diethyl 1-(2,4-dichlorophenyl)-5-methyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylate

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 401, 402, EPA 81-1

Deviations:

yes

Remarks:

intraperitoneal application

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

diethyl 1-(2,4-dichlorophenyl)-5-methyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylate

EC Number:

603-923-2

Cas Number:

135590-91-9

Molecular formula:

C16H18Cl2N2O4

IUPAC Name:

diethyl 1-(2,4-dichlorophenyl)-5-methyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylate

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG, Kastengrund, SPF breeding colony
- Age at study initiation: males approx. 7 weeks, females approx. 8 weeks
- Weight at study initiation: mean males 191 g, females 176 g
- Fasting period before study: from about 16 hours before to 3 - 4 hours after treatment
- Housing: in fully air-conditioned rooms in Makrolon cages (Type 4) on soft wood granulate in groups of 5 animals
- Diet: Altromin 1324 rat diet (Altromin GmbH, Lage/Lippe), ad libitum
- Water: tap water in plastic bottles, ad libitum
- Acclimation period: approx. 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

other: sesame oil

Doses:

500, 1000 mg/kg bw

No. of animals per sex per dose:

5

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: After treatment, the course of intoxication, the mortality rate and the times of death were recorded. Animals were weighed weekly. Lethally intoxicated animals were dissected and examined macroscopically.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 500 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Estimated (without 95 % confidence)

Mortality:

The mortality rates showed no sex-specific differences. The deaths mostly occurred during the day of application and the day thereafter:
1000 mg/kg: males 2/5 (d2), females 3/5 (d1 and d2)
500 mg/kg: males 0/5, females 0/5

Clinical signs:

The clinical signs of intoxication were largely the same for both males and females and were observed only in the 1000 mg/kg dose group. They started to emerge 30 minutes after application of the test substance. Surviving animals were free of signs of intoxication by the 3rd day of the study.
The clinical signs of intoxication such as flanks drawn in, squatting posture, stilted gait and irregular repiration were observed in nearly all animals. In addition, lethally intoxicated animals showed decreased or increased respiratory rate, coat bristling, decreased spontaneous activity, hypersensitivity to touch, prone position, palpebral fissure narrow and exhibited reduced or no placing reaction, no corneal reflex and/or reduced pawreflex to pinching.

Body weight:

There were no impairments of body weight gains.

Gross pathology:

Macroscopic examination of the males and females found dead during the study revealed the following abnormalities:
- liver with white spotted surface
- abdominal cavity filled with colourless fluid
- abdominal cavity filled with reddish fluid
- adipose tissue white spotted

The animals killed at the end of the observation period showed the following macroscopically visible changes:
- liver with white deposits
- adipose tissue white spotted
- white spots on mesenteric tissue
- pancreas with white deposits
- kidneys with white spotted surface
- kidneys with white deposits