2-[(3,5-dimethyl pyrazolyl)carbamoyl]ethyl methacrylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 - 25 Jul 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted on 17 December 2001

Deviations:

no

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-[(3,5-dimethyl-1H-pyrazole-1-carbonyl)amino]ethyl 2-methylprop-2-enoate

EC Number:

680-413-6

Cas Number:

217437-44-0

Molecular formula:

C12H17N3O3

IUPAC Name:

2-[(3,5-dimethyl-1H-pyrazole-1-carbonyl)amino]ethyl 2-methylprop-2-enoate

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan, INC.
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 8.5 to 9 weeks
- Fasting period before study: from the day prior to administration until 3 h after the administration
- Housing: individually in stainless steel cages with a stainless mesh floor (D38 cm × W24 cm × H18 cm)
- Diet: solid pellets Lab Diet #5002 (PMI Nutrition International), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

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

Remarks on environmental conditions:
Between July 8 and 21 and July 23, 2011, the humidity in the animal room exceeded the upper control limit (70%) for 5 to 30 min per occasion, several times per day. (Abnormal humidity persisted for approximately 40 min on July 12 and 1.5 h on July 18.)
Humidity most frequently exceeded the limit on July 9 (26 episodes), and the highest humidity (79%) was observed on July 9, 14, and 18.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: carboxymethyl cellulose (CMC)

Remarks:

1% aqueous solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: The test substance was not homogeneously dispersible in distilled water; however, it was dispersible in 1% CMC.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: In previous acute toxicity study performed on structurally similar derivates, no animals died at a dose of 300 mg/kg bw. As the test substance was not expected to cause animal deaths at 300 mg/kg bw, the initial dose was set at 2000 mg/kg bw in accordance with the guideline.

Doses:

2000 mg/kg bw (step 1 and 2)

No. of animals per sex per dose:

6 (3 per step)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs and behaviour within 30 min (0 h) and 1, 3 and 6 h after administration and further once daily for 14 days until terminal necropsy day. Body weight was measured immediately before administration (Day 0), and on Days 3, 7, and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

accordint to OECD 423 (1 dead animal in step 1)

Mortality:

One animal of step 1 was found dead on Day 1.

Clinical signs:

other: Immediately after administration, prone position in 1/6 animals, eyelid closure in 2/6 animals, ptosis in 3/6 animals, and decreased locomotor activity in 1/6 animals were observed. At 1 h after administration, eyelid closure in 3/6 animals, ptosis in 1/6

Gross pathology:

Necropsy revealed a dark red area of the glandular stomach mucosa (adherence of blood-like substance) in the animal that died on Day 1 and redness of ileum mucosa and thinning of ileum mucosa in 2/5 animals sacrificed at Day 14 for terminal necropsy.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

In this acute oral toxicity study in female rats 1/6 animals died at 2000 mg/kg bw and thus the LD50 value was > 2000 mg/kg bw.