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Toxicological information

Repeated dose toxicity: dermal

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 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