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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:
key study
Study period:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study was performed according to following guidelines: OECD 401 guideline, EPA FR Vol.50, No.188 (1985) and in compliance with the GLP Regulations. No significant deviations can be observed from the study guidelines, which could have an impact on the performed study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EPA FR,Vol.50,No.188,1985
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,4-dimethylpiperazine
EC Number:
203-412-0
EC Name:
1,4-dimethylpiperazine
Cas Number:
106-58-1
Molecular formula:
C6H14N2
IUPAC Name:
1,4-dimethylpiperazine
Details on test material:
- Name of test material (as cited in study report): Jeffcat DMP
Specific details on test material used for the study:
- Name of test material (as cited in study report): 6398-17-20
- Physical state: clear pale, yellow liquid
- Analytical purity: responsibility of the Sponsor
- Stability under test conditions: no apparent change in the physical state of the test article during administration
- Storage condition of test material: no data
- Other: specific gravity=0.852 gm/ml; pH=7 (litmus paper)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Wilmington, Massachusetts
- Age at study initiation: young adults
- Weight at study initiation: 297-390 g
- Fasting period before study: yes
- Housing: individually in stainless steel 1/2" wire mesh cages, sized in accordance with the "Guide for the Care and Use of LaboratoryAnimals" of the Institute of Laboratory Animal Resources, National Research Council.
- Diet (e.g. ad libitum): Wayne Teklad Lab Blox, ad libitum,
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period:min. 5d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C±3°C
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12h dark/12h light


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
1000, 1600 and 2000 mg/kg
(range-finding: 500 - 2500 - 5000 mg/kg)
No. of animals per sex per dose:
10 (5 male and 5 female)
Control animals:
other: not required according to the OECD 401 guidelines
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: dose range finding study: at approximately 1, 4, 24, 48 and 72 hours after dosing for pharmacological and toxicological effects; definitive LD50: at approximately 1, 4 and 24 hours after dosing and once daily through day 14 for pharmacological and toxicological effects. Viability was checked daily. Body weights were recorded on days 0, 7 and 14 or when found dead.
- Necropsy of survivors performed: yes
Statistics:
LD50 calculations performed via Litchfield and Wilcoxon on Pharmacological Calculations System, version 4.1.

Results and discussion

Preliminary study:
The dose-range-finding study (500, 2500 and 5000 mg/kg ) was performed. None of the animals died at 500 mg/kg. 2/2 animals died at both the 2500 and 5000 mg/kg dose levels. Based upon these results, a definitive LD50 was performed.

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 116.2 mg/kg bw
95% CL:
833.4 - 1 495
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 116.2 mg/kg bw
95% CL:
738.4 - 1 687.3
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 116.2 mg/kg bw
95% CL:
738.4 - 1 687.3
Mortality:
-4/10 animals died at the 1000 mg/kg dose level
-8/10 animals died at the 1600 mg/kg dose level
-10/10 animals died at the 2000 mg/kg dose level.
Clinical signs:
decreased activity, poor grooming, piloerection, salivation, abnormal gait and stance, ptosis, chromodacryorrhea, dyspnea, prostration and convulsions
Body weight:
d0-d7-d14: both male and female: body weight increase at the 1000 mg/kg dose level. In the other dose groups too many rats died before the end of the study to evaluate the evolution of body weight
Gross pathology:
-Necropsy of the animals dying on study revealed distended and/or fluid-filled stomachs, fluid filled intestines and discolored nasal discharge.
-Terminal necropsy of the remaining animals revealed mottled kidneys.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results from the Acute Exposure Oral Toxicity in rats, the definitive acute oral LD50 in males and females for the test substance was determined to be 1116.2 mg/kg (95%CL of 833.4 to 1495.0 mg/kg). The substance is considered to be classified as acute oral toxicant category 4 according to the criteria laid down in the CLP Regulation.

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