Tetrabutylammonium hydrogen sulphate

Endpoint summary

Description of key information

Estimated LD50 was considered to be 1261 mg/kg bw when rat were treated with N,N,N-tributylbutan-1-aminium hydrogen sulfate orally for24 hours.

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:

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 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: No data

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Tetrabutylammonium hydrogen sulphate (N,N,N-tributylbutan-1-aminium hydrogen sulfate)
- Molecular formula (if other than submission substance): C16H36N.HO4S
- Molecular weight (if other than submission substance): 339.537 g/mole
- Substance type: Organic

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

1261 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 261 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 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 "q" )  )

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 Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, single bonds  [N{v+5}] AND Suflur {v+4} or {v+6} AND Sulfate, linear [-O-SO2-O-] AND Sulfite, linear [-OS(=O)O-] by Organic functional groups (US EPA)

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anion AND Cation AND Quaternary ammonium salt AND Sulfuric acid derivative 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 >> 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 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 to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes 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 >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

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 Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F,Cl,Br,I,At OR Group 8 - Trans.Metals Fe,Ru,Os by Chemical elements

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.48

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.6

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

estimated LD50 was considered to be 1261 mg/kg bw when rat were treated with N,N,N-tributylbutan-1-aminium hydrogen sulfate orally.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 and considering the five closest read across substances, the acute oral toxicity in rats was predicted for N,N,N-tributylbutan-1-aminium hydrogen sulfate (CAS: 32503-27-8). LD50 value was estimated to be 1261 mg/kg bw for rats for24 hours.

Based on this value it can be concluded that the substance is considered to not toxic by oral route as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 261 mg/kg bw

Quality of whole database:

Data is Kimisch 2 and from QSAR Toolbox 3.4 (2017)

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

In different studies, N,N,N-tributylbutan-1-aminium hydrogen sulfate 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 rats for N,N,N-tributylbutan-1-aminium hydrogen sulfate 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 in rats was predicted for N,N,N-tributylbutan-1-aminium hydrogen sulfate (CAS: 32503-27-8). LD50 value was estimated to be 1261 mg/kg bw for rats for24 hours.

In another prediction done by SSS (2016) using Danish (Q) SAR Database, acute oral toxicity estimated in rats by using N,N,N-tributylbutan-1-aminium hydrogen sulfate orally. 50 % mortality observed at 590 mg/kg bw . Therefore, estimated LD50 was considered to be 590 mg/kg bw when rat were treated with N,N,N-tributylbutan-1-aminium hydrogen sulfate orally.

Also it is further supported experimental data by Sustainability Support Services (Europe) AB (2014) on structurally similar read across substance Tetrabutylammonium bromide (CAS No. 1643-19-2), acute Oral Toxicity was evaluated in Nine female Wistar Rats by using Tetrabutylammonium bromide in 2 steps performed as per OECD No. 423. The animals were fasted for minimum 16-18 hours prior to dosing and for 3-4 hours post dosing, with food withheld but drinking water provided ad libitum. Three rats of first group were dosed at 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 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, LD50 (cut-off value) was 500 mg/kg body weight when female Wistar Rats were treated with of Tetrabutylammonium bromide.

Thus, based on the above predictions and studies on N,N,N-tributylbutan-1-aminium hydrogen sulfate 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, N,N,N-tributylbutan-1-aminium hydrogen sulfate can be classified as ‘Category IV’ of acute oral toxicity. 

Justification for classification or non-classification

Based on the above predictions and studies on N,N,N-tributylbutan-1-aminium hydrogen sulfate 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, N,N,N-tributylbutan-1-aminium hydrogen sulfate can be classified as ‘Category IV’ of acute oral toxicity.