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Description of key information

The LD50 oral of substance registered is greater than 2000 mg/kg bw.  The LD50 dermal was greater than 2000 mg/kg bw. 

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:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: 16 weeks
- Housing: in groups of three in Makrolon type-4 cage swith wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no.42/04, ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
: PEG 300
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial.
- Lot/batch no. (if required): 1078164 12004034
- Source: FLUKA Chemie GmbH, CH-9471 Buchs
Doses:
limit concentration: 2000 mg/kg bw
No. of animals per sex per dose:
Control group: 3 female animals
Treatment group: 3 female animals
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
other: No clinical signs were observed during the course of the study. Red feces was observed from the 2-hour reading up to test day 3 in the first treated group and from test day 2 to 3 in the second treated group. Red discoloration of the softwood bedding was
Gross pathology:
No macroscopic findings were recorded at necropsy.
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
not relevant for classification and labelling
Executive summary:

In order to assess the acute oral toxicity potential of the test substance an OECD 423 test was performed in 2004. Two groups consisting of three female rats each, were treated with the substance by oral gavage administration at a dosage of 2000 mg/kg body weight. The vehicle was PEG300.

There were no deaths as a result of treatment with the test article. No clinical signs of toxicity were observed during the observation period. The body weight of the animals was within the physiological range of variability known for rats of this strain and age. No macroscopic findings were observed at necropsy.

The mean lethal dose of the substance after single oral administration to female rats, observed over a period of 14 days, could not be estimated. It can therefore be concluded that the LD50 is greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
2004/73/EC, B.3
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: 12 weeks
- Housing: in groups of three in Makrolon type-4 cage swith wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no.42/04, ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: approximately 10 % of the total body surface.
- Type of wrap if used: semi-occlusive dressing fixed with an elastic adhesive bandage

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 0.5g/mL
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 mL/kg bw
- Lot/batch no. (if required): 1078164 12004034
- Source: FLUKA Chemie GmbH, CH-9471 Buchs
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality / Viability: Daily during the acclimatization period, at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Body weights: On test days 1 (prior to administration), 8 and 15.
Clinical signs: Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
other: No clinical signs were observed during the course of the study. Red discoloration of the skin caused by the test item was observed from test day 2 to 4 in all animals and persisted up to test day 5 in six animals and up to test day 6 in one animal. Slight
Gross pathology:
No macroscopic findings were observed at necropsy.
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
not relevant for classification and labelling
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Two valid acute toxicity studies, oral and dermal, have been conducted with the registration substance.

The mean lethal dose of the substance after single oral administration to female rats, observed over a period of 14 days, could not be estimated. It can therefore be concluded that the LD50 is greater than 2000 mg/kg bw.

The mean lethal dose of the substance after single dermal administration to rats of both sexes, observed over a period of 14 days, could not be estimated. It can therefore be concluded that the LD50 is greater than 2000 mg/kg.

No study for acute inhalation toxicity is available. The test material is non- volatile and produced and handled in industry exclusively in aqueous solutions. There are no spraying operations. The likely route of human exposure to the substance is the dermal route. The test substance is of low toxicity after oral and dermal application to rats and exhibits no skin- or eye irritating potential. It is not a skin sensitizer in an LLNA test. Further, in a 28-day repeated oarl toxicity study in rats the substance has a NOAEL of 1000 mg/kg body weight. Thus, neither exposure via inhalation nor risks are expected via the inhalation route.

Justification for selection of acute toxicity – oral endpoint
The selected study was performed under GLP and in accordance with OECD TG 423. No other studies are available.

Justification for selection of acute toxicity – inhalation endpoint
According to "Column 2" in Annex VIII of Regulation (EC) No. 1907/2006 an acute inhalation toxicity study is not necessary because exposure of humans via inhalation is considered unlikely taking into account the vapour pressure and the physical form of the substance. Inhalation is not an exposure route of concern. As two endpoint studies on the most relevant exposure routes - an acute oral toxicity study as well as an acute dermal toxicity study - are available, testing for acute inhalation toxicity is not justified for scientific reasons as specified in the ECHA guidance on information requirements, Chapter R.7a (endpoint specific guidance, R.7.4.6.3).

Justification for selection of acute toxicity – dermal endpoint
The selected study was performed under GLP and in accordance with OECD TG 402. No other studies are available.

Justification for classification or non-classification

No adverse effect observed after acute oral application of the test substance at a dose of 2000 mg/kg bw.

No adverse effect observed after acute dermal application of the test substance at a dose of 2000 mg/kg bw.