Methomyl

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Test material

Test material information

Constituent 1

Reference substance name:

Methomyl

EC Number:

240-815-0

EC Name:

Methomyl

Cas Number:

16752-77-5

Molecular formula:

C5H10N2O2S

IUPAC Name:

(E)-[1-(methylsulfanyl)ethylidene]amino N-methylcarbamate

Test material form:

solid: crystalline

Specific details on test material used for the study:

Methomyl Technical
Lot number: DPX-X1179-599
Purity: 99.6%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, Pennsylvania.
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult (9-12 weeks)
- Weight at study initiation: 190-232 grams
- Fasting period before study: Yes
- Housing: Animals were singly housed in suspended stainless steel caging with mesh floors. Enrichment (e.g. nylabone) was placed in each cage. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet: Purina Rodent Chow #5012
- Water: Filtered tap water, ad libitum
- Acclimation period: 8-28 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18-21ºC
- Humidity: 34-65%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 2.5% w/v mixture in distilled water

Doses:

3.2, 10.1, 32 and 101 mg/kg b.wt.

No. of animals per sex per dose:

3.2 mg/kg: 1
10.1 mg/kg: 3
32 mg/kg: 3
101 mg/kg: 1

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for mortality, signs of toxicity, and behavioral changes changes within 30 minutes of dosing and during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing of until death occurred. Individual weights of the animals were recorded prior to test substance administration (initial) and again on Days 7 and 14 following dosing or after death.
- Necropsy of survivors performed: Yes

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

17.98 mg/kg bw

Based on:

test mat.

Mortality:

One animal dosed at 10.1 mg/kg and two dosed at 32 mg/kg died within one hour of test substance administration. The rat dosed at 101 mg/kg died within 30 minutes of test substance administration.

Clinical signs:

other: Clinical signs noted in the decedents prior to death of animals dosed at 10.1 mg/kg and 32 mg/kg included hypoactivity, tremors and/or prone posture. The surviving rats from these dose groups exhibited clinical signs including hypoactivity, tremors and/or

Gross pathology:

Gross necropsy of the decedent animals dosed at 10.1 mg/kg and 32 mg/kg revealed discoloration of the intestines. No gross abnormalities were noted for any of the euthanized animal dosed at 10.1 mg/kg and 32 mg/kg necropsied at the conclusion of the 14-day observation period. Gross necropsy of the decedent animal at 101 mg/kg revealed discoloration of the intestines.

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

Oral LD50 (Rat, female): 17.98 mg/kg

Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with rats to determine the potential for the test substance to produce toxicity from a single dose via the oral route in accordance with the OECD Guideline 425 and U.S. EPA Guideline OPPTS 870.1100.

Based on an estimated LD50 of 32 mg/kg, a Main Test was conducted using a default starting dose level of 10.1 mg/kg administered to one healthy female rat by oral gavage. Following the Up and Down procedure, two additional females were dosed at 10.1 mg/kg, one female was dosed at 3.2 mg/kg, three females were dosed at 32 mg/kg and one female was dosed at 101 mg/kg. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing or until death occurred. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) following dosing or after death. Necropsies were performed on all animals.

The animal dosed at 3.2 mg/kg survived and exhibited no clinical signs or body weight loss during the study. No gross abnormalities were noted for this animal when necropsied at the conclusion of the 14-day observation period.

One animal dosed at 10.1 mg/kg and two dosed at 32 mg/kg died within one hour of test substance administration. Clinical signs noted in the decedents prior to death included hypoactivity, tremors and/or prone posture. The surviving rats from these dose groups exhibited clinical signs including hypoactivity, tremors and/or piloerection on the day of dosing. All surviving animals recovered from these signs within one day post-dosing and appeared active and healthy for the remainder of the 14-day observation period, showing no body weight loss during the study. Gross necropsy of the decedents revealed discoloration of the intestines. No gross abnormalities were noted for any of the euthanized animal necropsied at the conclusion of the 14-day observation period.

The rat dosed at 101 mg/kg died within 30 minutes of test substance administration. Clinical signs noted in the decedent prior to death included hypoactivity and prone posture. Gross necropsy of the decedent revealed discoloration of the intestines.

Under the conditions of this study, the acute oral LD50 of the test substance is estimated to be 17.98 mg/kg of body weight (based on maximum likelihood) in female rats with a 95% profile-likelihood based confidence interval of 0 mg/kg (lower) to greater than 20000 mg/kg (upper).