2,2',4'-trichloroacetophenone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented study according to international accepted guidelines and GLP compliant.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Two steps of treatment procedure was inverted. (Human error.) Presumed Effect on the Study: NONE

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2',4'-trichloroacetophenone

EC Number:

224-218-2

EC Name:

2,2',4'-trichloroacetophenone

Cas Number:

4252-78-2

Molecular formula:

C8H5Cl3O

IUPAC Name:

2-chloro-1-(2,4-dichlorophenyl)ethan-1-one

Test material form:

solid: crystalline

Details on test material:

Test item: DICHLOROPHENACYL CHLORIDE (CAS 4252-78-2)
Batch No. T-5427
Colour: beige
Physical state: solid, crystalline powder
Active Ingredient Content (GC): 98.9 %
Storage: on cool and dry place, protected from light

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species and strain: Crl:(WI)Br rats
Source: TOXI COOP Zrt.
Hygienic level at arrival: SPF
Hygienic level during the study: Good conventional
Number of animals: 3 animals/group
Sex: Female, nulliparous and non pregnant animals
Age of animals: Young adult rat, 8 weeks old in first, second and third step
Body weight range at starting (first step): 164 - 168 g
Body weight range at starting (second step): 155 - 173 g
Body weight range at starting (third step): 158 - 165 g
Animal health: Only healthy animals were used for the study. Health status was certified by the study director.

Housing: Group caging (3 animals/cage)
Light: Artificial light, from 6 a.m. to 6 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: 10-15 air exchanges/hour by central air-condition system.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

acetone

Remarks:

Helianthi annui oleum raffinatum

Details on oral exposure:

A single oral administration - followed by a fourteen-day observation period - was performed by gavage.
Starting dose of 300 mg/kg bw was selected on the basis of the available information about the test item. The acute toxic class method was carried out involving a stepwise procedure with the use of 300 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 300 mg/kg bw dose level the test was continued at 2000 mg/kg bw dose level on further three female rats. Since two animals died in the second step by Day 1, three further female rats were treated with the first dose (300 mg/kg bw). No animal died in the third step, so the test was finished. (Deviation: The step 2 and step 3 was inverted as follows: the animals of group 2 were treated with 2000 mg/kg bw dose and the animals of group 3 was treated with 300 mg/kg bw dose, but it doesn't have any presumed effect on the study.)

All doses were formulated in the vehicle. Concentration of formulations was adjusted to maintain a treatment volume of 10 mL/kg bw. The test item was applied in a concentration of 30 and 200 mg/mL. Formulations were prepared just before the administration and stirred continuously during the treatment.

The day before treatment the animals were fasted. The food but not water was withheld overnight. The food was given back 3 hours after the treatment.

Doses:

300, 2000 mg/kg bw

No. of animals per sex per dose:

3 female/dose

Control animals:

no

Details on study design:

The observation period was 14 days. Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h, 5 h and 6 h after the treatment and twice each day for 14 days thereafter.
The body weights were recorded on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g.
At the end of the observation period rats were sacrificed and necropsy were performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

300 - 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No death occurred at 300 mg/kg bw single oral dose of the test item. All female rats in step 1 survived until the end of the 14-day observation period.
All rats dosed at 2000 mg/kg bw DICHLOROPHENACYL CHLORIDE (CAS 4252-78-2) died during the study. Two rats died on Day 1 and one animal died on Day 8. All deaths seemed to be consequences of systemic toxic effect of the test item. No death occurred at 300 mg/kg bw single oral dose of the test item. All female rats in step 3 survived until the end of the 14-day observation period.

Clinical signs:

other: In group 1 treated with 300 mg/kg bw dose: Increased activity (score +1), irritability (score +1), blood around the nose (score +1) and piloerection (score +1; +2) occurred in all animals. Vocalization (score +1), incoordination (score +1) and diarrhea (s

Gross pathology:

All rats treated with 2000 mg/kg bw dose of the test item spontaneously died during the study. An external necropsy findings as undernourishing, piloerection, blood around the nose and anus contaminated with feces was detected in one animal. An internal necropsy finding as autolysis was observed in all animals. It is normal physiological process after death.
The animals treated with 300 mg/kg bw survived until the scheduled necropsy on Day 15. Internal necropsy finding as pale kidneys was observed in two animals of group 1 and in two animals of group 3. This alteration could not be related to the test item toxic effect, but was regarded an individual variation. Most likely the observation is a congenital anomaly. No pathological changes were found related to the effect of the test item during the macroscopic examination of survivor animals.

Any other information on results incl. tables

Groups	Treatment		Lethality
	Test item	Dose(mg/kgbw)	Females
1	“dichlorophenacyl chloride” Step1	2000	3/3
2	“dichlorophenacyl chloride” Step2	300	2/3
3	“dichlorophenacyl chloride” Step3	300	0/3

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The method used, was not intended for the precise calculation of a precise LD50 value.
The test item was ranked into classes of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423.
Hazard Category: Acute Tox. 4

Executive summary:

Dose (mg/kg bw)	Mortality (dead/treated)	LD50 (mg/kg bw)	GHS category
300	0/6	between 300 and 2000	4