Ethyl [2-(4-phenoxyphenoxy)ethyl]carbamate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 Mar 1982 to 31 Mar 1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1981

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

May 1981

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

Aug 1978

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl [2-(4-phenoxyphenoxy)ethyl]carbamate

EC Number:

276-696-7

EC Name:

Ethyl [2-(4-phenoxyphenoxy)ethyl]carbamate

Cas Number:

72490-01-8

Molecular formula:

C17 H19 N O4

IUPAC Name:

ethyl [2-(4-phenoxyphenoxy)ethyl]carbamate

Test animals

Species:

rat

Strain:

Wistar

Remarks:

KFM-HAN

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 9 weeks
- Weight at study initiation: 198 - 234 g for males and 173 – 206 g for females
- Diet: Ad libitum (defined for acceptable contaminant levels)
- Water: tap water ad libitum (Quality according to the requirements of the Schweiz, lebensmittelbuch)
- Acclimation period: 1 week under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 10 Mar 1982 to 31 Mar 1992

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

VEHICLE
- Amount of vehicle: 20 mL/kg bw

Doses:

3000, 5000, 8000 and 10000 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
- Animals were observed five times at day 1 and than daily for the nature onset severity and duration of all gross or visible toxic or pharmacological effects as well as rare and time of death.
- The animals were weighed at the day of dosing and day 7 and 14 after the administration.
- All test animals were subjected to a complete necropsy following their sacrifice or spontaneous death. All organs abnormalities were recorded. From the following organ of all animals histopathological evaluation was made: heart, lung, liver, kidneys, spleen.

Statistics:

The Logit Model could not be applied to the observed rates of death. The LD50 was estimated without use of a statistic model.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

2/5 females given 10000 mg/kg bw were found dead on day 2 after treatment. No further mortality occurred.

Clinical signs:

other: In all dose groups, rats showed sedation, dyspnoea, ventral or curved body position, latero-abdominal position, diarrhoea and ruffled fur. Rats given 5000 mg/kg or higher doses showed exophtalmos and slight spasms. Rats given 8000 and 10000 mg/kg showed s

Gross pathology:

In all dose groups, lesions in the lungs, liver and kidney were noted which are commonly seen in rats of this strain and age. Splenic haemopoiesis was seen in nearly all animals. Gastric ulcer was noted in one high-dose male. In the two females that died during the study, slight to moderate unicellular and multicellular necrosis of the liver was observed.

Other findings:

SYMPTOMS
The main symptoms observed in the different dose groups were:
3000 mg/kg bw: sedation, dyspnoea ventral-, latero-abdominal-, curved body position, diarrhoea ruffled fur.
5000 mg/kg bw: sedation, dyspnoea, exophthalmos, ventral-, latero­ abdominal- curved body position, spasms, diarrhoea ruffled fur.
8000 mg/kg bw: sedation, coma, dyspnoea, exophthalmos, ventral-, latero-abdominal-, curved body position, spasms, tremor, diarrhoea, ruffled fur.
10000 mg/kg bw: sedation, dyspnoea, exophthalmos, latero-abdominal, curved body position, spasms, tremor, loss of weight, diarrhoea ruffled fur.
 The above mentioned symptoms were more pronounced in the higher dose groups. The surviving animals had recovered within 7 to 9 observation days.
 
NECROPSY
In two high-dose animals that died two days after the application, slight to moderate, unicellular and multicellular necrosis was noted in the liver.
Gastric ulcer was noted in one high-dose male.
Splenic haemopoiesis was noted in most animals of all groups,
A few other lesions observed in this study are commonly seen in rats of this strain and age.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of the test substance was found to be greater than 10000 mg/kg bw in both male and female rats.

Executive summary:

Groups of 5 male and 5 female Wistar KFM-HAN rats received a single oral dose of 3000, 5000, 8000 and 10000 mg/kg bw of the test substance in a study performed according to OECD TG 401 following GLP principles. 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. All animals were subjected to a complete gross necropsy following their sacrifice or spontaneous death.

The following death rates were observed: 0 % at 3000 mg/kg bw, 0 % at 5000 mg/kg bw, 0 % at 8000 mg/kg bw and 20 % at 10000 mg/kg bw.

The acute oral LD50 of the test substance in rats of both sexes observed over a period of 14 days was estimated to be greater than 10000 mg/kg bw.