Registration Dossier

Administrative data

Description of key information

According to the results on acute oral toxicity studies in rats and the value of LD50 from 107-427 mg/kg body weight , and the CLP criteria (1272/2008/EC), the category 3 - Danger should be considered. The substance is Toxic if swallowed H301.

Based on the two calculations to determine the LC50 (inhalation route) and the LD50 (dermal route), the registered susbtance N,N-BIS(2-HYDROXYETHYL)-p-PHENYLENEDIAMINE SULFATE was classified as Category 3 for acute dermal and inhalation toxicity, respectively, H311 "Toxic in contact with skin" and H332 "Toxic if inhaled".

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1975
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Acute oral toxicity or LD50 value was determined by oral administration of test substance to four dose groups of male rats. Animals were observed for mortality during the study period. The method followed in this study was comparable to the OECD guideline 401.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: 250-300 g
No other information on the test animals was provided in the study report.

ENVIRONMENTAL CONDITIONS
No details on the environmental condition were provided in the study report.
Route of administration:
oral: unspecified
Vehicle:
DMSO
Remarks:
10%
Details on oral exposure:
VEHICLE: DMSO (10%)
No other information on vehicle was provided in the study report.

MAXIMUM DOSE VOLUME APPLIED: Not reported

DOSAGE PREPARATION: Not reported
- Rationale for the selection of the starting dose: Not reported
Doses:
100, 200, 400 and 800 mg/kg bw
No. of animals per sex per dose:
5 males/ dose group
Control animals:
no
Details on study design:
- Duration of observation period following administration: Not reported
- Frequency of observations and weighing: Not reported
- Necropsy of survivors performed: Not reported
- Other examinations performed: Mortality
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
246 mg/kg bw
Based on:
test mat.
95% CL:
> 187 - < 325
Remarks on result:
other: LD50 was calculated by Weil Method (Biometrics, Sept. 1952)
Mortality:
Mortality observed at individual dose levels was as follows:
- 100 mg/kg bw: 0/5
- 200 mg/kg bw: 1/5
- 400 mg/kg bw: 5/5
- 800 mg/kg bw: 5/5
Clinical signs:
Not reported
Body weight:
Not reported
Gross pathology:
Not reported

Calculation of LD50 by the Weil Method (Biometrics, Sep. 1952)

Dose level (mg/kg bw)      Mortality

100                                          0/5

200                                          1/5

400                                          5/5

800                                          5/5

Constant ratio = 2.0

Da = Lowest dose level

d = log of constant

f = 0.3

Delta f = 0.2

v values = 0, 1, 5, 5

For K =3

Log M = log Da + d (f+1)

Log M =0 + 0.3010 (0.3+1)

Log M = 0 + 0.3010 (1.3)

Log M = 0.3913

Antilog of M = 246.2 (LD50)=246

 Log of confidence limits = log M ± 2d (delta f)

                                = 0.3913± 2 (0.3010) (0.2)

                               = 0.3913± 0.1204

                                =0.5117 ± 0.2709

Antilog 0.5117 = 324.8

Antilog 0.2709= 186.6

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The acute oral LD50 of N,N-Bis(2-Hydroxyethyl)-p-Phenylenediamine Sulfate was determined to be 246 mg/kg bw (95% CL: 187-325) when administered at dose levels of 100, 200, 400 and 800 mg/kg bw in male rats.
This test substance was therefore classified as OECD GHS Toxicity Category III (Toxic if swallowed).
Executive summary:

The objective of this study was to determine the acute oral toxicity of N,N-Bis(2-Hydroxyethyl)-p-Phenylenediamine Sulfate when administered once orally to male rats. 

A total of 20 male rats weighing 250-300 g were divided into four different treatment groups containing 5 rats each. The test substance was prepared in dimethyl sulfoxide (DMSO; 10%) and administered orally at dose levels of 100, 200, 400 and 800 mg/kg bw.

During the study period animals were observed for mortality.

All the animals in dose groups 400 and 800 mg/kg bw died during the study period. During the study, one of 200 mg/kg bw died during the study period. No mortality was observed at dose level of 100 mg/kg bw throughout the observation period. Clinical signs were not reported in the study.

LD50 of test substance was calculated by the Weil Method (Biometrics, Sep. 1952) and was determined to be 246 mg/kg bw with 95% confidence limit of 187-325.

Based on above, the acute oral LD50 of N,N-Bis(2-Hydroxyethyl)-p-Phenylenediamine Sulfate was determined to be 246 mg/kg bw (95% CL: 187-325) when administered at dose levels of 100, 200, 400 and 800 mg/kg bw in male rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From Mar. 03, 1979 to Mar. 27 1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Acute oral toxicity or LD50 value was determined by oral administration of test substance to four dose groups of male rats. Subsequently observations of clinical signs and deaths were made for 14 d. The method followed in this study was comparable to the OECD guideline 401.
GLP compliance:
no
Remarks:
(pre-GLP)
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tac N (SD)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: The male rats were obtained from Taconic Farms
- Age at study initiation: Not reported
- Weight at study initiation: 200-250 g
- Fasting period before study: Yes (overnight)

ENVIRONMENTAL CONDITIONS
No details on the environmental condition were provided in the study report.

EXPERIMENT INITIATION DATE: March 03, 1979
EXPERIMENT COMPLETION DATE: March 27, 1979
Route of administration:
oral: gavage
Vehicle:
other: aqueous methyl cellulose (1%)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4 % w/v
- Amount of vehicle: 1.25, 2.5, 5 and 10 mL/kg bw for 50, 100, 200 and 400 mg/kg bw respectively
- Justification for choice of vehicle: Not reported

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: Formulation of test substance was prepared as 4% w/v suspension in vehicle
- Rationale for the selection of the starting dose: Not reported
Doses:
50, 100, 200 and 400 mg/kg bw
No. of animals per sex per dose:
5 males/dose group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations: The animals were observed at 1, 3, 8 and 24 h after treatment and daily thereafter.
- Necropsy of survivors performed: Not reported
- Other examinations performed: Not reported
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
107.2 mg/kg bw
Based on:
test mat.
95% CL:
ca. 76.4 - ca. 150.3
Remarks on result:
other: LD50 was calculated by Weil Method (Biometrics, Sept. 1952)
Mortality:
Mortality observed at individual dose levels
- 50 mg/kg bw: 0/5
- 100 mg/kg bw: 2/5
- 200 mg/kg bw: 5/5
- 400 mg/kg bw: 5/5
Clinical signs:
Not reported

Calculation of LD50 by the Weil Method (Biometrics, Sep. 1952)

Dose level (mg/kg bw)      Mortality

50                                            0/5

100                                          2/5

200                                          5/5

400                                          5/5

Constant ratio = 2.0

Da = Lowest dose level

d = log of constant = 0.3

f = 0.1

Delta f = 0.24495

v values = 0, 2, 5, 5

For K =3

Log M = log Da + d (f+1)

Log M = 1.7 + 0.3 (1.1)

Log M = 1.7 + 0.33

Log M = 2.03

Antilog of M = 107.02 (LD50)

 

Log of confidence limits = log M ± 2d (delta f)

                                = 2.03 ± 2 (.3) (0.24495)

                               = 2.03 ± 0.147

                                =1.883 - 2.177

Antilog 1.883 = 76.4

Antilog 2.177 = 150.3

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The acute oral LD50 of N,N-Bis(2-Hydroxyethyl)-p-Phenylenediamine Sulfate was determined to be 107.02 mg/kg bw (95% CL: 76.4 - 150.3) when administered as 4% w/v suspension in 1% methyl cellulose at a dose level of 50, 100, 200 and 400 mg/kg bw. to Tac N (SD) male rats.

This test substance was therefore classified as OECD GHS Toxicity Category III (Toxic if swallowed)
Executive summary:

The objective of this study was to determine the acute oral toxicity of N,N-Bis(2-Hydroxyethyl)-p-Phenylenediamine Sulfate when administered as 4% w/v solution to male rats.

The test substance was prepared as 4% w/v suspension in (1%) aqueous methyl cellulose (vehicle) and administered orally at dose volumes of 0, 1.25, 2.5, 5 and 10 mL/kg bw.

A total of 20 male Tac N (SD) rats (source: Taconic Farms) weighing 200-250 g were divided into four different treatment groups containing 5 rats each .The dose levels employed in this study were:

50, 100, 200 and 400 mg/kg bw. Post treatment animals were observed for mortality at 1, 3, 8 and 24 h after treatment and daily thereafter for 14 d.

All the animals in dose groups 200 and 400 mg/kg bw died within 24 h of treatment; 2 animals of dose group 100 mg/kg bw died on Day 3 and 4 of the study. No mortality was observed at dose level of 50 mg/kg bw throughout the observation period. Clinical signs were not reported in the study.

LD50 of test substance was calculated by the Weil Method (Biometrics, Sep. 1952) and was determined to be 107.02 with 95% confidence limit of 76.4 - 150.3.

Based on above, the acute oral LD50 of N,N-Bis(2-Hydroxyethyl)-p-Phenylenediamine Sulfate was determined to be 107.02 mg/kg bw (95% CL: 76.4 - 150.3) when administered as 4% w/v suspension in 1% methyl cellulose at a dose level of 50, 100, 200 and 400 mg/kg bw. to Tac N (SD) male rats. This test substance was therefore classified as OECD GHS Toxicity Category III (Toxic if swallowed).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From March 06, 1979 to March 27, 1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Acute oral toxicity or LD50 value was determined by oral administration of test substance to four dose groups of male rats. Subsequently animals were observed for mortality for 14 d. The method followed in this study was comparable to the OECD guideline 401.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tac N (SD) strain
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: The male rats were obtained from Taconic farms
- Age at study initiation: Not reported
- Weight at study initiation: 200-250 gm
- Fasting period before study: Yes (overnight)
No other details on test animals were provided in the study report.

ENVIRONMENTAL CONDITIONS
No details on the environmental condition were provided in the study report.

EXPERIMENT INITIATION DATE: March 06, 1979
EXPERIMENT COMPLETION DATE: March 27, 1979
Route of administration:
oral: gavage
Vehicle:
other: aqueous methyl cellulose (1 %)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10% w/v
- Amount of vehicle: 0.2, 0.4, 0.8 and 1.6 mL/100 g bw for 200, 400, 800 and 1600 mg/kg bw, respectively
- Justification for choice of vehicle: Not reported

MAXIMUM DOSE VOLUME APPLIED: 16 mL/kg bw

DOSAGE PREPARATION: Dosing suspension was prepared as 10% w/v solution in 1% methyl cellulose aqueous solution.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Not reported
Doses:
200, 400, 800 and 1600 mg/kg bw
No. of animals per sex per dose:
5 animals/ dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: The animals were observed at 1, 3, 8 and 24 h after treatment and daily thereafter until Day 7 and on Day 14. Animals were weighed prior to treatment initiation. - Necropsy of survivors performed: Not reported
- Other examinations performed: Animals were observed for mortality.
Sex:
male
Dose descriptor:
LD50
Effect level:
427 mg/kg bw
Based on:
test mat.
95% CL:
> 304 - < 598
Remarks on result:
other: LD50 was calculated by Weil Method (Biometrics, Sept. 1952)
Mortality:
- Mortality observed at individual dose levels was as follows:
- 200 mg/kg bw: 0/5
- 400 mg/kg bw: 2/5
- 800 mg/kg bw: 5/5
- 1600 mg/kg bw: 5/5
Clinical signs:
Not reported
Body weight:
Not reported
Gross pathology:
Not reported

Calculation of LD50 by the Weil Method (Biometrics, Sep. 1952)

Dose level (mg/kg bw)      Mortality

200                                          0/5

400                                          2/5

800                                         5/5

1600                                       5/5    

Constant ratio = 2.0

Da = Lowest dose level

d = log of constant

f = 0.1

Delta f = 0.24495

v values = 0, 2, 5, 5

For K =3

Log M = log Da + d (f+1)

Log M = 2.3 + 0.3 (1.1)

Log M = 2.3 + 0.33

Log M = 2.63

Antilog of M = 427 (LD50) 

Log of confidence limits = log M ± 2d (delta f)

                                = 2.63 ± 2 (0.3) (0.24495)

                               = 2.63 ± 0.147

                                =2.63 ± 0.147

Antilog 2.483 = 304.1

Antilog 2.777 = 598.4

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute oral LD50 of N,N-Bis(2-Hydroxyethyl)-p-Phenylenediamine Sulfate was determined to be 427 mg/kg bw (95% CL: 304—598) when administered at dose levels of 200, 400 800 and 1600 mg/kg bw to Tac N (SD) male rats.
This test substance was therefore classified as OECD GHS Toxicity Category IV (Harmful if swallowed).
Executive summary:

The objective of this study was to determine the acute oral toxicity of N,N-Bis(2-Hydroxyethyl)-p-Phenylenediamine Sulfate when administered to male rats.

Test substance was prepared as 10% w/v suspension in (1%) aqueous methyl cellulose (vehicle) and administered orally at dose volumes of 0.2, 0.4, 0.8 and 1.6 mL/100 g bw.

A total of 20 male Tac N (SD) rats (source: Taconic Farms) weighing 200-250 g were divided into four different treatment groups containing 5 rats each .The dose levels employed in this study were:

200, 400, 800 and 1600 mg/kg bw. Post treatment animals were observed for mortality at 1, 3, 8 and 24 h after treatment and daily thereafter for 14 d.

All the animals in dose groups 800 and 1600 mg/kg bw died within 24 h of treatment and 2 animals of dose group 400 mg/kg bw also died within 24 h after treatment. No mortality was observed in the 200 mg/kg bw treatment group. Clinical signs were not reported in the study.

LD50 of test substance was calculated by the Weil Method (Biometrics, Sep. 1952) and was determined to be 427 mg/kg bw with 95% confidence limit of 304-598.

Based on above, the acute oral LD50 of N,N-Bis(2-Hydroxyethyl)-p-Phenylenediamine Sulfate was determined to be 427 mg/kg bw (95% CL: 304—598) when administered at dose levels of 200, 400 800 and 1600 mg/kg bw to Tac N (SD) male rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
107.2 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
key study
Study period:
February 2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
The calculation of acute toxicity values for N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE is based on the current understanding and knowledge of the test substance.
Qualifier:
no guideline required
Principles of method if other than guideline:
Using current knowledges and available experimental results on the test item, extrapolation calculation were performed in order to determine LC50inhalation and potential local effect on rats.
Test type:
other: extrapolation calculation.
Limit test:
no
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.9 mg/L air
Based on:
test mat.
Exp. duration:
4 h

Calculations:

Maximum volume of exposure in 4 hours:

0.074 L/min x 60 min x 4 hours = 17.76 L

Maximum achievable exposure regarding required 5 mg/L for 4 hours (OECD 403):

17.76 L x 5 mg/L = 88.8 mg/rat

88.8 mg/0.250 kg bw = 355 mg/kg bw

(caveat: this value is above the determined oral LD50 value)

Determination of the correction factor oral vs. inhalation route:

Ratio of 60% oral : 100% inhalation = 0.6

Determination of the LC50 calc inhal.:

[(107 mg/kg bw x 0.250 kg bw)/17.76L] x 0.6 = 0.90 mg/L

Hence, the LC50 for inhalation route was calculated at 0.90 mg/L

Conversion of LC50 calc inhal. to % (w/w):

1 L air: 1.2041 kg/m³ = 1204.1 g/m³ = 1204100 mg/m³ = 1204100/1000 L = 1201 mg/L

1201 mg = 100 %

0.90 mg/L air = 0.07% (w/w)

The concentration of 0.07% of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE is 14.3-fold lower than the highest diluted concentration tested in the in the rabbit Draize test (1%), at which concentration no irritation was observed.

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Based on the LC50, calc, inhalation value, N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE should be classified as Acute Tox Cat.3; H332: “Toxic if inhaled”, according to the CLP criteria.
Executive summary:

N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE is 1,4-phenylenediamine with a single methoxy-methyl substituent on the benzene ring in ortho position. Therefore, it is a member of the p-phenylenediamine family. 2-METHOXY-METHYL-P-PHENYLENEDIAMINE is an ingredient used in oxidative hair coloring products.

Based on the available in vivo acute toxicityand OECD guideline compliant repeat dose toxicity and genotoxicity studies performed to measure MTD doses on N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE,) to compare the impact of different exposure routes for systemic toxicity (ADME), the acute oral toxicity could be determined, as well as its acute inhalation toxic potential.

The acute oral toxicity of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE was investigated in rats in three studies and was determined to be between 107 and 427 mg/kg bw. These studies were not compliant with the OECD 423 test guideline but were considered to be useful for evaluation and, moreover, were confirmed using data from 28-Day repeated dose and UDS studies. For the calculations of the inhalation toxicity, an oral LD50 of 107 mg/kg bw was used for the route extrapolation calculations.

The acute inhalational toxicity of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE was determined using in vitro data from Caco-2 studies and the correlation of permeability in these assays to in vivo oral to estimate oral absorption. The predicted in vivo oral bioavailability was estimated to be between 20% and 60% of the applied dose. The oral bioavailability of structurally similar chemicals was almost 100%; therefore, the upper value of 60% was used for N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE. Using this value, the calculated LC50 for inhalation (LC50 calc inhal.) was calculated to be 0.90 mg/L. When this concentration is combined with the results of in vivo eye irritation studies it can be concluded that N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE would not have a local effect in the lungs.

Based on the LC50, calc, inhalation value, N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE should be classified as Acute Tox Cat.3; H332: “Toxic if inhaled”, according to the CLP criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
900 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
key study
Study period:
February
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
The calculation of acute toxicity values for N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE is based on the current understanding and knowledge of the test substance.
Qualifier:
no guideline required
Principles of method if other than guideline:
For the determination of the acute dermal toxicity, the bioavailability after topical application was used. Since there were no in vivo toxicokinetics studies conducted for the dermal route, this was predicted using scientifically accepted equations to derive the absorbed amount of an infinite dose of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE. The bioavailability via the dermal route was predicted to be lower (15% of the applied dose) than the oral bioavailability of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE, and it was in line with that of a structurally similar chemical (A160). The resulting LD50 for dermal toxicity (LD50 calc dermal) was calculated.
GLP compliance:
no
Remarks:
Not required
Test type:
other: extrapolation calculation
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
428 mg/kg bw
Based on:
test mat.

Calculation:

Determination of the correction factor oral vs. dermal route:

60% oral vs. 15% dermal = 4.0 (60 / 15 = 4.0)

Determination of the LD50 calc dermal for the sulfate salt:

107 mg/kg bw x 4.0 = 428 mg/kg bw Equation 10

Result:

LD50 calc dermal 2 N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE = 428 mg/kg bw

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The calculated LD50 value for the dermal toxicity of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE is 428 mg/kg bw. Therefore, it should be classified as Acute Tox Cat.3; H311: “Toxic in contact with skin”, according to the CLP criteria.
Executive summary:

For the determination of the acute dermal toxicity, the bioavailability after topical application was used. Since there were no in vivo toxicokinetics studies conducted for the dermal route, this was predicted using scientifically accepted equations to derive the absorbed amount of an infinite dose of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE. The bioavailability via the dermal route was predicted to be lower (15% of the applied dose) than the oral bioavailability of N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE, and it was in line with that of a structurally similar chemical (A160).

The resulting LD50 for dermal toxicity (LD50 calc dermal) was calculated to be 428 mg/kg bw. The approach to determine dermal toxicity using oral data is accepted by the German and EU regulatory agencies.

Based on these data, N,N-BIS(2-HYDROXYETHYL)-P-PHENYLENEDIAMINE SULFATE should be classified as Acute Tox Cat.3; H302: “Toxic if swallowed”, according to the CLP criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
428 mg/kg bw

Additional information

Acute oral toxicity studies have demonstrated that N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate possesses a moderate order of acute oral toxicity. Oral median lethal dose (LD50) values in male rats range from 107-427 mg/kg body weight. The oral median lethal dose of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate in male rats has been shown to be 246 mg/kg body weight in 10% dimethylsulfoxide, 107.2 mg/kg body weight as a 4% suspension in 1% aqueous methylcellulose and 427 mg/kg body weight as a 10% suspension in 1% aqueous methylcellulose.

The intraperitoneal median lethal dose in male rats has been shown to be between 16 mg/kg and 31 mg/kg body weight.

Based on the three availables studies quoted as Klimisch 4 (due to insufficient documentation), a weight of evidence approach was performed. On all the three studies, clinical signs results or bodyweights are missing. However, according to basic data, mortality and method given (according to scientific principle standard), these studies were considered relevant when taken together. The LD50 value were ranged from 107.2 to 427 mg/kg bw.

Two extrapolation calculations were performed for the registered substance according to available experimental results and current litterature. The LC50 inhalation was calculated at 0.90 mg/L. The LD50 dermal was calculated at 428 mg/kg bw/day.

Justification for classification or non-classification

According to the results on acute oral toxicity studies in rats and the value of LD50 from 107-427 mg/kg body weight , and the CLP criteria (1272/2008/EC), the category 3 - Danger should be considered. The substance is Toxic if swallowed H301.

Based on the two calculations to determine the LC50 (inhalation route) and the LD50 (dermal route), the registered susbtance N,N-BIS(2-HYDROXYETHYL)-p-PHENYLENEDIAMINE SULFATE was classified as Category 3 for acute dermal and inhalation toxicity, respectively, H311 "Toxic in contact with skin" and H332 "Toxic if inhaled".