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

Endpoint summary

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

Reference

Reference 1

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

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:

other: 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

Reference 2

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

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 or test system 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:

other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

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

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 or test system 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.