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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
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.
Justification for type of information:
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:
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.
Principles of method if other than guideline:
Acute oral toxicity study of test chemical was performed in rodents.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material:p-Phenylenediamine - Molecular formula :C6H8N2- Molecular weight :108.1432 g/mole - Substance type:Organic - Purity: 99.8%
Specific details on test material used for the study:
- Name of test material :p-Phenylenediamine - Molecular formula :C6H8N2- Molecular weight :108.1432 g/mole - Substance type:Organic

Test animals

Species:
rat
Strain:
other: Sprague-Dawley Crl:OFA(SD)
Sex:
female
Details on test animals 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 daysENVIRONMENTAL 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
Details on oral exposure:
no data available
Doses:
100, 75, 50, 25 mg/kg bw
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:
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 first female treated at 75 mg/kg had transitory treatment-related clinical signs (lachrymation and swelling of both conjunctiva), observed approximately 2 hours and 45 minutes to 6 hours after treatment. In addition subdued behaviour was noted 6 hours after treatment. No clinical signs were noted from day 1. Then a second female was treated at this dose level but died 2 hours and 45 minutes after treatment. Subdued behaviour, loss of balance, lateral decubitus and purplish paws were noted 2 hours after treatment up to death. Orange traces in the bedding, probably due to coloured urine, were observed on day 0 in both females. The female treated at 50 mg/kg had transitory treatment-related clinical signs, including lachrymation and swelling of both conjunctiva observed approximately 3 hours and 30 minutes after treatment and persisted up to 6 hours. In addition unsteady gait, tremors, subdued behaviour and/or piloerection were noted from approximately 5 hours up to 8 hours after treatment. No clinical signs were observed from day 1. Orange traces in the bedding, probably due to coloured urine, were observed on day 0. At 25 mg/kg, the only treatment-related observation was orange traces in the bedding, probably due to coloured urine, observed on day 0 in all females.
Body weight:
Though some individual body weights slightly exceeded the historical normal ranges, there was no effect of treatment on mean body weight or mean body weight gain in surviving animals during the study.
Gross pathology:
No macroscopic findings were seen in animals found dead during the study or at scheduled necropsy on day 14.
Other findings:
no data available

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The Minium lethal dose (MLD) value for acute oral toxicity test was considered to be 75 mg/kg bw,when female Sprague-Dawley Crl:OFA(SD) rats were treated with test chemical orally via gavage according to OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method).
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.