Registration Dossier

Administrative data

Description of key information

Oral (OECD 401), rat LD50 > 5 mL/kg bw, corresponding to 4820 mg/kg bw

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

 

Inhalation (OECD 403), rat LC50 > 1.86 mg/L air

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

 

Dermal (OECD 402), rat LD50 > 2000 mg/kg bw

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

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
no details given
Qualifier:
equivalent or similar to
Guideline:
other: French Pharmacopoeia IXth edition
Deviations:
not specified
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
mouse
Strain:
other: NMRI EOPS
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 20 g
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Doses:
5 mL/kg bw
No. of animals per sex per dose:
5 animals (male or female)
Control animals:
no
Details on study design:
- Other examinations performed: clinical signs, behavioral examinations
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 mL/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 840 mg/kg bw
Based on:
test mat.
Remarks on result:
other: calculated based on density of 0.968
Mortality:
No animals died.
Clinical signs:
No abnormal signs noted.
Other findings:
- Other observations: No abnormal behavioral effects noted
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Endpoint:
acute toxicity: oral
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
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 mL/kg bw
Based on:
test mat.
Remarks on result:
other: Source: CAS 620-67-7
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 820 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Source: CAS 620-67-7
Remarks:
converted from mL/kg bw based on a density of 0.964 g/mL (Spilker, 2011)
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Executive summary:

The acute oral toxicity of the target substance is estimated based on an adequate and reliable in vivo study of the structural analogue source substance propane-1,2,3-triyl trisheptanoate (CAS 620-67-7). The LD50 value determined is > 5 mL/kg bw corresponding to > 4820 mg/kg bw. 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 acute toxicity. Therefore, a LD50 value of > 4820 mg/kg bw for the target substance is considered for the hazard assessment and C&L purposes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group, breakdown products, and similar physico-chemical and toxicological properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
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
Sex:
male
Dose descriptor:
LC50
Effect level:
> 1.97 other: µL/L air (analytical)
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: Source CAS 73398-61-5
Remarks:
max. attainable concentration
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 1.86 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: Source CAS 73398-61-5
Remarks:
converted from µL/L by using a mean specific gravity value of 0.947
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Executive summary:

The acute inhalative toxicity of the target substance is estimated based on an adequate and reliable in vivo study of the structural analogue source substance triglycerides, mixed decanoyl and octanoyl (CAS 73398-61-5). The LC50 value determined after 6 h of exposure (nose only) is > 1.86 mg/L air. 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 acute toxicity. Therefore, a LC50 value of > 1.86 mg/L air for the target substance is considered for the hazard assessment and C&L purposes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group, breakdown products, and similar physico-chemical and toxicological properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Source: CAS 620-67-7
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Executive summary:

The acute dermal toxicity of the target substance is estimated based on an adequate and reliable in vivo study of the structural analogue source substance propane-1,2,3-triyl trisheptanoate (CAS 620-67-7). In a limit test a LD50 value of > 2000 mg/kg bw has been determined. 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 acute toxicity. Therefore, a LD50 value of > 2000 mg/kg bw for the target substance is considered for the hazard assessment and C&L purposes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group, breakdown products, and similar physico-chemical and toxicological properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

Additional information

Acute oral toxicity

Propane-1,2,3-triyl 2-ethylhexanoate was analyzed for acute oral toxicity in a study similar to OECD guideline 401. Five mice (sex not indicated) received a single oral dose of 4840 mg/kg bw (corresponding to 5 mL/kg bw). No clinical signs of toxicity and no mortality were observed. The acute LD50 in mice was > 4840 mg/kg bw. However, only basic data are given in the study report, therefore further information cannot be provided.

In an acute oral toxicity study with propane-1,2,3-triyl trisheptanoate (CAS 620-67-7), equivalent to OECD guideline 401, 5 male and 5 female Wistar rats were treated with 4820 mg/kg bw by oral gavage. The test compound was administered as single application and the animals were observed for a period of 14 days. No clinical signs of toxicity and no mortality were observed (Consultox, 1974). The acute LD50 in rats was > 4820 mg/kg bw.

 

Acute inhalation toxicity

There are no data available on the acute toxicity of propane-1,2,3-triyl 2-ethylhexanoate by inhalation. In order to fulfil the standard information requirements set out in Annex VIII, 8.5.2, 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.

In an acute inhalation toxicity study with glycerides, mixed decanoyl and octanoyl a LC50 of > 1.86 mgL/L air was determined, corresponding to 1.97 µL/L air (INBIFO, 1976). In this study, 10 male Sprague-Dawley rats were exposed (nose-only) to a nominal aerosol concentration of 28.1 µL/L for 6 h; the measured respirable test substance concentration was of 1.97 µL/ L air (particle size < 5-10 µm in diameter), which was the highest attainable concentration. No mortality and no clinical signs were observed during the whole study period. There were no abnormal findings at (histo-) pathological examination.

 

Acute dermal toxicity

There are no data available on the acute toxicity of propane-1,2,3-triyl 2-ethylhexanoate by the dermal route. In order to fulfil the standard information requirements set out in Annex VIII, 8.5.3, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006 read-across from the structurally related analogue substance propane-1,2,3-triyl-trisheptanoate (CAS 620 -67 -7) is conducted.

An LD50 > 2000 mg/kg was determined in a study with propane-1,2,3-triyl-trisheptanoate performed according to OECD guideline 402 (Hüls, 1993a). Five rats per sex were treated with the test substance for 24 h under semiocclusive conditions and were observed for 14 days after exposure. No mortality occurred and no clinical signs, no influence on body weights and no necropsy findings were observed.

 

Conclusion

The available data on the acute toxicity of propane-1,2,3-triyl 2-ethylhexanoate indicate a low oral toxicity with a LD50 of > 4840 mg/kg bw. This was supported by data from structural analogue substances for which low oral, dermal and inhalation toxicity was observed. LD50 values of > 4820 mg/kg bw (oral) and > 2000 mg/kg bw (dermal), and a LC50 > 1.86 mg/L air were observed. In conclusion, the available data on acute toxicity of propane-1,2,3-triyl 2-ethylhexanoate and structural analogue substances indicate that propane-1,2,3-triyl 2-ethylhexanoate is not acutely toxic.

 

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 oral, inhalation and dermal toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008 (CLP), and are therefore conclusive but not sufficient for classification.