Naphthenic acids, cobalt salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-09-22 to 2011-10-31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study eliable without restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

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

Test material information

Constituent 1

Reference substance name:

Naphthenic acids, cobalt salts

EC Number:

263-064-0

EC Name:

Naphthenic acids, cobalt salts

Cas Number:

61789-51-3

IUPAC Name:

λ²-cobalt(2+) bis(3-(3-ethylcyclopentyl)propanoate)

Test material form:

solid: pellets

Details on test material:

- Name of test material (as cited in study report): Cobalt naphthenate
- Physical state: dark violet to gray pellets
- Stability under test conditions: test substance was expected to be stable for the duration of testing
- Storage condition of test material: at room temperature and kept tightly capped and protected from light under nitrogen until use
- Solubility: soluble in water (293 mg/L at 20°C and 356 mg/L at 37°C)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS - Sprague-Dawley derived, albino
- Source: Harlan Laboratories
- Age at study initiation: 9 - 10 weeks
- Weight at study initiation: 185 - 222 g
- Fasting period before study: prior to each dosing, fasted overnight by removing the feed from their cages; Feed was replaced approximately 3 -4 hours after dosing.
- 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, 2011). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (ad libitum, except during fasting): HArlan Teklad Global 16% Protein Rodent Diet® #2016
- Water (ad libitum): filtered tap water
- Acclimation period: 9 - 19 days

During the fasting period, the rats were examined for health adn weighed (initial).

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 23°C
- Relative humidity: 33 - 91%
- Air changes: 15 hours
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: preliminary solubility testing conducted by the laboratory indicated that the substance was not soluble in distilled water or a 0.5% w/v solution of carboxymethylcellulsoe in distilled water and mixtures in excess of 40% (i.e., 50 - 80%) were too viscous to be administered properly.

MAXIMUM DOSE VOLUME APPLIED: individual doses were calculated based on the initial body weights, taking into account the density (as determiend by the laboratory) and concentration of the test mixture.

DOSAGE PREPARATION: prior to use, the test substance was ground in a coffee mill (Cuisinart, Model DCG-20N). The ground sample was administered as a 40% w/w mixture in corn oil.

Initially, a single animal received a limit dose of 5000 mg/kg. Due to the mortality of this animal, a Main test was conducted.

Doses:

175, 550, 1750 and 5000 mg/kg

No. of animals per sex per dose:

1 animal per 175 mg/kg dose level
1 animal per 550 mg/kg dose level
3 animals per 1750 mg/kg dose level
4 animals per 5000 mg/kg dose level (one animal from the limit test)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weights of the animals 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 behavioural changes during the first several hours post-dosing and a t 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.

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

Remarks on result:

other: LD50 based on an assumed sigma of 0.5.

Mortality:

175 and 550 mg/kg (1 animal per dose level):
Each animal from the above dose level survived test substance administration.
1750 mg/kg (3 animals):
All animals survived test substance administration.
5000 mg/kg (4 animals):
All animals died within three days of test substance administration.

Clinical signs:

other: 175 and 550 mg/kg (1 animal per dose level): Each animal from the above dose level appeared active and healthy.There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behaviour in either rat att hese dose levels. 1750 mg/kg (3 a

Gross pathology:

175 and 550 mg/kg (1 animal per dose level).
No gross abnormalities were noted for either of these animals when necropsied at the conclusion of the 14-day observation period.
1750 mg/kg (3 animals):
No gross abnormalities were noted for these animals when necropsied at the conclusion of the 14-day observation period.
5000 mg/kg (4 animals):
Gross necropsy of the decedents revealed dark intestines, mottled liver and distention of the stomach and/or intestines.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 (female rats): 3129 mg/kg bw (approx. 95% CL: 1750 - 5000 mg/kg)
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.