Registration Dossier

Administrative data

Description of key information

skin irritation/corrosion, rabbit (OECD 404): not irritating

Read-across from structural analogue source substances glycerides, mixed decanoyl and octanoyl (CAS 73398-61-5).

 

eye irritation, rabbit (OECD 405): not irritating

Read-across from structural analogue source substance propane-1,2,3-triyl triheptanoate (CAS 620-67-7).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only abstract available
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
limited data
GLP compliance:
not specified
Species:
rabbit
Strain:
other: New Zealand rabbits
Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
other: not required, untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
24 h
Observation period:
72 h
Number of animals:
3 males
Remarks on result:
other: Light erythema was noted in 2 animals, which were fully reversed with 72 hours after application. No edema could be detected in all animals.
Irritant / corrosive response data:
Light erythema was noted in 2 animals, which were fully reversed with 72 hours after application. No edema could be detected in all animals.
Interpretation of results:
other: inconclusive
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversiblity: not applicable
Remarks on result:
other: Source: CAS 73398-61-5
Irritation parameter:
edema score
Basis:
mean
Remarks:
of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Remarks on result:
other: Source: CAS 73398-61-5
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Executive summary:

The skin irritation / corrosion potential of the target substance is estimated based on an adequate and reliable in vivo study with the structural analogue source substance triglycerides, mixed decanoyl and octanoyl (CAS 73398-61-5). No edema formation was noted in any animal during the study period. The test item did not cause any skin reaction throughout the whole study period. As explained in the analogue justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the skin irritation / corrosion potential. Therefore, the target substance is also considered to exhibit no skin irritating properties.

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:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Remarks on result:
other: Source CAS 620-67-7
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Remarks on result:
other: Source CAS 620-67-7
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
mean out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Remarks on result:
other: Source CAS 620-67-7
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Remarks on result:
other: Source CAS 620-67-7
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Remarks on result:
other: Source: CAS 73398-61-5
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Remarks on result:
other: Source: CAS 73398-61-5
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of all 6 animals
Time point:
24/48/72 h
Score:
0.06
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: Source: CAS 73398-61-5
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all 6 animals
Time point:
24/48/72 h
Score:
0.06
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: Source: CAS 73398-61-5
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Executive summary:

The eye irritation potential of the target substance is estimated based on adequate and reliable in vivo studies of structural analogue source substances propane-1,2,3-triyl trisheptanoate (CAS 620-67-7) and triglycerides, mixed decanoyl and octanoyl (CAS 73398-61-5). Application of the unchanged source substance triglycerides, mixed decanoyl and octanoyl (CAS 73398-61-5) resulted in only slight to moderate effects on the iris and the conjunctivae (redness and chemosis). Iridal effects were fully reversible within 24 h, conjunctivae redness and chemosis were fully reversible within 48 h. Administration of the source substance propane-1,2,3-triyl trisheptanoate (CAS 620-67-7) resulted in marked hyperemia of some blood vessels in all animals. After 24-72 h, no further symptoms of irritation to the eye mucosae, cornea and iris were observed in any animal. Only the skin of the outer eyelids showed slight erythema after 24 h in all animals, which subsided after 48 h. All effects detected were fully reversible within the observation period of the respective studies. As explained in the analogue justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the eye irritation potential. Therefore, no significant eye irritation potential is identified for the target substance.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The potential of skin irritation of propane-1,2,3-triyl- 2-ethylhexanoate was tested in a study performed equivalently to OECD guideline 404 (EVIC-CEBA, 1989b), but only limited data are given. 0.5 mL of substance was applied to intact and abraded skin of three New Zealand rabbits under occlusive conditions for 24 h. While light erythema was noted in 2 animals, which was fully reversible within 72 h after application, no edema could be detected in any animal. Based on these observations, no irritation potential by propane-1,2,3-triyl- 2-ethylhexanoate was identified.

In order to fulfil the standard information requirements set out in Annex VIII, 8.1, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006 read-across from the structurally related analogue substance glycerides, mixed decanoyl and octanoyl (CAS 73398-61-5) is conducted. Glycerides, mixed decanoyl and octanoyl was investigated in a study according to OECD guideline 404 (Safepharm, 1988a). The undiluted test substance (0.5 mL) was applied to the shaved skin of six New Zealand White rabbits under semiocclusive conditions for 4 h. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 24, 48 and 72 h after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation time points. No signs of systemic toxicity were seen. The mean erythema and edema scores after 24, 48 and 72 h were 0 for all six animals. Thus, no irritation to skin was found.

 

Eye irritation

There are no data available on the eye irritation potential of propane-1,2,3-triyl 2-ethylhexanoate. In order to fulfil the standard information requirements set out in Annex VIII, 8.2, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006 read-across from the structurally related analogue substances propane-1,2,3-triyl trisheptanoate (CAS 620-67-7) and glycerides, mixed decanoyl and octanoyl (CAS 73398 -61 -5) is conducted.

In a study conducted according to GLP and OECD guideline 405, the structural analogue propane-1,2,3-triyl trisheptanoate was tested in three male Small White Russian rabbits which received an instillation of 0.1 mL into the right eye, while the left eye served as control (Hüls, 1993b). 24 h after instillation, the substance was removed by washing with water. 1, 24, 48 and 72 h later the eyes were examined and scored. As a result, the mean scores for cornea, iris, conjunctivae and chemosis were all 0 in all animals. Thus, no irritation to eyes was found.

A further eye irritation study was performed with glycerides, mixed decanoyl and octanoyl according to EPA OPP 81-4 and in compliance with GLP (Safepharm, 1988b). The undiluted test substance (0.1 mL) was instilled into the conjunctival sac of one eye of six New Zealand White rabbits. The eyes were examined and scored 1, 24, 48 and 72 h after application. At the 1 h reading, iridial inflammation was observed in 1/6 animals, which was fully reversible within 24 h, while mild to moderate conjunctivae effects were apparent in 6/6 animals. In 1/6 animals, mild conjunctivae redness and chemosis was still apparent after 24 h which was fully reversible at the 48 h reading. In the remaining 5/6 animals, conjunctivae irritation was fully reversible within 24 h. No adverse corneal effects were noted in any animal at any observation time point and no further local or systemic toxic effects were observed. The mean scores for conjunctivae and chemosis were 0.06 for all six animals. The effects on cornea and iris after 24, 48, and 72 h were scored 0 for all six animals. Thus, no irritation to eyes was found.

Conclusion

In conclusion, the available data on the skin and eye irritation potential of propane-1,2,3-triyl 2-ethylhexanoate and structural analogue substances indicate that propane-1,2,3-triyl 2-ethylhexanoate is not irritating to the skin and eye.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within the CSR.

Justification for classification or non-classification

Based on test substance data and read-across from structurally similar substances, the available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.