Diethyl carbonate

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

performed according to an official method by a renowned institution using "Diäthylcarbonat", no info about purity, origin or batch of the test substance, no GLP, no control animals, in general good documentation of methodology and evaluation of results

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations, Title 16, Section 1500.41

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: "Lippische Versuchstierzucht / Exertal 1"
- Sex: male
- Weight at study initiation: 2.3 kg (average)
- Housing: kept in single cages
- Diet ad libitum: "mümmel z"; English: "ssniff / Soest"
- Water ad libitum
- Acclimation period: 7-14 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-18
- Humidity (%): 40
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To: no data

Type of coverage:

occlusive

Preparation of test site:

other: hair cut with electric hair cutter and not scarified/scarified with scarificator

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 microliter

Duration of treatment / exposure:

24 h

Observation period:

8 d; times of observation, after start of application of test substance: 24 h (detailed: 24.5 h), 48 h (data not reported), 72 h, 8d

Number of animals:

6

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 h and 72 h

Score:

0.3

Reversibility:

other: no erythema at all; yes for edema

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 h and 72 h

Score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

>= 0 - <= 2

Max. score:

2

Reversibility:

fully reversible within: until 72 h

Remarks on result:

other: single scores: 0, 1, 1, 1, 1, 2; not scarified

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

>= 0 - <= 1

Max. score:

1

Reversibility:

fully reversible within: until 72 h

Remarks on result:

other: single scores: 0, 0, 0, 1, 0, 0; scarified

8 d value with no valuation for irritation index as value was “0” for all six animals, scarified and non-scarified areas.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: conclusion in study report

Conclusions:

The test substance diethyl carbonate was not irritating to rabbit skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test animal: mouse (not first choice as test animal for skin irritation test); results on skin irritation from a dose range finding test in the course of determining the skin sensitisation potential of diethyl carbonate

Qualifier:

according to guideline

Guideline:

other: OECD TG 429 (Skin sensitisation test)

Principles of method if other than guideline:

Preliminary irritation/toxicity screen test in the course of a skin sensitisation study with diethyl carbonate (there: dose range finding test).
See also under 7.4.1. Skin sensitisation (7.4.1.001) for further details.

GLP compliance:

yes (incl. QA statement)

Species:

mouse

Details on test animals or test system and environmental conditions:

Info specific to dose range finding animals in skin sensitisation test:

Species and strain: CRL: NMRI BR mice
Source: TOXI-COOP ZRT. H-1103, Budapest, Cserkesz u. 90.
Hygienic level at arrival: SPF
Hygienic level during the test: Good conventional

Justification of strain: The aim of the preliminary screen was to assess the ability of the test item causing irritation and/or systemic toxicity (not the sensitizing effect), CRL: NMRI BR mice were used in the pre-screen test for a better visibility of erythema and oedema.

Number of animals: 4 animals (2 animals/group);
Sex: Female, nulliparous, non pregnant
Age of animals: Young adult mice, 6-7 weeks old

Husbandry:
Animal health: Only healthy animals were used
Housing during acclimatization period: Grouped caging in small groups
Housing during the test: Grouped caging (4 animals/cage)
Cage type: Type II. Polypropylene / polycarbonate
Bedding: Laboratory bedding
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Housing/Enrichment: Mice were group-housed to allow social interaction, and with deep wood sawdust bedding, to allow digging and other normal rodent activities.

Food and Water Supply:
Animals received ssniff (R) SM R/M-Z+H complete diet for rats and mice produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, and tap water from municipal supply, as for human consumption, from a bottle ad libitum. For contents of standard diet for rats and mice and actual batch number of the diet see Appendix III.

Bedding:
Lignocel (R) Hygienic Animal Bedding produced by J. Rettenmaier & Söhne GmbH+Co.KG (D-73494 Rosenberger (Germany) Holzmühle 1) was available to animals during the study.

Identification of Animals:
The individual identification of the animals was performed by numbers on the tail. The cages were marked with identification cards, with information about study number, sex, dose group and individual animal numbers.

Randomization:
The animals were set in order of their body weight. The animals were randomly assigned to control and test groups using a randomization scheme. The randomization was checked by computer software according to the actual body weights verifying the homogeneity and deviations between the groups.

Amount / concentration applied:

100 % (the undiluted test item itself)
50 % in AOO (acetone:olive oil = 4:1 (v/v))

Irritation parameter:

erythema score

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

non of the animals showed any sign of irritation

According to the preliminary test results, test item concentration of 100 % (the undiluted test item) was selected as the highest test concentration in the main test (for skin sensitisation).

No mortality or any signs of systemic toxicity were observed. No signs of irritation (indicated by an erythema score ≥ 3 and/or an increased ear thickness of ≥ 25 % on any day of measurement) were observed in the treatment groups.

Results table:

Summarised table of erythema scores in the preliminary irritation/toxicity test:

Dose group	Animal no.	Ears	Day	Day	Day	Day	Day	Day	Day	Day	Day
			1	1	2	2	3	3	4	5	6
			PT	AT	PT	AT	PT	AT	NT	NT	NT
Diethyl carbonate 100 %	110	Left	0	0	0	0	0	0	0	0	0
Diethyl carbonate 100 %	110	Right	0	0	0	0	0	0	0	0	0
Diethyl carbonate 100 %	111	Left	0	0	0	0	0	0	0	0	0
Diethyl carbonate 100 %	111	Right	0	0	0	0	0	0	0	0	0
Diethyl carbonate 50 %	112	Left	0	0	0	0	0	0	0	0	0
Diethyl carbonate 50 %	112	Right	0	0	0	0	0	0	0	0	0
Diethyl carbonate 50 %	113	Left	0	0	0	0	0	0	0	0	0
Diethyl carbonate 50 %	113	Right	0	0	0	0	0	0	0	0	0

PT = prior to treatment

AT = after treatment

NT = no treatment

 

Interpretation of results:

not irritating

Remarks:

Migrated information

Conclusions:

Diethyl carbonate did not cause skin irritation in this test. All values of erythema scores were 0.
This is only supplementary data as the test is not officially acknowledged (e.g. by OECD) to evaluate the skin irritation properties of a substance.

Reference 3

Endpoint:

skin irritation / corrosion

Remarks:

no data

Type of information:

other: no data

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: only two one-sentence statements without background data; data from HSDB database; content in original publication that is referred to on HSDB was checked and verfied

GLP compliance:

not specified

As stated in HSDB database (http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB):

Human Toxicity Excerpts:
MODERATELY TOXIC BY INGESTION & INHALATION; STRONG IRRITANT.

[Hawley, G.G. The Condensed Chemical Dictionary. 9th ed. New York: Van Nostrand Reinhold Co., 1977., p. 287] **PEER REVIEWED**

Skin, Eye and Respiratory Irritations:
STRONG IRRITANT.

[Hawley, G.G. The Condensed Chemical Dictionary. 9th ed. New York: Van Nostrand Reinhold Co., 1977., p. 287] **PEER REVIEWED**

Reference 4

Endpoint:

skin irritation: in vitro / ex vivo

Remarks:

In-vitro data on skin irritation is not provided due to availability of in-vivo data.

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

performed according to an official method by a renowned institution using "Diäthylcarbonat", no info about purity, origin or batch of the test substance, no GLP, no control animals, in general good documentation of methodology and evaluation of results

Qualifier:

according to guideline

Guideline:

other: "Test for eye irritants", Code of Federal Regulations, Title 16, Section 1500.42

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: "Lippische Versuchstierzucht / Exertal 1"
- Sex: male
- Weight at study initiation: 2.3 kg (average)
- Housing: kept in single cages
- Diet ad libitum: "mümmel z"; English: "ssniff / Soest"
- Water ad libitum
- Acclimation period: 7-14 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-18
- Humidity (%): 40
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To: no data

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 microliter

Duration of treatment / exposure:

8 d (at no stage flushing of eye after substance was applied)

Observation period (in vivo):

8 d; times of observation, after application of test substance: 24 h, 48 h, 72 h, 8d

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing/flushing: not done

SCORING SYSTEM:

Irritation parameter:

cornea opacity score

Time point:

72 h

Score:

0

Irritation parameter:

iris score

Time point:

72 h

Score:

0

Irritation parameter:

conjunctivae score

Time point:

72 h

Score:

0

Irritant / corrosive response data:

Results of the test

(1)Cornea
(A) : 0 for all 6 animals after 24, 48, 72 h and 8 d
(B) : 0 for all 6 animals after 24, 48, 72 h and 8 d
(2)Iris
(A) : 0 for all 6 animals after 24, 48, 72 h and 8 d
(3)Conjunctiva
(A) : 0, 0, 0, 0, 1, 1 after 24 h; 0, 0, 0, 0, 0, 1 after 48 h; 0 for all 6 animals after 72 h and 8 d
(B) : 0 for all 6 animals after 24, 48, 72 h and 8 d
(C) : 0 for all 6 animals after 24, 48, 72 h and 8 d

24 h values, sums of a+b+c: 0, 0, 0, 0, 2, 2
48 h values, sums of a+b+c: 0, 0, 0, 0, 0, 2
72 h values, sums of a+b+c: 0, 0, 0, 0, 0, 0

Primary irritation value = (15*0 + 2 + 2 + 2) / 18 = 0.3
Classification: 0 – 10 = not irritating
On a scale of 0-110 for primary eye irritation, the substance has reached 0.3 in the present study and will therefore be classified as not irritating.

8d results not included in the calculation of irritation index. All values were zero.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: conclusion in study report

Conclusions:

The test substance diethyl carbonate was not irritating to the rabbits eye.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

not specified

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: only two one-sentence statements without background data; data from HSDB database; content in original publication that is referred to on HSDB was checked and verfied

As stated in HSDB database (http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB):

Human Toxicity Excerpts:
MODERATELY TOXIC BY INGESTION & INHALATION; STRONG IRRITANT.

[Hawley, G.G. The Condensed Chemical Dictionary. 9th ed. New York: Van Nostrand Reinhold Co., 1977., p. 287] **PEER REVIEWED**

Skin, Eye and Respiratory Irritations:
STRONG IRRITANT.

[Hawley, G.G. The Condensed Chemical Dictionary. 9th ed. New York: Van Nostrand Reinhold Co., 1977., p. 287] **PEER REVIEWED**

Reference 3

Endpoint:

eye irritation: in vitro / ex vivo

Remarks:

In-vitro data on eye irritation is not provided due to availability of in-vivo data.

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
The study was performed according to an official method (Code of Federal Regulations, Title 16, Section 1500.41).

Justification for selection of eye irritation endpoint:
The study was performed according to an official method ("Test for eye irritants", Code of Federal Regulations, Title 16, Section 1500.42).

Justification for classification or non-classification

The test substance diethyl carbonate was not irritating to rabbit skin (see endpoint record 7.3.1.001, study report, Saltigo, key data) as well as not irritating to the rabbits eye (see endpoint record 7.3.2.001, study report, Saltigo, key data). According to these results there is no need to perform a respiratory irritation test.