N-ethyl-N-methylcarbamoyl chloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

479-390-3

EC Name:

-

Cas Number:

42252-34-6

Molecular formula:

C4H8ClNO

IUPAC Name:

N-ethyl-N-methylcarbamoyl chloride

Test material form:

liquid

Remarks:

colourless.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: C0014
- Purity: 99.3%
- Expiration date of the lot/batch: 31 July 3008

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In refrigerator (2-8ºC) in the dark
- Stability under test conditions: stable

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, Horst, The Netherlands
- Age at study initiation: At least 6 weeks old.
- Weight at study initiation: At least 1.0 kg.
- Housing:Individually housed in labelled cages with perforated floors.
- Diet (e.g. ad libitum): Pelleted diet for rabbits ad libitum.
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: At least 5 days.
- Other: 3 male rabbits were used.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9-21.7 ºC
- Humidity (%): 42-61 %
- Air changes (per hr): 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light/12 hours dark

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL.

Duration of treatment / exposure:

Four hours

Observation period:

14 days.

Number of animals:

Three

Details on study design:

TEST SITE
- Area of exposure: The test subtance was applied to the skin of one flank using a metalline path of 2x3cm.
- Type of wrap if used: The patch was mounted with Micropore tape and wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After removing the dressing, the skin was cleaned of residual test item with tap water.
- Time after start of exposure: 4 hours.

SCORING SYSTEM:
Erythema and Eschar formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) preventing grading of erythema: 4

Oedema formation
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 mm): 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure: 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

2.3

Max. score:

3

Reversibility:

not fully reversible within: At termination (14 days after treatment) very slight erythema, very slight oedema and bald skin was observed in one animal. In the other two animals scaliness and bald skin were observed at termination.

Remarks on result:

other: The individual score for each animal was the same to the mean score.

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

3.3

Max. score:

4

Reversibility:

not fully reversible within: At termination (14 days after treatment) very slight erythema, very slight oedema and bald skin was observed in one animal. In the other two animals scaliness and bald skin were observed at termination.

Remarks on result:

other: The individual score for each animal was the same to the mean score.

Irritant / corrosive response data:

There was no evidence of corrosion on the skin.
The skin reactions persisted until day 14 after exposure.

Other effects:

Dry remnants of the test substance were present on day 1.
No staining of the treated skin by the test item was observed.
No signs of systemic toxicity were observed in the animals during the test period and no mortality occured.

Any other information on results incl. tables

Table 1. Individual skin irritation scores

Animal	610 (1)			626			632
Time after exposure	Erythema	Oedema	Comments	Erythema	Oedema	Comments	Erythema	Oedema	Comments
1 hour	2	3	B	2	4	B	2	3	B
24 hours	2	3	-	2	3		2	3	-
48 hours	2	3	-	2	3	F	2	3	F
72 hours	3	4	F	3	4	F	3	4	F
7 days	1	2	H, L	1	2	H, L	1	2	H, L
14 days	1	1	H	0	0	H, L	0	0	H, L

(1)= Sentinel

Comments:

B: Dry remnants of the subtance present

F: Reduced Flexibility of the skin

H: Bald skin

L: Scaliness

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Remarks:

EU

Conclusions:

The test item caused skin reactions which persisted until the end of the observation period (14 days). No evidence of corrosion was found.

Executive summary:

A study was performed to assess the skin irritation potential of the test item to the rabbit in accordance to OECD Guideline 404 (GLP study).The study was performed in a stepwise manner and was started by the treatment of a single rabbit (sentinel). The other two animals were treated in a similar manner 4 weeks later, after considering the degree of skin irritation observed in the first animal. Rabbits received a single four hour, semi-occlusive, dermal administration of approximately 0.5 mL of the test substance as supplied and were observed for 14 days. No signs of corrosion were noted. At termination very slight erythema, very slight oedema and bald skin was observed in one animal. In the other two animals scaliness and bald skin were observed at termination. The observed mean scores (24, 48 and 72h) for each animal were equal to the mean for all animals and were 2.3 for erythema and 3.3 for oedema. The test item was determined to be irritating to the skin (Category 2 according to CLP Regulation).