Ethoprophos

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979-08-27 to 1979-10-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethoprophos

EC Number:

236-152-1

EC Name:

Ethoprophos

Cas Number:

13194-48-4

Molecular formula:

C8H19O2PS2

IUPAC Name:

ethyl bis(propylsulfanyl)phosphinate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Microbiological Associates, Walkersville, Maryland
- Age at study initiation: not specified
- Weight at study initiation: 200 to 235 grams (males), 183 to 216 grams (females)
- Fasting period before study: overnight
- Housing: two animals/sex/dosage level in elevated wire-mesh cages
- Historical data: not specified
- Diet (ad libitum): commercial rodent ration (Purina Rodent Laboratory Chow®)
- Water (ad libitum): tap water
- Acclimation period: minimum of 3 weeks
- Method of randomisation in assigning animals to test and control groups: computerized randomization process (involved generating random numbers, assigning the numbers to the animals, ranking the random numbers, and assigning the animals to the groups)

ENVIRONMENTAL CONDITIONS
not specified

IN-LIFE DATES:
From: 1979-08-27 To: 1979-09-10 (females)
From: 1979-09-20 To: 1979-10-04 (males)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

0, 10, 20, 40, 80 mg/kg bw

No. of animals per sex per dose:

10 animals per sex and dose

Control animals:

yes

Remarks:

vehicle control group

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
All of the rats were observed for mortality and signs of toxic and pharmacologic effects at one, two, and four hours post-dose and twice daily thereafter for fourteen consecutive days. Individual body weights were recorded prior to treatment, at seven days, and at termination.
- Necropsy of survivors performed: yes, sacrifice by carbon dioxide asphyxiation

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 80 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 40 - < 80 mg/kg bw

Based on:

test mat.

Mortality:

No males dosed at 0, 10, 20, or 40 mg/kg bw or females dosed at 10 or 20 mg/kg bw were found dead throughout the fourteen-day observation period. Three males dosed at 80 mg/kg bw were found dead on Day 2. One female dosed at 0 mg/kg, one dosed at 40 mg/kg bw, and all ten females dosed at 80 mg/kg bw were found dead on or before Day 2. The LD50 for the males was estimated to be greater than 80 mg/kg of body weight, and the LD50 for the females was estimated to be greater than 40 mg/kg of body weight but less than 80 mg/kg of body weight.

Clinical signs:

other: other: see "Remark"

Body weight:

other body weight observations

Gross pathology:

No observable gross pathology was noted in most rats which were not found dead during the observation period. Findings noted in two surviving 40 mg/kg bw females and one 10 mg/kg bw male included bright red lungs, dark red areas in the lungs, and dark red lungs. Findings noted in rats found dead during the fourteen-day period included dark red or bright red lungs, slightly reddened stomach lining, thin or thickened stomach walls, feed and gas in the stomach, dark or pale liver, and reddish-yellow material, air, brownish-yellow fluid, and/or yellowish fluid in the intestines.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral LD50 of the test item in the rat was found to be >80 mg/kg bw (males) and 40-80 mg/kg bw (females) under the conditions of this study.

Executive summary:

In a acute oral toxicity study similar to OECD 401, Fischer 344 rats (10/sex/group) were gavaged with the test item dissolved in corn oil at dose levels of 0, 10, 20, 40 or 80 mg/kg bw and observed for 14 days. Deaths occurred within 24 hours of administration at 40 (1F) and 80 mg/kg bw (3M, 10F); one control animal also died as a result of mis-dosing. Signs of toxicity (soft faeces, depression, rough coat, urine staining, red staining of the eyes and nose) were observed in all treated groups; findings had generally resolved by 24-48 hours following dosing but persisted to Day 7-9 in individual animals at 40 and 80 mg/kg bw. With the exception of two females at 40 mg/kg bw animals are reported to have gained weight over the study period, however actual values are not reported. Gross necropsy did not reveal any treatment-related findings in survivors. Dark/bright red lungs, slightly reddened stomach lining, thin or thickened stomach walls, dark or pale liver and discoloured gastrointestinal tract contents were noted in decedents.

The acute oral LD50 of the test item in the rat was found to be >80 mg/kg bw (males) and 40-80 mg/kg bw (females) under the conditions of this study.