Tetrabutylammonium iodide

Endpoint summary

Description of key information

The skin sensitization potential of N,N,N-tributylbutan-1-aminium iodide(311-28-4) estimated by using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances N,N,N-tributylbutan-1-aminium iodide (311-28-4) was predicted to be not sensitizing to the skin of Crj:Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 from OECD QSAR toolbox v3.4 and the QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

Predication was done using OECD QSAR toobox v3.4

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Not specified

Specific details on test material used for the study:

Name of test material (as cited in study report): 1Butanaminium, N,N,Ntributyl,iodide
Molecular Formula: C16H36N.I
Molecular Weight: 369.367g/mol
Smiles notation: [N+](CCCC)(CCCC)(CCCC)CCCC.[IH]
Substance type: Organic
Physical state: not specified

Species:

guinea pig

Strain:

other: Crj:Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan, Inc.
- Age at study initiation: Five weeks old.
- Weight at study initiation: 277 - 315 g
- Housing: The animals were housed in a stainless wire hanger cage (36 cmD X 25 cmW X 18 cmH) in a barrier-system-animal room.
- Diet (e.g. ad libitum): Commercial diet (RC4) ad libitum
- Water (e.g. ad libitum): Mains water ad libitum (Kaizu-cho, Kaizu-gun, Gifu, Japan)
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature of 20 - 26 deg C.
- Humidity (%): Relatively 40 - 70%
- Air changes (per hr): 12 - 18 exchanges/hour
- Photoperiod (hrs dark / hrs light): Light for 12 hours followed by 12 hours darkness.

IN-LIFE DATES: From: Day 0 To: Day 25

Route:

intradermal and epicutaneous

Vehicle:

other: physiological saline and water for injection

Concentration / amount:

or intradermal induction :Test group: (1) Physiological saline + Freund's complete adjuvant (FCA), (2) 0.01% as suspension in physiological saline, (3) 0.01% of the substance + FCA
Control group: (1) Physiological saline + FCA, area (2) physiological saline, (3) Physiological saline + FCA
for epicutaneous application :
Test group: 10% as as suspension in water for injection
Control group: water for injection

Day(s)/duration:

48hr

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

0.5, 0.3, 0.1, 0.05, 0.03 and 0.01% as suspension in water.

Day(s)/duration:

24hr

Adequacy of challenge:

not specified

No. of animals per dose:

Total :15
Test group:10
control group :5

Details on study design:

No data available

Challenge controls:

No data available

Positive control substance(s):

not specified

Statistics:

Not specified

Positive control results:

No data available

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.01%

No. with + reactions:

0

Clinical observations:

No skin sensitization reaction observed

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode 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" )  )

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 OECD

Domain logical expression index: "g"

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 esters 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 >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides 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: "h"

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

Domain logical expression index: "i"

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: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.94

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.6

Interpretation of results:

other: Not sensitzing

Conclusions:

The skin sensitization potential of N,N,N-tributylbutan-1-aminium iodide (311-28-4) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. N,N,N-tributylbutan-1-aminium iodide (311-28-4) was predicted to be not sensitizing to the skin of Crj:Hartley guinea pig.

Executive summary:

The skin sensitization potential of N,N,N-tributylbutan-1-aminium iodide(311-28-4) estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances N,N,N-tributylbutan-1-aminium iodide (311-28-4) was predicted to be not sensitizing to the skin of Crj:Hartley guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studies, N,N,N-tributylbutan-1-aminium iodide(311-28-4)  has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction is based on in vivo experiments in guinea pig for target chemical N,N,N-tributylbutan-1-aminium iodide(311-28-4)  and its structurally similar read across substancesTributylamine (102 -82 -9). The predicted data using the OECD QSAR toolbox have also been compared with the experimental data of read across.

The skin sensitization potential of N,N,N-tributylbutan-1-aminium iodide(311-28-4) estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances N,N,N-tributylbutan-1-aminium iodide (311-28-4) was predicted to be not sensitizing to the skin of Crj:Hartley guinea pig.

Further supported by experimental data conducted by Benson A (SIDS Initial Assessment Report, CoCAM, 2014.) on structurally similar read across substance Tributylamine (102 -82 -9)inguinea pig. The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. Skin sensitization study of Tributylamine (102 -82 -9) was performed in guinea pig by Buehler test .The test showed no sign of skin sensitization in guinea pig. Therefore Tributylamine (102 -82 -9) was considered to be not sensitizing in guinea pig .

Thus based on the above predictions on N,N,N-tributylbutan-1-aminium iodide(311-28-4)  as well as its read across substances and applying weight of evidence, it can be concluded that N,N,N-tributylbutan-1-aminium iodide(311-28-4)  is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, N,N,N-tributylbutan-1-aminium iodide(311-28-4)  can be considered as not classified for skin sensitization effects.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, N,N,N-tributylbutan-1-aminium iodide(311-28-4)  can be considered as not classified for skin sensitization effects.