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Administrative data

Description of key information

LD50 acute oral toxicity (male and female; rat): > 10,000 mg/kg bw. LD50 acute dermal toxicity (male and female; rat): > 2,000 mg/kg bw (test item with low purity)

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:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(10/14 hour dark/light cycle, acclimation period = 4 days)
GLP compliance:
no
Remarks:
prior GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif RAIF (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba Geigy Ltd.
- Weight range at study initiation: 160 - 180 g
- Fasting period before study: overnight
- Housing: 5/cage (macrolon cages type IV)
- Diet: ad libitum; NAFAG Gossau SG
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 10/14
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 %
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: no data

DOSAGE PREPARATION: The test substance was suspended with polyethylene glycol (PEG 400). Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.
Doses:
4,640, 7,750 and 10,000 mg/kg bw
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 weighing: at least once (before application)
- Frequency of observation: after 1, 24, 48 hours, on day 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal died in the mid dose on day 14. No deaths were recorded in the low and high doses.
Clinical signs:
Within two hours of dosing, rats in all dose groups experienced sedation, dyspnoea, exophthalmus, curved position and ruffled hair. The surviving animals recovered within 8 days.
Body weight:
no data
Gross pathology:
No substance related gross organ changes were seen.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 000 mg/kg bw
Quality of whole database:
The study is comparable to OECD Guideline 401 (Acute Oral Toxicity), not GLP compliant and has Klimisch score 2.

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:
1997
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)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
92/69/EEC
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Hanlbm: WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wolferstrasse 4, CH-4414 Fullinsdorf/ Switzerland.
- Age at study initiation: Males: 8 weeks; Females: 11 weeks.
- Weight at study initiation: Males: 227-242 g; Females: 194-217 g
- Housing: During acclimatization in groups of five in Makrolon type-4 cages with standard softwood bedding ("Lignocel", SchillAG, CH-4132 Muttenz). During treatment and observation individually in Makrolon type-3 cages with standard softwood bedding.
- Diet: Pelleted standard Kliba 343, batch no. 88/97 rat maintenance diet (Kliba Miihlen AG, CH-4303 Kaiseraugst) available ad libitum. Analysed for bacteriological, chemical and contaminant
- Water: ad libitum; tap water (analysed for bacteriological, chemical and contaminant)
- Acclimation period: One week 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.
- Humidity (%): 40-70.
- Air changes (per hr): 10-15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Backs of the animals.
- % coverage: Approximately 10 % of the total body surface.
- Type of wrap if used: Covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Yes; with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hours.

TEST MATERIAL
Application volume/kg body weight: 2.0 mL.
Duration of exposure:
24 h
Doses:
2000 mg/kg body weight.
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:
Mortality / Viability: Four times during test Day 1 and once daily for surviving animals during Days 2-15.
Body weights: On test Day 1 (pre-administration), 8 and 15 for surviving animals.
Clinical signs: Each animal was examined for changes in appearance and behaviour (with special emphasis on the application area, except for the time when the semi-occlusive dressing was in place) four times during Day 1, and once daily for surviving animals during Days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: Yes.
Statistics:
No statistical analysis was used as no deaths occurred.
Preliminary study:
Not applicable.
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 signs of toxicity were observed.
Body weight:
The body weight of the animals was within the range of physiological variability known for rats of this strain and age. The slight loss of body weight in two female animals during the first observation week was considered to be a consequence of the semi-occlusive dressing used during treatment. Commonly, female animals prove to be more sensitive in relation to the effects on body weight caused by semi-occlusive dressing than male.
Gross pathology:
No treatment-related macroscopic findings were observed.
Other findings:
Signs of toxicity (local): No skin irritation was observed.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study is according to OECD Guideline 402 (Acute Dermal Toxicity), GLP compliant and has Klimisch score 2.

Additional information

Acute oral toxicity

In a standard acute oral toxicity study performed similarly to OECD TG 401, groups (5 rats/dose/sex) of overnight fasted Tif Raif rats were administered the test substance (no data on purity) via gavage. The test substance was administered at doses of 4640, 7750 and 10000 mg/kg bw in polyethylene glycol. Animals were subsequently observed for a period of 14 day in which time clinical signs of toxicity and cases of mortality were noted. Death occurred only in the mid dose level with 1 out of 10 animals found dead. No mortality occurred at the low and high dose groups. Hence the LD50 is higher than 10,000 mg/kg bw. Clinical signs of toxicity - seen in animals of all doses - set in 2 hours post application and lasted 8 days. These included; dyspnoea, exophthalmus, curved position and ruffled hair.

 

Acute dermal toxicity

In a limit test performed pursuant to the protocols of the OECD Test Guideline 402, the test article (low purity) was applied in a semi-occlusive fashion for 24 hours to the shaved skin of 5 (8 -11 weeks old) Hanlbm: WIST rats/sex at a dose level of 2,000 mg/kg bw. Animals were then observed for 14 days. No mortality was registered in the study. Neither clinical signs of systemic toxicity nor local irritation effects at the application site were observed during the 14 day observation period. Necropsy revealed no gross abnormalities. As no deaths occurred in the study, the LD 50 of the test article in rats is higher than 2,000 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 the purpose of classification. Based on the criteria laid down in Regulation (EC) No.1272/2008, classification for acute toxicity is not warranted.