Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw (rat); OECD Guideline Study, RCC 2001
Aucte dermal toxicity: LD50 > 2000 mg/kg bw (rat); OECD Guideline Study, RCC 2001

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:
18.10.2001 - 23.11.2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
not specified
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: HanBrl: Wist
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Animal Breeding Division, Fullinsdorf / Switzerland
- Age at study initiation: Males: 8 weeks, Females: 10 weeks
- Mean weight at study initiation: Females: 174.27 g; Males: 203.6 g
- Fasting period before study: 16 to 20 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.
- Housing: three per sex in Makrolon type-4 cages
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 73/01 (Provimi Kliba AG, Kaiseraugst/ Switzerland), ad libitum.
- Water (e.g. ad libitum): Community tap-water, from Itingen ad libitum.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 h / 12 h
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 body weight
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial performed before experimental starting date.
- Lot/batch no. (if required): 424718/142701

DOSAGE PREPARATION (if unusual): The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). The mixtures were prepared using a glass stick first then a magnetic stirrer.
Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
3
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
Mortality / Viability: Daily during acclimatization and twice daily during days 1-15.
Body weights: On test days 1 (pre-administration), 8 and 15.
Clinical signs: Daily during acclimatization and at least four times on test day 1 after the test item administration. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy: All surviving animals were killed at the end of the observation period and discarded after macroscopic examinations were performed. No organs or tissues were retained.
Statistics:
No statistical analysis was used.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality and no clinical signs were observed.
Mortality:
No deaths occurred.
Clinical signs:
Slight emaciation was evident in one female on the test days 5 and 6. All other animals were without clinical signs.

Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was determined to have an acute oral LD50 >2000 mg/kg bw (in the rat) under the conditions of the test. The substance is not orally toxic.
Executive summary:

In this guideline (OECD 423) study conducted with GLP, the acute oral LD50 of the test material (EC 438-340-0) to rats was determined to be >2000 mg/kg bw (both sexes). The test material was administered via gavage at a dose of 2000 mg/kg bw. The result of the test was not sufficient to trigger classification and labelling of the test material for acute toxicity under the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
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:
2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted February 24, 1987
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
July 31, 1992
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: HanBrl: WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Animal Breeding Division, Fullinsdorf / Switzerland
- Age at study initiation: Males: 9 weeks, Females: 12 weeks
- Mean weight at study initiation: Females: 204.08 g; Males: 240.16 g
- Fasting period before study: no data.
- Housing: Individually in Makrolon type-3 cages during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 73/01 (Provimi Kliba AG, Kaiseraugst/ Switzerland), ad libitum.
- Water (e.g. ad libitum): Community tap-water, from Itingen ad libitum.
- Acclimation period: 6 days

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:
polyethylene glycol
Remarks:
PEG 300
Details on dermal exposure:
TEST SITE
- Area of exposure: backs of the animals (One day before treatment, the backs of the animals were clipped with an electric clipper.)
- % coverage: approximately 10 % of the total body surface
- Type of wrap if used: The semi-occlusive dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was flushed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: Twenty-four hours after the application the dressing was removed.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): 0.33 g/ml
- For solids: The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). The mixture was prepared using a glass stick and then a magnetic stirrer.
Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.
The preparation was made shortly before the dermal application.

VEHICLE
- Amount(s) applied (volume or weight with unit): 6 ml/kg body weight
- Lot/batch no. (if required): 424718/142701
Duration of exposure:
24 h
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
> Mortality / Viability: Daily during acclimatization and twice daily during days 1-15.
> Body weights: On test days 1 (pre-administration), 8 and 15.
> Clinical signs: Daily during acclimatization and at least four times on test day 1 after the test item administration. Once daily during
days 2-15. All abnormalities were recorded.
- Necropsy: At the end of the observation period all animals were sacrificed. The animals were examined macroscopically and all abnormalities recorded. Thereafter, they were discarded.
Statistics:
No statistical analysis was used.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality and no clinical signs were observed.
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs were observed.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.
Other findings:
Signs of toxicity (local):
No signs of toxicity were noted.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was determined to have an acute dermal LD50 >2000 mg/kg bw (in the rat) under the conditions of the test. The substance is not dermally toxic.
Executive summary:

In this guideline (OECD 402) study conducted with GLP certification, the acute dermal LD50 of the test material (EC 438-340-0) to the rat was determined to be >2000 mg/kg bw (both sexes). The test material was administered under semi-occlusive conditions as a limit test (2000 mg/kg bw) to male and female for 24 hours, with a post application observation period of 15 days. The result of the test does not trigger classification of the test material as acutely toxic according to the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Additional information

Acute oral toxicity in rat:

The acute oral toxicity of the test article in 5 male rats and 5 female rats was tested according to OECD guideline 401 (RCC, 2001). A single dose of 2000 mg/kg body weight was administered through gavage. No mortality and only slight emaciation in one female on the test days 5 and 6 were observed. The animals showed normal body weight gain in this study. At autopsy, no macroscopic organ changes were observed.

The exploratory (approximate) acute oral LD50 for the test substance, when administered by gavage to the young adult albino rat, was estimated to be greater than 2000 mg/kg bw (Ciba, Geigy 1988). No mortality and only common symptoms in acute toxicity testing like piloerection, hunched posture, exophthalmos, and dyspnea were seen. The animals recovered within 6 to 7 days.

Acute dermal toxicity in rat:

A single dose of 2000 mg/kg bw, was administered to the backs of 5 male and 5 female rats according to OECD guideline 402 (RCC 2001). The test article was applied evenly over an area of 10% and covered with a semi-occlusive dressing. The rats were exposed to the test article for 24 hours. The rats were then observed for a further 15 days. No mortality and no systemic and local symptoms were observed and the LD50 was estimated to be greater than the administered dose of 2000 mg/kg bw.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral or dermal or inhalation toxicity under Regulation (EC) No. 1272/2008, fifth time in Directive EC 944/2013.