Pirimiphos-methyl

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 Jun 1999 to 10 Jul 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pirimiphos-methyl

EC Number:

249-528-5

EC Name:

Pirimiphos-methyl

Cas Number:

29232-93-7

Molecular formula:

C11H20N3O3PS

IUPAC Name:

O-2-(diethylamino)-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: The animals weighed 3439-3757 g at the beginning of the study
- Specification: Young adults - body weight in excess of 2 kg
- Housing: The rabbits were housed individually in cages suitable for animals of this strain and the weight range expected during the course of the study.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 ± 3°C
- Humidity: 30- 70%
- Air changes (per hr): A minimum of 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 Jun 1999 To: 10 Jul 1999

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: The undiluted test substance (0.5 mL) was applied, using a sterile disposable polypropylene syringe, to the test site (approximate size 2.5 cm x 2.5 cm) on the left flank of each rabbit .

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3

Details on study design:

TEST SITE
- Type of wrap if used: The treated area was covered with a piece of 4-ply surgical gauze (approximate size 2.5 cm x 2.5 cm), which was secured by two strips of surgical tape (approximate size 1 cm x 8 cm). This was covered by a piece of impermeable rubber sheeting (approximate size 35 cm x 13 cm) wrapped once around the trunk of the animal and secured with adhesive impermeable polyethylene tape.
- Area of exposure: The undiluted test substance (0.5 mL) was applied, using a sterile disposable polypropylene syringe, to the test site (approximate size 2.5 cm x 2.5 cm) on the left flank of each rabbit
- Observation time points: The Draize scale was used to assess the degree of erythema and oedema at the application sites approximately 1 hour and 1, 2 and 3 days after removal of the dressings and then at intervals for up to 7 days. Any other signs of skin irritation were also noted.

REMOVAL OF TEST SUBSTANCE
- Washing: The application site was gently cleansed free of any residual test substance using clean swabs of absorbent cotton wool soaked in clean warm water and was then dried gently with clean tissue paper. The application site was identified using a black waterproof marker-pen.

OTHER EXAMINATIONS:
- Throughout the study, the animals were observed daily for general signs of well-being. All animals were removed from the study at the end of the observation period.
- The body weight of each animal was recorded at the start of the study.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

animal: #1, #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 4 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Minimal oedema observed at one hour, fully reversible within 1 day.

Irritant / corrosive response data:

Very slight erythema was seen in one animal for 1 day and in another for 4 days after application. Very slight oedema was seen in one animal approximately 1 hour after application only, and in the other two animals for 3 days (but was not seen 1 day after application)

Other effects:

- Other adverse local effects: The test substance adhered to the application site of one animal, staining the skin yellow, but this did not prevent the assessment of irritation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance is a slight irritant following a single four-hour application to rabbit skin, but not sufficient for classification under CLP.

Executive summary:

A primary skin irritation test was conducted with male and female New Zealand White rabbits, in accordance with GLP and OECD TG 404, to determine the skin irritation potential of the substance after a single topical application. A group of 3 rabbits received a single four-hour application of 0.5 mL of the test substance to the shorn flank under occlusive conditions. The animals were assessed for up to 7 days for any signs of skin irritation. Following exposure, dermal irritation was evaluated by the method of Draize et al.

Very slight erythema was seen in two animals for up to 7 days and very slight oedema was seen in all three animals for up to 4 days. The mean erythema irritation scores for the time points after 24/48/72 hours were determined to be 0.3, 0 and 1 for animal 1 to 3. The mean oedema irritation scores for the time points after 24/48/72 hours were determined to be 0.67, 0.67 and 0 for animal 1 to 3. There were no additional signs of irritation.

The test substance is a slight irritant following a single four-hour application to rabbit skin, but not sufficient for classification under CLP.