Reaction mass of copper digluconate, sodium sulphate and copper sulphate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24. Apr. 2007 - 31. Aug. 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

OECD Guidelines for Testing of Chemicals, Section 4, number 404 "Acute Dermal lrritation 1 Corros ion", adopted April 24, 2002.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Commission Directive 2004/73/EC, B.4. "Acute Toxicity: Dermal lrritatíon/Corrosion", April 29, 2004.

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Directive 2001/59/EC

Version / remarks:

Commission Directive 2001/59/EC of 6 August 2001, Annex VI

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Copper di-D-gluconate

EC Number:

208-408-2

EC Name:

Copper di-D-gluconate

Cas Number:

527-09-3

Molecular formula:

C12H22CuO14

IUPAC Name:

copper(2+) bis(2,3,4,5,6-pentahydroxyhexanoate)

Constituent 2

Reference substance name:

Sodium sulphate

EC Number:

231-820-9

EC Name:

Sodium sulphate

Cas Number:

7757-82-6

Molecular formula:

H2O4S.2Na

IUPAC Name:

disodium sulfate

Constituent 3

Reference substance name:

Copper sulphate

EC Number:

231-847-6

EC Name:

Copper sulphate

Cas Number:

7758-98-7

Molecular formula:

CuSO4

IUPAC Name:

copper(2+) ion sulfate

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Test system: Young Adult New Zealand White Rabbit
- Rationale: Recognized by the international guidelines as the recommended test system.
- Source: Granja San Bernardo, Ctra. de Tarazona, s/n, 31522-Tulebras, Navarra {Spain)
- Total number of animals: 3
- Sex: Males
- Body weight at start of treatment: 2.5-3.0 kg
- ldentification: By numbered tags in the ears.
- Acclimatization: From 14 to 28 days.
- Veterinary inspection: During acclimatization the animals were examined by a veterinary surgeon to assure their satisfactory health status for use in the study.

HUSBANDRY
- Room number: Room 107
- Conditions: Standard Laboratory Conditions
Air-conditioned with ranges for room temperatura 21-23 °C, relative humidity 40-70% and 10-20 air changes per hour. Room temperatura and relatíve humidity were monitored contínuously. Values outside these ranges occurred but only for short periods. These transient variatíons are considerad not to have any influence on the study and therefore these data are not reported but are retained at RCC CIDA S.A. There was a 12-hour fluorescent light/12-hour dark cycle.
- Accommodation: lndividually in stainless steel cages (52 x 58 x 43 cm).
The cages were identified by a card stating the animal's number, sex and date of arrival, Study Number, Study Director's name, test item identification, dose level,
administration route, and date of treatment.
- Diet: Pelleted standard TEKLAD 2030 Global Rabbit diet was offered ad libitum (supplied by Harlan lnterfauna Ibérica, S.L, Ctra. Sant Miquel del Fai, Km. 3, 08182-Sant Feliu de Codines, Barcelona, Batch No. N495 and N516, Expiry Date: 4 and 26 June 2007) was offered ad libitum. Results of analyses for contaminants are archivad at RCC CIDA S.A.
- Water: Tap water ad libitum by means of an automatic drinking system. Results of bacteriological, chemical and contaminant analyses are archivad at RCC CIDA S.A.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

The test item was administered 0.5 mL/animal, the dose specified in the test guidelines for a liquid test item.

Duration of treatment / exposure:

The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing.

Observation period:

ONBSERVATIONS
- Viability/Mortality: Daily from acclimatization of the animals to the termination of test.
- Clinical signs: Daily during the acclimatization, on the day of application and in each observation time point.
- Body weights: At start of acclimatization, on the day of application and in each observation time point.
- Skin reaction: See sections 4.7 and 4.8.

Number of animals:

Three young adult New Zealand White rabbits.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

2812

Time point:

other: 1h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

2817

Time point:

other: 1h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

2819

Time point:

other: 1h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

2812

Time point:

24 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

2817

Time point:

24 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

2819

Time point:

24 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

2812

Time point:

48 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

2817

Time point:

48 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

2819

Time point:

48 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

2812

Time point:

72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

2817

Time point:

72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

2819

Time point:

72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 13

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

2819

Time point:

24 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 14

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

2812

Time point:

24 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 15

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

2817

Time point:

24 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 16

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

2812

Time point:

48 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 17

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

2817

Time point:

48 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 18

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

2819

Time point:

48 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 19

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

2812

Time point:

72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 20

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

2817

Time point:

72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 21

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

2819

Time point:

72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

SKIN OBSERVATION TIME POINTS AND TERMINATION
The skin reaction was assessed at approximately 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test item).
IRRITATION
The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and edema for each of the three animals was therefore 0.
No abnormal findings were observed on the treated skin of any animal 72 hours after treatment, the end of the observation time.

Other effects:

VIABILITY/MORTALITY/CLINICAL SIGNS
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
COLORATION
No staining produced by the test item of the treated skin was observed.
CORROSION
Neither alterations of the treated skin were observed nor were corrosiva effects evident on the skin.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item do not classified as Skin Irrit.

Executive summary:

The primary skin irrítatíon potential of the test item was investigated according to OECD test guideline no. 404. The test ítem was applied by topical semi-occlusive application of 0.5 ml to

the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing.

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and edema for each of the three animals was therefore 0.

The application of the test item to the skin resultad in no signs of irritation. The test ítem caused no staining of the treated skin. No corrosiva effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.

Thus, the test item did not induce damage to the skin.

Based upon the referred classification criteria (Commission Directiva 2001/59/EC of August 2001 ), SERGOMIL L60 is considerad to be "not irritating" to rabbit skin and, therefore, it is not necessary to assign it a risk phrase.