Registration Dossier

Diss Factsheets

Administrative data

Description of key information

LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From April 19 to May 3, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The test was conducted by means of Read Across approach. The reliability of the source study report is 1. Further information was attached at section 13
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
In two males the allowed initial body weight was exceeded by 2 and 3 g, respectively.
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif : RAIf (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited Animal Production 4332 Stein / Switzerland
- Weight at study initiation: 182 to 243 g
- Fasting period before study: Prior to dosing, the animals were fasted overnight.
- Housing: The animals were housed in Macrolon cages type 4, with standardized soft wood bedding (Société Parisienne des Sciures, Pantin, France)
- Diet: Rat diet (NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland) ad libitum
- Water: ad libitum
- Acclimation period: at least for 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour/day light cycle

Route of administration:
oral: gavage
Vehicle:
other: distilled water
Details on oral exposure:
VEHICLE
- Volume applied: 10 ml/kg body weight
Doses:
2000 mg/kg (males and females)
No. of animals per sex per dose:
5 per sex per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: - Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days: - Signs and symptoms: daily for 14 days; - Body weight: immediately before administration and on days 7 and 14
- Necropsy of survivors performed: yes, The animals were submitted to a gross necropsy at the end of the observation period.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities occurred in this study
Clinical signs:
Pilerection, hunched posture and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 3 days.

Necropsies

At necropsy, no deviations from normal morphology were found in all animals.

Interpretation of results:
other: Not classified according to the CLP Regulation
Conclusions:
LD50 > 2000 mg/kg bw
Executive summary:

Method:

The test substance was tested for its Acute Oral Toxicity according to OECD guideline 401 and EU Method B.l.

Observations:

Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 3 days. At necropsy, no deviations from normal morphology were found in all animals.

Results:

LD50 > 2000 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No studies on the "Acute Oral Toxicity" are available for the substance in itself.

Nevertheless studies were conducted with an analogue molecule (Similar Substance 01). Further information are reported in the Read Across justification attached to section 13.

Different available tests may be considered, that gives information on Acute Oral Toxicity.

The key study was performed according to OECD guideline 401, following administration of a single limit dose (2000 mg/kg bw). No mortality occurred during the study . Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 3 days. At necropsy, no deviations from normal morphology were found in all animals. The acute oral LD50 was determined to be > 2000 mg/kg bw.

The supporting study was performed according to OECD guideline 401. The rats were treated with the substance at multiples doses (1000, 2500, 5000 mg/kg bw) by oral administration. At a concentrations of 2500 mg/Kg a death occured after a day. At 5000 mg/Kg bw eight animals died after a day. The acute oral LD50 was determined to be 3644 mg/kg bw.

The results obtained with a further test, conducted according to a method similar to OECD guideline 401, showed a LD50 > 5000 mg/kg bw, which is in line with the results obtained in the tests described above.

Justification for classification or non-classification

According to the CLP Regulation (EC n. 1272/2008), acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

The oral LD50 value was established to be greater than 2000 mg/kg body weight, therefore the test substance is out of any classification limit for acute oral toxicity (oral acute toxicity Category 4: 300 < ATE ≤ 2000 mg/kg bw).