2-hexyldecanoic acid [4-(6-tert-butyl-7-chloro-1H-pyrazolo[1,5-b][1,2,4]triazol-2-yl)phenylcarbamoyl]methylester

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:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

adopted 1996

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 1996

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

adopted June 1996

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), adopted November 2000 and most recent partial revisions

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): UM-235
- Physical state: white powder
- Lot/batch No.: #SI-1
- Expiration date of the lot/batch: 01 Jan 2005
- Storage condition of test material: at room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany (strain: Crl:(WI) BR (outbred, SPF-Quality))
- Age at study initiation: 11 weeks
- Weight at study initiation: male (mean) 343 ± 18 g, female (mean) 212 ± 13 g (did not exceed ±20 % of the mean)
- Fasting period before study: a maximum of 20 hours, up to 3-4 hours after dosing
- Housing: group housing of 3 animals per cage in Makrolon cages (type IV) containing purified sawdust as bedding material
- Diet: standard pelleted laboratory animal diet (Altromin code VRF 1), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.1 - 24.5 (actual range)
- Humidity (%): 47 - 79 (actual range)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL (w/w) (calculated from dose volume of 10 mL/kg and dose of 2000 mg/kg bw)
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: based on trial formulations performed at the test lab

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for viabiliy and mortality: twice daily; clinical signs: at periodic intervals at the day of dosing and once daily thereafter until Day15 (for grading of symptoms see Table 1 under "any other information on material and methods including tables"); weighing: Day 1 pre-administration and on Days 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

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: No effects were observed up to and including the highest dose level. According to OECD 423, the LD50 cut-off value is set at 5000 mg/kg bw.

Mortality:

No mortalities occurred.

Clinical signs:

Piloerection in 3/3 males and 3/3 females was seen 2 and 4 hours after dosing, in females it was still visible 1 day after dosing. Hunched posture for 3/3 females was noted 4 hours after dosing, for 1/3 females hunched posture was still seen 1 day after dosing. 3/3 male animals showed hunched posture already 2 hours after dosing. For 1/3 males this clinical sign was still detectable 2 days after dosing, whereas for the other 2 males it was reversed by one and two days after dosing. Further, 3/3 females showed uncoordinated movements 2 and 4 hours after dosing and 1/3 females showed chromodacryorrhoea 2 and 4 hours after dosing (see Table 2).

Body weight:

Slight body weight loss or reduced body weight gain was noted in the males between Days 8 and 15 (9.5%). No effects on body weight were noted in the females (see Table 3)

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

Table 2. Table for acute oral toxicity.

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Males
2000	0/3/3	2 h - Day2	---	0
Females
2000	0/3/3	2 h - Day3	---	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           

 

Table 3. Body weights (g)

Sex/Dose Level	Animal	Day1	Day8	Day15
Females/2000 mg/kg bw	1	236	266	277
	2	216	245	254
	3	212	239	247
	Mean	221	250	259
	Standard deviation	13	14	16
	N	3	3	3
Males/2000 mg/kg bw	1	359	410	406
	2	323	371	372
	3	348	403	404
	Mean	343	395	394
	Standard deviation	18	21	19
	N	3	3	3

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

DSD: not classified
CLP: not classified