section 13.
Reason / purpose:
read-across: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
occlusive wrap used
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Acceptable guinea pig maximisation test that followed sound scientific principles.
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
Source: Dutchland Laboratory Animals
Sex: Female (30)
Age at study initiation: 1-2 months
Weight at study initiation: 345- 461g
Housing: Individually
Diet (e.g. ad libitum): Purina Guinea Pig Chow (pellets), ad libitum
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 22d

ENVIRONMENTAL CONDITIONS
Temperature (°F): 65-71
Humidity (%): 40-70%
Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
Intradermal Injection (sensitization; first phase): 5.0% (v/v) in vehicle and 5.0% (v/v) in Freund's Complete Adjuvant (FCA) (diluted with an equal volume of water)
Dermal Application: 50.0% (occlusive dressing)
Topical challenge: 0.5 mL of 0.5% (v/v) in vehicle (max dose w/o producing visible irritation)
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
Intradermal Injection (sensitization; first phase): 5.0% (v/v) in vehicle and 5.0% (v/v) in Freund's Complete Adjuvant (FCA) (diluted with an equal volume of water)
Dermal Application: 50.0% (occlusive dressing)
Topical challenge: 0.5 mL of 0.5% (v/v) in vehicle (max dose w/o producing visible irritation)
No. of animals per dose:
Control: Female (15)
Treatment: Female (15)
Details on study design:
Followed Magnusson and Kligman Guinea-Pig Maximization test (1969).
Briefly,
Day 0 – Induction of Sensitization by Intradermal Injection with and without adjuvant
A pair of 0.1 mL injections of the following solutions was intradermally administered to each of 3 sites in the clipped backs of the test animals. Site 1 –diluted FCA to both treated and control group; Site 2 – 5.0% MRD-83-205 in vehicle (treatment group) and undiluted vehicle (control group); Site 3 – 5.0% MRD-83-205 in diluted FCA (treatment group) and undiluted FCA (control group).

Day 7 – Induction by Occlusive Topical Application
0.5 mL of 50% MRD-83-205 (or vehicle for control animals) was topically applied over the injection sites on the shoulder of the treated group animal under an occlusive dressing for 48 hours.

Day 21 – Challenge by Occlusive Topical Application
0.5 mL of 0.5% MRD-83-205 in vehicle was topically applied to the animals under an occlusive dressing for 24 hours.

Animals were monitored for viability twice a day. Dermal reactions were scored according to the Draize methodology.

Challenge controls:
Vehicle controls were used for each of the induction treatments and for the challenge treatment.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
4 animals displayed an erythema score of 1
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 4 animals displayed an erythema score of 1.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
5
Total no. in group:
15
Clinical observations:
5 animals displayed an erythema score of 1
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 5.0. Total no. in groups: 15.0. Clinical observations: 5 animals displayed an erythema score of 1.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5% (v/v)
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
3 animals displayed an erythema score of 1; one animal displayed an erythema score of 2
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5% (v/v). No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 3 animals displayed an erythema score of 1; one animal displayed an erythema score of 2.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5% (v/v)
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
4 animals displayed an erythema score of 1
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5% (v/v). No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 4 animals displayed an erythema score of 1.
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
other: Not sensitising
Conclusions:
Based on the scores of dermal irritation, test substance MRD-83-205 would not be considered a dermal sensitizer under the EU GHS guidelines or under the EU requirements for dangerous substances and preparations guidelines.
Executive summary:

A Magnusson and Kligman Guinea-Pig Maximization test was conducted on 30 guinea pigs with MRD-83-205 . Following a preliminary irritation test, 15 guinea pigs were treated by intradermal injection (5.0% (v/v) vehicle or adjuvant/ MRD-83-205 ) to induce sensitization and then further sensitized by dermal application of 50.0% (v/v) MRD-83-205 . Guinea Pigs were challenged by topical application (0.5% (v/v) MRD-83-205 in corn oil). All animals survived to termination of study displaying an increase in weight over the initial values.  There was a very low incidence of clinical in-life observations noted throughout the test period.  Following topical challenge with 0.5% MRD-83-205, four out of 15 animals in both the treated and control groups displayed minimal irritation.  Based on the scores of dermal irritation, test substance MRD-83-205 would not be considered a dermal sensitizer under the EU GHS guidelines or under the EU requirements for dangerous substances and preparations guidelines.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983/05/10-1983/05/03
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: According or similar to OECD Guideline 406. GLP
Justification for type of information:
The justification for read across is provided as an attachment in IUCLID Section 13.
Reason / purpose:
read-across: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
occlusive wrap used
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Acceptable guinea pig maximisation test that followed sound scientific principles.
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
Source: Dutchland Laboratory Animals
Sex: Female (30)
Age at study initiation: 1-2 months
Weight at study initiation: 360- 425g
Housing: Individually
Diet (e.g. ad libitum): Purina Guinea Pig Chow (pellets), ad libitum
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 22d

ENVIRONMENTAL CONDITIONS
Temperature (°F): 65-71
Humidity (%): 40-70%
Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
Intradermal Injection (sensitization; first phase): 5.0% (v/v) in vehicle and 5.0% (v/v) in Freund's Complete Adjuvant (FCA) (diluted with an equal volume of water)
Dermal Application: 100.0% (occlusive dressing)
Topical challenge: 0.5% (v/v) in vehicle (max dose w/o producing visible irritation)
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
Intradermal Injection (sensitization; first phase): 5.0% (v/v) in vehicle and 5.0% (v/v) in Freund's Complete Adjuvant (FCA) (diluted with an equal volume of water)
Dermal Application: 100.0% (occlusive dressing)
Topical challenge: 0.5% (v/v) in vehicle (max dose w/o producing visible irritation)
No. of animals per dose:
Control: Female (15)
Treatment: Female (15)
Details on study design:
Followed Magnusson and Kligman Guinea-Pig Maximization test (1969).
Briefly,
Day 0 – Induction of Sensitization by Intradermal Injection with and without adjuvant
A pair of 0.1 mL injections of the following solutions was intradermally administered to each of 3 sites in the clipped backs of the test animals. Site 1 –diluted FCA to both treated and control group; Site 2 – 5.0% MRD-83-206 in vehicle (treatment group) and undiluted vehicle (control group); Site 3 – 5.0% MRD-83-206 in diluted FCA (treatment group) and undiluted FCA (control group).

Day 7 – Induction by Occlusive Topical Application
0.5 mL of neat MRD-83-206 (or vehicle for control animals) was topically applied over the injection sites on the shoulder of the treated group animal under an occlusive dressing for 48 hours.

Day 21 – Challenge by Occlusive Topical Application
0.5 mL of 0.5% MRD-83-206 in vehicle was topically applied to the animals under an occlusive dressing for 24 hours.

Animals were monitored for viability twice a day. Dermal reactions were scored according to the Draize methodology.

Challenge controls:
Vehicle controls were used for each of the induction treatments and for the challenge treatment.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
4 animals displayed an erythema score of 1
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 4 animals displayed an erythema score of 1.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
4 animals displayed an erythema score of 1
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 4 animals displayed an erythema score of 1.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5% (v/v)
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
3 animals displayed an erythema score of 1; one animal displayed an erythema score of 2
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5% (v/v). No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 3 animals displayed an erythema score of 1; one animal displayed an erythema score of 2.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5% (v/v)
No. with + reactions:
3
Total no. in group:
15
Clinical observations:
3 animals displayed an erythema score of 1
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5% (v/v). No with. + reactions: 3.0. Total no. in groups: 15.0. Clinical observations: 3 animals displayed an erythema score of 1.
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
other: Not sensitising
Conclusions:
Based on the scores of dermal irritation, test substance MRD-83-206 would not be considered a dermal sensitizer under the EU GHS guidelines or under the EU requirements for dangerous substances and preparations guidelines.
Executive summary:

A Magnusson and Kligman Guinea-Pig Maximization test was conducted on 30 guinea pigs with MRD-83-206. Following a preliminary irritation test, 15 guinea pigs were treated by intradermal injection (5.0% (v/v) vehicle or adjuvant/ MRD-83-206) to induce sensitization and then further sensitized by dermal application of 100.0% (v/v) MRD-83-206. Guinea Pigs were challenged by topical application (0.5% (v/v) MRD-83-206 in corn oil). All animals survived to termination of study displaying an increase in weight over the initial values.  There was a very low incidence of clinical in-life observations noted throughout the test period.  Following topical challenge with 0.5% MRD-83-206, four out of 15 animals in both the treated and control groups displayed minimal irritation.  Based on the scores of dermal irritation, test substance MRD-83-206 would not be considered a dermal sensitizer under the EU GHS guidelines or under the EU requirements for dangerous substances and preparations guidelines.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: According or similar to OECD Guideline 406. GLP
Justification for type of information:
The justification for read across is provided as an attachment in IUCLID Section 13.
Reason / purpose:
read-across: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
occlusive wrap used
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Acceptable guinea pig maximisation test that followed sound scientific principles.
Species:
guinea pig
Strain:
other: P Strain
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
Source: Shell Toxicology Laboratory, Breeding Unit.
Sex: Female (10) and Male (10); Controls: Males (5); Males (5)
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
Intradermal Injection (sensitization; first phase): 1.0% (w/v) in vehicle
Topical Induction: 50.0% w/v (occlusive dressing)
Challenge dose: 25% w/v
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
Intradermal Injection (sensitization; first phase): 1.0% (w/v) in vehicle
Topical Induction: 50.0% w/v (occlusive dressing)
Challenge dose: 25% w/v
No. of animals per dose:
Control: Male (5); Female (5)
Treatment: Female (10); Male (10)
Details on study design:
Followed Magnusson and Kligman Guinea-Pig Maximization test (1969).
Challenge controls:
Vehicle controls were used for each of the induction treatments and for the challenge treatment.
Positive control substance(s):
no
Reading:
other: immediately after challenge
Hours after challenge:
0
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: immediately after challenge. . Hours after challenge: 0.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
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: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
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: 10.0.
Reading:
other: immediately after challenge
Hours after challenge:
0
Group:
test group
Dose level:
25.0% w/v
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: other: immediately after challenge. . Hours after challenge: 0.0. Group: test group. Dose level: 25.0% w/v . No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25.0% w/v
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25.0% w/v. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25.0% w/v
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25.0% w/v . No with. + reactions: 0.0. Total no. in groups: 20.0.
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
other: Not sensitising
Conclusions:
Classification as a skin sensitizer is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/548/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

A Magnusson and Kligman Guinea-Pig Maximization test was conducted on 20 guinea pigs with Shellsol TD. Twenty guinea pigs were treated by intradermal injection (1.0% (w/v) Shellsol TD in vehicle) to induce sensitization and then further sensitized by dermal application of 50.0% (w/v) Shellsol TD. Guinea Pigs were challenged by topical application (25.0% (w/v) Shellsol TD in corn oil). All animals survived to termination of study.  There was a very low incidence of clinical in-life observations noted throughout the test period.  Following topical challenge with 25.0% (w/v) Shellsol TD, all animals were free of dermal irritation.  Classification as a skin sensitizer is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/548/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In Magnusson and Kligman Guinea-Pig Maximization test (OECD TG 406), C10-12 isoalkanes (<2% aromatics), C11-C14 n-alkanes (<2% aromatics) and C10-C13 (<2% aromatics) were not dermal sensitizers using a Magnusson and Kligman Guinea-Pig Maximization test (OECD TG 406). Moreover, in studies on human volunteers using C14-C20 aliphatics (<2% aromatics), there were no signs of irritation or sensitization effects of the test substances (IUCLID section 7.10.4).

Respiratory sensitisation

Endpoint conclusion
Additional information:

There are no reports of respiratory sensitization from C14-20 aliphatics (<2 % aromatics) in laboratory animals or humans. However, skin sensitization studies utilizing C9-14 aliphatics (<2 % aromatics) found no indication of skin sensitization in guinea pigs. Additional studies on C14-C20 aliphatics (<2% aromatics) in humans also found no indication of skin sensitization. With these observations, it is presumed that C14-20 aliphatics (<2% aromatics) will not be a respiratory sensitizing agents.

Justification for classification or non-classification

These findings do not warrant the classification of C14-20 aliphatics (<2 % aromatics) hydrocarbon solvents as a skin or respiratory sensitizer under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.