Registration Dossier

Administrative data

Description of key information

The test item did not produce any adverse effects after dermal as well as oral administration to rats.

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 17 AUG 1999 to 07 SEP 1999
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)
Version / remarks:
22 MAR 1996
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
30 SEP 1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: HanIbm: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: females 10 weeks, males 8 weeks
- Body weights at study initiation: females 161.7, 180.1, 181.1 g, males 223.9, 214.3, 218.8 g
- Fasting period before study: overnight 16-16.5 h
- Housing: groups of three in Makrolon type-4-cages with standard softwood bedding
- Diet: pelleted standard Kliba 3433, batch no. 39/99 rat maintainace diet, ad libitum
- Water: Community tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 3
- Humidity (%): 40-70
- 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: 200 g/L
- Amount of vehicle (if gavage): 10 mL
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: weighing on test day 1 (pre-administration), 8 and 15, observations four times during test day 1, once daily from day 2-15
- Necropsy of survivors performed: yes
- Other examinations performed: observation of changes in appearance and behaviour
Statistics:
No statistical analysis was done as no death occurred.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: exact LD50 not determinable due to absence of adverse toxic effect
Mortality:
No deaths occurred.
Clinical signs:
No clinical sign were observed.
Body weight:
Body weight was in the normal range of animals of this strain and age
Gross pathology:
No effects observed
Interpretation of results:
GHS criteria not met
Conclusions:
Single application of the limit dose of 2000 mg test substance per kg bw did not cause lethality in 3 male and 3 female HanIbm: WIST rats during the 14 day observation period, resulting in a LD50 > 2000 mg/kg bw.
Executive summary:

3 Male and 3 female rats (HanIbm: WIST) were subjected to test acute oral toxicity according to the acute class method (OECD TG 423, Limit test). The test substance was administered by gavage at the limit dose of 2000 mg/kg bw in polyethylene glycol. No animal died within the observation period, resulting in a LD50 > 2000mg/kg bw.

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

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:
From 31 AUG 1999 to 21 SEP 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 FEB 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
31 JUL 1992
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
other: HanIbm: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: females 12 weeks, males 9 weeks
- Weight at study initiation: females between 186.1 and 208.6 g, males between 207.0 and 255.5 g
- Fasting period before study: no
- Housing: during treatment and observationindividually in Makrolon type 3 cageswith standard soft bedding
- Diet: pelleted standard Kliba 24-3433-4, batch no. 39/99 rat maintainace diet, ad libitum
- Water: Community tap water, ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: 10

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with lukewarm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 6.0 mL/ kg bw
- Concentration (if solution): 33% [w/v]
- Constant volume or concentration used: yes
- For solids, paste formed: no
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations four times during test day 1 and once daily during days 2-15, weighing on test day 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic findings
Statistics:
No statistical analysis was used as no deaths ocurred.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: exact LD50 not determinable due to absence of adverse toxic effect, no indication of skin irritation up to the relevant limit dose level.
Mortality:
No deaths ocurred during the study.
Clinical signs:
Yellow staining and test article remnants on the application site were observed. Yellow staining persisted in two males and three females until day 13.
Body weight:
Body weights were within the range commonly recorded for animals of this strain and age.
Gross pathology:
No macroscopic findings were observed at necroscopy.
Interpretation of results:
GHS criteria not met
Conclusions:
Single dermal application of the limit dose of 2000 mg test substance per kg bw did not cause lethality in 5 male and 5 female HanIbm: WIST rats during the 14 day observation period, resulting in a LD50 > 2000 mg/kg bw.
Executive summary:

5 Male and 5 female rats (HanIbm: WIST) were subjected to test acute dermal toxicity according to the acute dermal toxicity test method (OECD TG 402, limit test). The test substance was applied semiocclusively to the animals backs at the limit dose of 2000 mg/kg bw in propylene glycol. After 24 h the test substnce was removed, the skin was washed clean and the animals were observed for 14 days. No animal died within the observation period, resulting in a LD50 > 2000mg/kg bw. No skin irritation was observed either.

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

Additional information

Justification for classification or non-classification

No classification

The test item did not produce any adverse effects after dermal as well as oral administration to rats.