Resin acids and Rosin acids, cobalt salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-04-11 to 2006-05-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Minor deviations with no effect on the study: - According to the guideline, when no deaths occurred at 300 mg/kg then another group of three animals should be test at the dose-level of 300 mg/kg. If again no deaths occurred then a group of three animals should be test at 2000 mg/kg. When no deaths occur at 2000 mg/kg then the test will be repeated at this dose-level. When again no animals die, the test item is recorded as not classified. In this study first an assay with 300 mg/kg was conducted and no deaths occurred. Then an assay at 2000 mg/kg was conducted and no deaths occured. In a third assay the dose level 2000 mg/kg was tested again and again no death occured. - According to the guideline, the test report must include a justification for the choice of the vehicle, if other than water. In this report no justification for the use of corn oil was given.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001-12-17

Deviations:

yes

Remarks:

, minor deviations with no effect on the study (see "rationale for reliability").

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Resin acids and Rosin acids, cobalt salts

EC Number:

273-321-9

EC Name:

Resin acids and Rosin acids, cobalt salts

Cas Number:

68956-82-1

IUPAC Name:

λ²-cobalt(2+) bis((1R,4aR,4bR,10aR)-1,4a-dimethyl-7-(propan-2-yl)-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene-1-carboxylate)

Details on test material:

- Name of test material (as cited in study report): Produit Y
- Name of test material (as cited in the EC inventory): Resin acids and Rosin acids, cobalt salts
- Physical state: Purple powder
- Storage condition of test material: At room temperature, protected from light and humidity and under argon gas.
No further information on the test material was stated.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: mean body weight +/- standard deviation of 202 +/- 6 g
- Fasting period before study: The animals were fasted for an overnight period of approximately 18 hours before dosing, but had free access to water. Food was given back approximately 4 hours after administration of the test item.
- Housing: The animals were housed in polycarbonate cages with stainless steel lid (48 cm X 27 cm X 20 cm). Each cage contained one to seven animals during the acclimation period and three rats of the same group during the treatment period. Each cage contained autoclaved sawdust (SICSA, Alfortville, France.)
- Diet: All animals had free access to SsniffR/M-H pelleted diet (SSNIFF Spezialdiäten, GmbH, Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 2 °C
- Relative humidity: 30 to 70 %
- Ventilation: approx. 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 / 12
No further information on the test animals was stated.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
The vehicle used was corn oil, batch No. 015K0115 (Sigma, Saint-Quentin-Fallavier, France).

MAXIMUM DOSE VOLUME APPLIED: The dosage form preparations were administered to the animals under a volume of 10 mL/kg. The volume administered to each animal was adjusted according to body weight determined on the day of treatment.

DOSAGE PREPARATION: On the day of treatment, the test item was ground to a fine powder using a mortar and pestle, then was prepared at the chosen concentrations in the vehicle.

CLASS METHOD
- Rationale for the selection of the starting dose: As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose-level of 300 mg/kg was chosen.
No further information on details on oral exposure was stated.

Doses:

300 mg/kg; 2000 mg/kg

No. of animals per sex per dose:

3 females (Since the dose-level 2000 mg/kg was tested twice 6 females were test at this dose-level)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day. The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: Yes, on day 15, all surviving animals wer killed by carbon dioxide asphyxiation. All study animals were subjected to a macroscopic examination as soon as possible after death. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.
- Other examinations performed: Type, time of onset and duration of clinical signs were recorded for each animal individually. The body weight gain of the treated animals was compared to that of CIT control animals with the same initial body weight.
No further information on details on study design was stated.

Statistics:

The interpretaiton of results was based on the flow charts of Annex 2 of the OECD Guideline No. 423, 17th December 2001 and of Annex 3 of the Directive 2004/73/EC, B.1 tris, 29th April 2004.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Dose-level of 300 mg/kg (three females):
No mortality was recorded.
Dose level of 2000 mg/kg (three females then confirmation on three other females):
No mortality was recorded.

Clinical signs:

other: Dose-level of 300 mg/kg (three females): Hypoactivity and hypersalivation were observed in 1/3 animals within 1 h 30 of treatment. No other clinical signs were noted thereafter, until the end of the observation period. Dose level of 2000 mg/kg (three fema

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions, the oral LD50 of the test item Produit Y was higher than 2000 mg/kg in female rats.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified.