α-bromo-m-toluonitrile

Endpoint summary

Description of key information

Acute Oral Toxicity: 

Acute oral toxicity dose was predicted based on OECD QSAR toolbox for target substance α-bromo-m-toluonitrile (28188-41-2) was estimated to be 2439.03 mg/kg bw for rats,and for differentstudies available on target substance α-bromo-m-toluonitrile (28188-41-2) using the Danish (Q)SAR Database was estimated to be 2700 mg/kg bw for rats;for the structurally similar read across substance4-methylbenzonitrile (104-85-8)was considered to be 3800 mg/kg bw for rats and for the closely related read across substance 1-Bromobutane (109-65-9) was considered to be 2761 mg/kg bw for rats. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, α-bromo-m-toluonitrile (28188-41-2) can be classified as category V of acute oral toxicity.

Acute Dermal Toxicity:

Acute dermal toxicity dose was predicted based on OECD QSAR toolbox for target substance α-bromo-m-toluonitrile (28188-41-2) was estimated to be 2663.34 mg/kg bw for rabbits,and for differentstudies available on structurally similar read across substance 1,3-Benzenedicarbonitrile (626-17-5) was considered to be >2000 mg/kg bw for rabbits and for the closely related read across substance 2,2-dichloro-1,1,1-trifluoroethane (306-83-2) was considered to be >2000 mg/kg bw for rabbits. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, α-bromo-m-toluonitrile (28188-41-2) was can be classified as category V of acute dermal toxicity.

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 QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3,2017

GLP compliance:

not specified

Test type:

other: estimated data

Limit test:

no

Specific details on test material used for the study:

- Name of the test material: α-bromo-m-toluonitrile
- IUPAC name: 3-(bromomethyl)benzonitrile
- Molecular formula: C8H6BrN
- Molecular weight: 196.046 g/mol
- Smiles: N#Cc1cc(CBr)ccc1
- Inchi: 1S/C8H6BrN/c9-5-7-2-1-3-8(4-7)6-10/h1-4H,5H2
- Substance type: Organic
- Physical state : Solid crystalline powder (Off white)

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available

Doses:

2439.03 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:

male

Dose descriptor:

LD50

Effect level:

2 439.03 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was 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 "g" )  and "h" )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and "p" )  and ("q" and "r" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) by Protein binding by OECD ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR SN2 OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> SN2 at an sp3 Carbon atom AND SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  AND SN2 >> Nucleophilic substitution on benzilyc carbon atom AND SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides AND SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) by Protein binding by OECD ONLY

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> Nucleophilic subsitution at sp3- Carbon atom OR SN2 >> Nucleophilic subsitution at sp3- Carbon atom >> alpha, omega-Dihaloalkanes by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkyl bromide AND Alkyl halide AND Aromatic compound AND Halogen derivative AND Nitrile by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Alcohol OR Alkyl chloride OR Alkyl iodide OR Anion OR Aryl chloride OR Aryl halide OR Carbonic acid derivative OR Carboxylic acid derivative OR Carboxylic acid ester OR Cation OR Hydroxy compound OR Phosphoric acid derivative OR Phosphoric acid ester OR Primary alcohol OR Quaternary ammonium salt OR Secondary alcohol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "p"

Similarity boundary:Target: N#Cc1cccc(CBr)c1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.16

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.19

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 was estimated to be 2439.03 mg/kg bw,when male Sprague-Dawley rats were orally exposed with α-bromo-m-toluonitrile (28188-41-2) orally.

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 α-bromo-m-toluonitrile (28188-41-2).The LD50 was estimated to be 2439.03 mg/kg bw,when male Sprague-Dawley rats were orally exposed with α-bromo-m-toluonitrile (28188-41-2) orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 439.03 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 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 QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3,2017

GLP compliance:

not specified

Test type:

other: no data available

Limit test:

no

Specific details on test material used for the study:

- Name of the test material: α-bromo-m-toluonitrile
- IUPAC name: 3-(bromomethyl)benzonitrile
- Molecular formula: C8H6BrN
- Molecular weight: 196.046 g/mol
- Smiles: N#Cc1cc(CBr)ccc1
- Inchi: 1S/C8H6BrN/c9-5-7-2-1-3-8(4-7)6-10/h1-4H,5H2
- Substance type: Organic
- Physical state : Solid crystalline powder (Off white)

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

No data available

Duration of exposure:

24 hours

Doses:

2663.34 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:

male/female

Dose descriptor:

LD50

Effect level:

2 663.34 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% Mortality was 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 7 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 ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and "o" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) by Protein binding by OECD ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR SN2 OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen 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, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  AND SN2 >> Nucleophilic substitution on benzilyc carbon atom AND SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Slightly reactive (GSH) OR Slightly reactive (GSH) >> Substituted haloacetamides (SN2) by Protein binding potency

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Similarity boundary:Target: N#Cc1cccc(CBr)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.59

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.44

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 value was estimated to be 2663.34 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively with α-bromo-m-toluonitrile (28188-41-2) by dermal application for 24 hours.

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 α-bromo-m-toluonitrile (28188-41-2).The LD50 was estimated to be 2663.34 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively α-bromo-m-toluonitrile (28188-41-2) by dermal application for 24 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 663.34 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

Additional information

Acute Oral Toxicity: 

In different studies, α-bromo-m-toluonitrile (28188-41-2) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for α-bromo-m-toluonitrile (28188-41-2) along with the study available on the structurally similar read across substance4-methylbenzonitrile (104-85-8) andthe closely related read across substance 1-Bromobutane (109-65-9). 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 α-bromo-m-toluonitrile (28188-41-2).The LD50 was estimated to be 2439.03 mg/kg bw,when male Sprague-Dawley rats were orally exposed with α-bromo-m-toluonitrile (28188-41-2) orally.

Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 2700 mg/kg bw on rats for α-bromo-m-toluonitrile (28188-41-2) having Reliability Index: 0.74 (moderate prediction quality).

This is further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank); US national Library of Medicine,2017) for the structurally similar read across substance4-methylbenzonitrile (104-85-8).Acute oral toxicity study was done in rats using test material 4-methylbenzonitrile(104-85-8).50% Mortality was observed at dose 3800 mg/kg bw. Hence,LD50 value was considered to be 3800 mg/kg bw,when rats were treated with 4-methylbenzonitrile(104-85-8)orally.

The above study was further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) ;U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank); US national Library of Medicine,2017) and NTRL (INITIAL SUBMISSION: ACUTE ORAL TOXICITY STUDY WITH N-BUTYL BROMIDE IN RATS, OTS0540435,1992) for the closely related read across substance 2,2-dichloro-1,1,1-trifluoroethane (306-83-2).Acute oral toxicity study was done inSprague Dawley albinorats using test material1-Bromobutane(109-65-9) at dose1000 mg/kg bw,1951.9 mg/kg bw,3872.6 mg/kg bw,7620.8 mg/kg bw and 15,000 mg/kg bw. 50 (25/sex) albino rats were received fromA. R. S. Sprague-Dawley, Madison, Wisconsin for the study. The initial body weight of males rats ranged from 189-230 gm and for females 195-225 gm. Rats were uniquely identified by an ear tag and individually housed in elevated wire-mash cages. Commercial rodent ration (Purina rodent laboratory chow) and tap water was provided ad libitum.Rats were acclimated to laboratory conditions for 1 week prior to initiation of treatment. Test material was administered by oral gavage following an overnight fast. All rats were observed for mortality and signs of toxicity and pharmacologic effects at one,two, and four hours postdose, and twice daily thereafter for 14 days consecutive days.Individual body weight were recorded prior to treatment, on Day 7, and at termination.50% Mortality was observed at dose 2760mg/kg bw and 3160.8 mg/kg bw.Clinical observations consisted of depression, rough coat,tremors, slight depression ,and red stain on eyes/or nose noted at all doses.At dose 1967.9, 3872.6,7620.8 and 15,000 mg/kg bw,soft faeces,ataxia,labord respiration, and urine stains were observed.At dose 1967.9,3872.6, and 7620.8 mg/kg bw,salivation and lacrimation was observed.At dose 3872.6,7620.8 and 15,000 mg/kg bw, prostration was observed.At dose 3872.6,7620.8 mg/kg bw, hunching was observed.All animals surviving to the termination of the study were found to gain weight. Gross pathology consisted of bright red discoloration of the lungs,and fluid in the thoracic cavity ,urinary bladder (dark black) , and stomach and intestine (clear yellow), as well as material in the stomach and intestine (dark red,greenish,oily black,compound like).Hence,LD50 value was considered to be 2760 mg/kg bw for males(95% CL 2234.1 - 3411.1 mg/kg bw) and 3160.8mg/kg bw for females(95% CL 2411.0 - 4143.85 mg/kg bw),when rats were treated with 1-Bromobutane(109-65-9)orally via gavage following 14 days of observation period.

Thus, based on the above studies on α-bromo-m-toluonitrile (28188-41-2) and it’s structurally similar and closely related 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, α-bromo-m-toluonitrile (28188-41-2) can be classified as category V of acute oral toxicity.

Acute Dermal Toxicity:

In different studies, α-bromo-m-toluonitrile (28188-41-2) has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for α-bromo-m-toluonitrile (28188-41-2) along with the study available on structurally similar read across substance 1,3-Benzenedicarbonitrile (626-17-5) and the closely related read across substance 2,2-dichloro-1,1,1-trifluoroethane (306-83-2).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 α-bromo-m-toluonitrile (28188-41-2).The LD50 was estimated to be 2663.34 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively α-bromo-m-toluonitrile (28188-41-2) by dermal application for 24 hours.

This is further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank) for the structurally similar read across substance 1,3-Benzenedicarbonitrile (626-17-5). In acute dermal toxicity study,rabbits were treated with 1,3-Benzenedicarbonitrile (626-17-5) in the concentration of 2000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 2000 mg/kg bw.Therefore, LD50 value was considered to be >2000 mg/kg bw,when rabbits were treated with 1,3-Benzenedicarbonitrile(626-17-5)by dermal application.

The above study was further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) ;U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank) and NTRL (ACUTE DERMAL TOXICITY STUDY OF HCFC-123 IN RABBITS, OTS0530597,1990) for the closely related read across substance 2,2-dichloro-1,1,1-trifluoroethane (306-83-2).In acute dermal toxicity study,Young adult male and female New Zealand White rabbits were treated2,2-dichloro-1,1,1-trifluoroethane(306-83-2)in the concentration of 2000 mg/kg bw by dermal application. The rabbits were housed singly in suspended, stainless steel, wire-mesh cages. Each rabbit was assigned a unique identification number which was recorded on a card affixed to the cage. Purina Certified High Fiber Rabbit chow- 15325 and water was provided ad libitum. Rabbits were quarantined, weighed end observed far general hearth for approximately 2 weeks.Animal rooms were maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20°C ± 2°C and relative humidity of 50% ± 10%. The test substance (approx. 99.98% pure)was applied to the clipped,intact skin of rabbits On the day before dosing, the hair of each rabbit were closely clipped to expose the back from the scapular to the lumber region.The test material was spread evenly over the entire exposed akin of each animal (approximately 190 square centimeters).The rabbits weighed between 1972 and 2169 grams on the day of dosing.immediately after application of the test material, sterile gauze pads were applied to the treated site. The rabbits were then wrapped with successive layers of plastic film, stretch gauze bandage and elastic adhesive bandage. Approximately 24 hours after treatment, the rabbits were removed from their cages and the wrappings were removed. Excess test material was washed from the animals' back with warm water and the skin dried with a paper towel.observations for clinical signs were made approximately 24 hours after dosing and then daily thereafter for 14 days (excluding weekends). Observations for mortalities were made daily throughout the study. The animals were weighed on days 1, 5, 7, and 14 following treatment.No mortality was observed in treated rabbits at dose 2000 mg/kg bw.Slight to moderate erythema was observed in 6 rabbits by one day after treatment.By day 5, no dermal irritation was observed. Slight body weight losses (up to 2% of initial body weight) were observed one day after treatment.Slight weight losses were observed in some rabbits on days 7 and 14. No gross pathological abnormalities were observed in any of the treated rabbits.Therefore, LD50 value was considered to be >2000 mg/kg bw for bothmale and female,whenNew Zealand Whiterabbits wereocclusively treated with2,2-dichloro-1,1,1-trifluoroethane(306-83-2)by dermal applicationfor 24 hours following 14 days of observation period.

Thus, based on the above studies on α-bromo-m-toluonitrile (28188-41-2) and it’s structurally similar 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, α-bromo-m-toluonitrile (28188-41-2) can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on α-bromo-m-toluonitrile (28188-41-2), it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, α-bromo-m-toluonitrile (28188-41-2) can be classified as category V for acute oral and dermal toxicity.