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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

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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: see 'Remark'
Remarks:
Details about origin of study report/performing laboratory. No info about origin of method, the analyses of symptoms, the batch and purity of "Diätyhlcarbonat". However, details about test animals and test conditions were stated and as no symptoms and stable body weights were found for a relatively high number of animals (10) the report is regarded as reliable.
Principles of method if other than guideline:
single dose of 5 ml/kg bw administered by a stomach probe to 10 male rats; observation of clinicals symptoms over a period of 14 days
GLP compliance:
no
Test type:
other: single dose limit test
Limit test:
yes
Species:
rat
Strain:
other: SPF rats, breeding strain Wistar TNO W 74
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: ca. 9 - 14 weeks
- Weight at study initiation: 169 g
- Fasting period before study: no data
- Housing: kept in conventional Makrolon cages type III and on dust-free wood granulate
- Grouping: animals kept in groups of 5
- Diet ad libitum: Altromin R 1324 (manufacturer: Altromin GmbH, Lage)
- Water ad libitum: tap drinking water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature, 22 +/- 1.5
- Humidity (%): 60 +/- 5
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12 (artificial lighting from 7 am to 7 pm)

IN-LIFE DATES: From: To: no data

Identification of animals: with picric acid marking on fur and codes on cages
Route of administration:
other: oral, with a rigid metal stomach probe
Vehicle:
unchanged (no vehicle)
Doses:
5 ml/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing at the time of administration and at the end of the 14-day observation period (alive animals);
examinations several times/d on 1st day (day of administration), normally 2 times/d and on weekends and holidays 1 time/d.

- Necropsy of survivors performed: yes/no: no data
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
weighing of body weights performed, limited data about other performed examinations:
"recording type, beginning, duration and intensity of clinical symptoms"
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 mL/kg bw
Based on:
test mat.
Remarks on result:
other: valid for all test animals (10)
Sex:
male
Dose descriptor:
LD50
Effect level:
> 4 876 mg/kg bw
Based on:
test mat.
Remarks on result:
other: This value was calculated by the author of this IUCLID dossier by multiplying the density of the test substance (0.9752 g/mL) with the measured LD50 volume (5 mL).
Mortality:
no mortality
Clinical signs:
none
Body weight:
stable

Information extracted from the study report:

Based on the test results the LD50 is > 5 ml/kg bw for male rats. No symptoms developed and the body weights were stable. Therefore, Diäthylcarbonat (engl.: diethyl carbonate) has proven to be relatively non-toxic in this acute toxicity test.

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: other: as concluded in study report
Conclusions:
According to the determined LD50 of > 5.0 mL/kg (4876 mg/kg) of the test substance diethyl carbonate by oral administration to male Wistar rats, the test substance is practically nontoxic.
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: acceptable publication
GLP compliance:
not specified
Test type:
other: acute oral toxicity study
Species:
rat
Strain:
other: Wistar-Stamm II BR 46
Sex:
male/female
Details on test animals and environmental conditions:
Weight of animals: 200-340 g
Route of administration:
other: oral: stomach tube
Vehicle:
olive oil
Doses:
22, 25, 28, 31, 34, 37 mL/kg
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
28 mL/kg bw
Based on:
test mat.
Remarks on result:
other: after 24 hours
Sex:
male/female
Dose descriptor:
LD50
Effect level:
27.7 mL/kg bw
Based on:
test mat.
Remarks on result:
other: after 10 days
Mortality:
the mortiliy of the animals was 100 % at the highest administered dose (37 mL/kg bw).

The predominant sign of toxicity was narcosis.

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The LD50 of the test substance diethyl carbonate administered via a stomach tube as a 60 % solution in olive oil is 27.7 mL/kg bw (observation period 10 days). The corrected value for the LD50 is > 15.0 g/kg bw.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: HSDB data (peer reviewed as stated there); original data source from Lewis (1996) could not be reviewed. No details on background data of LDLo value delivered (materials, methods, results).
Principles of method if other than guideline:
no information provided in data source
Test type:
other: no data
Species:
rat
Sex:
not specified
Dose descriptor:
LDLo
Effect level:
15 other: g/kg
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The high LDLo Rat oral 15 g/kg suggests a low acute oral toxicity of diethyl carbonate.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The dose-response-descriptor LD50 has to be used in stead of the TDLo used in this reference (Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance, R.7.4.1.2 Objective of the guidance on acute toxicity).
Principles of method if other than guideline:
Method: other: no data
GLP compliance:
not specified
Test type:
other: oral toxicity
Species:
mouse
Strain:
not specified
Sex:
not specified
Route of administration:
other: oral
Vehicle:
not specified
Control animals:
not specified
Sex:
not specified
Dose descriptor:
other: TDLo
Effect level:
500 mg/kg bw

Information given in Sax, N.I. Dangerous properties of industrial materials 6th ed., page 1006:

orl-mus TDLo: 500 mg/kg TFX:ETA, BCPCA6 2,168,59

Assumptions of the author of this IUCLID data set:

Mice were administered the test substance diethyl carbonate orally. No information is given on the experimental procedure of this oral toxicity test or the gender of the animals. Other toxic effects which seem to have been observed were equivocal tumorigenic effects (TFX:ETA, other toxic effects:equivocal tumorigenic agents). The determined TDLo (lowest toxic dose) was 500 mg/kg.

There is no information given on how the CODEN is to be used or interpreted.

The reference was listed in the BG Chemie Report (1984) but the mentioned author (MacDougal, J.R.) was not listed on page 1006 of Sax, N.I. Dangerous properties of industrial materials 6th ed.

Conclusions:
The determined value for the oral toxicity of the test substance diethyl carbonate was a TDLo (Lowest toxic dose) of 500 mg/kg in the mouse as testing organism. However, this low value was not used as key data for the endpoint acute toxicity oral, because the dose-response-descriptor has to be the LD50 (Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance, R.7.4.1.2 Objective of the guidance on acute toxicity) and not the here given TDLo. There is no information given on how the CODEN (BCPCA6 2,168,59) is to be used or interpreted confirming the fact not to use the given value as key data.
Endpoint:
acute toxicity: oral
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only a statement in Hawley Condensed Chemical Dictionary (handbook)

Cited from Hawley Condensed Chemical Dictionary (1977):

Moderately toxic by ingestion

Conclusions:
According to the cited reference the test substance diethyl carbonate was moderately toxic by ingestion. No information was given on what this result was based (no testing animal, no testing method).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 876 mg/kg bw
Quality of whole database:
Good quality of the data (study report).

Acute toxicity: via inhalation route

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Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: acceptable study report on the acute inhalative toxicity determined for male and female rats.
Principles of method if other than guideline:
Inhalation studies were carried out according to methods from Farbenfabriken Bayer A.G., Werk Wuppertal-Elberfeld, Germany.
GLP compliance:
no
Test type:
other: acute toxicity inhalative
Species:
rat
Strain:
other: Male and female Wistar-II-rats (weight 160-200 g), male and female Wistar-II-SPF-rats (weight 130-150 g) from the breeder Winkelmann, Kirchborchen, Germany;
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
other: probably whole body
Vehicle:
air
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Gas chromatography; Details on methodology see under 8 Analytical methods in this IUCLID dossier
Duration of exposure:
7 h
Remarks on duration:
on day 1
Concentrations:
4h on day 1: 17.75 mg/L (males), 18.30 mg/L (females);
7 h on day 1: 19.50 mg/L (males, females);
No. of animals per sex per dose:
20
Control animals:
no
Sex:
male/female
Dose descriptor:
other: NOEC
Effect level:
19.5 mg/L air
Based on:
test mat.
Exp. duration:
7 h
Remarks on result:
other: The endpoint NOEC was not mentioned in the study report and was assumed by the author of this IUCLID dossier as at this concentration no symptoms or deaths occurred.
Mortality:
0
Clinical signs:
other: none

No signs of toxicity or irritation were observed in any animal, nor died any rats. No changes in the inner organs of the animals were seen. According to these results the author of this IUCLID dossier assumed that the NOEC for the test substance diethyl carbonate was 19.5 mg/L.

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
According to the results of an acute toxicity inhalation study of the test substance diethyl carbonate in male and female rats, no signs of toxicity or irritation were observed at a concentration of 19.5 mg/L. At this concentration no deaths occurred. Regarding these results, the author of this IUCLID dossier assumed that the NOEC of diethyl carbonate (acute toxicity inhalation) is 19.5 mg/L. It can therefore be concluded that the substance should not be classified in any of the four categories. As the NOEC is assumed to be 19.5 mg/L it can be concluded that the corresponding LC50 should be much greater than 19.5 mg/L which represents the upper limit for classification in category 4 (10 < LC50 ≤ 20 mg/L, Guidance to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures (2009)).
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: acceptable study report on various acute and subacute inhalative toxicity trials in which the LC50 was determined for male and female rats
Principles of method if other than guideline:
no official test method; for detailed information about methodology is referred to various sources (see above under Data source)
GLP compliance:
no
Limit test:
yes
Species:
rat
Sex:
male/female
Details on test animals and environmental conditions:
Test animals:
Breeds/strain: Wistar-II-rats, Wistar-II-SPF-rats
It is unclear which of the two breeds was actually used or if the test animals were possibly from both breeds.

Animal supply:
Animals received from: breeder Winkelmann, Kirchborchen (Germany)
Animal weights: Wistar-II-rats (160-200 g), Wistar-II-SPF-rats (130-150 g)
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
other: presumably whole body
Vehicle:
other: mixture of equal amounts of alcohol and lutrol
Details on inhalation exposure:
The inhalation experiments were carried out with a dynamic inhalation device (NIESSEN, TIETZ, HECHT und KIMMERLE, Arch. Toxikol. 20, 44, 1963) developed by Farbenfabriken Bayer A.G., Werk Wuppertal-Elberfeld, Germany.

Diethyl carbonate was determined in the air being inhaled according to a modified method of H. GARSCHAGEN (Z. analyt. Chem. 241, 32, 1868; Weinberg and Keller 14, 131, 1967). The air being inhaled was conveyed through a vessel cooled down to -30 °C (absorption vessel). Determination by gas chromatography.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Gas Chromatography; Details on methodology see under 8 Analytical methods in this IUCLID dossier
Duration of exposure:
7 h
Remarks on duration:
on 1 day; 2 wk observation period post exposure
Concentrations:
LC50 determination: 1.83 mg/l (male rats); 1.268 mg/l (female rats)
No. of animals per sex per dose:
LC50 determination: 20 female rats; 20 male rats
Control animals:
other: from the information given in the study report the use of control animals is not apparent
Sex:
female
Dose descriptor:
LC50
Effect level:
> 1.268 mg/L air (analytical)
Remarks on result:
other: one of two stated rat breeds used or mixed - unclear from info given in study report
Sex:
male
Dose descriptor:
LC50
Effect level:
> 1.83 mg/L air (analytical)
Remarks on result:
other: one of two stated rat breeds used or mixed - unclear from info given in study report

In LC50 determination with female and male rats:

No animals died. No symptoms of irritation or toxicity were found.

Interpretation of results:
other: no mortalities and no signs of acute toxicity or irritation; low acute inhalation toxicity assumed; final conclusion about classification not possible
Conclusions:
The test was only performed at one concentration for male and female rats respectively. No signs for acute toxicity via the inhalation route were found up to concentrations of 1268 mg/m³ (female rats) and 1830 mg/m³ (male rats). It can therefore be assumed that the toxic potential via inhalation is low, as no animals died and no signs of toxicity were found.
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: acceptable study report on various acute and subacute inhalative toxicity trials
GLP compliance:
no
Limit test:
yes
Details on test animals and environmental conditions:
Test animals:
male NMRI mice
male and female Wistar-II-rats
male and female Wistar-II-SPF-rats
male and female rabbits (not purebred).
No further info how many rats from either strain were actually used in the experiment.

Animals received from: mice and rats from breeder Winkelmann, Kirchborchen (Germany), no data on deliverer of rabbits
Animal weights: NMRI-mice (18-24 g), Wistar-II-rats (160-200 g), Wistar-II-SPF-rats (130-150 g), rabbits (2.3-32 kg)
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
other: presumably whole body
Vehicle:
other: mixture of equal amounts of alcohol and lutrol
Details on inhalation exposure:
The inhalation experiments were carried out with a dynamic inhalation device (NIESSEN, TIETZ, HECHT und KIMMERLE, Arch. Toxikol. 20, 44, 1963) developed by Farbenfabriken Bayer A.G., Werk Wuppertal-Elberfeld, Germany.

Diethyl carbonate was determined in the air being inhaled according to a modified method of H. GARSCHAGEN (Z. analyt. Chem. 241, 32, 1868; Weinberg and Keller 14, 131, 1967). The air being inhaled was conveyed through a vessel cooled down to -30 °C (absorption vessel). Determination by gas chromatography.

In rooms of 2 m3 which were stocked with 2 rabbits, 10 rats and 20 mice respectively, diethyl carbonate was evenly distributed in the air with a fan every half hour within the exposure period of 4 h.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Remarks on duration:
on 1 day; 2 wk observation period post exposure
Concentrations:
test concentration 1: 0.235 mg/l;
test concentration 2: 2.179 mg/l
No. of animals per sex per dose:
2 rabbits, 10 rats and 20 mice (no detailed info about the sex of the test animals)
Control animals:
other: from the given information in the study report the use of control animals is not apparent
Dose descriptor:
other: NOEC
Effect level:
> 0.235 mg/L air (analytical)
Remarks on result:
other: for all tested rabbits, rats, mice
Dose descriptor:
other: NOEC
Effect level:
>= 2.179 mg/L air (analytical)
Remarks on result:
other: for all tested rabbits, rats, mice

No animals died. No symptoms of irritation (mucosas of eyes and noses) or toxicity were found in the tested rabbits, rats and mice.

Interpretation of results:
other: no mortalities and no signs of acute toxicity or irritation on mucosas of eyes or noses of the tested rabbits, rats and mice; low acute inhalation toxicity is assumed; classification not possible based on results
Conclusions:
Rabbits, rats and mice exposed to the test substance diethyl carbonate in an acute inhalative toxicity study as an aerosol (solution of substance in Lutrol and alcohol, 1:1) showed no signs of toxicity or irritation, no animals died. The highest concentration of the test substance provided in this experiment, 2.179 mg/L, can therefore be assumed to be the NOEC (as aerosol, assumed by the author of this IUCLID dossier).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
19 500 mg/m³
Quality of whole database:
Good quality of the data (study report).

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of acute toxicity – oral endpoint
Lowest determined acute oral toxicity level from a highly reliable data source

Justification for selection of acute toxicity – inhalation endpoint
Only available data on acute inhalation toxicity of diethyl carbonate vapour.

Justification for classification or non-classification

According to the determined LD50 of > 5.0 mL/kg (4876 mg/kg) of the test substance diethyl carbonate by oral administration to male Wistar rats, the test substance is practically nontoxic (study report, Bayer AG, 1980, see endpoint record 7.2.1.001, key data).

According to the results of an acute toxicity inhalation study of the test substance diethyl carbonate in male and female rats, no signs of toxicity or irritation were observed at a concentration of 19.5 mg/L. At this concentration no deaths occurred. Regarding these results, the author of this IUCLID dossier assumed that the NOEC of diethyl carbonate (acute toxicity inhalation) is 19.5 mg/L. It can therefore be concluded that the substance should not be classified in any of the four categories. As the NOEC is assumed to be 19.5 mg/L it can be concluded that the corresponding LC50 should be much greater than 19.5 mg/L which represents the upper limit for classification in category 4 (10 < LC50 ≤ 20 mg/L, Guidance to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures (2009)).

Acute toxicity dermal (data waiver): The low acute oral and inhalative toxicity of diethyl carbonate and the possibility to minimise dermal exposure by the use of effective gloves and protective clothing justifies a data waiver for this endpoint.