Pirimiphos-methyl

Endpoint summary

Description of key information

- Skin irritation: not irritating, male/female, New Zealand White rabbit, OECD TG 404, Johnson 1999

- Eye irritation: not irritating, male/female, New Zealand White rabbit, OECD TG 405, Johnson 1999

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

GLP compliance:

yes

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

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.

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

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

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

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

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 Jun 1999 to 27 Jun 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

1992

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

1998

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adults
- Weight at study initiation: 2842- 3495 g
- 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 (°C): 17 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15 changes
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 8 Jun 1999 To: 27 Jun 1999

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL of the test substance

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

1 female and 2 males

Details on study design:

SCORING SYSTEM: The eyes were examined and the Draize scale was used to assess the grade of ocular reaction approximately one hour and 1, 2 and 3 days after instillation. In addition, as an aid in the assessment of corneal damage, fluorescein staining was used at all readings from 1 day after instillation.

TOOL USED TO ASSESS SCORE: As an aid to assessment of the eye, all animals were placed in an artificial daylight chamber each time the eyes were examined. Both eyes of each rabbit were examined the day before dosing, The examination consisted of a visual assessment with the aid of fluorescein and only rabbits without any apparent eye defects or ocular irritation were used. Immediately after the instillation of the test substance, an assessment of the initial pain reaction of the rabbit was made using a six-point scale.

OTHER EXAMINATIONS:
- General health: Throughout the study, the animals were observed daily for general signs of well-being.
- Body weight: The animals were weighed prior to the start of the study.

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 1d

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 2d

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 3d

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 2d

Irritation parameter:

chemosis score

Basis:

animal: #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

There were no corneal or iridial effects. Conjunctival effects consisted of slight redness in all three animals for up to 2 days, slight chemosis in one animal approximately 1 hour after instillation and a slight discharge in all three animals approximately 1 hour after instillation. There were no additional signs of irritation. All signs of irritation had completely resolved 3 days after instillation.

Other effects:

- Clinical observations: There were no signs of ill-health in any animal during the study. Instillation into the eye caused practically no initial pain (class 1 on a 0-5 scale).

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the test substance was considered to be not irritating to the eyes of rabbits.

Executive summary:

A primary eye irritation test was conducted with male and female New Zealand White rabbits, in accordance with GLP and OECD TG 405, to determine the irritation potential of the substance after a single instillation into the eye. The test substance (0.1 mL) was instilled into one eye of each of the rabbits and an assessment of initial pain was made. The eyes were examined for 3 days, to assess the grade of ocular reaction.

Instillation into the eye caused practically no initial pain. The mean irritation scores for the time points after 24/48/72 hours were determined to be 0 for all animals for corneal opacity and iritis. For conjunctivae redness these scores were 0, 0.33 and 0.67 for animal 1 to 3. For chemosis these scores were 1, 0 and 0 for animal 1 to 3. Conjunctiva effects consisted of slight redness and a slight discharge in three animals, and slight chemosis in one animal. There were no additional signs of irritation. All signs of irritation had completely resolved 3 days after instillation.

Under the conditions of this study, the test substance was considered to be not irritating to the eyes of rabbits.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

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.

Eye irritation

A primary eye irritation test was conducted with male and female New Zealand White rabbits, in accordance with GLP and OECD TG 405, to determine the irritation potential of the substance after a single instillation into the eye. The test substance (0.1 mL) was instilled into one eye of each of the rabbits and an assessment of initial pain was made. The eyes were examined for 3 days, to assess the grade of ocular reaction.

Instillation into the eye caused practically no initial pain. The mean irritation scores for the time points after 24/48/72 hours were determined to be 0 for all animals for corneal opacity and iritis. For conjunctivae redness these scores were 0, 0.33 and 0.67 for animal 1 to 3. For chemosis these scores were 1, 0 and 0 for animal 1 to 3. Conjunctiva effects consisted of slight redness and a slight discharge in three animals, and slight chemosis in one animal. There were no additional signs of irritation. All signs of irritation had completely resolved 3 days after instillation.

Under the conditions of this study, the test substance was considered to be not irritating to the eyes of rabbits.

Justification for classification or non-classification

Based on the available information classification for skin and eye irritation/corrosion is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.