Oxalonitrile

Toxicity to birds

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to birds: acute oral toxicity test

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Ethanedinitrile, hydrogen cyanide (HCN), potassium cyanide and sodium cyanide can be considered as a chemical category, along with and acetone cyanohydrin (ACH, also known as 2-hydroxy-2-methylpropanenitrile), based on structural similarity, common breakdown/metabolic products in physical and biological systems, and similar physico-chemical properties. Particular attention is paid to the dissociation constant of HCN. Ethanedinitrile breaks down in aqueous solution into cyanide ion (CN-) and cyanate ion (OCN-) (Cotton and Wilkinson 1980). Ethanedinitrile due to its low log Kow (0.07) and relatively high solubility in water (2.34 g/L) needs to get dissolved in aqueous solutions in lungs to enter the body. The rate of hydrolysis of ethanedinitrile is very fast (Ajwa 2015). Also, in the vast majority of environmental and physiologic conditions, the cyanide salts will dissolve in water to form hydrogen cyanide. The physico-chemical hazards and toxicity therefore result from the activity of HCN. An ECETOC Task Force, in the 2007 ECETOC Joint Assessment of Commodity Chemicals (JACC) Report No. 53, “Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5)” supports the development of the chemical category inclusive hydrogen cyanide, sodium and potassium cyanides. Hydrogen cyanide (Index No.006-006-00-X) and salts of hydrogen cyanides (Index No.006-007-00-5) are both listed in Annex VI, Table 3.1 of Regulation (EC) No. 1272/2008, entry 006-007-00-5, and are restricted in comparable ways taking into account physical characteristics. Thus, the assignment of ethanedinitrile to a chemical category does not result in a less protective regulatory status.

Qualifier:

no guideline followed

Principles of method if other than guideline:

literature data

GLP compliance:

no

Test organisms (species):

other: Mallard (Anas platyrhynchos), American kestrel (Falco sparverius), Black vulture (Coragyps atratus), Eastern screech owl (Megascops asio), Japanese quail (Coturnix japonica), European starling (Sturnus vulgaris), Domestic chicken (Gallus domesticus)

Key result

Dose descriptor:

LD50

Effect level:

2.7 mg/kg bw

Remarks on result:

other: Anas platyrhynchos

Key result

Dose descriptor:

LD50

Effect level:

4.5 mg/kg bw

Remarks on result:

other: Falco sparverius

Key result

Dose descriptor:

LD50

Effect level:

4.8 mg/kg bw

Remarks on result:

other: Coragyps atratus

Key result

Dose descriptor:

LD50

Effect level:

8.8 mg/kg bw

Remarks on result:

other: Coragyps atratus

Key result

Dose descriptor:

LD50

Effect level:

9.4 mg/kg bw

Remarks on result:

other: Coturnix japonica

Key result

Dose descriptor:

LD50

Effect level:

21 mg/kg bw

Remarks on result:

other: Gallus domesticus

Species	Oral LD50, mg/kg bw
Mallard (Anas platyrhynchos)	2.7 (2.2 – 3.2)
American kestrel (Falco sparverius)	4.0 (3.0 – 5.3)
Black vulture (Coragyps atratus)	4.8 (4.4 – 5.3)
Eastern screech owl (Coragyps atratus)	8.8 (7.2 – 10.2)
Japanese quail (Coturnix japonica)	9.4 (7.7 – 11.4)
European starling (Sturnus vulgaris)	17 (14 – 22)
Domestic chicken (Gallus domesticus)	21 (12 – 36)

Conclusions:

LD50 values were determined.

Mallard LD50=2.7 mg/kg bw
American kestrel LD50=4.0 mg/kg bw
Black vulture LD50=4.8 mg/kg bw
Eastern screech owl LD50=8.8 mg/kg bw
Japanese quail LD50=9.4 mg/kg bw
European starling LD50=17 mg/kg bw
Domestic chicken LD50=21 mg/kg bw

Executive summary:

There are several single dose oral toxicity studies on NaCN .

Acute oral toxicity to birds:

Species	Oral LD50, mg/kg bw
Mallard (Anas platyrhynchos)	2.7 (2.2 – 3.2)

American kestrel (Falco sparverius)	4.0 (3.0 – 5.3)
Black vulture (Coragyps atratus)	4.8 (4.4 – 5.3)
Eastern screech owl (Megascops asio)	8.8 (7.2 – 10.2)
Japanese quail (Coturnix japonica)	9.4 (7.7 – 11.4)
European starling (Sturnus vulgaris)	17 (14 – 22)
Domestic chicken (Gallus domesticus)	21 (12 – 36)

Reference 2

Endpoint:

short-term toxicity to birds

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

Ethanedinitrile, hydrogen cyanide (HCN), potassium cyanide and sodium cyanide can be considered as a chemical category, along with and acetone cyanohydrin (ACH, also known as 2-hydroxy-2-methylpropanenitrile), based on structural similarity, common breakdown/metabolic products in physical and biological systems, and similar physico-chemical properties. Particular attention is paid to the dissociation constant of HCN. Ethanedinitrile breaks down in aqueous solution into cyanide ion (CN-) and cyanate ion (OCN-) (Cotton and Wilkinson 1980). Ethanedinitrile due to its low log Kow (0.07) and relatively high solubility in water (2.34 g/L) needs to get dissolved in aqueous solutions in lungs to enter the body. The rate of hydrolysis of ethanedinitrile is very fast (Ajwa 2015). Also, in the vast majority of environmental and physiologic conditions, the cyanide salts will dissolve in water to form hydrogen cyanide. The physico-chemical hazards and toxicity therefore result from the activity of HCN. An ECETOC Task Force, in the 2007 ECETOC Joint Assessment of Commodity Chemicals (JACC) Report No. 53, “Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5)” supports the development of the chemical category inclusive hydrogen cyanide, sodium and potassium cyanides. Hydrogen cyanide (Index No.006-006-00-X) and salts of hydrogen cyanides (Index No.006-007-00-5) are both listed in Annex VI, Table 3.1 of Regulation (EC) No. 1272/2008, entry 006-007-00-5, and are restricted in comparable ways taking into account physical characteristics. Thus, the assignment of ethanedinitrile to a chemical category does not result in a less protective regulatory status.

Qualifier:

according to guideline

Guideline:

OECD Guideline 205 (Avian Dietary Toxicity Test)

Deviations:

no

GLP compliance:

yes

Details on test organisms:

Mallard ducks (7 days of age)
American kestrel
Black vulture
Eastern screech owl
Japanese quail
European starling
Domestic chicken
Northern bobwhite quail

Total exposure duration (if not single dose):

5 d

No. of animals per sex per dose and/or stage:

10 juvenile (3 groups)

Nominal and measured doses / concentrations:

mallard duck
100, 178, 316, 562, and 1,000 mg NaCN/L (0, 53, 94, 168, 298, and 530 mg CN-/L)

Key result

Dose descriptor:

LD50

Effect level:

1.4 mg/kg bw

Basis for effect:

mortality

Remarks on result:

other: Mallard duck (Anas platyrhynchos)

Key result

Dose descriptor:

LD50

Effect level:

1.5 mg/kg bw

Basis for effect:

mortality

Remarks on result:

other: Mallard duck (Anas platyrhynchos)

Key result

Duration (if not single dose):

5 d

Dose descriptor:

LD50

Effect level:

18 mg/kg bw

Basis for effect:

mortality

Remarks on result:

other: Mallard duck (Anas platyrhynchos)

Key result

Dose descriptor:

LD50

Effect level:

2.1 mg/kg bw

Basis for effect:

mortality

Remarks on result:

other: American kestrel (Falco sparverius)

Key result

Dose descriptor:

LD50

Effect level:

2.5 mg/kg bw

Basis for effect:

mortality

Remarks on result:

other: Black vulture (Coragyps atratus)

Key result

Dose descriptor:

LD50

Effect level:

4.6 mg/kg bw

Basis for effect:

mortality

Remarks on result:

other: Eastern screech owl (Otus asio)

Key result

Dose descriptor:

LD50

Effect level:

5

Basis for effect:

mortality

Remarks on result:

other: Japanese quail (Coturnix japonica)

Key result

Dose descriptor:

LD50

Effect level:

9 mg/kg bw

Basis for effect:

mortality

Remarks on result:

other: European starling (Sturnus vulgaris)

Key result

Dose descriptor:

LD50

Effect level:

11.1 mg/kg bw

Basis for effect:

mortality

Remarks on result:

other: Domestic chicken (Gallus domesticus)

Key result

Duration (if not single dose):

5 d

Dose descriptor:

LD50

Effect level:

69 mg/kg bw

Basis for effect:

mortality

Remarks on result:

other: Northern bobwhite quail (Colinus virginianus)

Table 1. adopted form ECETOC (2007) showing the sensitivity of various bird species in acute and short-term dietary tests:

Species	Test substance	LD50 (mg CN‾/kg bw)	Dosing
Mallard duck (Anas platyrhynchos)	NaCN	1.4
Mallard duck (Anas platyrhynchos)	NaCN	1.5	Single dose
Mallard duck (Anas platyrhynchos)	NaCN	18	Dosing over 5 days (OECD 205)
American kestrel (Falco sparverius)	NaCN	2.1	Single dose
Black vulture (Coragyps atratus)	NaCN	2.5	Single dose
Eastern screech owl (Otus asio)	NaCN	4.6	Single dose
Japanese quail (Coturnix japonica)	NaCN	5	Single dose
European starling (Sturnus vulgaris)	NaCN	9	Single dose
Domestic chicken (Gallus domesticus)	NaCN	11.1	Single dose
Northern bobwhite quail (Colinus virginianus)	NaCN	69	Dosing over 5 days (OECD 205)

Executive summary:

A 5-day repeated exposure study according to OECD guideline 205 (OECD, 1984) was performed in groups of 10 juvenile (7 days of age) Mallard ducks (Anas platyrhynchos) receiving nominal concentrations of 0 (3 groups), 100, 178, 316, 562, and 1,000 mg NaCN/L (0, 53, 94, 168, 298, and 530 mg CN^-/L) in their drinking water. In an amendment to the report, the actual concentrations were given as 85.5 to 88.5, 152 to 158, 270 to 280, 481 or 855 mg NaCN/L, but the measured concentrations (following re-analysis of the samples) were considerably lower (11.0 to 26.5% of nominal), both on day 1 and day 4, and averaged 21.2, 28.2, 39.6, 53.1 or 96.7 mg CN^-/L. Following the original report, after the 5-day exposure period the animals received untreated drinking water. All birds were from the same hatch, pen-reared and phenotypically the same as wild birds. The birds were not mature and could not be differentiated by sex. The water was applied by a nipple water system. Body weights were determined at the beginning of the dosing period, on day 5 and at termination on day 8. Food and water consumption were recorded daily. No mortality was observed in the control or the 100 and 178 mg/L groups, while 4 out of 10 animals died at 316 mg/L and all (10/10) animals at 562 and 1,000 mg/L died during the dosing period. Signs of toxicity included loss of coordination, lower limb weakness, lethargy and depression and were first noted on day 2 in the 316 mg/L group. Mortalities in this group occurred on day 2 and day 4 (2 each). In the surviving animals the symptoms had disappeared by the morning of day 6. In the two high-dose groups mortalities occurred on day 2 (3/10) and day 3 (7/10). Signs of toxicity included reduced reaction to external stimuli, depression, lethargy, wing drop, loss of righting reflex, prostrate posture and gasping. They were first noted in the afternoon of day 1. No clinical signs were observed in the 2 lower dose groups. A statistically significant dose-related reduction in body-weight gain was observed in all dose groups. Birds dosed with 100 mg/L continued to show a reduction in body-weight gain during the observation period. The reduction in body-weight gain was accompanied by a marked dose-related reduction in feed and water consumption throughout the dosing and recovery periods. According to the authors, the birds receiving NaCN reduced their water consumption to a point where many of the deaths may well have been due to dehydration rather than to the treatment alone. Based on the original nominal concentrations, the 5-day LC₅₀was reportedly determined to be 340 mg NaCN/L (180 mg CN^-/L) or approximately 75 mg/kg bw using the average drinking water consumption (415 ml/kg bw) of the 316 mg NaCN/L group. The concentration at which no mortality occurred was 178 mg NaCN/L (94 mg CN­^-/L) or a dose of 55 mg/kg bw using the average drinking water consumption of 583 ml/kg bw at 178 mg NaCN/L. The lowest-observed effect level (LOEL), based on effects on body weight, feed and water consumption, was 100 mg NaCN/L (53 mg CN­^-/L) or 49 mg/kg bw using the average drinking water consumption of 916 ml/kg bw at that dose (Stenceet al, 1993a). Although the authors based their original evaluation on the nominal concentrations, the analytical concentrations were considerably lower. Therefore, the ECETOC Task Force considered it more appropriate to base the evaluation on the measured concentrations. The cyanide concentration at which no mortality occurred would be 28.2 mg/L or 16.4 mg/kg bw. The LC₅₀would correspond to approximately 43 mg/L or 17.8 mg/kg bw and the LOEL to 21.2 g/L or 19.4 mg/kg bw.The same authors conducted a similar experiment, using the same study design according to OECD guideline 205, in juvenile northern bobwhite quails (Colinus virginianus) (10 days of age). The quails (10/group) received nominal concentrations of 0, 100, 178, 316, 562 and 1,000 mg NaCN/L (0, 53, 94, 168, 298, 530 mg CN^-/L) in their drinking water for 5 consecutive days, followed by 3 days of observation. Analytical measurement of the test solutions confirmed the nominal concentrations with the exception of the 178 mg NaCN/L sample on day 5. That sample had only 9.14% of the nominal concentration. The evaluation was therefore based on the nominal concentrations. No mortality was observed in the controls or at 100, 178 and 316 mg/L, while 1 out of 10 animals died at 562 mg/L and all (10/10) animals at 1,000 mg/L died during the dosing period. Signs of toxicity included wing drop and lethargy at 178 mg/L (days 3 to 7) and, additionally, depression and reduced reaction to external stimuli at 316 mg/L (1 animal, day 0 to 7). At 562 mg/L, a single mortality was noted on day 6 and symptoms observed from day 0 to day 7 included, in addition to the symptoms in the other dose groups, loss of coordination. At 1,000 mg/L, mortalities occurred on days 0 and 1 (3 each), one each on day 2 and 3 and two on day 4. Signs of toxicity were observed from day 0. In the animals surviving the lower concentrations the symptoms had disappeared by the afternoon of day 7. A statistically significant dose-related reduction in body-weight gain was observed from 178 mg/L. Birds dosed with 100 mg/L did not show any effect on body weight gain compared to the control groups. The reduction in body weight gain at 178 to 1,000 mg/L was accompanied by a dose-related reduction in food and water consumption throughout the dosing and recovery periods. According to the authors, the birds receiving NaCN reduced their water consumption to a point where many of the deaths may well have been due to dehydration rather than to the treatment alone. Due to this fact, the intake of cyanide per kg of body weight in the two high-dose groups was in the range of the intake of the mid dose groups. The 5‑day LC₅₀was determined to be 705 mg NaCN/L (374 mg CN‾/L) or approximately 69 mg/kg bw using the average drinking water consumption (98 ml/kg bw) at 562 mg NaCN/L. The concentration at which no mortality occurred was 316 mg NaCN/L (168 mg CN‾/L) or 35 mg CN‾/kg bw using the average drinking water consumption of 210 ml/kg bw at 316 mg NaCN/L. The NOEL, based on effects on signs of toxicity, body weight, and water consumption, was 100 mg NaCN/L (53 mg CN-/L) or 33 mg CN‾/kg bw based on the average drinking water consumption of 330 ml/kg bw at that dose (Stenceet al, 1993b). 1,000 mg/L was accompanied by a dose-related reduction in food and water consumption throughout the dosing and recovery periods. According to the authors, the birds receiving NaCN reduced their water consumption to a point where many of the deaths may well have been due to dehydration rather than to the treatment alone. Due to this fact, the intake of cyanide per kg of body weight in the two high-dose groups was in the range of the intake of the mid dose groups. The 5‑day LC₅₀was determined to be 705 mg NaCN/L (374 mg CN‾/L) or approximately 69 mg/kg bw using the average drinking water consumption (98 ml/kg bw) at 562 mg NaCN/L. The concentration at which no mortality occurred was 316 mg NaCN/L (168 mg CN‾/L) or 35 mg CN‾/kg bw using the average drinking water consumption of 210 ml/kg bw at 316 mg NaCN/L. The NOEL, based on effects on signs of toxicity, body weight, and water consumption, was 100 mg NaCN/L (53 mg CN‾/L) or 33 mg CN‾/kg bw based on the average drinking water consumption of 330 ml/kg bw at that dose (Stence et al, 1993b).

Slopes of the dose-response curves were reported to be extremely steep for Mallards, which was also the most sensitive species (ECETOC 2007).

 

Table: adopted form ECETOC (2007) showing the sensitivity of various bird species in acute and short-term dietary tests.

Species	Test substance	LD50 (mg CN-/kg bw)	dosing
Mallard duck (Anas platyrhynchos)	NaCN	1.4
Mallard duck (Anas platyrhynchos)	NaCN	1.5	single dose
Mallard duck (Anas platyrhynchos)	NaCN	18	Dosing over 5 days (OECD 205)
American kestrel (Falco sparverius)	NaCN	2.1	single dose
Black vulture (Coragyps atratus)	NaCN	2.5	single dose
Eastern screech owl (Otus asio)	NaCN	4.6	single dose
Japanese quail (Coturnix japonica)	NaCN	5	single dose
European starling (Sturnus vulgaris)	NaCN	9	single dose
Domestic chicken (Gallus domesticus)	NaCN	11.1	single dose
Northern bobwhite quail (Colinus virginianus)	NaCN	69	Dosing over 5 days (OECD 205)

Original reports:

Stence M, Beavers JB, Jaber M, 1993a. Sodium cyanide: an LC50 study with the mallard using water borne exposure. Unpublished report HLO 481-93 amended 17 June 1993, project 112-306 by Wildlife International, Easton Massachusetts, USA. Du Pont de Nemours, Haskell Laboratory, Wilmington Delaware, USA; Degussa, Ridgefield New Jersey, USA; FMC, Princeton New Jersey, USA; Cyanco, Salt Lake City UTtah USA; ICI (Americas), Wilmington, Delaware, USA. 

Stence M, Beavers JB, Jaber M, 1993b. Sodium cyanide: an LC50 study with the northern bobwhite using water borne exposure. Unpublished report HLO 480-93 amended 17 June 1993, project 112-305A by Wildlife International, Easton, Massachusetts, USA. Du Pont de Nemours, Haskell Laboratory, Wilmington, Delaware, USA; Degussa, Ridgefiled, New Jersey, USA; FMC, Princeton, New Jersey, USA; Cyanco, Salt Lake City, Utah, USA; ICI (Americas), Wilmington, Delaware, USA.

Reference 3

Endpoint:

short-term toxicity to birds: acute oral toxicity test

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Ethanedinitrile, hydrogen cyanide (HCN), potassium cyanide and sodium cyanide can be considered as a chemical category, along with and acetone cyanohydrin (ACH, also known as 2-hydroxy-2-methylpropanenitrile), based on structural similarity, common breakdown/metabolic products in physical and biological systems, and similar physico-chemical properties. Particular attention is paid to the dissociation constant of HCN. Ethanedinitrile breaks down in aqueous solution into cyanide ion (CN-) and cyanate ion (OCN-) (Cotton and Wilkinson 1980). Ethanedinitrile due to its low log Kow (0.07) and relatively high solubility in water (2.34 g/L) needs to get dissolved in aqueous solutions in lungs to enter the body. The rate of hydrolysis of ethanedinitrile is very fast (Ajwa 2015). Also, in the vast majority of environmental and physiologic conditions, the cyanide salts will dissolve in water to form hydrogen cyanide. The physico-chemical hazards and toxicity therefore result from the activity of HCN. An ECETOC Task Force, in the 2007 ECETOC Joint Assessment of Commodity Chemicals (JACC) Report No. 53, “Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5)” supports the development of the chemical category inclusive hydrogen cyanide, sodium and potassium cyanides. Hydrogen cyanide (Index No.006-006-00-X) and salts of hydrogen cyanides (Index No.006-007-00-5) are both listed in Annex VI, Table 3.1 of Regulation (EC) No. 1272/2008, entry 006-007-00-5, and are restricted in comparable ways taking into account physical characteristics. Thus, the assignment of ethanedinitrile to a chemical category does not result in a less protective regulatory status.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Toxicity of mammals and birds towards cyanide is very similar when exposed via drinking water. Acute toxicity is primary hazard related to poisoning since cyanide is not bioaccumulative and sub lethal doses are rapidly metabolised and excreted. The only possible route of exposure for ethanedinitrile is inhalation.

GLP compliance:

no

Key result

Remarks on result:

not measured/tested

Conclusions:

Toxicity of mammals and birds towards cyanide is very similar when exposed via drinking water. Acute toxicity is primary hazard related to poisoning since cyanide is not bioaccumulative and sublethal doses are rapidly metabolized and excreted. The only possible route of exposure for ethanedinitrile is inhalation.

Executive summary:

Toxicity of mammals and birds towards cyanide is very similar when exposed via drinking water. Acute toxicity is primary hazard related to poisoning since cyanide is not bioaccumulative and sublethal doses are rapidly metabolized and excreted.The only possible route of exposure for ethanedinitrile is inhalation.

Reference 4

Endpoint:

short-term toxicity to birds

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Ethanedinitrile, hydrogen cyanide (HCN), potassium cyanide and sodium cyanide can be considered as a chemical category, along with and acetone cyanohydrin (ACH, also known as 2-hydroxy-2-methylpropanenitrile), based on structural similarity, common breakdown/metabolic products in physical and biological systems, and similar physico-chemical properties. Particular attention is paid to the dissociation constant of HCN. Ethanedinitrile breaks down in aqueous solution into cyanide ion (CN-) and cyanate ion (OCN-) (Cotton and Wilkinson 1980). Ethanedinitrile due to its low log Kow (0.07) and relatively high solubility in water (2.34 g/L) needs to get dissolved in aqueous solutions in lungs to enter the body. The rate of hydrolysis of ethanedinitrile is very fast (Ajwa 2015). Also, in the vast majority of environmental and physiologic conditions, the cyanide salts will dissolve in water to form hydrogen cyanide. The physico-chemical hazards and toxicity therefore result from the activity of HCN. An ECETOC Task Force, in the 2007 ECETOC Joint Assessment of Commodity Chemicals (JACC) Report No. 53, “Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5)” supports the development of the chemical category inclusive hydrogen cyanide, sodium and potassium cyanides. Hydrogen cyanide (Index No.006-006-00-X) and salts of hydrogen cyanides (Index No.006-007-00-5) are both listed in Annex VI, Table 3.1 of Regulation (EC) No. 1272/2008, entry 006-007-00-5, and are restricted in comparable ways taking into account physical characteristics. Thus, the assignment of ethanedinitrile to a chemical category does not result in a less protective regulatory status.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Inhalation is the only theoretically possible route of exposure for gaseous substances such as ethanedinitrile. However, there is no OECD guideline regarding the avian inhalation toxicity and EFSA guidance Risk Assessment for Birds and Mammals (EFSA Journal 2009; 7(12):1438) does not consider inhalation exposure as relevant and in a rare comment on inhalation it states that a certain model can be improved by including inhalation into the risk assessment. Albeit noticing that there are currently no examples for this being used in regulatory assessment of risks to wildlife, the US EPA test OPPTS 885.4100 Avian Inhalation Test works with the LD rather than the LC so oral data on cyanides might theoretically be used instead due to HCN excellent penetration properties. However, this test is not recommended by the Commission communication 2013/C 95/01 and is not very practical since it is designed for microbial organisms.

GLP compliance:

no

Test organisms (species):

other: chickens, rock doves and canaries

Control animals:

yes

Nominal and measured doses / concentrations:

0.119 mg/l

Details on examinations and observations:

When chickens, rock doves and canaries were exposed to 0.119 mg/L (119 mg/m3 = 101 ppm), chickens survived for 60 minutes (the maximum time recorded), pigeons died in 10 minutes, and canaries died in 3 minutes. Canaries survived concentrations 352, 119, 73, 68, 48, and 46 mg/m3 for approximately 2, 3, 3.5, 6, 15, and 27 minutes respectively.

Key result

Duration (if not single dose):

1 h

Dose descriptor:

other: survival

Effect level:

101 other: ppm

Remarks on result:

other: Gallus gallus domesticus

Key result

Duration (if not single dose):

0.17 h

Dose descriptor:

other: survival

Effect level:

101 other: ppm

Remarks on result:

other: Columba livia

Key result

Duration (if not single dose):

0.05 h

Dose descriptor:

other: mortality

Effect level:

101 other: ppm

Remarks on result:

other: Serinus canaria

Key result

Duration (if not single dose):

0.033 h

Dose descriptor:

other: mortality

Effect level:

352 other: mg/m3

Remarks on result:

other: Serinus canaria

Key result

Duration (if not single dose):

0.058 h

Dose descriptor:

other: mortality

Effect level:

73 other: mg/m3

Remarks on result:

other: Serinus canaria

Key result

Duration (if not single dose):

0.1 h

Dose descriptor:

other: mortality

Effect level:

68 other: mg/m3

Remarks on result:

other: Serinus canaria

Key result

Duration (if not single dose):

0.25 h

Dose descriptor:

other: mortality

Effect level:

48 other: mg/m3

Remarks on result:

other: Serinus canaria

Key result

Duration (if not single dose):

0.45 h

Dose descriptor:

other: mortality

Effect level:

46 other: mg/m3

Remarks on result:

other: Serinus canaria

Conclusions:

There are no inhalation data directly for ethanedinitrile to birds, the data for hydrogen cyanide were thus used instead.
Canary is reported to have “Extreme susceptibility to HCN”. The EFSA technical report “Outcome of the pesticides peer review meeting on general recurring issues in ecotoxicology” (EFSA, 2015) states that “the risk assessment could also be entirely based on studies from literature, when these have been judged as reliable and they show more adverse effects than the studies provided by the notifier.” Therefore, these data on canaries could be used for the risk assessment instead of the traditionally used quail species in the oral toxicity testing since it probably derives to more conservative protection values due to high sensitivity of canaries. Validity criteria or statistical power of this study cannot be compared with the relevant test guideline as there is no such guideline for avian inhalation. Extrapolation of this study to other species is good since canaries are regarded as having extreme susceptibility to HCN, other species should thus be less sensitive. Moreover, this solution is in line with the aim of reduction of animal testing by not duplicating existing animal studies.

Executive summary:

Inhalation is the only theoretically possible route of exposure for gaseous substances such as ethanedinitrile. However, there is no OECD guideline regarding the avian inhalation toxicity and EFSA guidance Risk Assessment for Birds and Mammals (EFSA Journal 2009; 7(12):1438) does not consider inhalation exposure as relevant and in a rare comment on inhalation it states that a certain model can be improved by includinginhalation into the risk assessment. Albeit noticing that there are currently no examples for this being used in regulatory assessment of risks to wildlife, the US EPA test OPPTS 885.4100 Avian Inhalation Test works with the LD rather than the LC so oral data on cyanides might theoretically be used instead due to HCN excellent penetration properties. However, this test is not recommended by the Commission communication 2013/C 95/01 and is not very practical since it is designed for microbial organisms.

 

Exposure ofbirdsis not expected as the fumigant is applied for treatment of wood in enclosed spaces.

 

There are no inhalation data directly for ethanedinitrile to birds, the data for hydrogen cyanide were thus used instead.

Chickens, pigeons, and canaries were exposed to HCN in the air and plotted the relationship between dosage and length of exposure. When all three species were exposed to 0.119 mg/L (119 mg/m³= 101 ppm), chickens survived for 60 minutes (the maximum time recorded), pigeons died in 10 minutes, and canaries died in 3 minutes. Canaries survived concentrations 352, 119, 73, 68, 48, and 46 mg/m³for approximately 2, 3, 3.5, 6, 15, and 27 minutes respectively.

Canary is reported to have “Extreme susceptibility to HCN”. The EFSA technical report “Outcome of the pesticides peer review meeting on general recurring issues in ecotoxicology” (EFSA, 2015) states that “the risk assessment could also be entirely based on studies from literature, when these have been judged as reliable and they show more adverse effects than the studies provided by the notifier.” Therefore, these data on canaries could be used for the risk assessment instead of the traditionally used quail species in the oral toxicity testing since it probably derives to more conservative protection values due to high sensitivity of canaries. Validity criteria or statistical power of this study cannot be compared with the relevant test guideline as there is no such guideline for avian inhalation. Extrapolation of this study to other species is good since canaries are regarded as having extreme susceptibility to HCN, other species should thus be less sensitive. Moreover, this solution is in line with the aim of reduction of animal testing by not duplicating existing animal studies.

Description of key information

There are no inhalation data directly for ethanedinitrile to birds, the data for hydrogen cyanide were thus used instead.

Canary is reported to have “Extreme susceptibility to HCN”. The EFSA technical report “Outcome of the pesticides peer review meeting on general recurring issues in ecotoxicology” (EFSA, 2015) states that “the risk assessment could also be entirely based on studies from literature, when these have been judged as reliable and they show more adverse effects than the studies provided by the notifier.” Therefore, these data on canaries could be used for the risk assessment instead of the traditionally used quail species in the oral toxicity testing since it probably derives to more conservative protection values due to high sensitivity of canaries. Validity criteria or statistical power of this study cannot be compared with the relevant test guideline as there is no such guideline for avian inhalation. Extrapolation of this study to other species is good since canaries are regarded as having extreme susceptibility to HCN, other species should thus be less sensitive. Moreover, this solution is in line with the aim of reduction of animal testing by not duplicating existing animal studies.

Acute inhalation toxicity to birds:

Inhalation is the only theoretically possible route of exposure for gaseous substances such as ethanedinitrile. However, there is no OECD guideline regarding the avian inhalation toxicity and EFSA guidance Risk Assessment for Birds and Mammals (EFSA Journal 2009; 7(12):1438) does not consider inhalation exposure as relevant and in a rare comment on inhalation it states that a certain model can be improved by including inhalation into the risk assessment. Albeit noticing that there are currently no examples for this being used in regulatory assessment of risks to wildlife, the US EPA test OPPTS 885.4100 Avian Inhalation Test works with the LD rather than the LC so oral data on cyanides might theoretically be used instead due to HCN excellent penetration properties. However, this test is not recommended by the Commission communication 2013/C 95/01 and is not very practical since it is designed for microbial organisms.

Exposure of birds is not expected as the fumigant is applied for treatment of wood in enclosed spaces.

There are no inhalation data directly for ethanedinitrile to birds, the data for hydrogen cyanide were thus used instead. 

LD50 values were determined.

Mallard LD50=2.7 mg/kg bw

American kestrel LD50=4.0 mg/kg bw

Black vulture LD50=4.8 mg/kg bw

Eastern screech owl LD50=8.8 mg/kg bw

Japanese quail LD50=9.4 mg/kg bw

European starling LD50=17 mg/kg bw

Domestic chicken LD50=21 mg/kg bw

 

Ethanedinitrile is a gas. Therefore, exposure to ethanedinitrile by oral route is not possible. Regarding exposure to HCN in solution (ECETOC, 2007) has described two avian studies according to OECD guideline 205. Based on the results and also other reported studies on short-term and acute avian toxicity (Table 8.1.1.3. – 1.), it is expected that additional testing in GLP conditions in traditional quail species would not bring more conservative values for risk assessment.

 

Inhalation is the route of exposure possible for gaseous substances such as ethanedinitrile.