2-chloro-p-phenylenediamine

Endpoint summary

Description of key information

Acute toxicity: oral

The acute oral toxicity study was conducted on male/female CFY strain rats to evaluate the toxic nature of the test compound 2-chloro-p-phenylenediamine.

35 male and 35 female rats of the CFY strain were administered by oral intubation with a 10% suspension in aqueous gum tragacanth (0.5%) at dosage levels 400, 640, 800. 1000,1260 and 1600 mg/kg bw. The acute oral median lethal dose (LD50) of 2-chloro-p-phenylenediamine in rat was observed to be 1,190 mg/kg bw with 95% CL of 1,070 - 1,320 mg/kg bw. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 2-chloro-p-phenyl enediamine (CAS No. 615-66-7) can be classify under category 4 compound at the tested dose levels.

 

Acute toxicity: dermal

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of administration of 2-chloro-p-phenylenediamine (CAS No. 615-66-7) in rabbits by the dermal route. 50% mortality was observed at 2364.13 mg/kg bw in treated rabbits.The acute dermal median lethal dose (LD50) of 2-chloro-p-phenylenediamine in rabbit was estimated to be 2364.13 mg/kg bw. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 2-chloro-p-phenylenediamine (CAS No. 615-66-7) does not classify as an acute dermal toxicant.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source.

Principles of method if other than guideline:

The acute oral toxicity study was conducted on male/female CFY strain rats to evaluate the toxic nature of the test compound 2-chloro-p-pheny lenediamine.

GLP compliance:

not specified

Test type:

other: No data available

Species:

rat

Strain:

other: CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % aqueous gum tragacanth

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 400, 640, 800, 1000, 1260 and 1600 mg/kg bw
- Amount of vehicle (if gavage): No data available
- Justification for choice of vehicle: No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

MAXIMUM DOSE VOLUME APPLIED: No data available

DOSAGE PREPARATION (if unusual): 10% suspension in aqueous gum tragacanth (0.5%) at dosage levels 400, 640, 800. 1000, 1260 and 1600 mg/kg bw.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No data available

Doses:

400, 640, 800, 1000, 1260 and 1600 mg/kg bw.

No. of animals per sex per dose:

35/sex/dose

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 190 mg/kg bw

Based on:

test mat.

95% CL:

1 070 - 1 320

Interpretation of results:

other: Category 4 based on CLP criteria

Conclusions:

The acute oral median lethal dose (LD50) of 2-chloro-p-phenylenediamine in rat was observed to be 1,190 mg/kg bw with 95% CL of 1,070 - 1,320 mg/kg bw.

Executive summary:

The acute oral toxicity study was conducted on male/female CFY strain rats to evaluate the toxic nature of the test compound 2-chloro-p-phenylenediamine.

35 male and 35 female rats of the CFY strain were administered by oral intubation with a 10% suspension in aqueous gum tragacanth (0.5%) at dosage levels 400, 640, 800. 1000,1260 and 1600 mg/kg bw. The acute oral median lethal dose (LD50) of 2-chloro-p-phenylenediamine in rat was observed to be 1,190 mg/kg bw with 95% CL of 1,070 - 1,320 mg/kg bw. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 2-chloro-p-phenyl enediamine (CAS No. 615-66-7) can be classify under category 4 compound at the tested dose levels.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 190 mg/kg bw

Quality of whole database:

Data is Klimisch 4 and from study report.

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:

Prediction is done using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached.

Qualifier:

no guideline available

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3 with log kow as the primary descriptor.

GLP compliance:

not specified

Test type:

standard acute method

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

No data available

Duration of exposure:

No data available

Doses:

2364.13 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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 364.13 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed.

Mortality:

50% mortality observed at 2364.13 mg/kg bw in treated rabbits.

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 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 "k" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anilines (amino-para) AND Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found OR SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.239

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.08

Interpretation of results:

other: not classified

Conclusions:

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of administration of 2-chloro-p-phenylenediamine (CAS No. 615-66-7) in rabbits by the dermal route. 50% mortality was observed at 2364.13 mg/kg bw in treated rabbits.The acute dermal median lethal dose (LD50) of 2-chloro-p-phenylenediamine in rabbit was estimated to be 2364.13 mg/kg bw.

Executive summary:

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of adm inistration of 2-chloro-p-phenylenediamine (CAS No. 615-66-7) in rabbits by the dermal route. 50% mortality was observed at 2364.13 mg/kg bw in treated rabbits.The acute dermal median lethal dose (LD50) of 2-chloro-p-phenylenediamine in rabbit was estimated to be 2364.13 mg/kg bw. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 2-chloro-p-phenylenediamine (CAS No. 615-66-7) does not classify as an acute dermal toxicant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 364.13 mg/kg bw

Quality of whole database:

The data is Klimicsh 2 and from OECD QSAR toolbox version 3.3 (2017).

Additional information

Acute toxicity: oral

In different studies, 2-chloro-p-phenylenediamine (CAS No. 615-66-7) 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 for 2-chloro-p-phenylenediamine along with the study available on structurally similar read across substances 2,6-dichlorobenzene-1,4-diamine (CAS No. 609 -20 -1) and 2,4,6-trichloroaniline (CAS No. 634-93-5). The studies are summarized as below:

 

The acute oral toxicity study was published in a Scientific Committee on Consumer Safety (SCCS) report (Opinion On 2-Chloro-p-phenylenediamine COLIPA n° A8,2013).This study was conducted on male/female CFY strain rats to evaluate the toxic nature of the test compound 2-chloro-p-phenylenediamine. 35 male and 35 female rats of the CFY strain were administered by oral intubation with a 10% suspension in aqueous gum tragacanth (0.5%) at dosage levels 400, 640, 800. 1000,1260 and 1600 mg/kg bw. The acute oral median lethal dose (LD50) of 2-chloro-p-phenylenediamine in rat was observed to be 1,190 mg/kg bw with 95% CL of 1,070 - 1,320 mg/kg bw.

 

In a similar type of study published in a Scientific Committee on Consumer Safety (SCCS) report (Opinion On 2-Chloro-p-phenylenediamine COLIPA n° A8,2013).The acute toxic effects of administration of 2-chloro-p-pheynelenediamine (CAS No. 615-66-7) in rats by the oral route was determined. The acute oral median lethal dose (LD50) of 2-chloro-p-phenylenediamine in rat was observed to be 729 mg/kg bw.

 

The above two studies are further supported by the experimental study published in a NTP report (1982).The study was conducted to evaluate the acute toxic effects of administration of 2,6-dichlorobenzene-1,4-diamine (CAS No. 609-20-1) in rats by the oral route. The acute oral median lethal dose (LD50) of 2,6-dichlorobenzene-1,4-diamine in rat was observed to be 700.0 mg/kg bw.

 

Moreover, the study was conducted by Lewis, R.J (Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 3231) to evaluate the acute toxic effects of administration of 2,4,6-trichloroaniline (CAS No. 634-93-5) in mouse by the oral route. The acute oral median lethal dose (LD50) of 2,4,6-trichloroaniline in mouse was observed to be 1180.0 mg/kg bw. 

 

So, based on the above mentioned studies for target substance 2-chloro-p-phenylenediamine (CAS No. 615-66-7) and to its read across substances, the median lethal dose (LD50) value was found to be in the range of 700.0 mg/kg b.wt. to 1190.0 mg/kg b.wt. Thus, on the basis of these LD50 value and according to CLP criteria for acute toxicity rating for the chemicals, it infers that 2-chloro-p-phenyl enediamine (CAS No. 615-66-7) can be classify under category 4 compound at the tested dose levels.

 

Acute toxicity: inhalation

According to column 2 of REACH Annex VIII, the acute toxicity inhalation study need not be conducted because exposure of humans via inhalation route is not likely taking into account the low vapour pressure of the substance 2-chloro-p-phenylenediamine , which is reported as 0.00206 mm Hg. Thus, exposure to inhalable dust, mist and vapour of the chemical 2-chloro-p-phenylenediamine is highly unlikely. Therefore this study is considered for waiver.

 

Acute toxicity: dermal

In different studies, 2-chloro-p-phenylenediamine (CAS No. 615-66-7) has been investigated for acute dermal 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 rabbits for 2-chloro-p-phenylenediamine along with the study available on structurally similar read across substance m-phenylenediamine (CAS No.- 108-45-2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data. The studies are summarized as below:

 

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of administration of 2-chloro-p-phenylenediamine (CAS No. 615-66-7) in rabbits by the dermal route. 50% mortality was observed at 2364.13 mg/kg bw in treated rabbits.The acute dermal median lethal dose (LD50) of 2-chloro-p-phenylenediamine in rabbit was estimated to be 2364.13 mg/kg bw.

 

Moreover, the toxicity study was examined by C. Burnett et al., (Journal of Toxicology and Environmental Health.Volume 2, 1977 - Issue 3, 657-662) to evaluate the acute toxic effects of administration of m-phenylenediamine (CAS No. 108-45-2) in rabbits by the dermal route. The acute dermal median lethal dose (LD50) of m-phenylenediamine in rabbit was observed to be 5000.0 mg/kg b.wt.

 

So, based on the above mentioned studies for target substance 2-chloro-p-phenylenediamine (CAS No. 615-66-7)nand to its read across substance, the median lethal dose (LD50) value was found to be in the range of 2364.13 mg/kg b.wt. to 5000 mg/kg b.wt. Thus, on the basis of these LD50 value and according to CLP criteria for acute toxicity rating for the chemicals, it infers that 2-chloro-p-phenylenediamine (CAS No. 615-66-7) does not classify as an acute dermal toxicant.

 

Justification for classification or non-classification

Based on the above mentioned studies on 2-chloro-p-phenylenediamine (CAS No. 615-66-7), it can be found that LD50 oral value is in the range of 300 to ≤ 2000 mg/kg b.wt and LD50 dermal value is >2000 mg/kg b.wt. Thus, by comparing these studies with the criteria of CLP regulation, it infers that the test substance 2-chloro-p-phenylenediamine (CAS No. 615-66-7)can be classify as an acute oral toxicant in category 4 whereas 2-chloro-p-phenylenediamine does not classify as an acute toxicant by the dermal route.