Registration Dossier

Administrative data

Description of key information

Based on available read across data (Magnusson and Kligman Guinea-Pig Maximization tests (OECD TG 406)), Undecane 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:
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:
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:
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 chemical
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 chemical
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 chemical
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:

There is no skin sensitsation data available for Undecane. However, data is available for structural analogues, Hydrocarbons, C10-C12, isoalkanes, <2% aromatics. Additionally, human data from structural analgoue 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, C10-C12, isoalkanes, <2% aromatics

A key Magnusson and Kligman Guinea-Pig Maximization test (Shell, 1977) was conducted on 20 guinea pigs with Hydrocarbons, C10-C12, isoalkanes, <2% aromatics. Twenty guinea pigs were treated by intradermal injection (1.0% (w/v) test material in vehicle) to induce sensitization and then further sensitized by dermal application of 50.0% (w/v) test material. Guinea Pigs were challenged by topical application (25.0% (w/v) test material 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) test material, all animals were free of dermal irritation. 

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 Undecane 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 Undecane will not be a respiratory sensitizing agent.

Justification for classification or non-classification

Based on available read across data, Undecane does 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).