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

Endpoint summary

Description of key information

Oral: LD50 >2000 mg/kg bw, rat, Matting 2015
Dermal:  LD50 >2000 mg/kg bw, rat, Matting 2015

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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

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.

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.

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

 

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-01-21 until 2014-02-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/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: Young adult.
- Weight at study initiation: 202-252 g.
- Fasting period before study: None.
- 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. Ssniff Spezialdiäten GmbH, D-59494, Soest, Germany
- Water: Municipal tap water ad libitum.
- Acclimation period: 6-8 Days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1-23.9
- Humidity (%): 24-48
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 January 2014 To: 06 February 2014

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back (shaved approximately24 hours before treatment).
- % coverage: Approximately 10%
- Type of wrap if used: Sterile gauze pads kept in contact with the skin by using a patch of adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes (body temperature water).
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

24 hours

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: Observed on the day of treatment, at 1 and 5 hours after the application of the test item, and once each day for 14 days thereafter. Body weights recorded on Day 0 (before treatment) and on Days 7 and 14.
- Necropsy of survivors performed: Yes

Statistics:

Not applicable (limit test, no mortality).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities.

Clinical signs:

There were no treatment related clinical signs or skin irritation.

Body weight:

There were no treatment related effects on body weight.

Gross pathology:

There were no treatment related macroscopic findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute median lethal dose (LD50) of the test item after single dermal administration was greater than 2000 mg/kg bw in male and female RccHan:WIST rats.

Executive summary:

A single administration of the test item at a dose of 2000 mg/kg body weight (bw) was applied dermally to 5 male and 5 female RccHan:WIST rats, followed by a 14-day observation period. The test item was applied as supplied. The application period was 24 hours. Clinical observations along with a check of viability and mortality were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Rats were killed and subjected to a gross macroscopic examination at the end of the 2-week observation period (Day 14).

No mortality occurred during the 14-day observation period after 24-hour dermal exposure to the test item in RccHan:WIST rats. No adverse clinical signs were observed after treatment with the test item or during the 14 day observation period. There were no treatment related effects on body weight or body weight gain during the observation period. There was no evidence of any treatment-related macroscopic findings at a dose level of of 2000 mg/kg bw at necropsy.

The acute median lethal dose (LD50) after a single dermal administration was greater than 2000 mg/kg bw in male and female RccHan:WIST rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Oral acute toxicity

Matting (2015) conducted a study in compliance with GLP and according to OECD guideline. The animals (rat Wistar) were treated with a single oral (gavage) dose of the test item at a dose level of 550 mg/kg bw (2 females) or 2000 mg/kg bw (5 females) followed by a 14 days observation period. 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.

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.

The study is considered complete, reliable and adequate. The acute oral toxicity value LD50 > 2000 mg/kg bw is carried forward for the purposes of risk assessment, and classification.

Dermal acute toxicity

Matting (2015) performed a limit test study carried out in compliance with GLP and according to OECD guideline. The animals were exposed 24 hours to the substance, after which they were kept in observation for 14 days. There were no adverse clinical signs noted in any animals throughout the study. Thus, the median lethal dose of the test item after single dermal administration was found to be greater than 2000 mg/kg bw.

The study is considered complete, reliable and adequate. The acute dermal toxicity value LD50 > 2000 mg/kg bw is carried forward for the purposes of risk assessment, and classification.

Justification for selection of acute toxicity – oral endpoint
Only one study was available, which was carried out according to recent guideline and under GLP.

Justification for selection of acute toxicity – dermal endpoint
Only one study was available, which was carried out according to recent guideline and under GLP.

Justification for classification or non-classification

Acute oral toxicity

The key value selected for the acute oral toxicity is LD50 > 2000 mg/kg bw. According to Regulation (EC) No. 1272/2008, Annex I, Part 3, Table 3.1.1., the substance in not classified as acutely toxic.

Acute dermal toxicity

The key value selected for the acute dermal toxicity is LD50 > 2000 mg/kg bw. The substance does not meet the criteria for classification and labelling for acute dermal toxicity as set out in Regulation (EC) No. 1272/2008, Annex I, Part 3, Table 3.1.1.