Hydrocarbons, C16-C18, isoalkanes, <2% aromatics

Endpoint summary

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

Reference

Reference 1

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.

Reference 2

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).