Dodecanenitrile

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 was considered to be 3400 mg/kg bw when rats were treated with Dodecanenitrile orally.

Acute inhalation toxicity:

LC50 was estimated to be 701 mg/L when Sprague-Dawley male and female rats were exposed with Dodecanenitrile by inhalation.

Acute Dermal toxicity:

LD50 was considered to be 4230.6 mg/kg bw when New Zealand White male and female rabbits were exposed with Dodecanenitrile by dermal application.

Based on the above values and comparing it with CLP classification criteria it can be concluded that the substance Dodecanenitrile is not toxic via oral, inhalation and dermal route of administration and considered as Not classified.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

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:

Data is from Authorized database

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

To determine acute oral toxicity in rat using Dodecanenitrile by OECD Guideline 401 Acute Oral Toxicity.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Dodecanenitrile
- Molecular formula (if other than submission substance): C12H23N
- Molecular weight (if other than submission substance): 181.321 g/mol
- Substance type: Organic

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

not specified

Doses:

3400 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 400 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality was observed

Mortality:

50 % mortality was observed at 3400 mg/kg bw in treated rats

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not toxic

Conclusions:

LD50 was considered to be 3400 mg/kg bw when rats were treated with Dodecanenitrile orally.

Executive summary:

In a acute oral toxicity study, rat were treated with Dodecanenitrile in the concentration of 3400 mg/kg bw orally. 50% mortality was observed at 3400 mg/kg bw in treated rats. Therefore, LD50 was considered to be 3400 mg/kg bw when rats were treated with Dodecanenitrile orally. Based on this value and comparing it with CLP classification criteria it can be concluded that the substance Dodecanenitrile is not toxic via oral route of administration and considered as Not classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 400 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from Hazardous Substances Data Bank

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Dodecanenitrile
- Molecular formula (if other than submission substance): C12H23N
- Molecular weight (if other than submission substance): 181.321 g/mol
- Substance type: Organic

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

not specified

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

701 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LC50

Effect level:

701 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" or "d" )  and "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and "l" )  and ("m" and ( not "n") )  )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Nitrile by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Nitrile by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Cyano, aliphatic attach [-C#N] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Nitrile by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Nitrile by Organic Functional groups

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Alkane, branched with tertiary carbon by Organic Functional groups

Domain logical expression index: "j"

Similarity boundary:Target: CCCCCCCCCCCC#N
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Similarity boundary:Target: CCCCCCCCCCCC#N
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: CCCCCCCCCCCC#N
Threshold=100%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Transition Metals by Groups of elements

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.31

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.74

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LC50 was estimated to be 701 mg/L when Sprague-Dawley male and female rats wer exposed with Dodecanenitrile by inhalation.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for Dodecanenitrile. The LC50 was estimated to be 701 mg/L when Sprague-Dawley male and female rats were exposed with Dodecanenitrile by inhalation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

70 100 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Dodecanenitrile
- Molecular formula (if other than submission substance): C12H23N
- Molecular weight (if other than submission substance): 181.321 g/mol
- Substance type: Organic

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

not specified

Duration of exposure:

24 hrs

Doses:

4231 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 231 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((("a" or "b" or "c" or "d" )  and "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and "l" )  and "m" )  and "n" )  and ("o" and ( not "p") )  )  and ("q" and "r" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Nitrile by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Nitrile by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Cyano, aliphatic attach [-C#N] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Nitrile by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Group 14 - Metalloids Si,Ge OR Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Cyano, aliphatic attach [-C#N] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "k"

Similarity boundary:Target: CCCCCCCCCCCC#N
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: CCCCCCCCCCCC#N
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: CCCCCCCCCCCC#N
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Similarity boundary:Target: CCCCCCCCCCCC#N
Threshold=100%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg AND Group CN Aqueous Solubility < 0.1 g/L AND Group CN log Kow > 4.5 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group All log Kow > 9 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 4.27

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.25

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 4231 mg/kg bw when New Zealand White male and female rabbits were exposed with Dodecanenitrile by dermal application.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Dodecanenitrile. The LD50 was estimated to be 4231 mg/kg bw when New Zealand White male and female rabbits were exposed with Dodecanenitrile by dermal application.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 231 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Additional information

Acute oral toxicity:

In different studies, Dodecanenitrile has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats and mices for Dodecanenitrile along with the study available on structurally similar read across substance Tetradecanenitrile (CAs no 629-63-0) and 3,7-Dimethyl-6-octenenitrile (CAs no 51566-62-2). The studies are summarized as below

In a experimental study summarized by U.S. Environmental Protection Agency (HSDB (Hazardous Substances Data Bank), U.S. Environmental Protection Agency Hazard Characterization Document, March 2012) and Toxicology/Regulatory Services, Inc. (FND HPV Nitriles Robust Summaries, Page 1-239, 201-14980, December 29, 2003), rat were treated with Dodecanenitrile in the concentration of 3400 mg/kg bw orally. 50% mortality was observed at 3400 mg/kg bw in treated rats. Therefore, LD50 was considered to be 3400 mg/kg bw when rats were treated with Dodecanenitrile orally.

In another study summarized by U.S. Environmental Protection Agency (HSDB (Hazardous Substances Data Bank), U.S. Environmental Protection Agency Hazard Characterization Document, March 2012) and Toxicology/Regulatory Services, Inc. (FND HPV Nitriles Robust Summaries, Page 1-239, 201-14980, December 29, 2003), rat were treated with Dodecanenitrile in the concentration of 2000 mg/kg bw orally. No mortality was observed at 2000 mg/kg bw in treated rats. Therefore, LD50 was considered to be > 2000 mg/kg bw when rats were treated with Dodecanenitrile orally.

Further supported by experimental study given by Opdykeet al(Food and Chemical Toxicology, Volume 38, Supplement 3, 2000, Pages s161-s163) on structurally similar read across substance Tetradecanenitrile (CAs no 629-63-0), Male and female rats and mice were treated with Tetradecanenitrile in the concentration of 4000 and 8000 mg/kg orally and observed for 10 days. No morality was observed at 8000 mg/kg bw in treated male and female rats and mice. Sedation and respiratory depression were observed in all the treated male and female rats and mice. Therefore, LD50 was considered to be > 8000 mg/kg bw when male and female rats and mice treated with Tetradecanenitrile orally.

This is further supported by experimental study given by U.S. National Library of Medicine (ChemIDplus, A TOXNET DATABASE Lite • Browse • Advanced, 2017), rat were treated with 3,7-Dimethyl-6-octenenitrile (CAs no 51566-62-2), rats were treated with 3,7-Dimethyl-6-octenenitrile in the concentration of 5300 mg/kg bw orally. 50% mortality observed at 5300 mg/kg bw in treated rats. Therefore, LD50 was considered to be 5300 mg/kg bw when rats were treated with 3,7-Dimethyl-6-octenenitrile orally.

Thus, based on the above studies on Dodecanenitrile and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Dodecanenitrile can be considered as Not classified for acute oral toxicity.

Acute inhalation toxicity:

In different studies, Dodecanenitrile has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats and mice for Dodecanenitrile along with the study available on structurally similar read across substance Propane (CAS no 74-98-6) and Butane (CAS no 106-97-8).The studies are summarized as below

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated forDodecanenitrile. The LC50 was estimated to be 701 mg/L when Sprague-Dawley male and female rats were exposed withDodecanenitrileby inhalation.

In another experimental study give by EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID Dataset, EUROPEAN COMMISSION – European Chemicals Bureau, 19-FEB - 2000)on structurally similar read across substance Propane (CAS no 74-98-6), Groups of 6 male or 6 female specific pathogen-free (SPS) Alderley Park rats were exposed to various concentrations of propane in air for 15 minutes.Deaths occurred during the exposure and were associated with depressant effects on the central nervous system (CNS). Also, lethal signs were observed in animals which are recovered within 10 minutes. Therefore, the acute inhalation toxicity study in rat by using Propane for exposure of 15 min was considered to be > 800000 mg/L of air.

Further supported byexperimental study give by EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID Dataset, EUROPEAN COMMISSION – European Chemicals Bureau, 19-FEB - 2000)on structurally similar read across substanceButane(CAS no 106-97-8), Rats were exposed to a range of butane concentrations in air for 4 hours.Following exposure, hydrocarbon accumulation in several organs was observed. The given test material is partially absorbed by rat tissue and partly transferred to brain, kidney, liver and perinephric adipose tissue. Hence, the acute inhalation toxicity study in rat by using Butane for exposure of 4 hours was considered to be 658 mg/l (658000 mg/m3) of air.

Thus, based on the above studies on Dodecanenitrile and its read across substances, it can be concluded that LD50 value is greater than 20000 mg/L of air. Thus, comparing this value with the criteria of CLP regulation, Dodecanenitrile can be considered as Not classified for acute inhalation toxicity.

Acute dermal toxicity:

In different studies, Dodecanenitrile has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats and mice for Dodecanenitrile along with the study available on structurally similar read across substance 3,7-Dimethyl-6-octenenitrile (CAS no 51566-62-2)andButane(CAS no 106-97-8).The studies are summarized as below

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Dodecanenitrile. The LD50 was estimated to be 4231 mg/kg bw when New Zealand White male and female rabbits were exposed with Dodecanenitrile by dermal application.

In another experimental study give by EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID Dataset, EUROPEAN COMMISSION – European Chemicals Bureau, 19-FEB - 2000)on structurally similar read across substance 3,7-Dimethyl-6-octenenitrile (CAS no 51566-62-2),rabbit were treated with 3,7-Dimethyl-6-octenenitrile in the concentration of 5000 mg/kg. No mortality was observed in treated rabbits at 5000 mg/kg bw. Therefore, LD50 was considered to be > 5000 mg/kg when rabbit was treated with 3,7-Dimethyl-6-octenenitrile by dermal application.

Further supported byexperimental study give by EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID Dataset, EUROPEAN COMMISSION – European Chemicals Bureau, 19-FEB - 2000)on structurally similar read across substanceDecane(CAS no 124-18-5),rat were treated with Decane in the concentration of 2000 mg/kg. No mortality and no gross pathological changes were observed in treated rats at 2000 mg/kg bw . Therefore, LD50 was considered to be > 2000 mg/kg bw, when rat was treated with Decane by dermal application.

Thus, based on the above studies and prediction on Dodecanenitrile and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Dodecanenitrile can be considered as Not classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies on Dodecanenitrile and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Dodecanenitrile can be considered as Not classified via oral, inhalation and dermal toxicity.

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