1,4-naphthoquinone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: Japanese White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Japan Laboratory Animals, Inc.
- Age at study initiation: 18 weeks
- Weight at study initiation: 3.09 Kg
- Housing: Individually in aluminium cages.
- Diet (e.g. ad libitum): Free access to pelleted rabbit diet.
- Water (e.g. ad libitum): tap water
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 25°C
- Humidity (%): 46 to 71%
- Air changes (per hr): 11 to 14 times per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

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): 0.5 g

Duration of treatment / exposure:

Seperate exposures of 3 minutes, one hour and four hours also with a control area all on the same animal.

Observation period:

1 hour after the 4 hour test substance exposure.

Number of animals:

Only one animal was required (as corrosive effects were observed)

Details on study design:

TEST SITE
- Area of exposure: Back of the rabbit
- % coverage: the test substance was applied on a 2.5 x 2.5 cm lint patch
- Type of wrap if used: Lint patch lined with linseed oil paper and moisturised with 0.5 mL of water. The patch was covered with tape and fixed.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The application areas were wiped with absorbent cotton wet with water.
- Time after start of exposure: 3 minutes, 1 hour and 4 hours.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days). 3 minutes, 1 hour and 4 hours of exposure (followed by 1 hour after each exposure period)

SCORING SYSTEM:
- Method of calculation: Draize criteria (1959).

METHOD:
- On the day of application, the back was separated into right and left along with the midline (head to tail) to prepare four areas for the substance to be applied. The following steps then occured:
- Application to the area exposed for three minutes. The test substance of 0.5 g was placed on a lint patch. The lint patch was applied to the application area as above. The lint patch on the application area was removed three minutes after application, the application area was wiped with absorbent cotton wet with water for injection and then the animal was returned into the cage.

- Application to the area exposed for an hour. As no corrosion changes were observed one hour after the removal of the test substance in the first step, the test substance was applied on another test area by the same procedures. The lint patch on the applied area was removed an hour after the application, the applied area was wiped by the same procedures in the first step and then the animal was returned into the cage.

- Application to the area exposed for four hours. As no corrosion changes were observed one hour after the removal of the test substance in the second step, the test substance was applied on another test area by the same procedures. A lint patch (2.5 × 2.5 cm) only, which was lined with oil paper at the same time, was applied on another application area to act as the control. The lint patch on the application site was removed four hours after application and the animal was returned to the cage. The wiping of the application area were performed by the same procedures in the earlier steps.

- Clinical signs were observed in the animal immediately after application and an hour after removal in each step. After the experiment was completed, the animal was euthanised.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 4 hour exposure, 1 hour observation

Score:

4

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: Scoring time for corrosion studies not 24/48/72 hours in isolation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 4 hour exposure, 1 hour observation

Score:

4

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: Scoring time for corrosion studies not 24/48/72 hours in isolation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Not relevant as test substance corrosion observed after 4 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Not relevant as test substance corrosion observed after 4 hours

Irritant / corrosive response data:

After 3 minutes of exposure no erythema or oedema was observed in the area exposed to the test substance at the time point of an hour after removal of application. No corrosive change was also observed.
Grade 1 erythema and grade 3 oedema were observed in the area exposed to the test substance for an hour, at the time of an hour after removal of application. No corrosive change was observed.
Grade 4 severe erythema (injuries in depth) and grade 4 severe oedema were observed at the time of an hour after removal of the test substance for the 4 hour exposure. Brown necrosis and occurrence of changes considered to be irreversible tissue damages were observed and therefore it was judged to be corrosive.

No further animals were tested as the substance showed conclusive corrosive effects leading to classification. There was also no skin reaction in the control area.

Other effects:

No other effects or signs of systemic toxicity were noted.

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

The test substance was deemed to be corrosive in an in vivo dermal irritation study with sub-categorisation in accordance with UN GHS and the CLP Regulation (EC No.1272/2008) possible.