Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from study report .

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

To assess the toxicity potential of test chemical after single oral administration in Wistar rats and an observation period of 14 days.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazole-5-sulphonamide

EC Number:

270-393-3

EC Name:

2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazole-5-sulphonamide

Cas Number:

68427-35-0

Molecular formula:

C20H19N3O5S

IUPAC Name:

2-[7-(diethylamino)-2-oxo-2H-chromen-3-yl]-1,3-benzoxazole-5-sulfonamide

Test material form:

solid: particulate/powder

Details on test material:

Identification:2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl] benzoxazole-5-sulphonamide Molecular Formula: C20H19N3O5SMolecular Weight: 413.452 g/moleAppearance: Yellow to yellowish orange powderBatch number: FG/15-16/1865AI Content: 100%Storage conditions : Room temperature (20 - 30 °C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: In-house animals, bred at Animal House, sa-FORD.- Age at study initiation:10-11 weeks at the time of dosing.- Weight at study initiation: Minimum: 142 g Maximum: 180 g (Individual body weights were within ± 20 % prior to treatment after overnight fasting)- Fasting period before study: overnight fasting- Housing: The animals were housed individually in polycarbonate cages (size 37 [cm] x 21 [cm], height 20 [cm]). Bedded with corn cobs (Sparconn Life Sciences Bangalore) SPAR – 32 /2016 and marked temporarily on tail, permanently on toe pad micro tattooing and cage cards. Individual cage cards were labelled with study no., study type, test system, group, dose, sex, animal number, experimental start, dosing date and completion date.experimental room floor and work tops were swept and mopped with disinfectant solution every day. All the cages and water bottles were changed at least twice every week.- Diet (e.g. ad libitum): All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum. Batch Nos.: 040316 and 040416.- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum via drinking bottles- Acclimation period: Animal nos. 01-03 were acclimatized for 6 days, 04-06 for 12 days, 07-09 for 17 days and 10-12 for 6 days prior to administration of the test item. ENVIRONMENTAL CONDITIONS- Temperature (°C): Minimum: 19.30 °C, Maximum: 23.10 °C- Humidity (%):Minimum, 43.30% Maximum: 67.00%- Air changes (per hr): More than 12 changes per hour- Photoperiod (hrs dark / hrs light):12 hour light and 12 hour dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Details on exposureVEHICLE- Concentration in vehicle: 300 and 2000 mg/kg body weight- Amount of vehicle (if gavage): 10 ml/kg body weight- Justification for choice of vehicle: Corn oil (Batch No- MR020116-MP Biomedicals) was selected as a vehicle based on solubility testing.- Lot/batch no. (if required):MR020116-MP MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg body weight DOSAGE PREPARATION (if unusual): The test item formed a homogenous suspension in corn oil and hence, it was selected as a vehicle. The desired quantity of the test item (300 mg and 2000 mg) was added to the mortar and triturated using pestle. The vehicle (corn oil) was added to the mortar slowly and mixed well. The formulation was then transferred to a calibrated measuring cylinder. The stock concentration of 200 mg/ml and 30 mg/ml was achieved by making up the volume to 10 ml in the measuring cylinder. CLASS METHOD (if applicable)- Rationale for the selection of the starting dose:The starting dose level was that, which most likely to produce mortality in some of the dosed animals. The starting dose level was selected as 300 mg/kg body weight as no information available in the pesticide manual. The time interval between treatment groups was determined by the onset, duration, and severity of toxic signs. Treatment of animals at the next dose was delayed until confidence of survival of the previously dosed animals is attained.

Doses:

300 and 2000 mg/kg body weight

No. of animals per sex per dose:

Total: 12 300 mg/kg bw (Step -I): 4300 mg/kg bw (Step -II): 42000 mg/kg bw (Step -III): 42000 mg/kg bw (Step -IV): 4

Control animals:

not specified

Details on study design:

Details on study design- Duration of observation period following administration: 14 days - Frequency of observations and weighing: Recorded on day 0 (prior to dosing) 7 and 14. - Necropsy of survivors performed: yes- Other examinations performed: clinical signs, body weight and gross pathology were examined.

Statistics:

No data available

Results and discussion

Preliminary study:

No data available

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Mortality:

No mortality was observed during the entire experimental period in treated female rats.

Clinical signs:

No clinical sign of toxicity was observed in 300 and 2000 mg/kg bw treated female rats.

Body weight:

Gain in body weight were observed on day 7 and 14, as compared to day 0 body weight, weighed prior to dosing in 300 and 2000 mg/kg bw treated female rats.

Gross pathology:

No external and Internal gross pathological abnormalities were observed in 300 and 2000 mg/kg bw treated female rats.

Other findings:

No data available

Any other information on results incl. tables

Individual Animal Mortality Record

Animal No.	Group/ Step/ Dose (mg/kg body weight)	Day of Observation (Day 0 to 14)
		Morning Observation	Evening Observation
01	G1/ Step-I/ 300	No mortality and morbidity	No mortality and morbidity
02		No mortality and morbidity	No mortality and morbidity
03		No mortality and morbidity	No mortality and morbidity
04	G1/ Step-II / 300	No mortality and morbidity	No mortality and morbidity
05		No mortality and morbidity	No mortality and morbidity
06		No mortality and morbidity	No mortality and morbidity
07	G2/ Step-III/ 2000	No mortality and morbidity	No mortality and morbidity
08		No mortality and morbidity	No mortality and morbidity
09		No mortality and morbidity	No mortality and morbidity
10	G2/ Step-IV/ 2000	No mortality and morbidity	No mortality and morbidity
11		No mortality and morbidity	No mortality and morbidity
12		No mortality and morbidity	No mortality and morbidity

Individual Animal Body Weight (g) andBody Weight Changes(%)

Animal No.	Group/ Step/ Dose (mg/kg body weight)		Body Weight (gram)			Body Weight Change (%)
		Dose Volume* (ml)	Day 0	Day 7	Day 14	Day 0-7	Day 0-14
01	G1/ Step-I/ 300	1.7	167	196	209	17.37	25.15
02		1.6	165	193	213	16.97	29.09
03		1.7	168	187	210	11.31	25.00
04	G1/ Step-II / 300	1.7	172	201	208	16.86	20.93
05		1.8	179	199	224	11.17	25.14
06		1.7	171	210	218	22.81	27.49
07	G2/ Step-III/ 2000	1.7	170	192	211	12.94	24.12
08		1.8	180	221	233	22.78	29.44
09		1.7	170	194	209	14.12	22.94
10	G2/ Step-IV/ 2000	1.5	148	168	180	13.51	21.62
11		1.4	144	182	197	26.39	36.81
12		1.4	142	166	192	16.90	35.21

Group/ Step/ Dose (mg/kg body weight)		Rats Body Weight (gram)			Body Weight Changes (%)
		Day 0	Day 7	Day 14	0-7	0-14
G1/ Step-I/ 300	Mean	166.67	192.00	210.67	15.21	26.41
	SD	1.53	4.58	2.08	3.39	2.32
	n	3	3	3	3	3
G1/ Step-II / 300	Mean	174.00	203.33	216.67	16.95	24.52
	SD	4.36	5.86	8.08	5.82	3.32
	n	3	3	3	3	3
G2/ Step-III/ 2000	Mean	173.33	202.33	217.67	16.61	25.50
	SD	5.77	16.20	13.32	5.37	3.47
	n	3	3	3	3	3
G2/ Step-IV/ 2000	Mean	144.67	172.00	189.67	18.93	31.21
	SD	3.06	8.72	8.74	6.67	8.34
	n	3	3	3	3	3

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

The acute oral toxicity dose (LD50) was considered to be >2000 mg/kg bw, when Wistar female rats were treated with test chemical via oral gavage route.

Executive summary:

The acute oral toxicity study of test chemical was conducted according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) in 12 Wistar female rats at the concentration of 300 and 2000 mg/kg bw and administered via oral gavage route. The given test chemical (100% pure) dissolved as a homogenous suspension in corn oil and hence, it was selected as a vehicle. The desired quantity of the test item (300 mg and 2000 mg) was added to the mortar and triturated using pestle. The vehicle (corn oil) was added to the mortar slowly and mixed well. The formulation was then transferred to a calibrated measuring cylinder. The stock concentration of 200 mg/ml and 30 mg/ml was achieved by making up the volume to 10 ml in the measuring cylinder. The animals were observed for mortality and clinical signs on day 0 (prior to dosing) 7 and 14. Necropsy was performed.No mortality was observed during the entire experimental period in treated female rats.No clinical sign of toxicity was observed in 300 and 2000 mg/kg bw treated female rats.Gain in body weight were observed on day 7 and 14, as compared to day 0 body weight, weighed prior to dosing in 300 and 2000 mg/kg bw treated female rats.No external and internal gross pathological abnormalities were observed in 300 and 2000 mg/kg bw treated female rats. Therefore, the acute oral toxicity dose (LD50) was considered to be >2000 mg/kg bw, when Wistar female rats were treated with test chemical via oral gavage route. Thus, comparing this value with the criteria of CLP regulation, given test chemical cannot be classified for acute oral toxicity.