Erythromycin, 9-oxime, monohydrochloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 6, 2006 to February 17, 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was performed according to the OECD Guideline 404 and EU method B.4, with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(Dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-14-ethyl-7,12,13-trihydroxy-10-(hydroxyimino)-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-3,5,7,9,11,13-hexamethyloxacyclotetradecan-2-one hydrochloride

Cas Number:

26116-57-4

Molecular formula:

C37H69ClN2O13

IUPAC Name:

(3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(Dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-14-ethyl-7,12,13-trihydroxy-10-(hydroxyimino)-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-3,5,7,9,11,13-hexamethyloxacyclotetradecan-2-one hydrochloride

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Erythromycin A-9 Oxime (E) Hydrochloride.
- Physical state: white powder.
- Lot/batch No.: B5310059
- Storage condition of test material: at ambient temperature, in the dark.
- Other:
pH: 6.16 (1% solution in deionised water, w/v, determined with a pH-Meter WTW pH340)

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-94633 Sulzfeld.
- Weight at study initiation:
Animal No. 101: 2.1 kg
Animal No. 102: 2.3 kg
Animal No. 103: 2.4 kg

- Housing: Individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 cm x 59 cm bottom area, 38 height.
- Diet (e.g. ad libitum): Altromin 2123 maintenance diet for rabbits, rich in crude fiber, ad libitum. Analysis of the feed for ingredients and contmainants is performed randomly by Altromin, D-32791 Lage, Germany. Hay. briquettes (supplied by SSniff, D-59494 Soest) are offered additionally as a dietary supplement.
- Water (e.g. ad libitum): Tap water from an automatic watering system, ad libitum.
- Acclimation period: 5 days (animal No. 101) and 12 days (animals Nos. 102 and 103)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 19 ºC (continous control and recording)
- Humidity (%): Average of 48.8% (continous control and recording)
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: deoinised water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): Samples with approximately 0.5 mg of the test substance were moistened with 1.0 mL deionised water.

Duration of treatment / exposure:

4 hours.

Observation period:

The skins of the animals were examined for local alterations one day before the administration of the test substance (after clipping of the hair) and immediately before the administration. The treated areas of the animals were examined for erythema/eschar and oedema as well as for other local alterations such as hyperplasia, scaling, discolouration, fissures, scabs and alopecia) approximately 1, 24, 48 and 72 hous after patch removal.

Number of animals:

3 animals (first the test substance was administered to one animal; as no corrosive effect was observed in the inital test, the test substance was administered to two additional animals)

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: "Blenderm" surgical tape, hypoallergenic, 3M, Medical products division, St. Paul, MN 551444, USA.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 hours.

SCORING SYSTEM:
Erythema/Eschar formation
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well-defined erythema
3 Moderate to severe erythema
4 Severe erythema

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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean 24 - 72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean 24 - 72 h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean 24 - 72 h

Score:

0

Max. score:

0

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: mean 24 - 72 h

Score:

0

Max. score:

0

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: mean 24 - 72 h

Score:

0

Max. score:

0

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean 24 - 72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

All areas to be treated with the test substance and all control areas were normal before the application and at each observation time.

Other effects:

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

All areas to be treated with the test substance and all control areas were normal before the application and at each observation time. Based on the results, the test substance is not a skin irritant.

Executive summary:

Assessment of the possible irritation/corrosion by the test substance following a single application to the intact skin of rabbits was determined according to the OECD Guideline 404 and B.4 EU Method, with GLP. 0.5 g of the test substance moistened with deionised water, was applied via a patch to a site of 2.5 cm x 2.5 cm of the intact skin of each of 3 New Zealand White rabbits and covered by a semi-occlusive dressing. The duration of exposure was 4 hours. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. All areas to be treated with the test substance and all control areas were normal before the application and at each observation time. Based on the results, the test substance is not a skin irritant.