Registration Dossier

Administrative data

Description of key information

Acute oral toxicity:
equivalent to OECD 401 and in compliance with GLP, RL2 (Duerden, 1994): LD50>2000 mg/kg bw
Acute inhalation toxicity:
according to OECD 403, no data on GLP compliance, RL2 (Parr-Dobrzanski, 1994): LC50>5.1 mg/L air
Acute dermal toxicity:
No data available

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
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:
limited data
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
corn oil
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Not specified
Control animals:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed.
Clinical signs:
No clinical signs of toxicity were observed.
Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
03 June 1996 - 17 Jun 1996
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:
Only basic data on test compound and procedure given
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
mouse
Strain:
Swiss
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Weight at study initiation: 22.6 g (mean)
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
2 mL/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: obervations were performed aily; weighing of body weights on Days 1, 7 and 14- Necropsy of survivors performed: no
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 mL/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 880 mg/kg bw
Based on:
test mat.
Remarks on result:
other: converted from mL/kg bw based on a density of 0.94 g/L (Sparc OnlineCalculator, 2009)
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
No effect on body weight was noted.

Body weight:

Animal #

36

37

38

39

40

Day 1

23.3

21.9

21.1

22.8

24.1

Day 7

27.5

24.1

22.8

22.7

22.1

Day 14

30.4

26.5

24.4

22.1

27.8

Animals had normal body weight gain.

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 1-4) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
22 Mar - 05 Apr 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (only few data on test item and animal husbandry were given)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
(No details on test material and limited data on animal husbandry)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Alpk:APfSD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Alderly Park, Cheshire, UK- Age at study initiation: approx. 7 weeks
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION- Source and rate of air: dried and filtered air- System of generating aerosols: glass concentric jet atomiser- Method of particle size determination: Marple Cascade Impactor- Temperature, humidity, pressure in air chamber: 20 L/minTEST ATMOSPHERE- Brief description of analytical method used: gravimetrically- Samples taken from breathing zone: yesTEST ATMOSPHERE (if not tabulated)- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.51 µm/2.51
Analytical verification of test atmosphere concentrations:
yes
Remarks:
particulate concentrations of the test atmospheres close to the animals breathing zone were measured gravimetrically
Duration of exposure:
4 h
Concentrations:
5.0 mg/L (nominal)5.10 mg/L (analytical)
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days - Frequency of observations and weighing: animals were observed for gross clinical abnormalities during exposure and were checked daily thereafter. A detailed examination was conducted after exposure on day 1 and on consecutive days, up to and including day 15. Individual body weights were recorded on day 1 and days 2, 3, 8 and day 15. - Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.1 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: Some clinical signs were noticed, which consisted of hunched position, chromodacryorrhea, piloerection, staining around nose and wet fur. These signs however occurred during or just after exposure and were clearly consistent with the use of restraint for
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy and histopathological examination revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
CLP: not classifiedDSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2 due to read-across) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group, common breakdown products, and similarities in PC/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 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
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

There are no sufficient data available for the acute toxicity of 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate (CAS 28510-23-8). In order to fulfil the standard information requirements set out in Annex IX, 8.6, 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, 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.

Acute Toxicity

CAS

28510-23-8

68424-31-7

Chemical name

2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate

Fatty acids, C5-10 (linear and branched and without 2-Ethylhexanoic acid), mixed esters with pentaerythritol

MW

356.55 g/mol

612.90 g/mol

Acute toxicity oral

Experimental result: LD50 > 2000 mg/kg bw

Experimental result: LD50 > 2000 mg/kg bw

Acute toxicity inhalation

RA: CAS 68424-31-7

Experimental result: LC50 > 5100 mg/m³

Acute toxicity dermal

-

-

 

The above mentioned substances are considered to be similar on the basis of the structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate (CAS 28510-23-8).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

Acute oral

In an acute oral toxicity study similar to OECD guideline 401 and in compliance with GLP, male and female rats were dosed with 2000 mg/kg bw test substance (Duerden, 1994). No detailed information on number of rats or oral administration was given. No clinical signs of toxicity were observed. As no mortality was observed, the LD50 was considered to be >2000 mg/kg bw.

Supporting data were available in an acute oral toxicity study equivalent to OECD guideline 401 (Bouffechoux, 1991). Five female Swiss mice received an oral dose of 2 mL/kg bw (corresponding to 1880 mg/kg bw based on a density of 0.94 g/L) test substance via gavage (limit test). No effect on body weight and no systemic toxicity were observed. As no mortality occurred during the 14-days observation period, the LD50 was considered to be >1880 mg/kg bw.

In conclusion, as no signs of toxicity were observed in studies in rats and mice and no mortality was observed neither in rats nor in mice,2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate is not acutely toxic after oral application. As no mortality occurred in the rats up to 2000 mg/kg bw the LD50 was set to >2000 mg/kg bw.

Acute Inhalation

There are no data available on the acute toxicity of2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate by inhalation.In order to fulfil the standard information requirements set out in Annex IX, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related analogue substanceFatty acids, C5-10 (linear and branched and without 2-Ethylhexanoic acid), mixed esters with pentaerythritolis conducted.

An acute inhalation study equivalent to OECD 403 is available forFatty acids, C5-10 (linear and branched and without 2-Ethylhexanoic acid), mixed esters with pentaerythritol (Parr-Dobrzanski, 1994). Five rats per sex were exposed (nose-only) to 5.1 mg/L (analytical concentration) of an aerosol of the test substance for 4 h. No mortality occurred within the 14-day observation period. Some clinical signs were noticed, which consisted of hunched position, chromodacryorrhea, piloerection, staining around nose and wet fur. These signs however occurred during or just after exposure and were clearly consistent with the use of restraint for exposure. No effect on body weights was noted. Pathological and histopathological examinations revealed no substance-related findings. The LC50 was considered to be >5.1 mg/L.

Conclusion

In conclusion, the available data on the acute toxicity of2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate and analogue substances indicate that 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate is not acutely toxic after oral and inhalation exposure, resulting in a LD50 > 2000 mg/kg bw and a LC50 >5.1 mg/L, respectively.

 


Justification for selection of acute toxicity – oral endpoint
The selected study is the most adequate and reliable study.

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the
identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data on acute toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.