Ethoprophos

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-04-21 to 1986-06-11

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

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:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat:
The rabbit is the system of choice since it has been used historically for this type of study and will allow the data to be compared to those for other compounds.
- Source: Gota-Frisco Farms
- Age at study initiation: not specified
- Weight at study initiation: 1.7 to 2.7 kg
- Housing: individually housed in suspended stainless steel wire mesh bottom cages
- Diet (ad libitum): Agway Prolab Rabbit Ration
- Water (ad libitum): yes
- Acclimation period: at least 7 days
- Method of randomisation in assigning animals to test and control groups:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 22
- Humidity (%): 30 - 70
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

IN LIFE DATES: From: 1986-05-20 To: 1986-06-11

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 8 x 10 cm (0.1 µL/mmE2)
- Type of wrap: a porous 8 ply gauze patch measuring 2 x 2 cm was secured over the treated skin and a stockinette sleeve placed around the animals trunk (non-irritating tape was used to secure both)

REMOVAL OF TEST SUBSTANCE
- Washing: test site was gently wiped with water soaked gauze
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied:
The dose volume was calculated for each animal according to the following formula, considering a density of 1090 mg/mL:
Dose Volume (mL) = (dosage level (mg/kg)) / (test item density) * body weight (kg)

- Constant volume used: no

Duration of exposure:

24 h

Doses:

- 3.6 mg/kg bw (test site: 70 mmE2)
- 6.0 mg/kg bw (test site: 120 mmE2)
- 16.7 mg/kg bw (test site: 300 mmE2)

No. of animals per sex per dose:

10 animals per sex and dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: three times on day of administration and once daily thereafter, mortality checks were performed twice daily (5 h apart).
Individual body weight was measured on days 1, 8 and 15, or at death.
- Necropsy of survivors performed: yes
- Clinical signs:
In addition to examination forb pharmacotoxic signs, particular attention was directed during clinical observations for tremors, convulsions, lethargy or other potential central nervous system effects.

Statistics:

The LD50 for each sex and for both sexes combined was computed by the method of Probit Analysis.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

8.5 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

9.3 mg/kg bw

Based on:

test mat.

Effect levels 3

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

7.9 mg/kg bw

Based on:

test mat.

Mortality:

Deaths occurred at 6.0 (3M, 1F), 10.0 (8M, 8F) and 16.7 mg/kg bw (9M, 8F).

Clinical signs:

other: other: see "Remark"

Body weight:

other body weight observations

Gross pathology:

Gross necropsy revealed discoloured gastrointestinal tract contents and red discolouration of the respiratory tract in decedents; no treatment-related findings were noted in survivors.

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

The acute dermal LD50 of the test item in the rabbit was calculated to be 7.9 mg/kg bw (males), 9.3 mg/kg bw (females) and 8.5 mg/kg bw (combined) under the conditions of this study.

Executive summary:

In a 1987 study similar to OECD 402, the test substance was applied for 24 hours under semi-occlusive conditions to the shorn dorsal skin of New Zealand White rabbits (10/sex/group) at dose levels of 3.6, 6.0, 10.0 or 16.7 mg/kg bw. Animals were observed for 14 days.
Deaths occurred at 6.0 (3M, 1F), 10.0 (8M, 8F) and 16.7 mg/kg bw (9M, 8F). Signs of toxicity were noted at 3.6 (loss of locomotor ability, ataxia, soft stools), 6.0 (additionally salivation, prostration, laboured breathing and diarrhoea), 10.0 and 16.7 mg/kg bw (additionally red fluid around the mouth). Transient weight loss was seen in a number of animals at all dose levels, however with the exception of one top dose male, all surviving animals gained weight over the study period. Gross necropsy revealed discoloured gastrointestinal tract contents and red discolouration of the respiratory tract in decedents; no treatment-related findings were noted in survivors.

The acute dermal LD50 of the test item in the rabbit was calculated to be 7.9 mg/kg bw (males), 9.3 mg/kg bw (females) and 8.5 mg/kg bw (combined) under the conditions of this study.