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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

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Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Justification for type of information:
Weight-of-Evidence approach has been applied to the target substance. As the target substance is hydrolytically unstable, the toxicity of the target substance lies in its hydrolysis products - isostearic acid and 2-propanol. The toxicity properties of both hydrolysis products have been well-investigated.
An adequate study based on human exposure to isostearic acid was available and conclusive. Therefore, according to column 2 of annex VII, an in vitro / in chemico study in unnecessary.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
The target substance is a hydrolytically unstable organotitatnate with hydrolysis half-life estimated to be with 1 hr, and with hydrolysis products being identified to be 2-propanol, isostearic acid and titanium dioxide. Because of the rapid hydrolysis, the influence of the target substance is related to the hydrolysis products.

Isostearic acid is the major hydrolysis product of the target substance. It’s toxicity property is used for read-across based on weight of evidence method.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Assessment of human data. Review of patch test data of humans following exposure
GLP compliance:
no
Remarks:
Non-GLP study that predates current guideline.
Type of study:
patch test
Justification for non-LLNA method:
Existing study conducted before REACH. Study conducted on human and adopted by peer-revieed journal.
Species:
other: human
Sex:
male/female
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
35%
Day(s)/duration:
3 week
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
35%
Day(s)/duration:
3 week
No. of animals per dose:
168
Details on study design:
Test material was applied at 48h intervals, 3 times per week for 3 weeks on the back of the subjects. The test area was occluded for 24 h before removal, and washed with distilled water.
Test sites were read at 48 h.
Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
35 %
No. with + reactions:
0
Total no. in group:
168
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
35%
No. with + reactions:
0
Total no. in group:
168
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Remarks:
expert judgment
Conclusions:
Assessment of extensive human data showed that there is no indication of sensitisation protential.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
The target substance is a hydrolytically unstable organotitatnate with hydrolysis half-life estimated to be with 1 hr, and with hydrolysis products being identified to be 2-propanol, isostearic acid and titanium dioxide. Because of the rapid hydrolysis, the influence of the target substance is related to the hydrolysis products.

Isostearic acid is the major hydrolysis product of the target substance. It’s toxicity property is used for read-across based on weight of evidence method.
Reason / purpose:
read-across source
Qualifier:
no guideline followed
Principles of method if other than guideline:
Assessment of human data. Review of patch test data of humans following exposure
GLP compliance:
no
Remarks:
Non-GLP study that predates current guideline.
Type of study:
patch test
Justification for non-LLNA method:
Existing study conducted before REACH. Study conducted on human and adopted by peer-revieed journal.
Species:
other: human
Sex:
male/female
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
35%
Day(s)/duration:
3 week
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
35%
Day(s)/duration:
3 week
No. of animals per dose:
168
Details on study design:
Test material was applied at 48h intervals, 3 times per week for 3 weeks on the back of the subjects. The test area was occluded for 24 h before removal, and washed with distilled water.
Test sites were read at 48 h.
Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
35 %
No. with + reactions:
0
Total no. in group:
168
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
35%
No. with + reactions:
0
Total no. in group:
168
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Remarks:
expert judgment
Conclusions:
Assessment of extensive human data showed that there is no indication of sensitisation protential.
Executive summary:

The study was conducted on isostearic acid, the strucural analogue and also the hydrolysis product of the target substance. As the target substance is hydrolytically unstable, its intrinsic property lies in the the hydrolysis products. The result is used as weight of evidence approach in hazard assessment.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

No studies were conducted on the target substance “Reaction product of Titanium tetraisopropanolate and Isooctadecanoic acid”. As the substance is hydrolytically unstable, the toxicity of the target substance lies in its hydrolysis products.

According to extensive human exposure research, isostearic acid is found to be non-sensitising to skin (CIR, 1983). 2-propanol is also non-sensitising.

Based on above findings, the target substance is considered not skin sensitizing.