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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline compliant study
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
O,O-diethyl phosphorochloridothioate
EC Number:
219-755-4
EC Name:
O,O-diethyl phosphorochloridothioate
Cas Number:
2524-04-1
Molecular formula:
C4H10ClO2PS
IUPAC Name:
O,O-diethyl phosphorochloridothioate
Details on test material:
- Name of test material (as cited in study report): EP-2 (O,O-diethyl phosphorochloridothioate)
- Physical state: clear, colourless liquid
- Analytical purity: 99.1%
- Lot/batch No.: 01127-02

Test animals

Species:
rabbit
Strain:
other: Mol:Russian, albino
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Mollegaard Breeding Centre ApS, Lille Skensved, Denmark
- Weight at study initiation: 1.9 - 2.5 kg
- Housing: single PPL cages, 45 x 55 cm, with perforated floor
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/-3 °C
- Humidity (%): 55 +/- 15%
- Air changes (per hr): 6/hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration (if solution): 99.1% (purity of the test substance applied)

Duration of treatment / exposure:
3 minutes and one hour
Observation period:
up to 35 days after treatment (evaluations were made at 30 min and 24, 48 and 72 hours and on days 7, 14, 21, 28 and 35 after exposure)
Number of animals:
4
Details on study design:
TEST SITE
- Area of exposure: 10 x 10 cm, divided into 4 fields (each 2.5 x 2.5 cm)
- Type of wrap if used: gauze patches were secured with adhesive tape and fixed with Scanpor tape loosely around the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after the exposure period, gauze patches were removed and skin washed with soap and lukewarm water.
- Time after start of exposure: 3 minutes or 1 hour

SCORING SYSTEM:
Erythema and Eschar Formation:
0 - no erythema
1 - very slight erythema (barely perceptible)
2 - well-defined erythema
3 - moderate to severe erythema
4 - severe erythema (beet redness) to slight eschar formation (injuries in depth)

Oedema formation:
0 - no oedema
1 - very slight oedema
2 - slight oedema (edges of area well defined by definite rising)
3 - moderate oedema (raised approximately 1 mm)
4 - severe oedema (raised more than 1 mm, extending beyond area of exposure)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of all four rabbits after exposure duration of 3 minutes
Time point:
other: 24, 48 and 72 hours
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
of all four rabbits after exposure duration of 3 minutes
Time point:
other: 24, 48 and 72 hours
Score:
3.9
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of all four rabbits after exposure duration of 1 hour
Time point:
other: 24, 48 and 72 hours
Score:
3.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Remarks:
of all four rabbits after exposure duration of 1 hour
Time point:
other: 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
In addition to the results stated above, scar formation was observed at three out of four rabbits exposed for one hour, confirming that skin changes induced by the test substance EP-2 were irreversible after one hour of exposure.
Other effects:
3 minutes exposure:
On day 7, thick brown crusts covering the exposed areas were seen.
On day 14, scattered white scales revealing intact skin underneath was observed in all of the rabbits.

1 hour exposure:
On day 7, a dark brown crust surrounded by a red zone was observed in two of the rabbits. A light brown crust surrounded by a red zone was observed in the two other rabbits.
On day 14, a thick brown crust was observed in all four rabbits. In two rabbits, a demarcation had started.
On day 21, small wounds and beginning scar formation were present in all rabbits.
On day 28, wounds were observed in one rabbit. Scar formation covering 60-80% of the test site was observed in two rabbits, and red thickened but intact skin was observed in one rabbit.
On Day 35, scar formation was observed in three rabbits and one rabbit had intact skin.

Any other information on results incl. tables

Results of skin irritation/corrosion assay of EP2 in rabbits:

 

Exposure time: 3 minutes

Rabbit No.

Weight [kg]

Test filed

Erythema – Eschar observed at hours

Mean Scores*

Oedema observed at hours

Mean Scores*

½

24

48

72

½

24

48

72

4914

1.9

Left

2

4

4

4

3.83

2

4

4

4

4.0

Right

2

3

4

4

2

4

4

4

4770

2.5

Left

3

3

3

3

3.0

4

4

4

3

3.67

Right

3

3

3

3

4

4

4

3

4817

2.3

Left

3

3

3

3

3.17

4

4

4

4

4.0

Right

2

3

3

4

3

4

4

4

4828

2.3

Left

3

3

3

3

3.0

4

4

4

4

4.0

Right

3

3

3

3

4

4

4

4

Mean of all rabbits:           3.3

Mean of all rabbits:           3.9

 

Exposure time: 1 hour

Rabbit No.

Weight [kg]

Test field

Erythema – Eschar observed at hours

Mean Scores*

Oedema observed at hours

Mean Scores*

½

24

48

72

½

24

48

72

4914

1.9

Left

2

3

4

4

3.67

2

4

4

4

4.0

Right

2

3

4

4

2

4

4

4

4770

2.5

Left

2

3

4

4

3.67

3

4

4

4

4.0

Right

2

3

4

4

3

4

4

4

4817

2.3

Left

2

3

4

4

3.33

3

4

4

4

4.0

Right

2

2

3

4

3

4

4

4

4828

2.3

Left

2

2

3

3

2.67

3

4

4

4

4.0

Right

2

2

3

3

3

4

4

4

Mean of all rabbits:           3.3

Mean of all rabbits:           4.0

 *       Mean scores for the individual animal were calculated by adding the scores obtained at 24, 48 and 72 hours and dividing by 6.

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information after 1 hour exposure (irritating after 3 minutes of exposure) Criteria used for interpretation of results: EU
Conclusions:
According to the criteria layed down in the Official Journal of the European Communities, L 257, 1983 and the directive of the commission 83/467/EEC of 1983, and based on the results obtained it is concluded that EP-2 shall be classified as skin irritating after 3 minutes and as corrosive after 1 hour of exposure.
Executive summary:

The primary skin irritant effect of EP-2 was investigated according to OECD guideline 404. Possible skin irritating / corrosive effects were studied after 3 minutes and 1 hour exposure in 4 rabbits each.

The mean scores (24, 48 and 72 hours after application) after 3 minutes of exposure were 3.3 for erythema and 3.9 for oedema in all animals combined. After one hour of exposure, the mean scores (24, 48 and 72 hours) were3.3 for erythema and 4.0 for oedema for all animals combined. Furthermore, scar formation was observed in three of the rabbits exposed for one hour.

According to the Official Journal of the European Commumities, L 257, 1983, EP-2 shall be classified as skin irritating after 3 minutes of exposure and as corrosive after one hour of exposure.