Oxalonitrile

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1960

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Four male albino rabbits whose weights averaged 4.5 pounds were closely clipped of their fur, restrained in a wooden stock, and placed in the chamber. An especially designed door, through which the rabbits heads extended into glass jarsmaintained under positive air pressure, prevented the rabbits from breathing cyanogen while their bodies were being exposed and also made observation of the heads of the rabbits possible. The bodies of the rabbits were exposed to ethanedinitrile concentration of 10,000 ppm for a period of 8 hours.

GLP compliance:

no

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:

Ethanedinitrile ≥ 99.5 %

Test animals

Species:

rabbit

Strain:

not specified

Remarks:

male albino rabbits

Details on test animals or test system and environmental conditions:

Four male albino rabbits whose weights averaged 4.5 pounds were closely clipped of their fur, restrained in a wooden stock, and placed in the chamber. An especially designed door, through which the rabbits heads extended into glass jarsmaintained under positive air pressure, prevented the rabbits from breathing cyanogen while their bodies were being exposed and also made observation of the heads of the rabbits possible. The bodies of the rabbits were exposed to ethanedinitrile concentration of 10,000 ppm for a period of 8 hours.

Test system

Type of coverage:

open

Preparation of test site:

clipped

Vehicle:

other: air

Controls:

no

Amount / concentration applied:

10,000 ppm

Duration of treatment / exposure:

8 hours

Observation period:

8 hours

Number of animals:

4

Details on study design:

Four male albino rabbits whose weights averaged 4.5 pounds were closely clipped of their fur, restrained in a wooden stock, and placed in the chamber. An especially designed door, through which the rabbits heads extended into glass jars maintained under positive air pressure, prevented the rabbits from breathing cyanogen while their bodies were being exposed and also made observation of the heads of the rabbits possible. The bodies of the rabbits were exposed to ethanedinitrile concentration of 10,000 ppm for a period of 8 hours.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0 <=

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0 <=

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Dermal exposure of rabbits to ethanedinitrile gas in an acute toxicity study indicates that ethanedinitrile is not a skin irritant. Dermal exposure of rabbits to 10,000 ppm (~21 g/m3) of ethanedinitrile for eight hours did not result in any clinical observations or macroscopic effects. None of the observation data meet requirements for labelling of EDN as a skin irritating substance, resulting from the requirements for substance classification according (ES) 1272/2008.

Other effects:

no other effects observed

Applicant's summary and conclusion

Interpretation of results:

other: CLP criteria not met

Conclusions:

Dermal exposure of rabbits to ethanedinitrile gas in an acute toxicity study indicates that ethanedinitrile is not a skin irritant. Dermal exposure of rabbits to 10,000 ppm (~21 g/m3) of ethanedinitrile for eight hours did not result in any clinical observations or macroscopic effects.

Executive summary:

Dermal exposure of rabbits to ethanedinitrile gas in an acute toxicity study indicates that ethanedinitrile is not a skin irritant. Dermal exposure of rabbits to 10,000 ppm (~21 g/m3) of ethanedinitrile for eight hours did not result in any clinical observations or macroscopic effects. None of the observation data meet requirements for labelling of EDN as a skin irritating substance, resulting from the requirements for substance classification according (ES) 1272/2008.

Materials and Methods               

Test material                                    Ethanedinitrile (Cyanogen), (NCCN)

Specification                                    Ethanedinitrile gas

Purity                                                  99.5% (0.5%–nitrogen, chlorine, cyanogen chloride)    

 

Test Animals             Rat        

Strain                          Albino rat – strain not reported

Source                        Not reported

Sex                              Males only

Age/weight at study initiation  135 g (average)                                              

Number of animals per group  13 groups of six rats – six different concentrations, six different time periods and control

 

Administration/Exposure          Inhalation

Postexposure period                 14 days

Concentration of test substance                           

Nominal concentration: 0, 533, 537, 851, 851, 1054, 1066, 2115, 2111, 4207, 4223, 8508, 8571 mg/m³ (0, 250, 250, 400, 400, 500, 500, 1000, 1000, 2000, 2000, 4000 and 4000 ppm)

Type of exposure                           Whole body

Duration of exposure                   120, 60, 45, 30, 15, 7.5 and 0 minutes

Controls                                          Not reported

 

Results and Discussion

Clinical symptoms         asphyxiation, lacrimation, upper respiratory tract irritation, pink coloration of the noticeable skin, blinking eyes, rubbing of forepaws over eyes and snout, huddling together with inactivity, slow gasping, tearful eyes, yellow fluid dripping from nares and mouth, restless and panic type movements, accentuated and poorly coordinated motions, bright pink coloration of the skin, laboured breathing, gasping, tremors, sluggishness, prostration, shallow breathing, death

 

Pathology                          Not reported

 

LC50                                  23,400 ppm / t; t= exposure duration in min

See the Table 5.2.3-2 Effects of the Acute Inhalation Exposures of Ethanedinitrile upon Male Albino Rats and a Time-concentration Graph which are enclosed below.

 

Summary and conclusion

Rats were housed in wire mesh cages within the chamber and exposed to a total of six different concentrations of ethanedinitrile and six different time periods. Survivors were observed for 14 days after exposure. Body weight of rats was measured before exposure and after 14 days.

The present study showed that rats withstood 250 ppm of ethanedinitrile for 120 min with only partial mortality and 500 ppm for 30 min with no deaths. In addition, the capacity of the rats in this study to tolerate the excessive concentrations of 1,000 and 2,000 ppm of ethanedinitrile for periods of approximately 15 and 7.5 min, respectively, points toward a lower toxicity.

Assuming transformation of one molecule of ethanedinitrile to one molecule of hydrogen cyanide, following approximate LC values may be calculated for HCN (t = exposure duration in min):

LC0= 15,900 mg/m³/t

LC50= 25,850 mg/m³/t

LC100= 41,050 mg/m³/t

Non-guideline study; the study from 1960 is not in the GLP system, but the method used is comparable to methods standardised by EU Directive 440/2008. 

 

Table 5.2.3-2: Effects of the Acute Inhalation Exposures of Ethanedinitrile Upon Male Albino rats

 

Concentration ofEthanedinitrile		Average Temp. (°C)	Length of exposure (min)	Length build-up period (min)	Mortality ratio (dead/dosed)	Initial average weight of rats (g)	Average weight gain after 14 days (g)
(ppm)	(mg/m^3)
4000	8571	22.8	7.5	3.0	3/6	162	44
4000	8508	25.0	15	3.0	6/6	156	-
2000	4223	27.2	7.5	1.5	0/6	126	55
2000	4207	28.3	15	1.5	6/6	121	-
1000	2111	27.2	15	0.5	0/6	123	52
1000	2115	26.7	30	0.5	6/6	123	-
500	1066	24.4	30	0.3	0/6	134	49
500	1054	27.8	45	0.3	6/6	122	-
400	851	25.0	45	0.25	0/6	144	46
400	851	25.0	60	0.25	6/6	137	-
250	537	22.2	60	0.15	0/6	160	59
250	533	24.4	120	0.15	4/6	127	38
Control	-	-	-	-	0/6	167	53