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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2006-04-25 to 2006-05-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP guideline study reliable without restrictions Minor deviations without an effect on the study: -According to the guideline, it is suggested to use rats between 200 and 300 g body weight. All the males had a body weight above 300 g (308 g - 326 g). - According to the guideline, the temperature of the experimental animal room should be 22 °C (+/- 3°C) and the relative humidity 30 - 70 %. In the study report it was stated that the temperature and relative humidity recorded in the animal room was sometimes outside of the target ranges specified in the Study plan According to the report, these deviations were not considerd to have compromised the validity or integrity of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 1987-02-24
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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
- Analytical purity: 83.7 %; (7.77 % total cobalt content)
- Batch No.: 06002
- Expiration date of the batch: 2007-04-30
- 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:
male/female
Details on test animals 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 315 +/- 7 g for males and 218 +/- 5 g for the females
- Fasting period before study:
- Housing: The animals were housed individually in polycarbonate cages with stainless steel lid (35.5 cm X 23.5 cm X 19.3 cm) 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. (One to seven animals of the same sex were housed in polycarbonate cages with stainless steel lid (48 cm X 27 cm X 20 cm. Each cage contained autoclaved sawdust (SICSA, Alfortville, France.)

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

Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: On the day before treatment the dorsal area of each animal was clipped (i.e approx. 5 cm X 7 cm for males and 5 cm X 6 cm for females) using an electric clipper. Only animals with healthy intact skin were used for the study. A single dose of 2000 mg/kg of the test item in its original form was placed on a hydrophilic gauze pad (pre-moistened with 2 mL of corn oil) and then applied to an area of the skin representing approx. 10 % of the total body surface of the animals, calculated according to Meeh's formula (i.e. approx. 5 cm X 7 cm for the males and 5 cm X 6 cm for the females). The test item and the gauze pad were held in contact with the skin for 24 hours by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
On removal of the dressing, any residual test item was removed using a cotton pad moistened by corn oil.

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg (The dose applied to each animal was adjusted according to the body weight determined on the day of treatment.)
No further information on details on dermal exposure was stated.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males / 5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 15 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 until day 15. The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15. The body weight gain of the treated animals was compared to that of CIT control animals with a similar initial body weight.
- Necropsy of survivors performed: Yes, on day 15, all animals were 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. From day 2, any local cutaneous reaction was recorded.
No further information on details on study design.
Statistics:
none

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occured during the study.
Clinical signs:
No clinical signs were observed during the study.
Body weight:
When compared to CIT hostorical control animals, a slightly reduced body weight gain was seen in 2/5 males all over the study, in 3/5 males between day 1 and day 8 (without any relevant consequence at the end of the observation period) and in 1/5 females between day 8 and day 15. The overall body weight gain of the other animals was similar to that of CIT historical control animals.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Other findings:
A brown colouration of the skin was noted in all the animals from day 2 until day 12 (4/5 males and 4/5 females), 14 (1/5 females) or 15 (end of the observation period) (1/5 males). this colouration has masked the evaluation of the cutaneous reactions in 4/5 males and 4/5 females from day 2 until day 12.
An oedema was noted in 1/5 males and 1/5 females from day 4 until day 7.
An erythema was observed in 1/5 males from day 2 until day 7 and in 1/5 females from day 2 until day 14.
Crusts were recorded in 1/5 females on days 13 and 14.
A residual of test item was noted in all the animals from day 2 until day 15 (end of the observation period).

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions, the dermal LD50 of the test item Resin acids and Rosin acids, cobalt salts was higher than 2000 mg/kg in rats.
According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations) on the approximation of the laws, regulations and administrative provisions relating to the classififcation, packaging and labeling of dangerous substances, concerning the potential toxicity by dermal route, the test item Resin acids and Rosin acids, cobalt salts should not be classified.