p-phenylenediamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Remarks:

The study was conducted according to guideline in effect at time of study conduct.

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Details on test material:

- Purity: 99.8%

Test animals

Species:

rat

Strain:

other: Sprague-Dawley Crl:OFA(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6 or 7 weeks
- Weight at study initiation: 132-186 g
- Fasting period before study: Animals were fasted for at least 16 hours before dosing. Food was given 3 to 4 hours after dosing.
- Housing: Animals were housed individually (during up and down procedure) or in groups of 4 or 5 (during acclimatisation period or main study) of the same sex in polycarbonate cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): ≥ 40 %
- Air Changes (per hr):minimum 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sterile water

Doses:

100, 75, 50, 25 mg/kg

No. of animals per sex per dose:

1, 2, 1, and 5 at 100, 75 , 50, and 25 mg/kg, respectively

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Morbidity/mortality checks and clinical observations were performed approximately 30 minutes, 1, 2, 4 and 6 hours after administration of the test substance, then twice daily during the observation period. Additional observations were performed in some animals on day 0.
- Frequency of weighing: Individual body weights were recorded on day 0 before treatment, then on days 2, 7 and 14.
- Necropsy of survivors performed: Yes; Animals found dead during the study were necropsied. All surviving animals were sacrificed and necropsied after the final observation (day 14).

Statistics:

No statistical analyses were performed. Body weight data were compared with historical control data concurrently available at the testing facility.

Results and discussion

Preliminary study:

The study was conducted according to an up and down procedure in order to determine the Maximum Tolerated Dose (MTD) then a main study was performed with 5 females. The starting dose level was 100 mg/kg, as chosen by the Study Sponsor. The first female initially received the test item at the starting dose level of 100 mg/kg and died 90 minutes after dosing. Based on the clinical observations of the first female (severe clinical signs and death), a second female received a lower dose level of 75 mg/kg. As no death occured, a third female received the same dose level (75 mg/kg) to confirm the toxicity observed. As mortality was noted at 75 mg/kg in 1/2 females, a fourth female was treated at the dose level of 50 mg/kg. As severe clinial signs were observed in the female treated at 50 mg/kg, an additional female was treated at the dose level of 25 mg/kg. No relevant clinical signs were observed, therefore the up and down procedure was considered ended and 4 additionnal females received the same dose level.

Effect levels

Sex:

female

Dose descriptor:

other: minimum lethal dose

Effect level:

75 mg/kg bw

Mortality:

One animal died at 100 mg/kg within 90 minutes and one animal died at 75 mg/kg 2 hours and 45 minutes after treatment.

Clinical signs:

other: Treatment-related clinical signs, including marked subdued behaviour and unsteady gait, were observed in the female dosed at 100 mg/kg one hour after treatment. Orange traces in the bedding, probably due to coloured urine, were observed on day 0. The firs

Gross pathology:

No macroscopic findings were seen in animals found dead during the study or at scheduled necropsy on day 14.

Applicant's summary and conclusion

Conclusions:

This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability). The minimum lethal dose was 75 mg/kg of body weight in female rats

Executive summary:

Under the designated experimental conditions of the study, a single administration of the test substance by the oral route to female Sprague-Dawley rats induced deaths at 100 and 75 mg/kg and severe clinical signs at 50 mg/kg. No mortality and no clinical signs were noted at 25 mg/kg, whereas orange traces in the bedding were observed, probably related to orange-coloured urine. In conclusion, the minimal lethal dose of the test substance following single oral gavage to fasted rats was 75 mg/kg, the maximal non-lethal dose was 50 mg/kg and the no observed adverse effect level (NOAEL) was 25 mg/kg.