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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
In the study investigations are described which cannot be subsumed under a testing guideline, but which are nevertheless well documented and scientifically acceptable.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2001

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In the study investigations are described which cannot be subsumed under a testing guideline, but which are nevertheless well documented and scientifically acceptable.
GLP compliance:
no
Test type:
other: Moving average method of Gad and Weil (1989)
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium 2-oxoglutarate
EC Number:
206-167-8
EC Name:
Disodium 2-oxoglutarate
Cas Number:
305-72-6
Molecular formula:
C5H6O5.2Na
IUPAC Name:
disodium 2-oxopentanedioate
Test material form:
not specified
Details on test material:
a-ketoglutarate (a-ketoglutaric acid, disodium salt; a-KG)was purchased from Sigma, St. Louis, USA

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002 (M.P.), India
- Females nulliparous and non-pregnant: not indicated
- Age at study initiation: not indicated
- Weight at study initiation: Females: 150-200 g
Males: 150-200 g (males between 350–380 g were used for physiological studies)
- Fasting period before study: overnight
- Housing: bedding of rice husk in polypropylene cages
- Diet: standard pellet diet (Amrut Feeds, Pranav Agro, Delhi, India) ad libitum
- Water: ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
physiological saline
Details on oral exposure:
VEHICLE: Physiological saline 0.9% Sodium Chloride
MAXIMUM DOSE VOLUME APPLIED: < 10 ml

Doses:
2000, 4000, 5000, 10000 mg/kg bw
No. of animals per sex per dose:
4 female, 4 male
Additionally 24 female and 32 male rats received only physiological saline (6 per sex) or 2000 mg/kg bw for haematology, biochemistry, organ/body weight index, histology and physiological studies
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not specified
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,
- Two rats each of the control group (treated with phisiological saline) and six each receiving 2000 mg/kg test item were sacrificed 1 h, 24 h and 7 days after treatment for haematology, biochemistry, organ/body weight index (organ weight × 100/animal body weight) and histology.

- Hematology: standards hematological analysis was performed at various time intervals after blood collections from the retro-orbital plexus under
light ether anaesthesia.
- Biochemistry: Serum alkaline phosphatase (ALP), ¿-glutamyl transferase (¿-GT), lactate dehydrogenase (LDH), glutamyl pyruvate transaminase (GPT), glutamyl oxaloacetate transaminase (GOT), protein, glucose, creatinine, urea, cholesterol and inorganic phosphorus were measured by commercial diagnostic kits from Ranbaxy Laboratories/Merck India/Miles India.
Na+ and K+ were measured by flame photometry (Systronics 128, India).
- Urine analysis: after 24 h and 7 days of treatment urine samples were pooled and examined for pH, nitrite proteins, glucose,ketones, urobilinogen, bilirubin and haemoglobin using the Combur-8-Test (Boehringer Mannheim, Germany).

-Physiology: Rats were anaesthetized with urethane (1.6 g kg-1) intraperitoneally and various physiological parameters were recorded at different
time intervals. Rectal temperature was also recorded.
Parameters measured: respiratory rate, blood pressure, mean arterial pressure, heart rate. Neuromuscular transmision was meassured on the gastracnemius muscle by estimulation of the sciatic nerve.
Statistics:
The data were analysed by one-way ANOVA followed by Dunnett’s test using SigmaStat software (Jandel Scientific Inc., USA).
Statistical significance was estimated at the 5% level.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
7 100 mg/kg bw
Based on:
test mat.
Mortality:
All the animals receiving 10 g/kg bw died within 2–3 h.
Clinical signs:
other: No signs or symptoms of toxicity on surviving animals
Gross pathology:
Performed on separate animals that received a dose of 2000 mg/kg bw and were sacrificed after 1 h, 24 h and 7 days of treatment.
Organ/body weight index for vital organs did not show any significant changes.
Other findings:
Haematology, biochemistry, physiology and histology of animals that received 2000mg/kg bw did not show significant changes.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
alpha-Ketoglutarat (CAS 305-72-6) has an LC50 of 7100 mg/kg by oral route in the rat.

In conclusion the substance does not need to be classified acc. to the Globally Harmonized Classification System (GHS) and acc. to the current EU Regulation on classification, labeling and packaging (CLP) (EC) No 1272/2008.