2-amino-5-chlorobenzophenone

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Remarks:

intravenous

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD Principales of Good Laboratory Practice and the “Chemikaliengesetz” (Chemicals Act) of the Federal Republic of Germany

Version / remarks:

EEC Guide-Line 92/69/EEC, Annex I, dated 29th December 1992

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-5-chlorobenzophenone

EC Number:

211-949-7

EC Name:

2-amino-5-chlorobenzophenone

Cas Number:

719-59-5

Molecular formula:

C13H10ClNO

IUPAC Name:

(2-amino-5-chlorophenyl)(phenyl)methanone

Test material form:

solid: particulate/powder

Test animals

Species:

mouse

Strain:

other: Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

Age at study initiation: male: 33 days, femals:35 days
Weight at study initiation: male: 26.6g±1.6, female: 24.2g±1.8
Fasting period before study: 16 to 20 hours before and up to 2 hours after administration
Housing: individual accommodation in type II Makroion cages with softwood granulate bedding
Diet (e.g. ad libitum): Flitered, demineralized water, adjusted to Ph=2.6±0.3 with hydrochloric acid, was freely available to the animals in bottles
Acclimation period: 7days

Administration / exposure

Route of administration:

intravenous

Vehicle:

DMSO

Details on exposure:

The single intravenous administration was performed with a Hamilton syringe from Hamilton Bonaduz AG Typ Nr. 1710 TLL P/N: 81022/00, and a No.20 cannula, batch No. E592 802 from Beetan-Dickinsan into a tail vein.
The rate of injection was approx.. 0.1ml/sec
ADMINISTRATION VOLUME: 1ml/kg body weight.
The day of administration counted as day 1 for each treated animal

Doses:

25mg/kg
40mg/kg
60mg/kg

No. of animals per sex per dose:

5 animals/dose/sex
40 animals in total (20 males and 20 females)

Control animals:

yes

Details on study design:

Duration of observation period following administration: 14 days
Frequency of observations: On the day of administration (day 1= day of the treatment) the animals were observed throughout the working day.
Thereafter, up to the 14th day, they were observed twice daily (in the morning and in the afternoon). On weekends and holidays, they were observed once daily (in the morning).
Weighing: All study animals were weighed one day before the study start (day -1 = fasting day) and before treatment. The surviving animals were weighed on the 8th and 15th study day.
Necropy of survivors performed: yes
Other examinations performed: All animals that died intercurrently were autopsied and examined macroscopically. The findings were recorded.
After a 14 day Observation period, the surviving animals were exsanguinated under deep Pentobarbital narcosis (40 mg/kg.s.c injection), autopsied and examined macroscopically.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

49.1 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

41.1 mg/kg bw

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

45.2 mg/kg bw

Based on:

test mat.

95% CL:

> 34.7 - < 53.7

Mortality:

12 of 40 treated animals died. Death occurred within 1 day after administration

Clinical signs:

After the administration of the test compound, the following symptoms were seen:
Males: 25mg/kg: Sternal or lateral recumbency, tachypnea, and tonic-clonic convulsions.
Males: 40mg/kg: Sternal or lateral recumbency, dyspnea, tachypnea, exophthalmia and tonic-clonic convulsions.
Males: 60mg/kg: Sternal or lateral recumbency, dyspnea, exophthalmia and tonic-clonic convulsions.
Females: 25mg/kg: Sternal or lateral recumbency, tachypnea, and tonic-clonic convulsions.
Females: 40mg/kg: Sternal or lateral recumbency, dyspnea, tachypnea, exophthalmia and tonic-clonic convulsions.
Females: 60mg/kg: Sternal or lateral recumbency, dyspnea, tachypnea, exophthalmia and tonic-clonic convulsions.

Body weight:

The body weights of the animals were not influenced by the administration of the compound

Gross pathology:

No macroscopic organ or tissue findings at the autopsy of animals which died within 5min after administration were registered. One female animal which died within 1 day after administration of 60mg/kg b.w., showed macroscopically marked congestion of the liver.
At autopsy after an observation period of 2 weeks one animal showed congestion of the liver and one animal showed tail necrosis and loss of tailtip.

Any other information on results incl. tables

For the male animals the LD50 was estimated as 41.1mg/kg i.v (24h, 7 and 14 days) and for the female animals as 54.5mg/kg i.v (24h) and 49.1 mg/kg i.v (7 and 14 days). A common evaluation of both genders leg to an LD 50 of 47.2 mg/kg i.v and the 95% confidence interval (38.7-58.6]mg/kg i.v for the data observed 24h after application and to an LD 50 of 45.2mg/kg i.v and the 95% confidence interval [37.4-53.7]mg/kg i.v for the data observed 7 and 14 days after application.

Applicant's summary and conclusion

Conclusions:

The approx.. LD50 of 2-AMINO-5-CHLOROBENOPHENONE i.v. in OF1 mice is 45.2mg/kg for both gender (LD50 of 41.1 mg/kg b.w. for males and 49.2 mg/kg for females)

Executive summary:

An acute toxicity study with 2-AMINO-5-CHLOROBENOPHENONE batch 043H3449, was performed in mice from 22.05.1996 to 05.06.1996.

The compound was dissolved in Dimethylsulfoxid solution and administered intravenously. Five males and five females per group were treated.

After administration of 25,40 and 60mg/kg (administration volume: 1ml/kg body weight: administration rate 0.1ml/sec) and an observation period of 14 days, the following toxicity data were established:

2-AMINO-5-CHLOROBENOPHENONE, approx. LD50 i.v. mouse

Male: 41.1mg/kg

Female:49.1mg/kg

Male+female: 45.2mg/kg

12 of 40 treated animals died Death occurred within 1 day after administration