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Description of key information

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a contract research organization. The study is scientifically valid and the report is fully adequate for assessment, despite some minor restrictions (e.g. due to limited reporting).
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
of 1981
Deviations:
yes
Remarks:
Due to physicochemical properties of the test material and to achieve the high target doses dose volumes could not be kept constant but increased with increasing dose up to the double volume of that recommended by OECD401 for non-aqueous dose formulations
Qualifier:
according to
Guideline:
other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA, 1959
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Wistar rats, strain: Winkelmann, Paderborn (SPF-Quality) with appropriate range of bodyweight at study start.
- Weight at study initiation (day of dosing): Males: minimum 200 g, maximum 216 g,
Females: minimum 195 g, maximum 206 g.
- Housing: Group housing with up to 5 animals by sex in cages.
- Fasting period: From 16 hours before test start
- Diet (except for fasting period): Commercially available standard laboratory animal diet:
"Rat/Mouse Maintenance" from Altromin, Lage, Germany
- Water was provided ad libitum

ENVIRONMENTAL CONDITIONS

The animal room was maintained at:
- Temperature (°C): 22 ± 1°C
- Relative Humidity (%): 45 to 55%
- Photoperiod (artificial lighting): 12 h/day
Route of administration:
oral: gavage
Vehicle:
other: Emulsion in mixture of CMC (carboxymethyl cellulose) and Tween 20 containing 50% of the test substance
Details on oral exposure:
- Dose formulation: 50% of the test substance in vehicle, i.e. emulsion at the maximum practical concentration
- Dose volume: The administered volume of test material formulation increased with increasing dose thus achieving quite high target doses.
Individual dose volume was calculated based on individual bodyweight
- For different doses and dose volumes, see Table 1 in "Any other information on materials and methods incl. tables"
- Rationale for doses selected: Based on a pre-test, which was not detailed in the study report.
Doses:
see Table 1 in "Any other information on materials and methods incl. tables"
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:
It has not been clearly specified in the report at what time points clinical signs and mortality were recorded, but the following records have been
reported:
Clinidal signs: At least shortly after dosing (Day 0) and at 7 and 14 days post dosing.
Mortality: At least at 24 hours, 7 days and 14 days post dosing.
Weighing of each animal: All animals on Day 0 for calculation of individual dose volume and on Day 14 (end of observation period).
- Necropsy: All animals were necropsied at termination of the study.

Statistics:
LD50 was estimated for 24 hours and 14 days post dosing. Determination of a slope function was inappropriate as there were no deaths in both dose groups.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No deaths at 5000 or 10000 mg/kg.
Mortality:
There were no deaths during the 14-day observation period post dosing:
Single Dose at: Mortality
5000 mg/kg bw 0/5 (m); 0/5 (f)
10000 mg/kg bw 0/5 (m); 0/5 (f)
Clinical signs:
Shortly after dosing and 7 and 14 days afterwards clinical signs attributable to the treatment with the test material were not evident.
Body weight:
There were no adverse effects on body weight.
Gross pathology:
Macroscopic pathology findings attributable to the treatment with the test material were not evident.
Interpretation of results:
other: not classified according to EU regulation
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

The acute oral toxicity study demonstrated that the LD50 of WS400130 is higher than the limit dose of 2000 mg/kg b.w.

As detailed in the justification for data waiving, the conduct of an acute dermal toxicity study would not have added relevant toxicological hazard information.

The conduct of an acute inhalation toxicity study with WS400130 is not warranted, as the inhalation exposure of humans to WS400130 is unlikely because of its very low vapour pressure and because it is a higly viscous liquid.

Justification for classification or non-classification

In the acute oral toxicity study, all animals survived the dose of 10000 mg/kg. Therefore, classification of WS400130 for acute oral toxicity is not required [REGULATION (EC) 1272/2008].

 

Non-classification of WS400130 by the dermal route was reasonable, because of the absence of effects indicative of relevant systemic toxicity (apart from the sensitization response) and/or local irritation in all available in vivo toxicity studies with WS400130 and the systemic exposure probably being higher by the oral than by the dermal administration route.

 

Non-classification of WS400130 by the inhalation route was justified, because WS400130 has a very low vapour pressure and is a highly viscous liquid, making the inhalation exposure of humans to vapour or a droplet aerosol unlikely.