[Name confidential or not available]

Endpoint summary

Description of key information

Oral rat (standard acute method):   LD50 > 8000 mg/kg bw  (no mortality at 8000 mg/kg bw)
Acute dermal rat:                                Waiving, as this study was considered to be scientifically unjustified.      
Acute inhalation rat:                           Exposure based waiving: Exposure of humans to WS400506 by the inhalation route is unlikely, because of its 
                                                               low vapour pressure and because of its wax like physical appearance with a freezing/pour point of only 30°C.

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:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

of 1981

Deviations:

yes

Remarks:

Dose volumes could not be kept constant but increased with increasing dose up to the double volume of that recommended by OECD401 for aqueous dose formulations. Numbers of animals used were confined to 3 males and 3 females per dose group.

Qualifier:

according to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA, 1959

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Remarks:

Certified by BAM according to DIN EN 45001.

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Wistar rats, strain: Winkelmann, Paderborn (SPF-Quality) with appropriate range of bodyweight at study start.
- Bodyweight at study start (day of dosing): Males: minimum 210 g, maximum 225 g,
Females: minimum 190 g, maximum 206 g.
- Housing: Group housing with up to 3 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): 22.5 ± 2°C
- Relative Humidity (%): 50 to 60%
- Photoperiod (artificial lighting): 12 h/day

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

- Dose formulation: Suspension: 20% test material in vehicle (water) and warmed to body temperature (40°C).
Administration of the dose formulation to the animals at body temperature.
- Dose volume: 1.0, 2.0 and 4.0 mL / 100 g bw attaining test material doses of 2000, 4000 and 8000 mg/kg bw, respectively.
Individual dose volume was calculated based on individual bodyweight.
- Rationale for doses selected: Based on a pre-test, which was not detailed in the study report.

Doses:

WS400506: 2000, 4000 and 8000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

yes

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 occasionally over 24 hours after dosing and at 7 and 14 days post dosing.
Mortality: At least at 24 hours and 14 days post dosing.
Weighing of each animal: All animals on Day 0 for calculation of individual dose volume, and on Days 7 and 14 (end of observation period).
- Necropsy: All animals were necropsied at termination of the study.
- Control animals were untreated. As animals from a stock culture served as controls, apparently these were not necropsied concurrent with dosed animals.

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 the present study.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 8 000 mg/kg bw

Based on:

test mat.

Remarks:

WS400506

Remarks on result:

other: No deaths at 2000, 4000 or 8000 mg/kg bw

Mortality:

There were no deaths during the 14-day observation period post dosing:
Single Dose of WS400506 at: Mortality
2000 mg/kg bw 0/3 (m); 0/3 (f)
4000 mg/kg bw 0/3 (m); 0/3 (f)
8000 mg/kg bw 0/3 (m); 0/3 (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. There was a subjective impression that animals in the top dose group behaved a little more apathic within 24 hours post dosing than control animals from a stock culture. This was attributed to the high administration volume in this dose group, rather than to the test substance itself.

Body weight:

There were no adverse effects on body weight gain.

Gross pathology:

Macroscopic pathology findings attributable to the treatment with the test material were not evident.

Interpretation of results:

other: not classified

Remarks:

according to Regulation (EC) 1272/2008

Conclusions:

In view of the attained absence of mortality at doses of WS400506 up to 8000 mg/kg bodyweight, the outcome of the present study does not necessitate any classification and labelling regarding acute oral toxicity according to Regulation (EC) 1272/2008. In addition, sex-related differences in toxicity of the test material after single oral administration were not evident.

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

Justification for classification or non-classification

In the acute oral toxicity study, all animals survived a single dose of WS400506 up to 8000 mg/kg. Therefore, classification of WS400506 for acute oral toxicity is not required according to Regulation (EU) 1272/2008.

 

Non-classification of WS400506 by the dermal route was reasonable, because of the absence of effects indicative of relevant systemic toxicity and/or local irritation in all studies with WS400506 and because the systemic exposure probably being higher by the oral than by the dermal administration route.

 

Non-classification of WS400506 by the inhalation route was justified, because WS400506 has a very low vapour pressure and is of wax like appearance with a freezing/pour point of only 30°C, making the inhalation exposure of humans to vapour or an inhalable dust aerosol unlikely.