Registration Dossier

Administrative data

Description of key information

The test item was applied oral and dermal to rats to evaluate the acute toxicity of the substance (GLP, OECD 423 and 402).

LD50 after oral administration > 2000 mg/kg bw. Signs of toxicity were not observed. LD50 after dermal application> 2000 mg/kg bw. Signs of toxicity were not observed. A test on acute inhalative toxicity was not performed.

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:
2002
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)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: HanBrl: Wist (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: RCC Ltd, Biotechnology and Animal Breeding Division, Fuellinsdorf / Switzerland- Age at study initiation: males = 8 weeks, females = 10 weeks- Weight at study initiation: males = 187.7 - 210.4 g, females = 181.5 - 184.9 g- Fasting period before study: 16 to 20 hours- Housing: three per sex in Makrolon type-4 cages with wire mesh tops and standardized softwood bedding- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 77/01 (Provimi Kliba AG, Kaiseraugst/ Switzerland) ad libitum.- Water (e.g. ad libitum): Community tap-water, from Itingen ad libitum- Acclimation period: one weekENVIRONMENTAL CONDITIONS- Temperature (°C): 22 ± 3- Humidity (%): 30-70- Air changes (per hr): 10-15- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light/12 hours dark
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Remarks:
PEG 300
Details on oral exposure:
VEHICLE- Lot/batch no. (if required): 430424/1 54701 (animal nos. 1-3), 430424/1 25001 (animal nos. 4-6)MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Clinical signs were noticed 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. Weighing was done on test days 1 (pre-administration), 8 and 15.- Necropsy of survivors performed: yes
Statistics:
Not necessary
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred during the study.
Clinical signs:
No clinical signs were noted during the course of the study.
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
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:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: HanBrl: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: RCC Ltd, Biotechnology and Animal Breeding Division, Fuellinsdorf / Switzerland- Age at study initiation: males = 8 weeks, females = 7-8 weeks- Weight at study initiation: males = 215.9 - 233.9 g, females = 180.1 - 210.7 g- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation.- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 57/02 (Provimi Kliba AG, Kaiseraugst/ Switzerland) ad libitum.- Water (e.g. ad libitum): Community tap water from Fuellinsdorf ad libitum.- Acclimation period: one weekENVIRONMENTAL CONDITIONS- Temperature (°C): 22 ± 3- Humidity (%): 30-70- Air changes (per hr): 10-15- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light/ 12 hours dark
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Details on dermal exposure:
TEST SITE- % coverage: approximately 10 % of the total body surfaceREMOVAL OF TEST SUBSTANCE- Washing (if done): with lukewarm tap water- Time after start of exposure: Twenty-four hours after the application.TEST MATERIAL- Amount(s) applied (volume or weight with unit): 6.66 g/kg bw- Concentration (if solution): 30 %
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Clinical signs were noticed daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. Weighing was done on test days 1 (prior to administration), 8 and 15. Mortality / Viability was notice daily during acclimatization and twice daily during days 1-15.- Necropsy of survivors performed: yes, at the end of the observation period
Statistics:
No statistical analysis was used.
Key result
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:
No systemic or local signs of toxicity were observed during the study period.
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
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Additional information

There are reliable studies available to assess the acute oral and dermal toxicity of the test substance.

A GLP conform study was performed to assess the acute toxicity following oral administration of the test substance in HanBrl: WIST rats according to OECD guideline 423 (RCC Ltd, 2002). To a group of six fasted animals (three males and three females) a single oral dose of the test material preparation (dose volume: 10 ml/kg bw) in PEG 300 at a dose level of 2000 mg/kg body weight was given. The animals were examined for clinical signs daily during the acclimatization period, four times during test day 1 and once daily during test days 2-15. Mortality/viability was recorded daily during the acclimatization period and together with clinical signs at the same time intervals on test day 1 and twice daily on test 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. All animals survived until the end of the study period. No clinical signs were evident during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy.  

Under the conditions of this study the median lethal dose of the test substance after oral application was found to be greater than 2000 mg/kg body weight for the male and female animals.

A GLP conform study was performed to assess the acute toxicity following dermal administration of the test substance in HanBrl: WIST rats according to OECD guideline 402 (RCC Ltd, 2002). Five male and five female rats were treated with the test substance (purity: 98.4 weight-%; dose volume: 6.66 g/kg bw) at 2000 mg/kg by dermal application. The test item was diluted in vehicle (PEG 300) at a concentration of 30 % (w/w) and administered at an amount dosage of 6.66 g/kg. The application period was 24 hours.

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 twice daily during test days 1-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No clinical signs were observed during the observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. Under the conditions of this study the median lethal dose of the test substance after dermal application was found to be greater than 2000 mg/kg body weight for the male and female animals.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) 1272/2008. Based on this data the substance does not need to be classified for acute toxicity under Regulation (EC) No. 1272/2008.