Registration Dossier

Administrative data

Description of key information

Valid acute toxicity studies with the test substance are available for the oral and the dermal route. In a study conducted according to OECD guideline 423 the oral LD 50 was greater than 2000 mg/kg bw (rat, RCC743477, 1999). In a study conducted according to OECD guideline 402 the dermal LD 50 was greater than 2000 mg/kg bw (rat, RCC743488, 1999).

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD-guideline and GLP-compliant study report
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(1996)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain as stated in the report: Hanlbm: WIST (SPF)
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation:Females: 10 weeks, Males: 8 weeks
- Weight at study initiation: no data
- Housing: Groups of three in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet:ad libitum
- Water:ad libitum
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22±3°C
- Humidity (%):40-70% (values above 70% during cleaning process possible)
- Air changes (per hr):10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12/12

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/ml
- Amount of vehicle: 10 ml/ kg bw
- Justification for choice of vehicle: solubility

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:
Mortality: Four times during test day 1 and once daily during days 2-15.
Body weights: On test day 1 (pre-administration), 8 and 15.
Clinical signs: Each animal was examined for changes in appearance and behavior four times during day 1, and once daily during days 2-15. A description of all abnormalities was recorded.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was used as only one death occurred.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One of three males was found dead 3 hours after treatment. None of the treated females died.

Clinical signs:
Ruffled fur was observed in one male on test day 3. No clinical signs were noted during the observation period in all other surviving animals.
Body weight:
The body weight of the surviving animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Single oral administration of 2000 mg/kg bw test article to female and male rats resulted in one unscheduled death, ruffled fur and no clinical signs or macroscopic findings. Thus, the LD50 was above 2000 mg/kg bw for both sexes.
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD-guideline and GLP-compliant study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
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
- Strain as stated in the report: Hanlbm: WIST (SPF)
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: 9 weeks (males), 12 weeks (females)
- Housing: During acclimatization in groups of five in Makrolon type-4 cages with standard softwood bedding. During treatment and observation individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet: Pelleted standard Kliba 3433 rat maintenance diet, ad libitum
- Water: Tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22±3°C
- Humidity (%):40-70% (values above 70% during cleaning process possible).
- Air changes (per hr):10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12/12
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: 10 % of the total body surface

REMOVAL OF TEST SUBSTANCE
- Washing: 24 h after application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels

TEST MATERIAL
- Amount applied: 4.0 ml/kg bw
- Constant volume or concentration used: yes

Duration of exposure:
24 h
Doses:
2000 mg/kg body weight
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: 15 days
- Frequency of observations for mortality and clinical symptoms: 4-times on first day, afterwards once daily
- Frequency of weighing: On first day, day 8 and day 15
- Necropsy of survivors performed: yes, all animals were sacrified and subjected to gross pathology
Statistics:
No statistical analysis was used as no deaths occurred.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: None of the treated animals died. No clinical signs were observed.
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 animals of this strain and age (details table 1).
Gross pathology:
No macroscopic findings were observed at necropsy.

Body weight of male and female rats after dermal treatment with 2000 mg/kg bw of test article

Body weight in grams:

Sex

Animal No.

Day of treatment

Day 8

Day 15

Male

1

235.8

259.5

281.6

2

235.1

252.8

269.6

3

231.3

258.2

279.8

4

247.3

277.4

300.5

5

240.1

262.1

278.6

female

6

201.4

207.7

216.2

7

223.5

230.0

227.4

8

207.9

226.7

228.9

9

199.1

203.3

212.0

10

205.7

207.5

223.4

 

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
After dermal application of 2000 mg/kg bw test article to female and male rats for 24 h under semi-occlusive conditions according to OECD 402 (1987) no mortality was observed. Thus, the LD50 was above 2000 mg/kg bw for both sexes.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

After single oral administration of 2000 mg/kg bw test article to female and male rats according to OECD guideline 423 (1996) and a 14 days recovery period, 1/3 males and 0/3 females died (RCC743477, 1999). Ruffled fur was observed in one of the two surviving males on test day 3. No clinical signs were noted during the observation period in all other animals. No macroscopic findings were observed at necropsy. Thus, the LD50 was above 2000 mg/kg bw for both sexes.

After dermal application of 2000 mg/kg bw test article to female and male rats for 24 h under semi-occlusive conditions according to OECD 402 (1987) and a 14 days recovery period, no mortality was observed (RCC743488, 1999). No systemic or local signs of toxicity were seen. Thus, the LD50 was above 2000 mg/kg bw for both sexes. 

No valid data on acute toxicity regarding the inhalative route are available.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute toxicity under Directive 67/548/EEC.

                               

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 toxicity under Regulation (EC) No. 1272/2008.

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute toxicity under Directive 67/548/EEC.

                               

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 toxicity under Regulation (EC) No. 1272/2008.