Registration Dossier

Administrative data

Description of key information

Based on available data (Magnusson and Kligman Guinea-Pig Maximization tests (OECD TG 406)), Hydrocarbons, C11-C14, n-alkanes, <2% aromatics is not considered to be a skin sensitizer.

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:
1983/05/10-1983/05/03
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: According or similar to OECD Guideline 406. GLP
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
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 % (v/v)
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
4 animals displayed an erythema score of 1
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 % (v/v)
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
4 animals displayed an erythema score of 1
Key result
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
Key result
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
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:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation data is available for Hydrocarbons, C11-C14, n-alkanes, <2% aromatics. Additionally, human data from structural analogue Hydrocarbons, C14 -C19, isoalkanes, cyclics, <2% aromatics is available. 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.

 

Hydrocarbons, C11-C14, n-alkanes, <2% aromatics

A key Magnusson and Kligman Guinea-Pig Maximization test (Exxon, 1983) 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 substance Hydrocarbons, C11-C14, n-alkanes, <2% aromatics would not be considered a dermal sensitizer under the EU GHS guidelines or under the EU requirements for dangerous substances and preparations guidelines.

  

Human Data

 

Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics

In a supporting study (ExxonMobil, 1988), including three phases, the potential of the test substance (Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics) to cause dermal irritation and sentization in humans with or without UV irradiation was examined. A preliminary Phase I study was conducted to determine the Minimum Erythemogenic Dose (MED) for each member of a group of thirty panelists when the skin is irradiated by UV-B light. The least duration of UV-B exposure which produced erythema of Grade 1 or greater was selected as the MED value for each panelist. One volunteer was dropped out at the end of the phase II of the study.

 

Twenty-nine humans were exposed to the test substance for 24 hours followed by UV-B and UV-A irradiation (during three weeks). Then, exposure to the test substance was repeated for 24 hours. Dermal examinations occured at 24, 48 and 72 h test substance post-exposure. Dermal irritation and damage was scored according to a modified Draize scale. The most severe reaction noted in all experimental paradigms was noted as a "1" for slight erythema. The test substance did not elicit any effects which could be construed as a characteristic of a phototoxic propensity or of a primary irritant. The test substance showed no evidence being a photocontact allergen and no evidence of being either a primary irritant or a contact allergen. Under these test conditions, Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics was not classified as an irritant to skin or a skin sensitiser.

 

The phase II supporting study (ExxonMobil, 1988) was performed in order to determine the Phototoxicity and the Primary irritancy propensities of the test substance (Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics) in human skin. The Phase II study was performed with a panel of 30 volunteers. The test substance was diluted at 50% w/w in petrolatum and 0.3 g of solution were applied to skin of volunteers under semi-occlusive patches for a period of 24 hours. The control site was also covered with a similar semi-occlusive bandage without test substance. After exposure, skin examinations were conducted. After first exposure, participants received 0.3 g of undiluted test substance (or water for negative control site) on the same sites, which was removed after 10 minutes. Then, for the phototoxicity determination, the right arm was exposed to 15 min UV-A followed by 1 MED of UV-B. The left arm was not exposed to UV to determine the primary irritancy. Both arms were examined for dermal irritation at 24, 48 and 72 hours after exposure. Skin reaction was not observed in any subjects. Under the test conditions, Hydrocrabons, C14-C19, isoalkanes, cyclics, <2% aromatics did not elicit any effects which could be construed as characteristic of a phototoxic propensity or a primary irritant.

 

The phase III supporting study (Exxon, 1988), was conducted to determine the potential of the test substance (Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics) to cause dermal irritation and sensitization in humans. 112 humans were exposed to the test substance. Induction applications were made to a site on the back (0.2 mL test substance, neat) using an occlusive patch for a total of four, 24 hour applications over the course of one week. Due to 16 subjects developing an erythema score of 4, it was decided that a 50/50 w/w test substance diluted in petrolatum would be applied to an alternate test site using a semi-occlusive patch for the duration of the experiment. Applications were held in place via a semi-occlusive patch for 24 hours and subjects were examined daily for dermal effects before receiving a fresh application of 50/50 w/w test material for a total of 9 additional applications. A 3-5 day rest period followed the last induction application. A challenge application was applied to a naive site on the back that consisted of a 50% (w/w) of test substance preparation held in place by a semi-occlusive patch for a total of 4 -24 hour applications.

 

There was no indication that the test substance possesses a skin-sensitizing propensity as there were no recordable skin irritations noted in any of the patients. When the test substance, neat is applied under occluded conditions, the severe irritation that occurs would indicate that it would be considered a dermal irritant. However, when a 50% (w/w) solution of the test substance is applied under thus, would not be considered a dermal irritant. Based on the test population of 112 subjects and under the conditions of this study, Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics at 50% equal or lower concentrations did not demonstrate a potential for eliciting dermal irritation or sensitization.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There are no reports of respiratory sensitization from Hydrocarbons, C11-C14, n-alkanes, <2% aromatics in laboratory animals or humans.  However, skin sensitization studies utilizing structural analogues found no indication of skin sensitization in guinea pigs.  With these observations, it is presumed that Hydrocarbons, C11-C14, n-alkanes, <2% aromatics will not be respiratory sensitizing agents.

Justification for classification or non-classification

Based on available read across data, Hydrocarbons, C11-C14, n-alkanes, <2% aromatics do not meet the criteria for classification as skin or respiratory sensitizers under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).