1-(2,4,6-trichlorophenyl)acetone O-methyloxime

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-01-21 until 2014-02-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was carried out following OECD guideline 425 and in compliance with GLP. The method description is well documented. Statistical treatment of results, clinical signs and mortality were reported.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-(2,4,6-trichlorophenyl)acetone O-methyloxime

EC Number:

807-534-0

Cas Number:

1228284-89-6

Molecular formula:

C10H10Cl3NO

IUPAC Name:

1-(2,4,6-trichlorophenyl)acetone O-methyloxime

Test material form:

other: liquid

Details on test material:

- Physical state: Brown liquid
- Purity test date: 25 September 2013
- Expiration date of the lot/batch: End September 2015
- Stability under test conditions: Stable until end September 2015
- Storage condition of test material: Room temperature (<30°C), protected from light and humidity

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories S.r.l., S.Pietro al Natisone (UD), Zona Industriale Azzida, 57, 33040, Italy
- Strain: RccHan:WIST
- Age at study initiation: 8-11 weeks
- Weight at study initiation: 166-187 g
- Fasting period before study: Yes (overnight)
- Housing: Individually in Type II. polypropylene/polycarbonate cages
- Diet: Ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" ad libitum (except for overnight pre-dose fast and for 3 hours post dose). Ssniff Spezialdiäten GmbH, D-59494 Soest Germany
- Water: Municipal tap water ad libitum
- Acclimation period: At least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3-23.9
- Humidity (%): 34-62
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 January 2014 To: 25 February 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE: Corn oil
DOSAGE PREPARATION: Test item was melted in a water bath at a temperature not exceeding 50°C prior to formulating with corn oil.
DOSE VOLUME: 10 mL/kg body weight

Doses:

2000 and 550 mg/kg bw

No. of animals per sex per dose:

2 females at 550 mg/kg bw, 5 females at 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed individually after dosing at 30 minutes, 1, 2, 3, 4, and 6 hours and once each day for 14 days thereafter. Body weights were recorded on Days -1 (prior to the removal of food), 0 (prior to administration), 7 and 14.
- Necropsy of survivors performed: Yes

Statistics:

As the AOT425StatPgm program could not estimate an exact LD50 in this case, due to the pattern of mortality. In line with the OECD guideline, an alternative calculation method was used. Probit analysis was performed, within the SPSS PC+4.0 package. This is the standard validated statistical software package used at this facility for Probit analysis on acute studies for LD50 and LC50 calculations.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

2 830 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities at 550 mg/kg. Mortality was observed in one animal (1/5) dosed at 2000 mg/kg bw on Day 2.

Clinical signs:

At 550 mg/kg, the following were seen: decreased activity (1/2), hunched back (1/2) and piloerection (1/2). All animals were symptom free from 1 day after the treatment.
At 2000 mg/kg, the following were seen: decreased activity (5/5), hunched back (5/5), prone position (5/5), incoordination (5/5), piloerection (3/5) and irritability (4/5). All surviving animals were symptom free from Day 4 after treatment.

Body weight:

There were no treatment related body weight changes.

Gross pathology:

There was no treatment related macroscopic findings in surviving animals. In the 2000 mg/kg animal that was found dead, the following findings were recorded in the lungs: collapsed; dark discoloration, red, diffuse all lobes; foamy material, white.

Any other information on results incl. tables

Table 1: Acute oral toxicity in the rat (mortality data)

Animal number	Dose (mg/kg bw)	Volume dosed (mL)	Mortality
5101	550	1.7	Survived
5102	2000	1.7	Survived
5103	2000	1.8	Survived
5104	2000	1.9	Died (Day 2)
5105	550	1.8	Survived
5106	2000	1.9	Survived
5089	2000	1.9	Survived

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute oral median lethal dose LD50 of the test item was greater than 2000 mg/kg bw in RccHan:WIST female rats. The value for the LD50 calculated by Probit analysis is 2830 mg/kg bw (confidence limits could not be calculated).

Executive summary:

An acute oral toxicity (up and down procedure) study was conducted with 7 animals (female RccHan:WIST rats). Animals were treated with a single oral (gavage) dose of the test item at a dose level of 550 (2 animals) or 2000 (5 animals) mg/kg body weight (bw) followed by a 14 day observation period. The animals were fasted overnight prior to treatment and food was returned 3 hours after dosing. All animals were observed individually after dosing at 30 minutes, 1, 2, 3, 4 and 6 hours post treatment and once each day for 14 days thereafter. Body weight was measured on Day -1 (prior to removal of food), Day 0 (prior to administration) and weekly thereafter. All animals were examined macroscopically at the end of the study.

No mortality was observed at the dose level of 550 mg/kg bw. Treatment at 550 mg/kg bw caused decreased activity (1/2), hunched back (1/2) and piloerection (1/2). All animals were symptom free from 1 day after the treatment. Mortality was observed in one animal (1/5) on Day 2 at 2000 mg/kg bw dose level. Treatment at 2000 mg/kg bw caused decreased activity (5/5), hunched back (5/5), prone position (5/5), incoordination (5/5), piloerection (3/5) and irritability (4/5). All surviving animals were symptom free from Day 4 after treatment. There were no treatment related body weight changes. Body weights were within the range commonly recorded for this strain and age. There was no evidence of the test item-related observations at the dose level of 550 mg/kg bw at necropsy.

Under the conditions of this study, the acute oral median lethal dose LD50 of the test item was greater than 2000 mg/kg bw in RccHan:WIST female rats. The value for the LD50 calculated by Probit analysis is 2830 mg/kg bw (confidence limits could not be calculated).