Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Magnusson and Kligman guinea pig maximization test
Principles of method if other than guideline:
Sensitization was induced in guinea pigs by intradermal injections of both test substance and Complete Freunds Adjuvant and the inductions process supplemented 7 days later by test substance applied to the shoulder injection sites under occlusion. 14 days later the animals were challenged by occluded path: further challenges were made at weekly intervals as required.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
pre-existing in vivo study report available.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
purity stated at 100%

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
male

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
other: see below
Concentration / amount:
Injection induction, 2.5% in 0.01% Dobs/Saline; Application induction, 100% (neat); Application challenge, 50% in isopropanol
Day(s)/duration:
14 days
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol (absolute)
Concentration / amount:
50%
Day(s)/duration:
24 hours
Adequacy of challenge:
not specified
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol (absolute)
Concentration / amount:
50%
Day(s)/duration:
24 hours
Adequacy of challenge:
not specified
No.:
#3
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol (absolute)
Concentration / amount:
50%
Day(s)/duration:
24 hours
Adequacy of challenge:
not specified
No. of animals per dose:
10
Details on study design:
For each of 10 guinea pigs weighing about 320 g, six 0.1 mL intradermal injections are made close together within a 2 x 4 cm area of the shoulder region as follows:
2 injections of test substance in solvent at the chosen intradermal injection concentration
2 injections of test substance at the chosen intradermal injection concentration in 50% Complete Fruends Adjuvant (CFA) in saline
2 injections of 50% CFA in saline

7 days later senziation is boosted by placing over the shoulder injections site a 2 x 4 cm filter paper patch saturated with test substance at the selected concentration. The patch is occluded with Blenderm and held in place by Poroplast, and is left in place for 48 hours.

14 days after application of the shoulder patch, the guinea pigs are challenged on the flank by occluded patch. For each animal an 8 mm diameter filter paper patch in a patch test cup is saturated with test solution and the cup applied to the shaved flank: it is held in place by Poroplast wound around the turnk. 24 hours later the patch is removed and the reaction stie examined 24 hours and 48 hours after removal of the patch.
Challenge controls:
Treated controls: 4 guiinea pigs of the same sex and weighting about 320 g are treated exactly as for the test animals as described abovle, except that test substance is omitted from the intradermal injection and covered patch induction proccedures. The animals are challenged exactly as for the test animals.

Untreated controls: At each challenge, 4 previously untreated animals of the same sex and weight the same as the test animals are each 'challenged' as for the test animals.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
2 animals with barely perceptible erythema
Remarks on result:
no indication of skin sensitisation
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:
3 animals with barely perceptible erythema
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Acetyl Tributyl Citrate did not induce sensitization in guinea pigs in maximization assay.
Executive summary:

Acetyl Tributyl Citrate did not induce sensitization in guinea pigs in maximization assay.