Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
from 1989-11-28 to 1989-12-21
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation. For read-across justification see Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study undertaken prior to the introduction of the LLNA (OECD TG 429 originally adopted April 2002)
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Age at study initiation: not mentioned
- Weight at study initiation: 380 g (mean weight of the test animals); 376 g (mean weight of the control animals)
- Housing: 1 - 5 animals in Makrolon cages type IV
- Diet (e.g. ad libitum): G4 complete feed for guinea pigs ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5 - 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route:
intradermal and epicutaneous
Vehicle:
other: maize germ oil
Concentration / amount:
- Concentrations used for induction: intradermal treatment: 10% test substance in maize germ oil; dermal treatment: 100% test substance
- Concentration in Freunds Complete Adjuvant (FCA): 10% test substance in a mixture of FCA and maize germ oil (1:1)
- Concentrations used for challenge: 100 %
Route:
epicutaneous, occlusive
Vehicle:
other: maize germ oil
Concentration / amount:
- Concentrations used for induction: intradermal treatment: 10% test substance in maize germ oil; dermal treatment: 100% test substance
- Concentration in Freunds Complete Adjuvant (FCA): 10% test substance in a mixture of FCA and maize germ oil (1:1)
- Concentrations used for challenge: 100 %
No. of animals per dose:
test group: 20 animals
control group: 10 animals
Details on study design:
RANGE FINDING TESTS:
A test substance concentration of 100% were tested in a preliminary study, no further details were mentioned

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 1st exposure: intracutaneous injections (0.1 cm³); 2nd exposure: epicutaneous for 48 hours; evaluation after 1 and 24 hours each
- Concentration in Freunds Complete Adjuvants (FCA): 10% test substance in a mixture of FCA and maize germ oil (1:1)
- Test group: dermal: undiluted test substance (2 x 4 cm patch)
- Control group: maize germ oil (2 x 4 cm patch)
- Frequency of applications: day 0: intradermal treatment, day 6: pretreatment with sodium dodecyl sulphate (10% in vaseline) and day 7: dermal treatment
- Duration: 3 weeks
- Concentrations: 100% test substance

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on day 21
- Exposure period: dermal application for 24 hours
- Test groups: undiluted test substance (2 x 2 cm patch)
- Control group: undiluted test substance (2 x 2 cm patch)
- Site: left flanks
- Concentrations: 100% v/v
- Evaluation (hr after challenge): 48 and 72 hours after application
Challenge controls:
see above B. Challenge exposure
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
None
Remarks on result:
not measured/tested
Reading:
2nd reading
Hours after challenge:
72
Group:
positive control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
None
Remarks on result:
not measured/tested

RESULTS OF PILOT STUDY: no irritation at concentrations of 100% test substance

RESULTS OF TEST

- Sensitization reaction: 0/20

- Clinical signs: Local reactions after intradermal application (test and control animals after 1 and 24 hours): All FCA treated injections sites showed severe erythema, edema and necrosis. The animals treated with 10% test substance in maize germ oil showed well defined erythema and edema.

Local reactions after patch test (48 hours): 1 hour after patch removal, test and control animals: whole application area showed erythema and edema, as well as inflamed or bloody lesions, restlessness of the animals and scratching in the application area.

24 hours after patch removal: Some animals showed erythema and eschar formation in the whole application area.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters showed no sensitising effect on guinea pig skin under the described test conditions.
Executive summary:

A structural analogue of the substance (1,2,4 -Benzenetricarboxylic acid, mixed decyl and octyl triesters) has been tested for dermal sensitisation in guinea pigs by the Magnusson and Kligman maximisation test according to OECD guideline 406. No response was observed at challenge and, on the basis of these results, the substance was regarded as having no sensitising effect on the skin of guinea pigs.

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

Dermal sensitisation of a structurally related substance, an ester of 1,2,4 -benzenetricarboxylic acid mixed octyl and decyl ester has been examined in a maximisation test in guinea pigs. No evidence of skin sensitisation was observed in any of the treated animals.

(Q)SAR modelling using the OASIS database indicates that the substance itself is not predicted to exhibit skin sensitisation based on the lack of functional groups in the structure capable of protein binding.


Migrated from Short description of key information:
Skin sensitisation - Not sensitising

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification with regard to skin sensitisation is not justified based on the observed lack of response in the relevant study(ies) and taking into account the provisions laid down in Council Directive 67/548/EEC and CLP (1272/2008/EC).