Reaction mass of 3-(difluoromethyl)-1-methyl-N-[(1RS,4SR,9RS)-1,2,3,4-tetrahydro-9-isopropyl-1,4-methanonaphthalen-5-yl]pyrazole-4-carboxamide and of 3-(difluoromethyl)-1-methyl-N-[(1RS,4SR,9SR)-1,2,3,4-tetrahydro-9-isopropyl-1,4-methanonaphthalen-5-yl]pyrazole-4-carboxamide; isopyrazam

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Jan 2014 to 16 May 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

632-619-2

EC Number:

632-619-2

Cas Number:

881685-58-1

Molecular formula:

C20 H23 F2 N3 O

IUPAC Name:

632-619-2

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan:(WIST))

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult rats, 9 - 11 weeks old
- Weight at study initiation: 171 - 181 g
- Fasting period before study: The night before treatment
- Housing: Individual caging, cage Type II, polypropylene/polycarbonat. Lignocel Bedding for Laboratory animals was available to animals during the study.
- Diet: Autoclavable complete diet for rats and mice – breeding and maintenance. Ad libitum
- Water: Tap water. Ad libitum
- Acclimatisation period: At least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4 – 24.6
- Humidity (%): 32 – 70
- Air changes (/hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 Jan 2014 To: 18 Feb 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % Carboxymethyl cellulose in water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mL/kg bw
- Amount of vehicle (if gavage): 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually after dosing at 30 minutes, then 1, 2, 3, 4 and 6 hours post treatment and once each day for 14 days thereafter. Body weight was measured at the start and on day 7 and 14.
- Necropsy of survivors performed: yes. All animals were euthanised at the end of the observation period by exsanguination under pentobarbital anaesthesia. All animals were subjected to gross macroscopic evaluation. The cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets and the animals were discarded.

Statistics:

- From the body weights, the group means and their standard deviations were calculated.
- The LD50 was calculated using the AOT425StatPgm programme (version 1.0, 2001).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no deaths during the study.

Clinical signs:

other: Decreased activity in one animal at 1 hour after the treatment. The animal was symptom free from 2 hours after the treatment.

Gross pathology:

There was no evidence of macroscopic observations in animals terminated on day 14.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median LD50 of the test material was estimated to be > 2000 mg/kg bw in female rats.

Executive summary:

Five female RccHan:(WIST) rats were given a single oral (gavage) dose of 2000 mg/kg bw of the test material formulated in 0.5% carboxymethyl cellulose in a study according to OECD TG 425 and GLP principles. Prior to dosing, the animals were fasted overnight. The animals were observed individually after dosing at 30 minutes, then 1, 2, 3, 4 and 6 hours post treatment and once each day for 14 days thereafter for any signs of systemic toxicity and their body weights were recorded. All animals were examined macroscopically at the end of the study.

No deaths occurred during the study. Decreased activity in one animal at 1 hour after the treatment was recorded. The animal was symptom free from 2 hours after the treatment. There were no treatment related body weight changes. There was no evidence of the macroscopic observations in animals terminated at day 14.

Upon an acute oral administration of the test material and a 14 day post treatment observation period, the median LD50 in female rats was found to be > 2000 mg/kg bw.