3-bromoquinoline

Endpoint summary

Description of key information

Acute oral toxicity: 

LD50 was estimated to be 2921 mg/kg bw, when Tif: RAIf (SPF) male and female rats were treated with 3-Bromoquinoline orally by intubation.

Acute Dermal toxicity: 

LD50 was estimated to be 2957 mg/kg bw, when New Zealand White male and female rabbits were treated with 3-Bromoquinoline by dermal application occlusively.

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 3.3 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 : 3-Bromoquinoline
- Molecular formula : C9H6BrN
- Molecular weight : 208.057 g/mol
- Smiles notation : c12c(ncc(c1)Br)cccc2
- InChl : 1S/C9H6BrN/c10-8-5-7-3-1-2-4-9(7)11-6-8/h1-6H
- Substance type: Organic
- Physical state: Liquid

Species:

rat

Strain:

other: Tif: RAIf (SPF) strain

Sex:

male/female

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:

2921 mg/kg bw

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:

male/female

Dose descriptor:

LD50

Effect level:

2 921 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 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Direct acting epoxides formed after metabolic activation AND SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives AND SN2 >> SN2 at an activated carbon atom AND SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Halopyrdines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR 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 >> Alkyl phenols 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 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 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine 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 by DNA binding by OECD

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Aliphatic amines (Mucous membrane irritation) Rank C OR Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.05

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.38

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2921 mg/kg bw, when Tif: RAIf (SPF) male and female rats were treated with 3-Bromoquinoline orally by gavage..

Executive summary:

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 3-Bromoquinoline (5332-24-1). The LD50 was estimated to be 2921 mg/kg bw, when Tif: RAIf (SPF) male and female rats were treated with 3-Bromoquinoline orally by gavage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 921 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR Toolbox version 3.3

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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 : 3-Bromoquinoline
- Molecular formula : C9H6BrN
- Molecular weight : 208.057 g/mol
- Smiles notation : c12c(ncc(c1)Br)cccc2
- InChl : 1S/C9H6BrN/c10-8-5-7-3-1-2-4-9(7)11-6-8/h1-6H
- Substance type: Organic
- Physical state: Liquid

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 hours

Doses:

2957 mg/kg bw

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:

male/female

Dose descriptor:

LD50

Effect level:

2 957 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 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Direct acting epoxides formed after metabolic activation AND SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives AND SN2 >> SN2 at an activated carbon atom AND SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Halopyrdines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes OR Low reactive OR Low reactive >> N-substituted aromatic amides OR Moderate reactive OR Moderate reactive >> Glycidyl ether epoxides by DPRA Cysteine peptide depletion

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition to quinoid structures OR AN2 >> Michael-type addition to quinoid structures >> Phenols by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Pyridine AND Quinoline/ Isoquinoline by Organic Functional groups

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Pyridine AND Quinoline/ Isoquinoline by Organic Functional groups

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Pyridine AND Quinoline/ Isoquinoline by Organic Functional groups

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Pyridine AND Quinoline/ Isoquinoline by Organic Functional groups

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.81

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.38

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2957 mg/kg bw, when New Zealand White male and female rabbits were treated with 3-Bromoquinoline by dermal application occlusively.

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 3-Bromoquinoline (5332-24-1). The New Zealand White male and female rabbits were treated with 3-Bromoquinoline2 at a concentration 2957 mg/kg bw for 4 hours by dermal application occlusively. 50% mortality was observed at 2957 mg/kg bw. Therefore, LD50 was estimated to be 2957 mg/kg bw, when New Zealand White male and female rabbits were treated with 3-Bromoquinoline by dermal application occlusively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 957 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR Toolbox version 3.3

Additional information

Acute oral toxicity:

In different studies, 3-Bromoquinoline (CAS no 5332-24-1) 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 mice for 3-Bromoquinoline along with the study available on structurally similar read across substance 2-chloro-4,6-bis(isopropylamino)-1,3,5-triazine (CAS no: 139-40-2) and 2-Chloro-4-ethylamine-6-isopropylamine-1,3,5-triazine (CAS no: 1912-24-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. 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 oral toxicity was estimated for 3-Bromoquinoline (5332-24-1). The LD50 was estimated to be 2921 mg/kg bw, when Tif: RAIf (SPF) male and female rats were treated with 3-Bromoquinoline orally by intubation.

In experimental study done on structurally similar read across substance 2-chloro-4,6-bis(isopropylamino)-1,3,5-triazine (CAS no: 139-40-2) by U.S. National Library of Medicine (ChemIDplus 2017) and RTECS, the acute oral toxicity study was conducted in rat at the concentration of 3840 mg/kg bw orally. 50% mortality was observed at 3840 mg/kg bw. Therefore, LD50 was considered to be 3840 mg/kg bw, when rat was treated with 2-chloro-4,6-bis(isopropylamino)-1,3,5-triazine orally.

In another experimental study supported by Raju Kacham (Encyclopedia of Toxicology (Second Edition), Pages 534–535, 2005), for the structurally similar read across substance 2-chloro-4,6-bis(isopropylamino)-1,3,5-triazine (CAS no: 139-40-2), the acute oral toxicity study was conducted in rat at the concentration of 3850 mg/kg bw orally. No mortality was observed at 3850 mg/kg bw. Therefore, LD50 was considered to be >3850 mg/kg bw (3850–7000 mg/kg bw), when rat was treated with 2-chloro-4,6-bis(isopropylamino)-1,3,5-triazine orally.

This is further supported by experimental study by Raju Kacham (Encyclopedia of Toxicology (Second Edition), Pages 534–535, 2005), U.S. National Library of Medicine (ChemIDplus) and RTECS,for the structurally similar read across substance 2-chloro-4,6-bis(isopropylamino)-1,3,5-triazine (CAS no: 139-40-2), the acute oral toxicity study was conducted in mouse at the concentration of 3840 mg/kg bw orally. 50% mortality was observed at 3180 mg/kg bw. Therefore, LD50 was considered to be 3180 mg/kg bw, when mouse was treated with2-chloro-4,6-bis(isopropylamino)-1,3,5-triazineorally.

In another study summarized by J. W. Hauswirth and L. T. Wetzel (In: Ballantine LG, McFarland JE, Hacke (tt DS, eds. Triazine herbicides: risk assessment. Washington, DC: Oxford University Press; 370–83: 1998), for the structurally similar read across substance 2-Chloro-4-ethylamine-6-isopropylamine-1,3,5-triazine (CAS no: 1912-24-9). The acute oral toxicity study was conducted in rat at the concentration of 3000 mg/kg bw orally. No mortality was observed at 3000mg/kg bw. Therefore, LD50 was considered to be >3000 mg/kg bw, when rat was treated with 2-Chloro-4-ethylamine-6-isopropylamine-1,3,5-triazine orally.

Thus, based on the above studies on 3-Bromoquinoline (CAS no 5332-24-1) and it’s 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, 3-Bromoquinoline can be classified as category V of acute oral toxicity.

Acute Dermal toxicity:

In different studies, 3-Bromoquinoline (CAS no 5332-24-1) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits and rats for 3-Bromoquinoline along with the study available on structurally similar read across substance 1-Chloro-4-nitrobenzene (100-00-5) and 1,1,1-Tris(4-hydroxyphenyl)ethane (CAS no: 27955-94-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. 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 3-Bromoquinoline (5332-24-1). The New Zealand White male and female rabbits were treated with 3-Bromoquinoline at a concentration 2957 mg/kg bw for 4 hours by dermal application occlusively. 50% mortality was observed at 2957 mg/kg bw. Therefore, LD50 was estimated to be 2957 mg/kg bw, when New Zealand White male and female rabbits were trated with 3-Bromoquinoline by dermal application occlusively.

In another experimental study supported by U.S. National Library of Medicine (ChemIDplus,2017) and National Toxicology Program (National Toxicology Program Toxicity Report Series Number 33, NIH Publication 93-3382, July 1993), for the structurally similar read across substance 1-Chloro-4-nitrobenzene (100-00-5), the acute dermal toxicity study was done in rabbits at the concentration of 3040 mg/kg bw. 50% mortality was observed at dose 3040 mg/kg bw. Hence, the LD50 value was considered to be 3040 mg/kg bw, when rabbits were treated with 1-Chloro-4-nitrobenzene by dermal application.

This is further supported by U.S. National Library of Medicine (ChemIDplus) and National Technical Reports Library (OTS0530499-1, 1991), for the structurally similar read across substance 1,1,1-Tris(4-hydroxyphenyl)ethane (CAS no: 27955-94-8). The Acute dermal toxicity study was done in rats. A group of 10 CD rats (5 of each sex) was treated with 2000 mg/kg of test material (99% pure Batch No. SN7741, stored in original container in darkness at room temperature) administered as water based slurry. The material was spread over a 5 x 5 cm area of clipped skin and covered with gauss and then an impermeable bandage. The material was left on the skin for 24 hours after which the dressing was removed and the remaining material removed with warm water and the site blotted dry. Animals were observed for 14 days after removal of the dressing, were sacrificed on the 14th day after removal of the test substance, and submitted to a necropsy for examination of possible macroscopic effects on the major organs.

After 14 days of observation, body weight gained normally by animals. All organs appeared normal on necropsy. No adverse clinical signs were observed and the application site was free of local irritation throughout the 14 day observation period. No mortality was observed at dose 2000 mg/kg bw. Therefore, the LD50 value was considered to be >2000mg/kg bw, when rats were treated with 1,1,1-Tris(4-hydroxyphenyl)ethane (27955-94-8) by dermal application.

Thus, based on the above studies on 3-Bromoquinoline (CAS no 5332-24-1) 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, 3-Bromoquinoline can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and pridiction on 3-Bromoquinoline (CAS no 5332-24-1) 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, 3-Bromoquinoline can be classified as category V of acute oral and dermal toxicity.