(7R)-7-(4-carboxybutanamido)cephalosporanate amidohydrolase (enzyme substance)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 15-JUN-2002 to 01-JUL-2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The test was performed according to OECD guideline and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Deviations from the maximum level of temperature occurred (with a maximum of 1 °C). It was considered not to have affected the study integrity.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

deoxyribose-phosphate aldolase EC 4.1.2.4.

Cas Number:

9026-97-5

Molecular formula:

Not applicable, please see remarks

IUPAC Name:

deoxyribose-phosphate aldolase EC 4.1.2.4.

Constituent 2

Reference substance name:

Protein as a constituent of enzyme deriving from the fermentation or extraction process

Molecular formula:

Not available. See remarks.

IUPAC Name:

Protein as a constituent of enzyme deriving from the fermentation or extraction process

Constituent 3

Reference substance name:

Inorganic salts as a constituent of enzyme deriving from the fermentation or extraction process

Molecular formula:

Not available. See remarks.

IUPAC Name:

Inorganic salts as a constituent of enzyme deriving from the fermentation or extraction process

Constituent 4

Reference substance name:

Carbohydrates constituent of enzyme deriving from the fermentation or extraction process.

Molecular formula:

Not available. See remarks.

IUPAC Name:

Carbohydrates constituent of enzyme deriving from the fermentation or extraction process.

Constituent 5

Reference substance name:

Lipids as a constituent of enzyme deriving from the fermentation or extraction process

Molecular formula:

Not available. See remarks.

IUPAC Name:

Lipids as a constituent of enzyme deriving from the fermentation or extraction process

Test material form:

liquid

Remarks:

Tests based on dissolved material in the concentrate

Details on test material:

- Name of test material (as cited in study report): Aldolase (IUB 4.1.2.4)
- Substance type: enzyme
- Physical state: liquid
- Stability under test conditions: data not available
- Storage condition of test material: In freezer in the dark

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: 7-9 weeks
- Weight at study initiation: 1557g to 1662g
- Housing: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5cm)
- Diet: Standard laboratory rabbit diet (Teklad Global Rabbit Diet, code 2030, Harlan, Blackthorn, England) approx. 100 g. per day
- Water: Free access to tap-water
- Acclimation period: at least 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature: 21 +/- 3°C
- Humidity: 30-70%
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day


IN-LIFE DATES: data not available

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: undiluted

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 (in a first time one single rabbit, and 2 other 13 days later)

Details on study design:

TEST SITE
- Area of exposure: the test substance was applied to the skin of one flank, using a metalline patcht of 2x3 cm
- % coverage: data not available
- Type of wrap if used: the patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes (with water)
- Time after start of exposure: 4 hours


SCORING SYSTEM: erythema and edema were scored in accordance with OECD guideline

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1, 24, 48, 72h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48, 72h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

No skin irritation was caused by 4 hours exposure to ALDOLASE (I.U.B. 4.1.2.4).
There was no evidence of a corrosive effect on the skin.

Other effects:

No staining of the treated skin by the test substance was observed.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1 : individual skin irritation scores

Animal #	339 (sentinel)			370			371
Time after exposure	erythema	oedema	comments	erythema	oedema	comments	erythema	oedema	comments
1 hour	0	0	-	0	0	-	0	0	-
24 hours	0	0	-	0	0	-	0	0	-
48 hours	0	0	-	0	0	-	0	0	-
72 hours	0	0	-	0	0	-	0	0	-

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results and according to the EC criteria, ALDOLASE (I.U.B. 4.1.2.4) does not have to be classified and has no obligatory labelling requirement for skin irritation

Executive summary:

The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, B.4, "Acute Toxicity - Skin irritation" and OECD No.404, "Acute Dermal Irritation/Corrosion".

Three rabbits were exposed to 0.5 ml of ALDOLASE (I.U.B. 4.1.2.4), applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure.

No skin irritation was caused by 4 hours exposure to ALDOLASE (I.U.B. 4.1.2.4).

Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), ALDOLASE (I.U.B. 4.1.2.4) does not have to be classified and has no obligatory labelling requirement for skin irritation.