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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:
2010-11-17 to 2010-12-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Cobalt 2-ethylhexanoate- Physical state: Purple solid- Storage condition of test material: At room temperature- Stability under test conditions: test substance was expected to be stable for the duration of testing.- Solubility: Soluble in water (6.30 g/L at 37°C)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Ace Animals, Inc., Boyertown, PA- Age at study initiation: 9 - 12 weeks- Weight at study initiation: 158 - 211 g- Fasting period before study: Naive rats were fasted overnight.- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 1996). Litter paper was placed beneath the cage and was changed at least three times per week.- Diet: Purina Rodent Chow # 5012; feed was replaced approx. three hours after final dosing.- Water (ad libitum): Filtered tap water- Acclimation period: 6-28 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 16-23- Relative humidity (%): 17-65; humidity was below the targeted lower limit for 13 days during the study. A portable humidifier was used to increase the humidity levels during this time.- Air changes (per hr): 14- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Carboxymethylcellulose (CMC) in distilled water.
Details on oral exposure:
VEHICLE- Concentration in vehicle: The test substance was administered as a 30% w/w mixture in 0.5% w/w solution of CMC in distilled water.- Justification for choice of vehicle: Preliminary solubility testing conducted by EPSL, indicated that the test material was insoluble in distilled water and corn oil, and mixtures in 0.5%CMC in excess of 30% (i.e., 40-80%) were too viscous to be administered properly.MAXIMUM DOSE VOLUME APPLIED:5,000 mg/kgDOSAGE:Individual doses were calculated based on the initial body weights, taking into account the specific gravity (determined by EPSL) and concentration of the test mixture. Due to high volume of test suspension to be administered (27.64 mL/kg) to the 5,000 mg/kg dose group, each animal´s dose was equally divided into two portions and administered approx. two hours apart.Initially, a single animal received a limit dose of 5,000 mg/kg. Due to the mortality of this animal, the Main test was conducted. Using the default starting level of 175 mg/kg and following the Up and Down procedure, eight additional females were dosed.
Doses:
175, 550, 1,750 or 5,000 mg/kg
No. of animals per sex per dose:
1 animal per 175 mg/kg dose level1 animal per 550 mg/kg dose level3 animals per 1,750 mg/kg dose level3 animals per 5,000 mg/kg dose level
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Individual body weights were recorded prior to test substance administration (initial) and again on Days 7 and 14 (termination) following dosing or after death. The animals were observed for mortality, signs of gross toxicity and behavioral changes during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing or until death occurred. - Necropsy of survivors performed: yes; surviving rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all decedents and euthanized animals. Tissues and organs of the thoracic and abdominal cavities were examined.- Other examinations performed: Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observations of tremors, convulsions, salivation, diarrhea and coma.
Statistics:
The Acute Oral Toxicity (Guideline 425) Statistical Program (Westat, version 1.0, May 2001) was used for all data analyses including: dose progression selections, stopping criteria determinations and/or LD50 and confidence limit calculations.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
3 129 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 750 - <= 5 000
Mortality:
All animals of the 175, 550, 1750 mg/kg dose levels survived the test substance administration.All animals of the 5000 mg/kg dose level died within five days of test substance administration.
Clinical signs:
All animals of the 175, 550, 1750 mg/kg dose levels appeared active and healthy during the study; no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour were noted.Toxic signs noted in the decedents of the 5000 mg/kg dose level group prior to death included nasal and mouth discharge, irregular respiration, hypoactivity, hunched posture, ano-genital staining, soft feces, diarrhea and/or reduced fecal volume.
Body weight:
All animals of the 175, 550, 1750 mg/kg dose levels gained body weight.
Gross pathology:
For all animals of the 175, 550, 1750 mg/kg dose levels no gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-days observation period.Gross necropsy of the decedents of the 5000 mg/kg dose level group revealed moderatly red to extremely discolouration of the lungs and/or liver, and distention of the intestines and/or stomach.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the acute oral LD50 of cobalt 2-ethylhexanoate is estimated to be 3,129 mg/kg of body weight in female rats with an approx. 95% confidence interval of 1,750 mg/kg (lower) to 5,000 mg/kg (upper).According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified.According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified.