Tetrabutylammonium iodide

Endpoint summary

Description of key information

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 1-Butanaminium, N,N,N-tributyl-, iodide (1:1). The LD50 was estimated to be 754.7 mg/kg bw when rats were orally exposed with 1-Butanaminium, N,N,N-tributyl-, iodide (1:1).

.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

other information

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 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 1-Butanaminium, N,N,N-tributyl-, iodide (1:1)
- Molecular formula (if other than submission substance): C16H36N.I
- Molecular weight (if other than submission substance): 369.367 g/mole
- Substance type: Organic

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: unspecified

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

No data

Doses:

754.7 mg/kg bw

No. of animals per sex per dose:

No data

Control animals:

not specified

Details on study design:

No data

Statistics:

No data

Preliminary study:

No data

Sex:

female

Dose descriptor:

LD50

Effect level:

754.7 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

No data

Clinical signs:

other: No data

Gross pathology:

No data

Other findings:

No data

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Cationic (quaternary ammonium) surfactants by US-EPA New Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Ammonium salt AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Nitrogen, single bonds  [N{v+5}] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anion AND Cation AND Quaternary ammonium salt by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type conjugate addition to activated alkene derivatives OR AN2 >> Michael-type conjugate addition to activated alkene derivatives >> Alpha-Beta Conjugated Alkene Derivatives with Geminal Electron-Withdrawing Groups OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR SN2 OR SN2 >> Alkylation OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen and Sulfur Mustards OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic phenylureas OR SN2 OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphates by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols OR AN2 >> Nucleophilic addition to monopyridone moiety of paraquot or diquat OR AN2 >> Nucleophilic addition to monopyridone moiety of paraquot or diquat >> Bipyridilium Herbicides OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) >> Heterocyclic Aromatic Amines OR Ionic interaction OR Ionic interaction >> Electrostatic interaction of tetraalkylamonium ion with protein carboxylates OR Ionic interaction >> Electrostatic interaction of tetraalkylamonium ion with protein carboxylates >> Tetraalkylammonium ions OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Radical reactions OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR Radical reactions >> ROS generation and protein carbonylation OR Radical reactions >> ROS generation and protein carbonylation >> Bipyridilium Herbicides OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  >> Heterocyclic Aromatic Amines OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Anion AND Cation AND Quaternary ammonium salt by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as 1,2-aminoalcohol OR Alcohol OR Alkylarylether OR Amine OR Aromatic compound OR Carbonic acid derivative OR Carboxylic acid OR Carboxylic acid derivative OR Carboxylic acid salt OR CO2 derivative (general) OR Dialkylether OR Ether OR Guanidine OR Heterocyclic compound OR Hydroxy compound OR Phosphoric acid derivative OR Primary alcohol OR Primary aliphatic amine OR Primary amine OR Sulfenic acid derivative OR Sulfonic acid OR Sulfonic acid derivative OR Sulfuric acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Cationic (quaternary ammonium) surfactants by US-EPA New Chemical Categories

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.587

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.18

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 value was estimated to be 754.7 mg/kg bw for rats.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the acute oral toxicity in rats was predicted for 1-Butanaminium, N,N,N-tributyl-, iodide (1:1) (CAS: 311-28-4). LD50 value was estimated to be 754.7 mg/kg bw for rats.

Based on this value it can be concluded that the substance is considered to toxic by oral route as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

754.7 mg/kg bw

Quality of whole database:

Data is from Klamisch 2 and

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, 1-Butanaminium, N,N,N-tributyl-, iodide (1:1)has been investigated for acute oral 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 mice and rats for 1-Butanaminium, N,N,N-tributyl-, iodide (1:1) along with the study available on structurally similar read across substance Tetrabutylammonium bromide (CAS no 1643-19-2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 1-Butanaminium, N,N,N-tributyl-, iodide (1:1). The LD50 was estimated to be 754.7 mg/kg bw when rats were orally exposed with 1-Butanaminium, N,N,N-tributyl-, iodide (1:1).

In another experimental study conducted by Elliset al(Journal of Pharmaceutical Sciences Vol. 69. No. 3 (March 1980) pp327-331), mice were treated with 1-Butanaminium, N,N,N-tributyl-, iodide (1:1) in the concentration of 1600 mg/kg orally and observed for 72 hours.60 % Mortality was observed in treated mice at 1600 mg/kg. Therefore, LDLo (LD60) was considered to be 1600 mg/kg when mice were treated with 1-Butanaminium, N,N,N-tributyl-, iodide (1:1) orally. 

Further supported by experimental study given by ChemIDplus Toxnet Database (2017), rats were treated with 1-Butanaminium, N,N,N-tributyl-, iodide (1:1) orally in the concentration of 1990 mg/kg bw. 50 % mortality was observed in treated rats at 1990 mg/kg bw. Therefore, LD50 was considered to be 1990 mg/kg when rat were treated 1-Butanaminium, N,N,N-tributyl-, iodide (1:1) orally.

Also it is further supported by prediction done by SSS (2017) using Danish EPA Model, 50 % mortality observed at 590 mg/kg bw . Therefore, estimated LD50 was considered to be 590 mg/kg bw when mice were treated Tetrabutylammonium iodide orally.   

This is supported by experimental study conducted by Sustainability Support Services (Europe) AB (2014) for read across, acute Oral Toxicity was evaluated in Nine Wistar female rats by using Tetrabutylammonium bromide as per OECD No. 423. Three rats of first group were dosed with starting dose of 300 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 300 mg/kg body weight and no mortality was observed. Hence three rats of second group were dosed with 2000 mg/kg weight. All the rats at 2000mg/kg were found dead on day 0 post dosing. Hence, further dosing was stopped.Body weights were re­corded on day 0 (prior to dosing) 7 and 14. Body weight gain was observed in all surviving animals treated with 300 mg/kg body weight, during the 14 day observation period, as compared to day 0. At 300 mg/kg, all the six animals were observed normal throughout the experiment period. At 2000 mg/kg, animal no. 7 was observed with mild tremors at 30 minutes, mild to moderate abdominal breathing at 30 minutes and 1 hour and sternal recumbency at 1 hour followed by found dead. Animal nos. 8 and 9 were observed with mild tremors, moderate abdominal breathing, sternal recumbency and moderate salivation at 30 minutes followed by found dead. No external gross pathological changes were seen in all the six animals treated with 300 mg/kg body weight during terminal sacrifice. At 2000 mg/kg, animal no. 7 was observed with no abnormalities, whereas animal nos. 8 and 9 were observed with wet around mouth. No internal gross pathological changes were seen in all the six animals treated with 300 mg/kg body weight during terminal sacrifice. At 2000 mg/kg, all three animals were observed with severe red discoloration of all lobes lungs and test item was observed in stomach and intestine. Therefore, acute oral LD50 (cut-off value) of Tetrabutylammonium bromide was considered to be 500 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that Tetrabutylammonium bromide (CAS No. 1643-19-2) exhibits acute oral toxicity in “Category 4” with LD50 >300 to ≤2000 mg/kg body weight.

Thus, based on the above studies and predictions on 1-Butanaminium, N,N,N-tributyl-, iodide (1:1) and its read across substances, it can be concluded that LD50 value is less than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-Butanaminium, N,N,N-tributyl-, iodide (1:1) can be classified as “Category IV” of acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 1-Butanaminium, N,N,N-tributyl-, iodide (1:1) and its read across substances, it can be concluded that LD50 value is less than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-Butanaminium, N,N,N-tributyl-, iodide (1:1) can be classified as “Category IV” of acute oral toxicity.