Registration Dossier

Administrative data

Description of key information

There are 2 acute toxicity studies available using different exposure routes : L 50 (oral): >5000 mg/kg bw and LC50 >2868 mg/m³/4 h. Thus, there is no need to conduct an additional acute toxicity study using the dermal route.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: similar to the respective guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
10 male Wistar rats received single oral dose of 5000 mg/kg bw dissolved in 1% Tragant and were observed for clinical signs of intoxication, body weight development, mortaliy over a period of 14 days. At the end of the observation time all animals undergo gross pathological examination.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: 9 weeks
- Weight at study initiation: 180 g
- Housing: groups of 5
- Diet ad libitum
- Water ad libitum
- Acclimation period: some days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/1
Route of administration:
oral: gavage
Vehicle:
other: traganth
Details on oral exposure:
10 male Wistar rats received single oral dose of 5000 mg/kg bw dissolved in 1% Tragant
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 males
Control animals:
no
Details on study design:
10 male Wistar rats received single oral dose of 5000 mg/kg bw dissolved in 1% Tragant and were observed for clinical signs of intoxication, body weight development, mortaliy over a period of 14 days. At the end of the observation time all animals undergo gross pathological examination.
Statistics:
no
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: no clinical signs, no mortality
Mortality:
0/10
Clinical signs:
no clicical signs observed
Body weight:
body weight development in the normal range
Gross pathology:
the animals sacrificed at the end of the study did not show any noticeable pathological findings.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Executive summary:

10 male Wistar rats received single oral dose of 5000 mg/kg bw dissolved in 1% Traganth and were observed for clinical signs of intoxication, body weight development, mortality over a period of 14 days. At the end of the observation time all animals undergo gross pathological examination. No animal died, no clinical signs were observed, all animals gained weight and no gross pathological findings were detected at the terminal sacrifice. Thus the LD50 is > 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
rat study according to the respective guideline and GLP and evaluated with Klimisch score 2

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: according to OECD TG and GLP
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 2 month
- Weight at study initiation: 180-200 g
- Fasting period before study:
- Housing: before test : singly and during test in groups
- Diet ad libitum
- Water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 40-60
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
target concentration 5000 mg/m³
mean gravimetric concentration 2868 mg/m³
maximum technically attainable concentration
inlet air flow 28 l/min (concurrent control : air. 15 l/min)
exhaust air flow: 23.8 l/min (concurrent control: 12.8 l/min)
mean temperature 22.4.°C (concurrent control: 22.4°C
mean rel humidity 10.3 % (concurrent control: 5.1 %)
Mass Median Aerodynamic Diameter(MMAD) 4.78 µm
Aerosol Mass < 3 µm: 22 %
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
target concentration 0 or 5000 µg/m³ (maximum technically attainable mean concentration: 2868 mg/m³)
No. of animals per sex per dose:
5 rats /sex and concentration
Control animals:
yes
Details on study design:
according to the respective guideline , 2 weeks post exposure observation
To identify exposure related effects, comparisons with an appropriate vehicle control were performed. This control was exposed to an atmosphere using essentially similar exposure conditions as were used for the test substance.
body weight determination on days 1, 3, 7 and weekly thereafter
deaths were recorded
clinical signs and appearance and behavior of each rat were recorded
Necropsy was performed
and gross pathological changes were notet (if available)
Statistics:
one-way ANOVA
The particle-size distribution was analyzed using an ANDERSEN critical orifice
cascade impactor.
Mass Median Aerodynamic Diameter (MMAD): Construct a 'Cumulative Percent
Found - Less Than Stated Particle Size' Table, calculate the total mass of test
substance collected in the cascade impactor.
Calculation of Geometric Standard Deviation (GSD): Refer to the log probability
graph used to calculate the Mass Median Aerodynamic Diameter
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2 868 mg/m³ air (analytical)
Exp. duration:
4 h
Mortality:
no rat died
Clinical signs:
other: no specific clinical signs were observed
Body weight:
Comparisons between the control and the exposure group did not reveal changes in body weights of toxicological significance



in body weights of no toxicological significance
Gross pathology:
-Animals sacrificed at the end of the observation period:
No macroscopic findings
Other findings:
no further data

Target concentration: 5000 mg/m³

Gravimetric concentration: 2868 mg/m³

MMAD:                             4.78 µm

GSD                                   1.82

Aerosol Mass <3 µm:       22.0 %

Mass recovered:              2228 mg/m³

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Executive summary:

A study on acute inhaltion toxicity of Macrolex Rot EG on rats has been conducted in accordance with OECD TG 403. A group of male and female rats was nose-only exposed to the dry powder aerosol of the test article at an actual concentration of 2868 mg/m³.. No animal died, no clinical findings and no pathotlogical changes were noted. Therefore, the results can be summarized as follows:

LC50 (rat) > 2868 mg/m³, the maximum technically attainable concentration.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
2 868 mg/m³
Quality of whole database:
guideline study under GLP conditions and evaluated with Klimisch score 1

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

ORAL ROUTE

10 male Wistar rats received single oral dose of 5000 mg/kg bw dissolved in 1% Traganth and were observed for clinical signs of intoxication, body weight development, mortality over a period of 14 days. At the end of the observation time all animals undergo gross pathological examination. No animal died, no clinical signs were observed, all animals gained weight and no gross pathological findings were detected at the terminal sacrifice. thus The LD50 is > 5000 mg/kg bw.

INHALATION ROUTE

A study on acute inhalation toxicity of Macrolex Rot EG on rats has been conducted in accordance with OECD TG 403. A group of male and female rats was nose-only exposed to the dry powder aerosol of the test article at an actual concentration of 2868 mg/m³.. No animal died, no clinical findings and no pathotlogical changes were noted. Therefore, the results can be summarized as follows:

LC50 (rat) > 2868 mg/m³, the maximum technically attainable concentration.

DERMAL ROUTE

There is no data on acute toxicity available using the dermal exposure route. According to Regulation (EC) No. 1907/2006 (REACH) ANNEX VIII column 2 in addition to the acute toxicity using the oral route for substances other than gases at least the acute toxicity data for one other route should be provided. This recommendation is fulfilled because there is an acute inhalation toxicity study according to the respective guideline and GLP evaluated with Klimisch score 1. Thus, there is no need to conduct an acute toxicity study using the dermal route.


Justification for selection of acute toxicity – oral endpoint
only avaialble rat study according to the respective guideline and GLP and evaluated with Klimisch score 2

Justification for selection of acute toxicity – inhalation endpoint
only available study: performed according to the actuell guideline and GLP and evaluated with Klimisch score 1

Justification for selection of acute toxicity – dermal endpoint
There is no data on acute toxicity available using the dermal exposure route. According to Regulation (EC) No. 1907/2006 (REACH) ANNEX VIII column 2 in addition to the acute toxicity using the oral route for substances other than gases at least the acute toxicity data for one other route should be provided. This recommendation is fulfilled because there is an acute inhalation toxicity study according to the respective guideline and GLP evaluated with Klimisch score 1. Thus, there is no need to conduct an acute toxicity study using the dermal route.

Justification for classification or non-classification

based on the available data no classification or labelling is required.