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Description of key information

The acute toxicity of the test item was investigated in an acute toxicity study on rats. The test animals showed no clinical signs (and no mortality) up to the limit dose after oral administration. Hence, the LD50 is above 2000 mg/Kg bw.

The subsequent evaluation on the necessity of a acute test via a second route was done in accordance with Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance, Version 6.0, July 2017, p 374f.

A DermWin calculation shows a dermally absorbed dose of 1.5*10 -6 to 2.8 -10 -5 mg/cm2/event. Based on the very low dermally absorbed rate and the absence of systemic effects after acute oral administration, a study on acute dermal toxicity is not required.

Furthermore, based on the lack of systemic toxicity after acute oral adminsitration, it is more than evident that an acute study on inhalation would not show any different outcome. Therefore, and due to animal welfare reasons a study on acute inhalation is not required.

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:
October 11, 2001 - December 6, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
March 22, 1996
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
Official Journal of the European communities No. L 248, September 30, 1996
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: 158 - 192g
- Fasting period before study: 17 hours before until up to 4 hours after treatment
- Housing: separately in type III Makrolon cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 22°C
- Humidity (%): 50-58%
- Photoperiod (hrs dark / hrs light): 12 hour light - 12 hour dark regime

IN-LIFE DATES: From: day 1 To: day 15
Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
Methocel K4M Premium solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 g/L
- Amount of vehicle (if gavage): 20 ml/kg
- Justification for choice of vehicle: well tolerated and established standard vehicle

Doses:
2000 mg/kg
No. of animals per sex per dose:
3 (m) / 3 (f)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: day 1, 2, 4, 6, 8, 11, 13 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
Standard statistical methods have been applied for data processing.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
All rats survived the observation period.
Clinical signs:
No signs of toxicity were seen in the 3 male and 3 female rats after treatment with 2000 mg/kg.
Body weight:
The body weight development of the rats was inconspicuous during the study.
Gross pathology:
The gross pathological examination revealed no organ alterations.

Study design

The test material was tested for acute toxicity in rats after single oral administration of 2000 mg/kg body weight. Directly before administration the test material was prepared with aqueous Methocel K4M Premium solution as the vehicle. The study was performed according to the OECD Guideline for Testing of Chemicals, No. 423.

Results

No signs of toxicity were seen in the rats (3 males, 3 females) after treatment with 2000 mg/kg of the test item.
The body weight development of the rats was inconspicuous during the study.
There were no deaths during the course of the study.
The gross pathological examination revealed no organ alterations.

Conclusion

Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD50value is higher than 2000 mg/kg after single oral administration in rats.

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.
Executive summary:

This study was performed according to GLP and is fully compliant OECD TG 423. Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification

A classification and labelling for acute toxicity is not warranted.