Registration Dossier

Administrative data

Description of key information

Skin irritation (OECD 404): not irritating, analogue approach
Eye irritation (OECD 405) not irritating, analogue approach

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (limited reporting)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
limited documentation
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Commercial breeder (not further specified)
- Age at study initiation: approx. 10 -13 weeks
- Weight at study initiation: 4017 - 4802 g
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 30 - 60 min, 24, 48 and 72 h
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: left flank of the dorso-lumbar region
- Type of wrap if used: semiocclusive dressing, not further specified

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the application site was decontaminated using clean warm water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritant / corrosive response data:
Very slight erythema was observed in all animals 30- 60 min (2 animals) or 24 h (1 animal) after patch removal. The effects were reversible within 48 h (1 animal) or 72 h (2 animals) respectively. No edema or other irritation was observed.
Other effects:
No further local or systemic effects were reported.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not irritating
DSD: not irritating
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (limited reporting)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
limited documentation
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: commercial breeder (not further specified)
- Age at study initiation: approx. 10 -13 weeks
- Weight at study initiation: 3185 - 3390 g
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
72 h
Reading time points: 2, 24, 48 and 72 h
Number of animals or in vitro replicates:
3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no
SCORING SYSTEM: Draize scoring system, modified form of the system described by Kay and Calandra (1962) was used for interpretation
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: revesibility not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
out of animal #2 and 3
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritant / corrosive response data:
No corneal or iritial effects were observed. Conjunctival effects included slight redness and slight to moderate discharge. The effects had completely regressed by Day 3. Dried secretions on the upper and lower eyelids were present 1 day after dosing in 1 animal.
Other effects:
No or slight initial pain was observed.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

There are no animal data available for the irritation/corrosion of 3,5,5-trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB). In order to fulfil the standard information requirements set out in Annex VIII, 8.1 and 8.2, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substance 3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 844198-63-3), is selected as source for risk assessment.

Skin Irritation

Skin irritation - Animal Data

Since no animal studies investigating the skin irritation potential of 3,5,5-trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB) are available, in accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read across from the structurally related analogue substance 3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 84418-63-3) as conducted.

3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 84418-63-3) was investigated in a primary skin irritation study according to OECD 404 (McCall, 1991). The shaved left flank of the dorso-lumbar region of 3 New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semi-occlusive conditions. After exposure the skin was cleaned from the residual test substance using warm water. The rabbits were observed for 3 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48, 72 hours after removal of the test substance. Very slight erythema was observed in all animals 30- 60 min (2 animals) or 24 h (1 animal) after patch removal. The effects were reversible within 48 h (1 animal) or 72 h (2 animals) respectively. No edema or other irritation was observed.

 

Skin irritation - Human Data

Supplementary data is also available from a human patch test with 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB, CAS 84418-63-3) conducted with 12 volunteers (Boue-Grabot, 2005). The undiluted substance was applied to the upper back of the volunteers for 24 hours. Readings were done 30 minutes, 1 hour and 24 hours following patch removal. No severe skin reactions were observed and the primary skin irritation index was calculated to be 0.

 

Eye irritation

Two in vitro eye irritation studies were conducted with 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB, CAS 84418-63-3).

In a HETCAM assay 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB, CAS 84418-63-3) was tested for its acute eye irritation potential in vitro (Boue-Grabot, 2005). The chorioallantoic membranes of chicken eggs were exposed to the test substance. The primary irritancy score was reported to be 0. Thus, the test material is not considered corrosive to the eyes in this test but further evaluation regarding irritation potential is necessary.

In another in vitro study with limited reporting 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB, CAS 84418-63-3) was tested for its cytotoxicity in fibroblasts (Boue-Grabot, 2005). The Ocular Irritation Index in fibroblasts (IOeq) based on cytotoxicity was found to be 1.9. Based on expert judgement the substance is considered to have a slight irritating potential under in vivo conditions.

Since no reliable in vivo studies investigating the eye irritation potential of 3,5,5-trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substance 3,5,5 trimethylhexanoic acid, hexaesters with dipentaerythritol (monoconstituent, CAS 84418-63-3) was conducted.

3,5,5 trimethylhexanoic acid, hexaesters with dipentaerythritol (monoconstituent, CAS 84418-63-3) was tested for its eye irritation potential according to OECD Guideline 405 (McCall, 1992). 0.1 mL of the undiluted test substance was instilled into the conjunctival sac of three New Zealand White rabbits. The animals were observed for 72 hours. Eye irritation was scored according to the Draize method 2, 24, 48 and 72 hours after application. No corneal or iritial effects were observed. Conjunctival effects included slight redness and slight to moderate discharge. The effects had completely regressed by Day 3. Dried secretions on the upper and lower eyelids were present 1 day after dosing in 1 animal.

 

Conclusion for skin and eye irritation

In conclusion, in vitro studies and human data on 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB, CAS 84418 -63 -3) as well as one in vivo reliable skin and eye irritation study for the structurally related substance 3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 84418-63-3) are available. In vitro and human data on 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB, CAS 84418-63-3) did not show indication that the substance has irritating potential for the skin or the eyes. Similarly, both in vivo studies did not show indications that 3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 84418-63-3) has irritating potential for the skin or the eyes. Therefore, classification of the target substance 3,5,5 -trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB) for skin or eye irritation is not necessary.


Justification for selection of skin irritation / corrosion endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on skin/eye irritation potential do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.