Pirimiphos-methyl

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1 Jun 1999 to 27Jul 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 401 (Acute Oral Toxicity)

Version / remarks:

1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1992

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

1998

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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: 8-12 weeks old
- Weight at study initiation: Males: 270-381 g, females: 191-241 g
- Fasting period before study: The rats were fasted overnight immediately prior to dosing.
- Housing: A maximum of 5 rats was housed per cage, sexes separately, in cages suitable for animals of this strain and the weight range expected during the course of the study.
- Diet and water: Supplied by an automatic system were available ad libitum.
- Acclimation period: The animals were housed under the experimental conditions for at least 5 days, prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): A minimum of 15 changes per hour.
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: 1 Jun 1999 to 27Jul 1999

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10 mg/kg

Doses:

500, 1000 and 2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations clinical signs: The animals were observed for signs of systemic toxicity twice following dosing on day 1. Subsequent observations were made daily, up to day 15.
- Frequiency of weighing: Prior to fasting (day -1), immediately before dosing (day 1) and on days 8 and 15.
- Clinical signs including body weight and systemic toxicity
- Post mortem: Examination of all thoracic and abdominal viscera. All abnormalities were recorded but tissues were not submitted for histopathological examination.

Statistics:

LC50 values and 95% confidence intervals were determined.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 414 mg/kg bw

Based on:

test mat.

95% CL:

> 1 000 - < 2 000

Mortality:

Following a dose of 500 mg/kg and 1000 mg/kg, none of the animals died. Following a dose of 2000 mg/kg, all the animals were killed in extremis on days 2 or 3. Overview of the results were provided in table 1 in “Any other information on results incl. tables”

Clinical signs:

other: Signs of slight or moderate toxicity were seen in all animals, with complete recovery by day 5 in the males and day 8 in the females (some females had stained fur until day 10/13)

Gross pathology:

Following a dose of 500 mg/kg, one female had pelvic dilatation of the kidney. This is a common spontaneous finding which is considered to be unrelated to treatment. Following a dose of 1000 mg/kg, there were no macroscopic abnormalities in any animal. Following a dose of 2000 mg/kg, treatment-related abnormalities comprised staining/discharge from the eye, red nares, fluid stomach contents and (in one female) reddening of the pancreas.

Any other information on results incl. tables

Table 1. Cumulative mortality data

Dose level (mg/kg)	Day Number	Number of Deaths
		Male	Female
500	-	0	0
	15 (total)	0/5	0/5
1000	-	0	0
	15 (total)	0/5	0/5
2000	2  3	5  0	2  3
	15 (total)	5/5	5/5

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of the test substance is estimated to be 1414 mg/kg (95% confidence limits 1000, 2000) to male and female rats.

Executive summary:

Groups of five male and five female Alpk:APrSD rats received a single oral dose of 500, 1000 or 2000 mg/kg of the test substance in a study performed under GLP according to OECD TG 401. 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. Animals in extremis and those surviving to the end of the study were killed and subjected to a macroscopic examination post-mortem.

Following a dose of 500 mg/kg, none of the animals died. Signs of slight systemic toxicity were seen in most animals, with complete recovery by day 5. All animals showed an overall body weight gain during the study. There were no treatment-related abnormalities at examination post mortem. Following a dose of 1000 mg/kg, none of the animals died. Signs of slight or moderate toxicity were seen in all animals, with complete recovery by day 5 in the males and day 8 in the females. All animals showed an overall body weight gain during the study. There were no macroscopic abnormalities at examination post-mortem. Following a dose of 2000 mg/kg, all the animals were killed in extremis on days 2 or 3. At examination post mortem, treatment-related abnormalities comprised staining/discharge from the eye, red nares, fluid stomach contents and (in one female) reddening of the pancreas.

Based on these findings, the acute oral median lethal dose (LD50) of the test substance is estimated to be 1414 mg/kg (95% confidence limits 1000, 2000) to male and female rats.