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Description of key information

Sensitization:
- skin: not sensitizing (modified Buehler test)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 31 May 1979 To 11 Jul 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
occlusive patch held for 24 hours instead of 6 hours; 10 instead of 20 animals
Principles of method if other than guideline:
Modified Buehler-test with 10 inductions
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Currently no LLNA study is available for assessment. The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.
Species:
guinea pig
Strain:
other: albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: between 300 and 400 g
- Housing: housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CFR part 3
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%; 0.5 g
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%; 0.5 g
No. of animals per dose:
5 male and 5 female
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: 20 d
- Test groups: 10 animals
- Control group: no
- Site: the same intact skin test site
- Patch: gauze patch was placed over the treated area and an impervious material was wrapped tightly around the trunks of the animals to hold the patch in place.
- Frequency of applications: every second day
- Duration: 24 h
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: after a 14 day rest period
- Exposure period: 24 h
- Test groups: 10 animals
- Control group: no
- Site: other skin site than used for induction
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48 h

SCORING
Sites were examined for irritation (if any) using the Draize Method of Scoring.
Challenge controls:
no
Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Group:
positive control
Remarks on result:
not measured/tested
Group:
negative control
Remarks on result:
not measured/tested

Individual scoring:

Animal Sex Irritation Readings after application No. Challenge
1 2 3 4 5 6 7 8 9 10 24 h 48 h
1 M Erythema 0 0 0 0 0 0 0 0 0 0 0 0
Edema 0 0 0 0 0 0 0 0 0 0 0 0
2 M Erythema 0 0 0 0 1 1 1 1 1 1 0 0
Edema 0 0 0 0 0 0 0 0 0 0 0 0
3 M Erythema 0 0 0 0 1 1 1 1 1 1 0 0
Edema 0 0 0 0 0 0 0 0 0 0 0 0
4 M Erythema 0 0 0 0 0 0 0 0 0 0 0 0
Edema 0 0 0 0 0 0 0 0 0 0 0 0
5 M Erythema 0 0 0 0 1 1 1 1 1 1 0 0
Edema 0 0 0 0 0 0 0 0 0 0 0 0
6 F Erythema 0 0 0 0 0 0 0 0 0 0 0 0
Edema 0 0 0 0 0 0 0 0 0 0 0 0
7 F Erythema 0 0 0 0 0 0 0 0 0 0 0 0
Edema 0 0 0 0 0 0 0 0 0 0 0 0
8 F Erythema 0 0 0 0 0 1 1 0 1 1 0 0
Edema 0 0 0 0 0 0 0 0 0 0 0 0
9 F Erythema 0 0 0 0 0 0 0 0 0 0 0 0
Edema 0 0 0 0 0 0 0 0 0 0 0 0
10 F Erythema 0 0 0 0 0 0 0 0 0 0 0 0
Edema 0 0 0 0 0 0 0 0 0 0 0 0

The test substance was not a primary irritant. It is not a skin sensitizer.

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Buehler test

An in vivo study where sensitization to skin was evaluated on five male and five female albino guinea pigs that were treated with 0.5 g of di-(2 -propylheptyl) phthalate of 91.3% purity [8.7% 2-propylheptyl/4-methyl-2-propylhexyl/di-(4 -methyl-2 -propylexyl) phthalate] on the shaved skin of their backs covered by gauze patches was conducted (Biosearch Inc. 1982). Following 24 hours contact, the patches were removed and patches with fresh sample were then applied. This procedure was then repeated 10 times. After a following rest period of two weeks, a challenge dose was applied to skin sites different from the original test sites for 24 hours. Resulting irritation effects were evaluated 24 hours after each initial exposure, and 24 and 48 hours after the challenge application using the Draize method. Since no animals showed erythema or edema after 24 and 48 hours, di-(2-propylheptyl) phthalate was found to be not sensitizing to skin.

QSAR

This result is supported by an in silico study. The structure of Di-(2-propylheptyl)phthalate did not give any indication for sensitizing properties (for both the parent and metabolites) by using a quantitative structure-activity relationship (QSAR): the validated OASIS-LMC.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

QSAR indicated no skin sensitizing potential. Due to the negative result in a modified Buehler test, no classification according to GHS criteria is warranted.