Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
from 1998-09-21 to 1998-10-16
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tri (hexyl, octyl, decyl) citrate
- Substance type: pure active substance
- Physical state: liquid
- Storage condition of test material: room temperature in a closed container

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: approx. 4 - 5 weeks
- Weight at study initiation: 301 - 311 g
- Housing: animals were kept in groups (max. group size 10 animals) in Terluran - cages on Altromin saw fiber bedding
- Diet (e.g. ad libitum): Altromin 3122 maintenance diet for guinea pigs ad libitum
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: not mentioned


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: 1998-09-21 To: 1998-10-16

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 % in induction exposures and challenge
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 % in induction exposures and challenge
No. of animals per dose:
10 animals in the test group, 5 in control group
Details on study design:
RANGE FINDING TESTS: Four animals were topically treated with the test item. No signs of irritation were recorded after a contact period of 24 h. Therefore the maximum concentration was chosen for the inductions and the challenge.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 1st exposure: intracutaneous injections (0.1 mL); 2nd exposure: epicutaneous for 48 hours
- Site: according to guideline
- Frequency of applications: day 0: intradermal treatment, day 6: pretreatment with sodium lauryl sulphate (0.5 mL, 10% in vaseline) and day 7: dermal treatment
- Duration: 20 days
- Concentrations:
Induction, 1st stage:
Test group: Injection 1: Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline; injection 2: test item 100%; injection 3: test item 50% (v/v) in Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline
Control group: Injection 1: Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline; injection 2: NaCL (0.9%); injection 3: NaCl (0.9%) 50% (v/v)in Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline
Induction, 2nd stage:
Test group: 100% test item
Control group: 100% NaCl (0.9%)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on day 20
- Exposure period: 24 hours
- Test group: test item and NaCl (0.9%) as intraspecific control
- Control group: same as test group
- Site: left flanks for test substance, right flanks for NaCl
- Concentrations: 100%
- Evaluation: 24, 48 and 72 h after patch removal
Challenge controls:
see above
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole (reliability check, not in parallel with the test)

Results and discussion

Positive control results:
60% of the positive control animals showed sensitization reactions 24 and 48 hours after end of challenge treatement (positive cotnrol substance concentrations: 2% at induction I phase, 25% at induction II phase, 15% at challenge)

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No other signs of toxicity observed, animals showed normal food intake and weight gain.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No other signs of toxicity observed, animals showed normal food intake and weight gain..
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No other signs of toxicity observed, animals showed normal food intake and weight gain.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No other signs of toxicity observed, animals showed normal food intake and weight gain..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
None of the 10 animals of the test group showed allergic skin reactions until 72 hours after patch removal as compared to the intraspecific application of NaCl (0.9%) and to the animals of the control group. The sensitization rate after application of Tri (hexy, octy, decyl) citrate was 0%. Under the test contions described the test item showed no sensitizing properties.