Pirimiphos-methyl

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 Jun 1999 to 8 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 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1992

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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:

rat

Strain:

other: Alpk:APfSD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Approximately 8-12 weeks old at the start of the study.
- Weight at study initiation: Males weighed 275-307 g and the females weighed 189-232 g
- Housing: The rats 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): 22±3
- Humidity (%): 30-70
- Air changes (per hr): A minimum of 15 changes
- - Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: FROM: 23 Jun 1999 TO: 8 Jul 1999

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Preparation of the test site: The day prior to application of the test substance, the hair was removed with a pair of veterinary clippers from an area, at least 7 cm x 7 cm, on the dorso-lumbar region of each animal.
- Area of exposure: The estimated amount applied per unit area of skin exposed was 9.8 - 14.5 mg/cm^2 for males and 6.7 - 8.2 mg/cm^2 for females (dorso-lumbar region)
- Coverage: Each dressing consisted of a foil backed patch (approximately 7 cm x 7 cm) to cover the treated area and was held in position using cohesive bandage (approximately 15 cm x 7.5 cm) around which was secured two pieces of surgical tape (approximately 2.5 cm wide).

REMOVAL OF TEST SUBSTANCE
- At the end of the 24-hour contact period, the dressings were carefully cut, using blunt tipped scissors, removed and discarded. The skin, at the site of application, was 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.

TEST MATERIAL
- Amount applied: To achieve the required dose of 2000 mg/kg, the volume applied was adjusted to take into account the specific gravity of the test substance. (As the specific gravity was 1.15, a dose-volume of 1.74 mL/kg was applied). The volume of the dose was calculated for each animal according to its weight at the time of dosing

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Frequency of observations and weighing: The animals were observed twice between one and five hours after application (only gross abnormalities were noted at this time as the presence of the dressings may have affected the behaviour and movement of the rats). Subsequent observations for signs of systemic toxicity and skin irritation were made once daily up to day 15. The animals were weighed immediately before dosing (day 1) and on days 8 and 15.
- Necropsy of survivors performed: yes. This involved an external observation and a careful examination of all thoracic and abdominal viscera. All abnormalities were recorded but tissues were not submitted for histopathological examination.

Statistics:

The acute dermal median lethal dose was estimated from the mortality data.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died

Clinical signs:

other: No signs of systemic toxicity

Gross pathology:

One male had a speckled thymus. This is considered to be spontaneous finding which is incidental to treatment with the test substance.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of the test substance is estimated to be in excess of 2000 mg/kg to male and female rats.

Executive summary:

A group of 5 male and 5 female Alpk:APrSD (Wistar-derived) rats received a single dermal occlusive application of 2000 mg/kg of the test substance in a study performed under GLP and according to OECD TG 402. The animals were assessed daily for the following 14 days for any signs of systemic toxicity and their body weights were recorded at intervals throughout the study. At the end of the study all the animals were killed and subjected to a macroscopic examination post mortem.
None of the animals died and there were no signs of systemic toxicity. Signs of slight skin irritation were seen in all animals but had completely resolved by day 7. All animals showed an overall body weight gain during the study. There were no compound-related abnormalities at examination post-mortem.

Based on these findings, the acute dermal LD50 of the test substance is estimated to be in excess of 2000 mg/kg to male and female rats.