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Description of key information

Oral (OECD 401/423), rat: LD50 >5000 mg/kg bw (RA from CAS 19321-40-5 and CAS 62125-22-8)

Inhalation: Data waiving

Dermal (OECD 402), rat: LD50 >2000 mg/kg bw (RA from CAS 62125-22-8)

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:
key study
Study period:
29 Apr - 13 May 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Wistar strain Crl:(WI) BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: males: 275 g ± 20 g, females: 188 g ± 12 g
- Fasting period before study: overnight before until 3-4 h after dosing
- Housing: 3 animals/sex/cage in polycarbonate cages, containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Helmond, The Netherlands)
- Diet: standard laboratory animal diet, Carfil Quality BVBA, Oud-Turnhout, Belgium, ad libitum
- Water: tap-water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes: approx. 15 (air conditioned room)
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.17 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed twice daily for mortality. Individual body weights were determined weekly (Days 1 (pre-administration), 8 and 15). Animals were observed for clinical signs at periodic intervals on Day 1 and once daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 Cut-off value according to OECD TG 423 can be considered
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed during the study period.
Body weight:
No effect on body weight was noted.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 Sep - 01 Oct 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (no data on purity of test substance).
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Adopted 12 May 1981
Deviations:
yes
Remarks:
(no data on purity of test substance)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Weight at study initiation: males: 283 g ± 4.2 g, females: 178.4 g ± 2.4 g
- Fasting period before study: overnight before until 4 h after dosing
- Housing: individually in Macrolon cages
- Diet: standard laboratory animal diet, RMH-B, Hope Farms, Woerden, The Netherlands, ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 - 80
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5.5 mL/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: frequency of observations not given. Individual body weights were determined weekly (Days 0 (pre-administration), 7 and 14).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No symptoms of systemic toxicity were observed during the study period.
Body weight:
No effect on body weight was noted.
Gross pathology:
No treatment related gross alterations were found at macroscopic examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
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:
Please refer to the Additional Information field in the endpoint study summary
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Croda, 1997
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Croda, 1984a
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 1 and 2) and consistent studies, from two reference substances with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products, similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details). The selected studies are 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

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 Sep - 01 Oct 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study wit acceptable restrictions (no data on test substance purity).
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Adopted 12 May 1981
Deviations:
yes
Remarks:
(no data on test substance purity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Weight at study initiation: males: 301.2 g ± 3.7 g, females: 196.8 g ± 5.4 g
- Housing: individually in Macrolon cages
- Diet: standard laboratory animal diet, RMH-B, Hope Farms, Woerden, The Netherlands, ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 - 80
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped skin of the dorsal area of the trunk
- % coverage: approx. 10 % of the total body surface
- Type of wrap: The test material was held in contact with the skin with surgical gauze fixed on alumina foil with vaseline. This was fixed with successively tape and flexible bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: residual test material was removed with tap water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2.2 mL/kg bw
- Concentration: 100%
- Constant volume or concentration used: yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily cage-side observations were done. Individual body weights were determined weekly (Days 0 (pre-administration), 7 and 14).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No symptoms of systemic toxicity were observed during the study period.
Body weight:
No effect on body weight was noted.
Gross pathology:
No treatment related gross alterations were found at macroscopic examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the Additional Information field in the endpoint study summary
Reason / purpose for cross-reference:
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: Croda, 1984b
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2 ) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products, similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details). The selected study is thus sufficient 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.

Additional information

Justification for read-across

There is no data available for the acute toxicity of Fatty acids, C16-18 (even numbered) and C18-unsatd., branched and linear, tri- and tetraesters with pentaerythritol (CAS 85186-72-7). 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 the 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 comparable pattern as a result of structural similarity, the substances pentaerythritol tetraoleate (CAS 19321-40-5) and 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) are selected as source substances.

 

Acute toxicity: oral

In summary, two reliable acute toxicity studies via the oral route are available for the source substances pentaerythritol tetraoleate (CAS 19321-40-5) and 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8).

 

CAS 19321-40-5

An acute oral toxicity study performed with pentaerythritol tetraoleate according to OECD guideline 423 and in compliance with GLP is available (Croda, 1997). In this study following the acute toxic class method three fasted Wistar rats of each sex were administered a single dose of 2000 mg/kg bw of the test substance in a stepwise procedure via oral gavage. The animals were observed for 14 days after administration. No mortalities were observed and no clinical signs of systemic toxicity were noted in any animal during the entire study period. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. Therefore, the acute oral LD50 value was considered to be greater than 2000 mg/kg bw in male and female rats. Moreover, in accordance with OECD guideline 423, the acute oral LD50 cut-off value of the test substance is considered to be >5000 mg/kg bw.

 

CAS 62125-22-8

Another acute oral toxicity study performed with 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) according to OECD guideline 401 and in compliance with GLP is available (Croda, 1984a). In this study five fasted Wistar rats of each sex were administered a single dose of 5000 mg/kg bw of the test substance via oral gavage. The animals were observed for 14 days after administration. No mortalities occurred and no clinical signs of systemic toxicity were observed during the study period. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The acute oral LD50 value was considered to be greater than 5000 mg/kg bw for male and female rats.

 

Acute toxicity: dermal

CAS 62125-22-8

A key acute dermal toxicity study performed according to OECD guideline 402 and in compliance with GLP with 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125 -22-8) is available (Croda, 1984b). In this limit test five Wistar rats of each sex were exposed to a single dose of 2000 mg/kg bw of the test substance for 24 h via occlusive dressing and observed for 14 days post-application. No clinical signs of systemic toxicity were reported and no mortalities occurred during the observation period. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Since the exposed skin area of all animals showed no local reactions (neither erythema nor edema) and macroscopic post mortem examination revealed no abnormalities, the acute dermal LD50 value was considered to be greater than 2000 mg/kg bw.

 

Conclusion for acute toxicity

The reliable data available for the source substances indicate a very low level of acute toxicity following the oral and dermal route, as LD50 values were greater than the currently applied limit values. No information on acute inhalation toxicity is available for either the target or the source substances. Therefore, as the available data did not identify any hazard for acute toxicity, Fatty acids, C16-18 (even numbered) and C18-unsatd., branched and linear, tri- and tetraesters with pentaerythritol (CAS 85186-72-7) is not considered to be hazardous following acute exposure.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Fatty acids, C16-18 (even numbered) and C18-unsatd., branched and linear, tri- and tetraesters with pentaerythritol (CAS 85186-72-7), data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach, the available data on acute toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.