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Description of key information

Skin sensitisation

Based on available read across data (Magnusson and Kligman Guinea-Pig Maximization tests (OECD TG 406)), Hydrocarbons, C16-C18, Isoalkanes, <2% Aromatics is not considered to be a skin sensitizer.

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:
read-across from supporting substance (structural analogue or surrogate)
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:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
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 chemical
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 chemical
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 vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There is no skin sensitisation data available for Hydrocarbons, C16-C18, Isoalkanes, <2% Aromatics. However, data is available for structural analogue hydrocarbons, C11-C14, n-alkanes, <2% aromatics. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

In a key read across study (ExxonMobil, 1983), a Magnusson and Kligman Guinea-Pig Maximization test was conducted on 30 guinea pigs with the test material (Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics). Following a preliminary irritation test, 15 guinea pigs were treated by intradermal injection (5.0% (v/v) vehicle or adjuvant/ test material) to induce sensitization and then further sensitized by dermal application of 100.0% (v/v) test material. Guinea Pigs were challenged by topical application (0.5% (v/v) test material 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% test material, four out of 15 animals in both the treated and control groups displayed minimal irritation. Based on the scores of dermal irritation, test material would not be considered a dermal sensitizer under the Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There are no reports of respiratory sensitization for Hydrocarbons, C16-C18, Isoalkanes, <2% Aromatics in laboratory animals or humans. However, skin sensitization studies utilizing a structural analogue found no indication of skin sensitization in guinea pigs. With these observations, it is presumed that Hydrocarbons, C16-C18, Isoalkanes, <2% Aromatics will not be a respiratory sensitizer.

Justification for classification or non-classification

Based on available read across data, Hydrocarbons, C16-C18, Isoalkanes, <2% aromatics does not meet the criteria for classification as a skin or respiratory sensitizer under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).