Resin acids and Rosin acids, cobalt salts

Endpoint summary

Description of key information

Acute oral toxicity:
LD50(female rats)>2000mg/kg bw
Acute toxicity, dermal:
LD50(male/female rats)>2000mg/kg bw
Acute toxicity, inhalation:
LC50 (male and female rats, 4 hours) > 5 mg/L air 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

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

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.

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-01-25 to 2011-03-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

2009-09-07

Deviations:

yes

Remarks:

at one concentration of the main study 5 males and 5 females were used.

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2009-11-12

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at start of administration: males: approx. 8 weeks; females:approx. 9 weeks
- Weight at start of administration: males: 231 - 257 g; females: 207 - 257 g
- Fasting period before study: feeding was discontinued approx. 16 hours before exposure; only tap water was then available ad libitum
- Housing: granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages. The cages were changed and cleaned twice a week; kept by sex in groups of 2 -3 animals in MAKROLON cages (type III plus)
- Diet (please refer to "Fasting period before study" above): commercial diet, ssniff® R/M-H V1534 served as food (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 adaptation days; the animals were randomised before use. The animals were acclimatised to the test apparatus for approx. 1 hour on 2 days prior to testing. The restraining tubes did not impose undue physical, termal or immobilization stress on the animals.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C +/- 3 °C (maximum range)
- Relative humidity: 55 % +/- 15 % (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

>= 3.129 - <= 3.241 µm

Geometric standard deviation (GSD):

>= 2.75 - <= 3

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: the study was carried out using a dynamic inhalation apparatus (RHEMA-LABORTECHNIK, 65719 Hofheim/Taunus, Germany) (air changes/h (≥ 12 times)) with a nose-only exposure of the animals according to KIMMERLE & TREPPER. The apparatus consists of a cyclindrical exposure chamber (volume 40 L) which is able to hold 10 animals in pyrex tubes at the edge of the chamber in a radial position.

- System of generating particulates/aerosols: the dust of the test material was generated with a rotating brush dust generator (RBG 1000, PALAS GmbH Partikel und Lasermesstechnik, 76229 Karlsruhe, Germany).
The generator was fed with compressed air (5.0 bar) from a compressor (ALUP Kompressorenfabrik, 73257 Köngen, Germany). (air was taken from the surrounding atmosphere of the laboratory room and filtered using an in-line disposable gas-filter).
At the bottom of the exposure chamber, the air was sucked off at a lower flow rate than it was created by the dust gnereator in order to produce a homogeneous distribution and a positive pressure in the exposure chamber (inflow 900 L/h,, outflow 800 L/h).
A manometer and an air-flow meter (ROTA Yokogawa GmbH & Co. KG, 79664 Wehr/Baden, Germany) were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked hourly and corrected if necessary.
The exhaust air was drawn through gas wash-bottles.

- Temperature, humidity, oxygen content, carbon dioxide content: the oxygen content in the inhalation chamber was 21 %. It was determined at the beginning and at the end of the exposure with a DRÄGER Oxygen-analysis test set (DRÄGER Tube oxygen 67 28 081). Carbon dioxide concentration did not exceed 1 %.
Temperature (19.5 °C +/- 0.1 °C (main study- 5.07 mg/L air), 21.1 °C +/- 0.1 °C (main study- 1.07 mg/L air), 20.3 °C +/- 0.1 °C (satellite group- 5.04 mg/L air) or 21.3 °C +/- 0.1 °C (satellite group-1.06 mg/L air)) and humidity (56.9 % +/- 0.2 % (main study - 5.07 mg/L air), 61.5 % +/- 0.2 % (main study - 1.07 mg/L air), 50.0 % +/- 0.6 % (satellite group - 5.04 mg/L air) or 60.5 % +/- 0.2 (satellite group-1.06 mg/L air)) were measured once every hour with a climate control monitor (testo 175-HZ data logger).

The whole exposure system was mounted in an inhalation facility to protect the laboratory staff from possible hazards.

The exposure was initiated by placing the animals' noses into the exposure chamber after equilibration of the chamber concentration for at least 15 minutes (t95 approximately 8 minutes).

Before initiating the study with the animals, a pre-test was carried out with the exposure system in order to verify that under the experimental settings chosen, the limit concentration of 5 mg/L air could be achieved by gravimetric analysis.

The tests with the main study animals and the recovery animals were conducted in the same inhalation chamber but on different days. Between the exposure times the chamber was cleaned carefully.

- Method of particle size determination: an analysis of the particulate size distribution was carried out twice during the exposure period using a cascade impactor according to MAY (MAY, K.R. Aerosol impaction jets, J. Aerosol Sci. 6, 403 (1975), RESEARCH ENGINEERS Ltd., London N1 5 RD, UK).
The dust from the exposure chamber was drawn through the cascade impactor for 5 or 10 minutes at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance (SARTORIUS, type 1601 004, precision 0.1 mg). Deltas of slides' weight were determined.
The mass median aerodynamic diameter (MMAD) was estimated by means of non-linear regression analysis. The 32 µm particle size range and the filter (particle size range < 0.5 µm) were not included in the determination of the MMAD in order not to give undue weight to these values.
The Geomteric Standard Deviation (GSD) of the MMAD was calculated from the quotient of the 84.1 %- and the 50 %-mass fractions, both obtained from the above mentioned non-linear regression analysis.
In addition, a sample of approx. 10 g test material was taken from the exposure chamber to determine the median physical particulate size with a CILAS 715 by My-Tec, 91325 Adelsdorf, Germany. This determination was non-GLP.

TEST ATMOSPHERE
- Brief description of analytical method used: the actual dust concentration in the inhalation chamber was measured gravimetrically with an air sample filter (Minisart SM 17598 0.45 µm) and pump (Vacuubrand, MZ 2 C (Membrane Pump, Vacuubrand GmbH + Co. KG, 97877 Wertheim/Main, Germany)) controlled by a rotameter. Dust samples were taken once every hour during the exposure. For that purpose, a probe was placed close to the animals' noses and air was drawn through the air sample filter at a constant flow of air of 5 L/min for 1 minute. The filters were weighed before and after sampling (accuracy 0.1 mg). The correct loading of the filter was checked by the airflow via the rotameter and by a positive weight increase of the filter after the sampling period of 1 minute.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
Main study:
5.07 +/- 0.01 mg/L air concentration: MMAD: 3.129 µm; GSD: 3.00 µm
1.07 +/- 0.01 mg/L air concentration: MMAD: 3.241 µm; GSD: 2.92 µm
Satellite group:
5.04 +/- 0.02 mg/L air concentration: MMAD: 3.219 µm; GSD: 2.99 µm
1.06 +/- 0.02 mg/L air concentration: MMAD: 2.919 µm; GSD: 2.75 µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

please refer to "details on inhalation exposure" above

Duration of exposure:

4 h

Concentrations:

Main study:
actual concentration: 5.07 +/- 0.01 mg/L air concentration and 1.07 +/- 0.01 mg/L air concentration
nominal concentration: 6.11 mg/L air and 1.67 mg/L air
Satellite group:
actual concentration: 5.04 +/- 0.02 mg/L air concentration and 1.06 +/- 0.02mg/L air concentration
nominal concentration: 6.11 mg/L air and 1.67 mg/L air

No. of animals per sex per dose:

Main study:
5.07 mg/L air concentration: 3 males / 3 females
1.07 mg/L air concentration: 5 males / 5 females
Satellite group:
5.04 mg/L air concentration: 3 males / 3 females
1.06 mg/L air concentration: 3 males / 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 24 hours (satellite group) and 14 days (main study)
- Frequency of observations and weighing: during and following exposure, observations were made and recorded systematically; individual records were maintained for each animals. Careful clinical examinations were made at least twice daily until all symptoms subsided, thereafter each working day. Observations on mortality were made at least once daily (in the morning starting on test day 2) to minimize loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals.
Cageside observations included, but were not limited to: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, as well as somatomotor activity and behaviour pattern.
Particular attention was directed to observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The animals were also observed for possible indications of respiratory irritation such as dyspnoea, rhinitis etc..
Individual weights of animals were determined once during the acclimatisation period, before the exposure on test day 1, on test days 2, 8 and 15 and at death. Changes in weight were calculated and recorded when survival exceeded one day. At the end of the test, all surviving animals were weighed and sacrificed.
- Necropsy of survivors performed: yes
Necropsy of all main study and satellite animals (8 + 6 males and 8 + 6 females) was carried out and all gross pathological changes were recorded:
- satellite animals: necropsy at 24 hours after cessation of exposure, as this is likely to be the time at which any signs of respiratory irritation would have manifested;
- main study animals: necropsy at the end of the 14- day observation period, also to assess whether any respiratory tract irritation persist or abates.
Autopsy and macroscopic inspections of rats which died prematurely were carried out as soon as possible after exitus.
Histopathology:
All main study and satellite animals were subjected to the same level of histopathological examination upon necropsy at the end of the respective observation period. During histopathology, attention was paid to alterations that might be indicative of respiratory irritation, such as hyperaemia, oedema, minimal inflammation, thickened mucous layer.
The following organs of all animals were fixed in 10 % (nose, i.e. head without brain, eyes and lower jar) or 7 % (other organs) buffered formalin for histopathological examination:
- nose (5 levels of the nasal turbinates): the tip and Level 1 of the nose were taken from the cut just anterior to the incisor teeth. With tip removed, Level 2 was taken approximately 2 mm posterior to free tip of the incisor teeth. Level 3 was cut through the incisive papilla. Level 4 was cut through the middle of the second palatal ridge, which is located just anterior to the molar teeth. Level 5 was cut through the middle of the molar teeth. All sections were embedded face down to yield a section from the anterior section, except the nose tip was embedded posterior surface down.
- larynx
- trachea
- lungs (five levels)
Paraffin sections were prepared of all above mentioned organs and stained with haematoxylin eosin.

Statistics:

Due to low mortality and small number of animals at the lethal concentration no LC50 calculation according to FINNEY was carried out.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Main study
2 of 3 males died at the 5.07 mg/L air concentration level on test days 3 and 4, respectively.
No mortality occurred at the 1.07 mg/L air concentration level
Satellite group:
No mortality occurred at the 5.04 or 1.06 mg/L air concentration level.

Clinical signs:

other: Main study A 4-hour inhalation exposure to cobalt resinate at a concentration of 5.07 mg/L air revealed slight ataxia, slight to moderate tremor and slight dyspnoea (reduced frequency of respiration with increased volume) on test day 1 immediately after e

Body weight:

Body weight gain of the surviving animals was in the expected range.

Gross pathology:

Oedematous, dark-red stained discoloured lungs or lungs with large red-brown areas were observed in the two prematurely deceased male animals or lungs with white foci in the survivng male animal at the dose level of 5.07 mg/L of the main study (14-day sacrifice). The respective female animals of this dose level did not show any pathological findings. Red foci in the lungs were observed in all 3 of 3 male and 3 of 3 female satellite animals (24-hour sacrifice) at dose level of 5.04 mg/L. At the dose level of 1.07 mg/L none of the 5 of 5 male or 5 of 5 female animals of the main study (14-day sacrifice) showed any pathological findings. All 3 of 3 male and 3 of 3 female satellite animals ( 24-hour sacrifice) revealed slightly haemorrhagic lungs at the dose level of 1.06 mg/L.

Interpretation of results:

GHS criteria not met

Conclusions:

LC50 (male and female rats, 4 hours) > 5 mg/L air
Based on the results of the histopathological and macroscopic investigations, cobalt resinate does not require classification for respiratory irritation.
According to the EC Regulation No. 1272/2008 and subsequent regulations, cobalt resinate does not require classification for acute inhalation toxicity or specific target organ toxicity -single exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-04-25 to 2006-05-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987-02-24

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/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 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.

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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured during the study.

Clinical signs:

other: No clinical signs were observed during the study.

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).

Interpretation of results:

GHS criteria not met

Conclusions:

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Justification for selection of acute toxicity – oral endpoint
Key study.

Justification for selection of acute toxicity – inhalation endpoint
Key study.

Justification for selection of acute toxicity – dermal endpoint
Key study.

Justification for classification or non-classification

Acute oral toxicity

The reference Pelcot (2007) is considered as the key study for acute oral toxicity and will be used for classification. Female Sprague-Dawley rats were dosed at 300 mg/kg and 2000 mg/kg orally via gavage. During the conduct of the study no mortalities occurred at the highest dose group

LD50 oral, rat >2000 mg/kg bw

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic are not met since the ATE is above 2000 mg/kg body-weight, hence no classification required.

 

Specific target organ toxicant (STOT) – single exposure: oral

According to Pelcot (2007) the classification criteria acc. to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification of 300 mg/kg bw and at the guidance value, oral for a Category 2 classification of 2000 mg/kg bw. No classification required.

 

Acute dermal toxicity

The reference Pelcot (2007) is considered as the key study for acute dermal toxicity and will be used for classification. No mortalities occurred during the conduct of the study

LD50 dermal, rat >2000 mg/kg bw

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic are not met since the ATE is above 2000 mg/kg body-weight, hence no classification required.

 

Specific target organ toxicant (STOT) – single exposure: dermal

According to Pelcot (2007) the classification criteria acc. to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, dermal for a Category 1 classification of 300 mg/kg bw and at the guidance value, dermal for a Category 2 classification of 2000 mg/kg bw. No classification required.

 

Acute inhalation toxicity

The reference Haferkorn (2011) is considered as the key study for acute inhalation toxicity and will be used for classification. Male and female Sprague-Dawley rats were exposed either to 5.07 and 1.07 mg/L air (main study, observation period 14 days) or to 5.04 and 1.06 mg/L air (satellite group; observation period 24 hours) for 4 hours. No mortality occurred at the 1.07 mg/L air concentration in the main study, but premature death (2/3 males) occurred at the 5.07 mg/l air concentration. No mortality occurred in the satellite groups. The LC50 is greater than 5 mg/L air.

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic are not met since the ATE is above 5.0 mg/L, hence no classification is required.

 

Specific target organ toxicant (STOT) – single exposure: inhalation

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, inhalation are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, inhalation for a Category 1 classification of≤1 mg/L/4h and at the guidance value, inhalation for a Category 2≤5 mg/L/4h - > 1 mg/L/4h. No additional classification required.