2-(4-tert-butylphenyl)-6-cyano-5-[bis(ethoxycarbonylmethyl)carbamoyloxy]-1H-pyrrolo[1,2-b][1,2,4] triazole-7-carboxylic acid 2,6-di-tert-butyl-4-methylcyclohexylester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 Jul - 08 Aug 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No. 8147, November 2000, including the most recent partial revisions

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

448-050-6

EC Name:

-

Cas Number:

444065-11-6

Molecular formula:

C41 H57 N5 O8

IUPAC Name:

2,6-di-tert-butyl-4-methylcyclohexyl 5-{[bis(2-ethoxy-2-oxoethyl)carbamoyl]oxy}-2-(4-tert-butylphenyl)-6-cyano-1H-pyrrolo[1,2-b][1,2,4]triazole-7-carboxylate

Details on test material:

- Name of test material (as cited in study report): UC-141
- Physical state: White powder
- Analytical purity: 99.7% (area %), 98.2% (mass %)
- Lot/batch No.: CE-203
- Expiration date of the lot/batch: 1 Jan 2005
- Storage condition of test material: At room temperature in the dark

Test animals

Species:

rat

Strain:

other: Wistar Crl:(WI)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzveld, Germany
- Age at study initiation: Approximately 11 weeks
- Weight at study initiation: 344 g (mean, males) and 227 g (mean, females)
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance
- Housing: Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany)
- Diet: Standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.2-24.5
- Humidity (%): 44-83
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

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

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: According to OECD 423, if the acute oral toxicity of a substance is expected to be low, a limit test may be performed with the highest dose level of 2000 mg/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Step 1: 3 males
Step 2: 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations of mortality were made twice daily; observations of clinical signs were made several times on day 1 and daily thereafter, graded according to a severity scale of 1-4; weighing was performed weekly on day 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: Yes, all gross pathological changes were recorded

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off according to OECD 423

Mortality:

There was no mortality during the 14-day study period.

Clinical signs:

Uncoordinated movements were noted in all males 2-4 hours after adminstration, lasting until day 2 in 2/3 animals. One male had a hunched posture from 2 hours after dosing until day 3. No clinical signs were observed in the females.

Body weight:

There were no effects on body weight.

Gross pathology:

Necropsy and histopathological examination revealed no substance-related findings.

Any other information on results incl. tables

Table 1: Mortality and clinical signs

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Males
2000	0/3/3	1 h - 3 days	-	0
LD50 > 2000 mg/kg bw
Females
2000	0/0/3	-	-	0
LD50 > 2000 mg/kg bw

                                                                                           

* first number = number of dead animals                                 

 second number = number of animals with clinical signs         

 third number = number of animals used                               

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified