Oxalonitrile

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

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:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Oxalonitrile

EC Number:

207-306-5

EC Name:

Oxalonitrile

Cas Number:

460-19-5

Molecular formula:

C2N2

IUPAC Name:

carbononitridic cyanide

Test material form:

gas

Specific details on test material used for the study:

Purity: 97.5% w/w (0.4% w/w – hydrogen cyanide, inert gases-balance)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source
Received from SAGE® Labs on August 24 and November 2, 2016.

Sex
5 Males and 5 Females. Females assigned to test were nulliparous and non-pregnant.

Age/weight at study initiation
Young adult (9–10 weeks)/males 288–376 g and females 190–252 g at experimental start

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

nose only

Vehicle:

clean air

Duration of exposure:

4 h

Remarks on duration:

postexposure period 14 days

Concentrations:

Exposure concentrations: 63.14 ppm, 128.02 ppm, 181.56 ppm

No. of animals per sex per dose:

25 animals totally, three concentrations totally – For concentration 128.02 ppm – 5 animals (males only), for two other concentrations – 10 animals for each concentration

Control animals:

yes

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

136.45 ppm

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

> 181.56 ppm

Applicant's summary and conclusion

Interpretation of results:

other: CLP Acute tox. 2 H220

Conclusions:

Acute inhalation toxicity GLP study, based on 4-hours nose-only exposure of albino rats, was performed. In this study 3 concentrations (63.14, 128.02, and 181,56 ppm) of ethanedinitrile were tested. Both males and females were tested only for two of the concentrations – 63.14 and 181.56 ppm, and males were tested also for the concentration 128.02 ppm. While at concentration of 63.14 ppm all of tested animals survived, all tested males and one female died at concentration 181.56 ppm within one day. One male died within one day at concentration 128.02 ppm. Based on these data, LC50 for ethanedinitrile was determined to 136.46 ppm for males and greater than 181.56 ppm for females.

Executive summary:

Materials and Methods                              

Test material                                   

Ethanedinitrile (NCCN)

Specification                                    

Ethanedinitrile–gas

Purity                                                  

97.5% w/w (0.4% w/w–hydrogen cyanide, inert gases-balance)          

 

Test Animals                                    

Rat        

Strain                                                 

Albino rat – Sprague-Dawley derived

Source                                                

Received from SAGE® Labs on August 24 and November 2, 2016.

Sex                                                     

5 Males and 5 Females. Females assigned to test were nulliparous and  non-pregnant.

Age/weight at study initiation 

Young adult (9–10 weeks)/males 288–376 g and females 190–252 g at experimental start                                   

Number of animals per group 

25 animals totally, three concentrations totally – For concentration 128.02 ppm – 5 animals (males only), for two other concentrations – 10 animals for each concentration

Control animals                                              

No

 

Administration/Exposure          

Inhalation

Postexposure period                 

14 days

Concentration of test substance                        

Exposure concentrations: 63.14 ppm, 128.02 ppm, 181.56 ppm

Type of exposure                          

Nose-only

Duration of exposure                  

4 hours

 

Results and Discussion

 

First tested concentration – 63.14 ppm

All animals survived exposure to the test atmosphere. Following exposure,three animals exhibited nasal discharge and four animals exhibited irregular respiration. In addition, three males and one female exhibited ano-genital staining. However, the animals recovered by Day 3 and appeared active and healthy for the remainder of the 14-day observation period. No gross abnormalities were noted for the animals when necropsied at the conclusion of the 14-day observation period.

 

Second tested concentration – 128.02 ppm

One male died within one day of exposure to the test atmosphere. Prior to death, the animal was hypoactive and exhibited irregular respiration and prone posture. Following exposure, thesurviving animals were hypoactive, exhibited irregular respiration and/or prone posture. However, the animals recovered by Day 4 and appeared active and healthy and gained weight for the remainder of the 14-day observation period.Gross necropsy of the decedent revealed discoloration of the lungs and liver and distention of the intestines and stomach. No gross abnormalities were noted for the surviving animals when necropsied at the conclusion of the 14-day observation period

 

 

Third tested concentration – 181.56 ppm

Five males and one female died within one day of exposure to the test atmosphere.Prior to death, three animals were hypoactive and exhibited irregular respiration and prone posture. There were no toxic effects noted prior to death of the three remaining animals. Following exposure, the surviving animals were hypoactive exhibited irregular respiration and/or prone posture. However, the animals recovered by Day 3 and appeared active and healthy for the remainder of the 14-day observation period. Gross necropsy of the decedents revealed discoloration of the lungs and/or distention of the intestines and stomach. No gross abnormalities were noted for either of the surviving animals when necropsied at the conclusion of the 14‑day observation period.

 

LC50      

Under the conditions of this study, the acute inhalation defined LC50 of ethanedinitrile calculatedby Probit Analysis was 136.46 ppm of the test substance per liter of air in male rats with 95% Confidence Limits of 170.84 (upper) and 109.01 ppm (lower). The data does not permit calculation of the LC50 for females by Probit Analysis. The LC50 for females is greater than 181.56 ppm.

 

 

Summary and conclusion

 An acute inhalation toxicity test was conducted with rats to determine the potential for ethanedinitrile to produce toxicity from a single exposure via the inhalation (nose-only exposure) route. Experiments were performed according to guidelines mentioned above and in accordance with good laboratory practice (GLP). Under the conditions of this study, the acute inhalation defined LC50 of ethanedinitrile calculatedby Probit Analysis was 136.46 ppm of the test substance per liter of air in male rats with 95% Confidence Limits of 170.84 (upper) and 109.01 ppm (lower). The data does not permit calculation of the LC50 for females by Probit Analysis. The LC50 for females is greater than 181.56 ppm.