3,4-dicyanoaniline

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from authoritative database.

Data source

Reference

Reference Type:

other: authoritative database

Title:

Single oral administration toxicity test using 1,2-dicyanobenzene rats

Author:

Ministry of Health, Labour and Welfare, Ministry of the Environment and National Institute of Technology and Evaluation.

Year:

2010

Bibliographic source:

J-CHECK Japan Chemicals Collaborative Knowledge database, 2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Acute oral toxicity study of 1,2-Dicyanobenzene (91-15-6) in rat.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phthalonitrile

EC Number:

202-044-8

EC Name:

Phthalonitrile

Cas Number:

91-15-6

Molecular formula:

C8H4N2

IUPAC Name:

1,2-Dicyanobenzene

Details on test material:

Name: 1,2-Dicyanobenzene
InChI: 1S/C8H4N2/c9-5-7-3-1-2-4-8(7)6-10/h1-4H
Smiles: c1(c(cccc1)C#N)C#N
- Molecular formula (if other than submission substance):C8H4N2
- Molecular weight (if other than submission substance):128.134 g/mol
- Substance type:Organic
- Physical state:yellow powder
- Purity: 98.7%
- Impurities (identity and concentrations):1.3%

Specific details on test material used for the study:

Name: 1,2-Dicyanobenzene
InChI: 1S/C8H4N2/c9-5-7-3-1-2-4-8(7)6-10/h1-4H
Smiles: c1(c(cccc1)C#N)C#N
- Molecular formula (if other than submission substance):C8H4N2
- Molecular weight (if other than submission substance):128.134 g/mol
- Substance type:Organic
- Physical state:yellow powder
- Purity: 98.7%
- Impurities (identity and concentrations):1.3%

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Remarks:

IGS, SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: Charles River Japan Co., Ltd.
- Age at study initiation: 5 weeks old
- Weight at study initiation: The body weight ranged from 124 to 145 g for males and 106 to 120 g for females.
- Fasting period before study: The rats were fasted for about 17 hours.
- Housing: Animals were housed in a polycarbonate cage spread with laboratory animal floor coverings with 5 animals (same sex) per cage.
- Diet (e.g. ad libitum): solid feed
- Water (e.g. ad libitum): Freely ingested ultraviolet irradiated tap water after
filtering by 5 μm.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 ° C
- Humidity (%): 55 ± 15%
- Air changes (per hr): ventilation at about 12
times / hour
- Photoperiod (hrs dark / hrs light): lighting 12 hours / day (7: 00-19: 00) throughout the entire rearing period.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 5 mL/ kg

Doses:

0, 30, 60, 120, 240 and 480 mg / kg

No. of animals per sex per dose:

Total = 60 (sex/dose)

Control animals:

yes

Remarks:

Total = 10 (Male/Female)

Details on study design:

Details on study design
- Duration of observation period following administration: 14 days
- Frequency of observations: Mortality and general conditions were observed over 10 days, 30 minutes, 1, 3 and 6 hours on the administration day, once a day for 14 days thereafter; and weighing: Body weight was measured on days 4, 8, and 15 immediately before administration.
- Necropsy of survivors performed: yes
- Other examinations performed: Animals were observed for clinical signs.

Statistics:

Mortality rate was calculated by the Probit method.

Results and discussion

Preliminary study:

not specified

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

85 mg/kg bw

Based on:

test mat.

95% CL:

50 - 143

Remarks on result:

other: 50% mortality was observed

Mortality:

At 240 and 480 mg/kg group - All animals were died,
At 120 mg/kg group - 4 animals were died, and At 60 mg/kg group - 1 animal was died from 30 minutes to 6 hours after administration.

Clinical signs:

other: In deceased animals, decline in locomotor activity, convulsions, and stains around the mouth were found in the male and female 120, 240 and 480 mg/kg groups, and in addition to this symptom, the prone position, abnormal vocalization, aberrant tail and cya

Gross pathology:

not specified

Other findings:

not specified

Any other information on results incl. tables

Table – Mortality and LD50 values in rats after single oral administration of1,2-Dicyanobenzene

Sex	Dose (mg/kg)	Number of Animals	Number of dead animals								Mortality (%)	LD50 values (95% confidence limits)
			Day: 1	2	3	4	5	6	7	8-15
Male	0	5	0	0	0	0	0	0	0	0	0	85 mg/kg (50-143 mg/kg)
	30	5	0	0	0	0	0	0	0	0	0
	60	5	1	0	0	0	0	0	0	0	20
	120	5	4	0	0	0	0	0	0	0	80
	240	5	5								100
	480	5	5								100
Female	0	5	0	0	0	0	0	0	0	0	0	85 mg/kg (50-143 mg/kg)
	30	5	0	0	0	0	0	0	0	0	0
	60	5	1	0	0	0	0	0	0	0	20
	120	5	4	0	0	0	0	0	0	0	80
	240	5	5								100
	480	5	5								100

 

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

LD50 was considered to be 85 mg/kg with 95% confidence limit 50 to 143 mg/kg bw, when Male and female SD rats were treated with 1,2-Dicyanobenzene (91-15-6) via oral route.

Executive summary:

Acute oral toxicity study of 1,2-Dicyanobenzene (91-15-6) was conducted in 60 Crj: CD (SD) IGS, SPF male and female rat at the concentration of 0, 30, 60, 120, 240 and 480 mg/kg. The test substance (Purity - 98.7%; Obtained from - Showa Denko K.K., Tokyo, and lot number - CRL-981130) was administered in a 0.5% CMC-Na aqueous solution as volume 5 mL/kg. Mortality and general conditions were observed over 10 days, 30 minutes, 1, 3 and 6 hours on the administration day, once a day for 14 days thereafter. Body weight was measured on days 4, 8, and 15 immediately before administration.Animals were observed for clinical signs. Mortality rate was calculated by the Probit method. At 240 and 480 mg/kg group - All animals were died, At 120 mg/kg group - 4 animals were died, and At 60 mg/kg group - 1 animal was died from 30 minutes to 6 hours after administration. In deceased animals, decline in locomotor activity, convulsions, and stains around the mouth were found in the male and female 120, 240 and 480 mg/kg groups, and in addition to this symptom, the prone position, abnormal vocalization, aberrant tail and cyanosis were observed in male and female 240 And 480 mg/kg group. In the 60 mg/kg group of male, there was only a decline in locomotor activity and walking abnormality. In the female 60 mg / kg group, only convulsions and contamination around the mouth were observed.

In the surviving animals, 4 cases of female 60 mg /kg group showed a decline in locomotor activity 6 hours after administration, one of them showed a decrease in locomotor activity and irregular respiration on day 2 which recovered after that.No abnormality was found in body weight of surviving animals. Therefore, LD50 was considered to be 85 mg/kg with 95% confidence limit 50 to 143 mg/kg bw, when Male and female SD rats were treated with 1,2-Dicyanobenzene via oral route.