2-nitro-p-phenylenediamine

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Final Report on the Safety Assessment of 2-Nitro-p-Phenylenediamine and 4-Nitro-o-Phenylenediamine

Author:

COSMETIC INGREDIENT REVIEW

Year:

1985

Bibliographic source:

JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY, Volume 4, Number 3, 1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

To determine the repeated dose toxicity of the test chemical when applied dermally to rabbits

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-nitro-p-phenylenediamine

EC Number:

226-164-5

EC Name:

2-nitro-p-phenylenediamine

Cas Number:

5307-14-2

Molecular formula:

C6H7N3O2

IUPAC Name:

2-nitrobenzene-1,4-diamine

Constituent 2

Reference substance name:

2 nitro p phenylenediamine

IUPAC Name:

2 nitro p phenylenediamine

Details on test material:

- Name of test material (as cited in study report):2 nitro p phenylenediamine- Substance type:Organic- Physical state:Solid

Test animals

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALSSource: No dataAge at study initiation: No dataWeight at study initiation: No data Fasting period before study: No dataHousing: No dataDiet (e.g. ad libitum):No dataWater (e.g. ad libitum):No dataAcclimation period: No dataENVIRONMENTAL CONDITIONSTemperature (°C): No dataHumidity (%): No dataAir changes (per hr):No dataPhotoperiod (hrs dark / hrs light): No data

Administration / exposure

Type of coverage:

other: The application site was approximately 10 percent of the body surface.

Vehicle:

other: hydrogen peroxide activator

Details on exposure:

TEST SITEArea of exposure: shaved backs% coverage: 10 percent of the body surface.TEST MATERIAL-Amount(s) applied (volume or weight with unit): 1000, 2000, and 4000 mg/kg/dayConcentration (if solution):Constant volume or concentration used: yes/no: Yes For solids, paste formed: yes/no : No

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

20 days exposure and 14 days observation

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:1000, 2000, and 4000 mg/kg/dayBasis:

No. of animals per sex per dose:

male and female rabbits (number unspecified).

Control animals:

yes

Details on study design:

No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes / No / No data: No dataDETAILED CLINICAL OBSERVATIONS: Yes / No / No data: No dataDERMAL IRRITATION (if dermal study): Yes / No / No data: YesBODY WEIGHT: Yes / No / No data: Yes FOOD CONSUMPTION: No dataFOOD EFFICIENCY: No dataWATER CONSUMPTION: Yes / No / No data: No dataOPHTHALMOSCOPIC EXAMINATION: Yes / No / No data : No dataHAEMATOLOGY: Yes / No / No data: Yes.CLINICAL CHEMISTRY: Yes / No / No data: YesURINALYSIS: Yes / No / No dataYesNEUROBEHAVIOURAL EXAMINATION: Yes / No / No data: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see table) / No / No data: YesHISTOPATHOLOGY: Yes (see table) / No / No data: Yes

Other examinations:

No data

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

No clinical signs of toxicity were observed. Two rabbits died during the test period in the 1000mg/kg group, 2 died in the 2000mg/kg group, 1 died in the 4000mg/kg dye-treated group, and 1 died in the control group. These deaths were attributed to naturally occurring disease; the incidence and severity of disease may have been increased due to the stress of the severe local skin reactions and the dosing procedure

Dermal irritation:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Description (incidence):

No clinical signs of toxicity were observed. Two rabbits died during the test period in the 1000mg/kg group, 2 died in the 2000mg/kg group, 1 died in the 4000mg/kg dye-treated group, and 1 died in the control group. These deaths were attributed to naturally occurring disease; the incidence and severity of disease may have been increased due to the stress of the severe local skin reactions and the dosing procedure

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

There were adverse effects on body weight in the treated rabbits during the test period, but body weights were comparable to the controls during the observation period.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

There were no significant adverse findings in the Hematological parameters

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

There were no significant adverse findings in clinical chemistry parameters

Urinalysis findings:

effects observed, treatment-related

Description (incidence and severity):

There were no significant adverse findings in the urinalyses.

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

No significant gross or microscopic alterations were observed in the tissues and organs of the rabbits killed at the end of the study or in any treated animals that died during the study, except for the skin.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

No significant gross or microscopic alterations were observed in the tissues and organs of the rabbits killed at the end of the study or in any treated animals that died during the study, except for the skin.

Histopathological findings: neoplastic:

not specified

Details on results:

Dermal Irritation:From Day 5 to Day 20 of the test period, local skin reactions were characterized by escharosis, with subsequent sloughing of the skin at the application site in the treated animals. By the end of the 14 day observation period, the skin appeared normal. At the dye application site in a few animals, edema and/or hyperkeratosis was observed.

Effect levels

Dose descriptor:

NOAEL

Effect level:

4 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

A hair dye composite containing 0.55 percent 2NPPD was diluted 1:1 with a hydrogen peroxide activator and applied in doses of 1000, 2000, and 4000 mg/kg/day for 20 days to the shaved backs of groups of male and female rabbits (number unspecified). The application site was approximately 10 percent of the body surface.The NOAEL for repeated exposure to 2NPPD dermally in rabbits is 4000mg/kgday

Executive summary:

A hair dye composite containing 0.55 percent 2NPPD was diluted 1:1 with a hydrogen peroxide activator and applied in doses of 1000, 2000, and 4000 mg/kg/day for 20 days to the shaved backs of groups of male and female rabbits (number unspecified). The application site was approximately 10 percent of the body surface.

There was also a group of untreated control animals. The skin of 2 animals from each group was abraded prior to composite application. The rabbits were observed for a further 14 days after the test period. Two rabbits died during the test period in the 1000mg/kg group, 2 died in the 2000mg/kg group, 1 died in the 4000mg/kg dye-treated group, and 1 died in the control group. These deaths were attributed to naturally occurring disease; the incidence and severity of disease may have been increased due to the stress of the severe local skin reactions and the dosing procedure

No clinical signs of toxicity were observed. There were adverse effects on body weight in the treated rabbits during the test period, but body weights were comparable to the controls during the observation period. There were no significant adverse findings in the hematological and clinical chemistry parameters or in the urinalyses. No significant gross or microscopic alterations were observed in the tissues and organs of the rabbits killed at the end of the study or in any treated animals that died during the study, except for the skin.

The NOAEL for repeated exposure to 2NPPD dermally in rabbits is 4000mg/kgday