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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 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 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:
No data available
Body weight:
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.