Registration Dossier

Administrative data

Description of key information

Not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
performed 2016
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2016-01-12 to 2016-03-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP compliant study report. The Maximization test was selected since the test item is a surfactant and the Local Lymph Node Assay as preferred alternative has shown to provide false positive results for surfactants.
Justification for type of information:
The analogue approach is used for the hazard assessment of toxicological, eco-toxicological and environmental fate endpoints for the registration Pentamid™ KH (EC 934-047-1). The hypothesis is that data can be read-across between Pentamid™ KH and its structural analogues, based on structural similarity and common breakdown/metabolic products (Scenario 1 of the Read-Across Assessment Framework (RAAF, ECHA, 2015)).

For mammalian toxicity the “parent” substances show no significant systemic or dermal toxicity in mammals and vertebrates. One of the metabolic products of Pentamid™ KH, the well-studied terephthalic acid, has no significant systemic toxicity. The amine metabolite, however, shows diffuse mammalian systemic toxicity at moderate concentrations. This metabolite is employed in the risk assessment, in agreement with the European Union draft Risk Assessment Report of 2008.

The sole classification for Pentamid™ KH is the precautionary aquatic chronic 4 category, based on low water solubility and a log Kow higher than 4.

Read-across data, all evaluated as reliable according to Klimisch scores of 1 or 2, to estimate the toxicity of the registered substance is used for fulfilling the data requirements of the REACH registration and classifying potential hazards. This read-across approach is adequate for the purposes of risk assessment and classification and labeling.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
no data
Specific details on test material used for the study:
Clariant Hostagel HT 300 (N-octadecyterephthalamate and 37437-26-6
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
PRELIMINARY irritation study:
intradermal injections:
2%, 5%, 10%, 20%, the highest concentration being the maximum concentration that could technical be injected.
Epidermal application
2%, 5%, 10%, 20%, the highest concentration being the maximum concentration that could technical be applied. Based on the results in the initially treated animals, two additional animals were epidermally treated in a similar manner with 50% at a later stage.
MAIN-Study:
Induction:
- intradermal: test item at 5% concentration
- epidermal: 50% test item concentration
Challenge:
- epidermal: 50% test item concentration
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
PRELIMINARY irritation study:
intradermal injections:
2%, 5%, 10%, 20%, the highest concentration being the maximum concentration that could technical be injected.
Epidermal application
2%, 5%, 10%, 20%, the highest concentration being the maximum concentration that could technical be applied. Based on the results in the initially treated animals, two additional animals were epidermally treated in a similar manner with 50% at a later stage.
MAIN-Study:
Induction:
- intradermal: test item at 5% concentration
- epidermal: 50% test item concentration
Challenge:
- epidermal: 50% test item concentration
No. of animals per dose:
10
Positive control substance(s):
yes
Remarks:
ALPHA-HEXYLCINNAMICALDEHYDE
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other:
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none observed.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none observed
Remarks on result:
other:
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 % . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none observed.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
test item at 50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other:
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: test item at 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
test item at 50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: test item at 50%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
20%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 20%. No with. + reactions: 7.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
20%
No. with + reactions:
6
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 20 %. No with. + reactions: 6.0. Total no. in groups: 10.0.
Interpretation of results:
other: Not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
There was no evidence that source analogue substance caused skin hypersensitivity in the guinea pig, since no responses were observed in the experimental animals in response to a 50% test item concentration in the challenge phase. This result indicates a sensitization rate of 0 per cent. The target substance is not classified for skin sensatisation according to Regulation EC No. 1272/2008.
Executive summary:

In order to assess the potential of the source test item to induce skin sensitization a Magnusson &

Kligman maximization study in guinea pigs according to OECD 406 guideline was performed.

Test item concentrations selected for the main study were based on the results of a preliminary

study. In the main study, ten experimental animals were intradermally injected with a 5%

concentration and epidermally exposed to a 50% concentration. Five control animals were

similarly treated, but with vehicle alone (corn oil). Approximately 24 hours before the epidermal

induction exposure all animals were treated with 10% SDS. Two weeks after the epidermal

application all animals were epidermally challenged with a 50% test item concentration and the

vehicle. No skin reactions were evident after the challenge exposure in the experimental and

control animals.

There was no evidence that the source substance caused skin hypersensitivity in the guinea

pig, since no responses were observed in the experimental animals in response to a 50% test

item concentration in the challenge phase. This result indicates a sensitisation rate of 0 per cent; the target substance is not classified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

A close structural analogue to the registered substance was tested in an OECD 406 study and found to be non-sensitsing. The criteria for classification for acute sensitisation according to Regulation EC No. 1272/2008 are not met.