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Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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:
other: Code of Federal Regulations, Title 16, Section 1500.41
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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.
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:
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. certificate)
Species:
mouse
Details on test animals 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.
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**

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

Referenceopen allclose all

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:
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.
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**

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.