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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 0.0003 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.

Therefore, and due to the fact that inhalation is not likely, a study on acute inhalation is not required.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-09-27 to 2006-10-24
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:
12-2001
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
Remarks:
HsdCpb:WU
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: 8 - 9 weeks
- Weight at study initiation: 158 - 205 g
- 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): 20-22
- Humidity (%): 48 - 70%
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Days 1 to 15
Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
Methocel® K4M Premium solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 g/L
- Amount of vehicle (if gavage): 10 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 (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 the rats survived the observation period.
Clinical signs:
No signs of intoxication occurred after treatment.
Body weight:
Body weight development of the treated rats was normal.
Gross pathology:
At necropsy, no organ alterations were seen.

Study design

The test item 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 vehicle. This GLP study was performed according to the OECD GL 423.

Results

No signs of intoxication occurred after treatment and all the rats survived the observation period. Body weight development of the treated rats was normal. At necropsy, no organ alterations were seen.

Conclusion

For regulatory purposes, the median lethal dose (LD50), after an observation period of 15 days can be declared as > 2000 mg/kg.

Interpretation of results:
GHS criteria not met
Conclusions:
For regulatory purposes, the median lethal dose (LD50), after an observation period of 15 days can be declared as > 2000 mg/kg.
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:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
For this endpoint information from structural similar compounds is available. The studies for these similar compounds were performed according to GLP and the methods applied are fully compliant with OECD TG 423. See chapter 13 report for a more detailed justification.
Reason / purpose:
read-across source
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
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

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

Justification for selection of acute toxicity – oral endpoint
This study was performed according to GLP and the methods applied are fully compliant with OECD TG 423.

Justification for selection of acute toxicity – dermal endpoint
On 15 July 2014 the Competent Authorities for REACH and CLP (Caracal) have agreed that substances that are not toxic in acute oral tests need no longer be tested for acute dermal toxicity. Caracal agreed on proposals to amend REACH Annex VIII (point 8.5.3) so that substances that have not shown oral acute toxicity up to a limit dose of 2000 mg/kg bodyweight would not also require dermal data. The test material does not provide evidence for acute oral toxicity. The LD50 exceeds 2000 mg/kg bw. Therefore no further testing for dermal toxicity is justified.

Justification for classification or non-classification

Based on the provided information there is no need for classification according to the EU Regulation (EC) No 1272/2008 on Classification,Labelling and Packaging of Substances and Mixtures.