Potassium carbamoylcarbamate

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:

other: Study performed under GLP/OECD guideline without deficiency.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

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:

Potassium carbamoylcarbamate

EC Number:

247-728-7

EC Name:

Potassium carbamoylcarbamate

Cas Number:

26479-35-6

Molecular formula:

C2H4N2O3.K

IUPAC Name:

potassium N-carbamoylcarbamate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report):Potassium Allophonate
- Physical state:powder
- Analytical purity:83.8%
- Storage condition of test material: Room temperature in the dark.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Male New Zealand White rabbits from Harlan UK Ltd, Bicester (HsdIf:NZW strain).
- Age at study initiation: 12 to 13 weeks old.
- Weight at study initiation: 2.2 to 2.5 kg
- Housing:Individually housed in cages.
- Diet (e.g. ad libitum):Global Diet 2930C (Harlan Teklad, Bicester, UK) was freely available to the animals at all times.
- Water (e.g. ad libitum):Mains water was provided, ad libitum, via cage-mounted water bottles.
- Acclimation period: 7 to 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):15 to 21 degrees C
- Humidity (%):Humidity did not fall below the limit specified in the protocol (45%).
- Air changes (per hr):15 to 20
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From 14 February 2012 to 28 February 2012.

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 (volume or weight with unit):500 mg

VEHICLE
- Amount(s) applied (volume or weight with unit):none

Duration of treatment / exposure:

4 hours

Observation period:

15 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: A 30 x 20 mm area on the closely clipped dorsum.
- % coverage:100%
- Type of wrap if used: none

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Lightly brushed clean of any solid residues and swabbed with moist cotton wool.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erythema & eschar Grade
No erythema 0
Very slight erythema 1
Well-defined erythema 2
Moderate erythema 3
Severe erythema (beet redness) or eschar formation preventing reading of erythema 4

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

The scores for erythema and oedema at the 24 and 72 hour readings were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test article.

Primary Irritation Index Classification of Irritancy

0 Non irritant
>0 to 2 Mild irritant
>2 to 5 Moderate irritant
>5 to 8 Severe irritant

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Score:

ca. 0.5

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 h

Score:

0.333

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

other: very slight erythema in one animal

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48 h

Score:

0.333

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

other: very slight erythema in one animal

Results 5

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 h

Score:

0.667

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

other: well-defined erythema in one animal

Results 6

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

- Very slight erythema was noted at one treated skin site at 24 and 48 hours after patch removal. Well-defined erythema was noted at this site 72 hours after patch removal with very slight erythema and fissuring present on Day 8. No evidence of skin irritation was noted at this treated skin site on Day 15.
- No evidence of skin irritation was noted at the other two treated skin sites during the observation period.

Any other information on results incl. tables

Table1
Individual dermal reactions

Animal number, sex, initial body weight and final body weight	Dermal reaction	Observation time after removal of patches
		Imm	1 hour	24 hours	48 hours	72 hours	7 days	14 days
4M (2.3 - 2.4 kg)	Erythema/Eschar formation	0	0	1	1	2	1	0
	Oedema formation	0	0	0	0	0	0	0
	Other	-	-	-	-	-	FS	-
5M (2.5 - 2.6 kg)	Erythema/Eschar formation	N/A	0	0	0	0	N/A	N/A
	Oedema formation	N/A	0	0	0	0	N/A	N/A
	Other	N/A	-	-	-	-	N/A	N/A
6M (2.2 - 2.4 kg)	Erythema/Eschar formation	N/A	0	0	0	0	N/A	N/A
	Oedema formation	N/A	0	0	0	0	N/A	N/A
	Other	N/A	-	-	-	-	N/A	N/A
Sum of 24  and 72 hour readings (S)					:	3
Primary Irritation Index (S/6)					:	3/6 = 0.5
Classification					:	MILD IRRITANT

Key:

Imm         Immediately after removal of patch

FS           Fissuring

N/A         Not applicable

Table 2
Individual Daily and Mean Scores for Dermal Irritation Following 4 Hour Exposure

Dermal reaction	Observation Time	Individual Scores � Rabbit Number and Sex
		4M	5M	6M
Erythema/Eschar Formation	24 Hours	1	0	0
	48 Hours	1	0	0
	72 Hours	2	0	0
Total		4	0	0
Mean Score		1.3	0.0	0.0
Oedema Formation	24 Hours	0	0	0
	48 Hours	0	0	0
	72 Hours	0	0	0
Total		0	0	0
Mean Score		0.0	0.0	0.0

 

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The test article produced a primary irritation index of 0.5 and was classified as a MILD IRRITANT to rabbit skin according to the Draize classification
scheme. The test article did not meet the criteria for classification as irritant or corrosive according to the Globally Harmonized System of
Classification and Labelling of Chemicals (GHS).