Registration Dossier

Administrative data

Description of key information

LD50 Oral >2000mg/kg bw
LD50 Dermal >2000mg/kg bw

LD50 Inhalation > 5.01 mg/L

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:
from 2011-04-19 to 2011-05-19 (experimental phase)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
from 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
from December 2002
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
other: RccHan: WIST(SPF)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 10 weeks
- Weight at study initiation: 173.8 - 183.4 g
- Fasting period before study: 19 to 22 hours before treatment, with free access to water
- Housing: In groups of up to five in Makrolon type-4 cages during acclimatization. Individually in Makrolon type-3 cages during treatment and observation. Cages were equipped with wire mesh tops and standard softwood bedding including paper enrichment.
- Diet (e.g. ad libitum): Pelleted rodent maintenance diet ad libitum, except for the overnight fasting period and approximately 3 hours post dose.
- Water (e.g. ad libitum): Community tap water ad libitum
- Acclimation period: At least 5 days under laboratory conditions, after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1% CMC in purified water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 55 and 200 mg/mL
- Amount of vehicle (if gavage):
94.5 mg/kg CMC (55 mg/mL preparation)
80 mg/kg CMC (200 mg/mL preparation)
Calculation: amount CMC in 10 mL preparation= 1% · (10000 mg preparation - x mg substance per 1000 mg preparation), where x is 55 and 200 mg, respectively
- Justification for choice of vehicle: The vehicle was chosen after non-GLP solubility testing. Purified water and 0.5% CMC in purified water were found unsuitable vehicles for oral gavage application, as the test item could not be sufficiently dispersed in either vehicle. By grinding the test item in a mortar and pestle together with 1% CMC in purified water, a 20% (weight:weight) dispersion of the test item suitable for oral gavage application was obtained.
- Lot/batch no. (if required): 0001414646
- Purity: not reported

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): Dose formulations were prepared shortly before each treatment using a magnetic stirrer and a spatula as homogenizers. The test item was weighed on a suitable precision balance and supplied to a mortar. By using a pestle, the test item and almost all of the vehicle was ground to a dispersion. This dispersion was transferred to a volumetric beaker and the vehicle was added up to the defined volume (weight:volume).
Doses:
550 mg/kg bw and 2000 mg/kg bw
No. of animals per sex per dose:
1 female at 550 mg/kg bw
3 females at 2000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were examined daily during acclimatization and mortality and clinical signs were assessed. All animals were examined for mortality and clinical signs before treatment, once within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2 to 15. Mortality was assessed twice daily on test days 2 to 15. Body weights were recorded on the last day of acclimatization (prior to removal of food), on test day 1 (prior to treatment) and on test days 8 and 15. All animals were weighed, necropsied and examined macroscopically and discarded at the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight, macroscopy
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred during the course of the study.
Clinical signs:
No clinical signs were observed in any animal during acclimatization and in the animal treated with 550 mg/kg (animal no. 1). Slightly ruffled fur was observed in all three animals treated with 2000 mg/kg (animals no. 2, no. 3 and no. 4) after treatment on test day 1. In one animal treated with 2000 mg/kg (animal no. 3), ruffled fur was still observed on test day 2. No clinical signs were observed in these animals from test day 2 until the end of the observation period.
Body weight:
The body weights were within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose (LD50) of the test item after single oral administration to female rats, observed over a period of 14 days, is greater than 2000 mg/kg bw. The study is considered to be adequate and reliable.
Executive summary:

An acute oral toxicity test with 4 animals (female RccHan:WIST(SPF) rat) was conducted under GLP according to OECD TG 425.

Dosing started in one female animal at a dose level of 550 mg/kg. As no death occurred and no severe clinical signs were observed at this dose level, the next female was treated at a dose level of 2000 mg/kg. Two more females were treated at a dose level of 2000

mg/kg, as at this dose no deaths occurred and no severe clinical signs were observed.

All animals were examined for clinical signs before treatment, once within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2 to 15. Mortality was assessed before treatment, once within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 (with the clinical signs) and twice daily during test days 2 to 15. Body weights were recorded on the last day of acclimatization (prior to removal of food), on test day 1 (prior to treatment) and

on test days 8 and 15. All animals were examined macroscopically after being sacrificed at the end of the observation period.

No deaths occurred during the course of the study. No clinical signs were observed in any animal during acclimatization and in the animal

treated with 550 mg/kg. Slightly ruffled fur was observed in all three animals treated with 2000 mg/kg after treatment on test day 1. In one animal treated with 2000 mg/kg, ruffled fur was still observed on test day 2. No clinical signs were observed in these animals from test day 2 until the end of the observation period. The body weights were within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

The median lethal dose (LD50) of the test item after single oral administration to female rats, observed over a period of 14 days, is greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
1

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Remarks:
The study on acute inhalation was conducted solely to comply with a non-EU national registration requirement, and has been provided here in accordance with REACH, Article 22(1)e.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 21 October 2014 to 10 December 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
traditional method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and
Services, Germany GmbH, Sandhofer Weg 7, D-
97633 Sulzfeld
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 - 11 weeks old
- Weight at study initiation: males: 366-452g; females: 219-235g
- Fasting period before study: No
- Housing: Animals were grouped by sex (up to 5 animals per cage) in Type III solid floor cages with stainless steel mesh lids.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 30-70%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
3.71 µm
Geometric standard deviation (GSD):
2.52
Details on inhalation exposure:
The animals were exposed, nose-only, to an atmosphere of the test item using a TSE Rodent Exposure System (TSE Systems GmbH, Bad Homburg, Germany). This system comprised of 2 concentric anodised aluminium chambers and a computer control system incorporating pressure detectors and mass flow controllers. Fresh aerosol from the generation system was constantly supplied to the inner plenum (distribution chamber) of the exposure system from where, under positive pressure, it was
distributed to the individual exposure ports. The animals were held in polycarbonate restraint tubes located around the chamber which allowed only the animal’s nares to enter the exposure port. After passing through the animal’s breathing zone, used aerosol entered the outer cylinder from where it was exhausted through a suitable filter system. Atmosphere generation was therefore dynamic. Airflows and relative pressures within the system were constantly monitored and controlled by the computer system thus ensuring a uniform distribution and constant flow of fresh aerosol to each exposure port (breathing zone). The flow of air through each port was at least 0.7 L/min. This flow rate was considered adequate to minimise re-breathing of the test atmosphere as it is about twice the respiratory minute volume of a rat. Homogeneity of the test atmosphere within the test chamber and amongst the exposure ports was not specifically determined during this study. However, chambers of this design have been fully validated and have shown to produce evenly distributed atmospheres in the animals’ breathing zones.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5 mg/L
No. of animals per sex per dose:
10 rats (5 male and 5 female)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- all animals observed individually at hourly intervals during exposure, as soon as possible following removal from restrains at the end of exposure, 1 hour after exposure and twice daily for 14 days
- Individual bodyweights were recorded prior to treatment on the day of exposure (Day 0) and on Days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes macroscopic examination and special attention given to the respiratory tract.
Preliminary study:
A single sighting exposure was performed prior to the main study with 2 males and 2 females at the target concentration of 5 mg/L. No significant clinical signs were recorded on day of exposure and during whole two weeks of the observation period.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.01 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals survived until the end of the observation period.
Clinical signs:
No significant clinical signs were recorded on day of exposure and during whole two weeks of the observation period. Wet fur and/or fur staining were recorded in animals on the day of exposure and day following exposure. These observations were considered to be related to the restraint and exposure procedures and, in isolation, were considered not to be of toxicological relevance.
Body weight:
Normal bodyweight gain was noted for all exposed animals during the observation period. Slight bodyweight loss was noted during period Days 1-3 in some animals from the sighting (1/4) and main groups (3/10).
Gross pathology:
No necropsy findings were observed in any animals
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, no deaths occurred in a group of 10 rats (5/sex) exposed to the mean achieved concentration of 5.01 mg/L for 4 hours. The acute inhalation median lethal concentration of the test item, in CRL: (WI) Wistar strain rats is therefore considered to be greater than 5.01 mg/L.
Executive summary:

The acute inhalation toxicity of the test substance was assessed in 10 (5 male and 5 female) CRL: (WI) Wistar strain rats according to the OECD guideline 403.

The animals were exposed to the mean achieved concentration of 5.01 mg/L test item during 4 hours using a nose-only exposure system. The animals were observed during 14 days after exposure.

The mean achieved atmosphere concentration was 5.01 mg/L. The MMAD (Mean Mass Aerodynamic Diameter) was 3.71 μm ± 2.52 (GSD [Geometric Standard Deviation]).

No mortality occurred during the course of the study. No significant clinical signs were recorded on day of exposure and during whole two weeks of the observation period. No necropsy findings were observed in any animals exposed to the test substance.

The acute inhalation median lethal concentration of test item, in CRL: (WI) Wistar strain rats is therefore considered to be greater than 5.01 mg/L.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
5 000 mg/m³
Quality of whole database:
1

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:
from 2011-04-19 to 2011-05-12 (experimental phase)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted February 24, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
from May 31, 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
from August 1998
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: RccHan: WIST(SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: males: 9 weeks, females: 11 weeks
- Weight at study initiation: males: 244.1 g - 259.6.g, females: 190.6 g - 212.2 g
- Fasting period before study: No
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding, including paper enrichment. Individually in Makrolon type-3 cages and under similar conditions during treatment and observation.
- Diet (e.g. ad libitum): Pelleted Rat-Mouse Diet ad libitum.
- Water (e.g. ad libitum): Community tap water ad libitum.
- Acclimation period: At least 5 days, under laboratory conditions and after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: backs of the animals
- Type of wrap if used: The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with lukewarm tap water and dried with disposable paper towels
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Constant volume or concentration used: not applicable (only 1 concentration)
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit):The test item was moistened with purified water before application to obtain a dry paste.
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight (applied by weight as supplied by the Sponsor)
No. of animals per sex per dose:
group 1: 1 male, 1 female (Animal no. 1 and 2, treated 2 days before the other rats)
group 2: 4 males, 4 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were examined daily during acclimatization and mortality and clinical signs were assessed. All animals were examined for clinical signs before treatment, once within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2 to 15. Local dermal signs were assessed once daily from test day 2 to 15. Mortality was assessed before treatment, once within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 (with the clinical signs) and
twice daily during days 2 to15. Body weights were recorded on test day 1 (prior to administration) and on test days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, local dermal signs, body weight, macroscopy
Preliminary study:
2 rats (1 male (animal no. 1), 1 female (animal no. 2)) were treated 2 days before the other rats. The findings for these were:

- no deaths, no clinical signs, no macroscopic findings
- body weights within commonly recorded range
- focal crusts on test days 4 to 6 in male rat
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the course of the study.
Clinical signs:
No clinical signs were observed during the course of the study.
Body weight:
Two females (animal no. 7 and animal no. 10) slightly lost body weight after treatment (4% and 6 %, respectively). The body weights of the other animals were within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Other findings:
Local dermal signs: One male (animal no. 1) showed focal crusts on test days 4 to 6 and one female (animal no. 8) showed desquamation on test days 7 to 10. No local dermal signs were recorded in these animals after test day 10 and no local dermal signs were recorded in any other animal.

Local Dermal Signs

Animal

no./sex

Dose [mg/kg]

Local dermal signs (max grade)*

Test day

2

3

4

5

6

7

8

9

10

11

12

13

14

15

1 / M

2000

Focal crusts

.

.

1

1

1

.

.

.

.

.

.

.

.

.

1 / F

2000

No abnormality recorded.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

2 / M

2000

No abnormality recorded.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

3 / M

2000

No abnormality recorded.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

4 / M

2000

No abnormality recorded.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

5 / M

2000

No abnormality recorded.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

6 / F

2000

No abnormality recorded.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

7 / F

2000

No abnormality recorded.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

8 / F

2000

Desquamation

.

.

.

.

.

1

1

1

.

.

.

.

.

.

9 / F

2000

No abnormality recorded.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

10 / F

2000

No abnormality recorded.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

* Local dermal signs were assessed according to Draize

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose (LD50) of the test item after single dermal administration to rats of both sexes, observed over a period of 14 days, is greater than 2000 mg/kg body weight. The study is considered to be adequate and reliable.
Executive summary:

In an acute dermal toxicity test performed under GLP according to OECD TG 402, 5 male and 5 female RccHan:WIST (SPF) rats were treated with the test item at a dose level of 2000 mg/kg by dermal application. The test item was applied by weight as supplied by the Sponsor. For better dermal contact, the test item was moistened with purified water before application.

All animals were examined for clinical signs before treatment, once within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2 to 15. Local dermal signs were assessed once daily from test day 2 to 15. Mortality was assessed before treatment, once within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 (with the clinical signs) and twice daily during test days 2 to15. Body weights were recorded on test day 1 (prior to administration) and on test days 8 and 15. All animals were examined macroscopically after being sacrificed at the end of the study.

No deaths occurred during the course of the study and no clinical signs were observed. One male showed focal crusts on test days 4 to 6 and one female showed desquamation on test days 7 to 10. No local dermal signs were recorded in these animals after test day 10 and no local dermal signs were recorded in any other animal. Two females slightly lost body weight after treatment (4% and 6 %, respectively). The body weights of the other animals were within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

The median lethal dose (LD50) of the test item after single dermal administration to rats of both sexes, observed over a period of 14 days, is greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
1

Additional information

An acute oral toxicity test with 4 animals (female RccHan:WIST(SPF) rat) was conducted under GLP according to OECD TG 425.

Dosing started in one female animal at a dose level of 550 mg/kg. As no death occurred and no severe clinical signs were observed at this dose level, the next female was treated at a dose level of 2000 mg/kg. Two more females were treated at a dose level of 2000 mg/kg, as at this dose no deaths occurred and no severe clinical signs were observed.

All animals were examined for clinical signs before treatment, once within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2 to 15. Mortality was assessed before treatment, once within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 (with the clinical signs) and twice daily during test days 2 to 15. Body weights were recorded on the last day of acclimatization (prior to removal of food), on test day 1 (prior to treatment) and on test days 8 and 15. All animals were examined macroscopically after being sacrificed at the end of the observation period. No deaths occurred during the course of the study. No clinical signs were observed in any animal during acclimatization and in the animal treated with 550 mg/kg. Slightly ruffled fur was observed in all three animals treated with 2000 mg/kg after treatment on test day 1. In one animal treated with 2000 mg/kg, ruffled fur was still observed on test day 2. No clinical signs were observed in these animals from test day 2 until the end of the observation period. The body weights were within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

The median lethal dose (LD50) of the test item after single oral administration to female rats, observed over a period of 14 days, is greater than 2000 mg/kg body weight.

In an acute dermal toxicity test performed under GLP according to OECD TG 402, 5 male and 5 female RccHan:WIST (SPF) rats were treated with the test item at a dose level of 2000 mg/kg by dermal application. The test item was applied by weight as supplied by the Sponsor. For better dermal contact, the test item was moistened with purified water before application.

All animals were examined for clinical signs before treatment, once within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2 to 15. Local dermal signs were assessed once daily from test day 2 to 15. Mortality was assessed before treatment, once within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 (with the clinical signs) and twice daily during test days 2 to15. Body weights were recorded on test day 1 (prior to administration) and on test days 8 and 15. All animals were examined macroscopically after being sacrificed at the end of the study.

No deaths occurred during the course of the study and no clinical signs were observed. One male showed focal crusts on test days 4 to 6 and one female showed desquamation on test days 7 to 10. No local dermal signs were recorded in these animals after test day 10 and no local dermal signs were recorded in any other animal. Two females slightly lost body weight after treatment (4% and 6 %, respectively). The body weights of the other animals were within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

The median lethal dose (LD50) of the test item after single dermal administration to rats of both sexes, observed over a period of 14 days, is greater than 2000 mg/kg body weight.

To comply with non-EU national registration requirements, an acute inhalation toxicity test with 10 (5 male and 5 female) CRL:(WI) Wistar strain rats was conducted under GLP according to OECD TG 403.

The animals were exposed to the mean achieved concentration of 5.01 mg/L test item during 4 hours using a nose-only exposure system. The animals were observed during 14 days after exposure.

The mean achieved atmosphere concentration was 5.01 mg/L. The MMAD (Mean Mass Aerodynamic Diameter) was 3.71 μm ± 2.52 (GSD [Geometric Standard Deviation]).

No mortality occurred during the course of the study. No significant clinical signs were recorded on day of exposure and during whole two weeks of the observation period. No necropsy findings were observed in any animals exposed to the test substance.

The acute inhalation median lethal concentration of the test item, in CRL: (WI) Wistar strain rats is therefore considered to be greater than 5.01 mg/L.

Justification for classification or non-classification

Acute oral toxicity

The acute oral toxicity of the substance is > 2000 mg/kg. As a result it does not meet the criteria for classification according to Directive 67/548/EEC, Annex VI, 3.2.3 (as amended).

 

The acute oral toxicity of the substance is > 2000 mg/kg. As a result it does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.1.2.

Acute dermal toxicity

The acute dermal toxicity of the substance is > 2000 mg/kg. As a result it does not meet the criteria for classification according to Directive 67/548/EEC, Annex VI, 3.2.3 (as amended).

 

The acute dermal toxicity of the substance is > 2000 mg/kg. As a result it does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.1.2.

Acute Inhalation toxicity

The acute Inhalation toxicity of the substance is > 5.01 mg/L. As a result it does not meet the criteria for classification according to Regulation (EC) No. 1272/2008.