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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test was performed before REACH was inforce.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Witamol 218
- Substance type: product
- Physical state: liquid
- Stability under test conditions: not mentioned
- Storage condition of test material: not mentioned
- Other: none

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
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 %
Challengeopen allclose all
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

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
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:

1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters was tested for dermal sensitisation in guinea pigs by the Magnusson and Kligman maximisation test according to OECD guideline 406 (12 May 1981).

The sensitising potential of 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters was determined using a test group of 20 and a control group of 10 animals. All reactions, especially the formation of erythema and oedema, were assessed 48 and 72 hours after the challenge treatment. The maximum concentration which caused no dermal irritation in a prelinminary test was found to be 100% test substance (as supplied).

The following concentrations of test substance were used for the induction treatments: the test substance was employed in a 10% mixture with maize germ oil for the intracutaneous injection, while the 100% test substance (as supplied) was used for the dermal treatment.

The preliminary test showed that the undiluted test substance caused no dermal irritation. In order to induce slight to moderate dermal inflammation, 24 hours before the dermal induction treatment the skin in the injection area was pretreated with sodium dodecyl sulphate (10% in vaseline).

All FCA treated injections sites (diluted 1 +1 with maize germ oil), assessed 1 and 24 hours after intradermal induction treatment, showed severe erythema, edema and necrosis. The control animals had comparable signs of irritation at the injection sites.

The reactions to the dermal induction treatment for 48 hours were described as follows: 1 hour after patch removal, test and control animals showed erythema and edema in the whole application area, as well as inflamed or bloody lesions, the animals were restless and showed scratching in the application area. 24 hours after patch removal some animals showed erythema and eschar formation in the whole application area.

The first challenge treatment was carried out with the undiluted test substance (100%). No signs of dermal irritation were found on the test animals or the control animals 48 and 72 hours after the challenge treatment. No second challenge was carried out.

On the basis of these results, 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters was assessed as having no sensitising effect on the skin of guinea pigs.