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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Remarks:
source of read across
Adequacy of study:
key study
Study period:
10 January 2017 to 1 february 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Reference substance name:
Similar Substance 01
IUPAC Name:
Similar Substance 01

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Strain: RccHan™:WIST
- Females (if applicable) nulliparous and non-pregnant:yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 152-201 g
- Fasting period before study: overnight before dosing and 3-4 hours after dosing
- Housing: solid-floor polypropylene cages furnished with woodflakes (maximum 4/cage)
- Diet: 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: solubility

MAXIMUM DOSE VOLUME APPLIED: 10 mL

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: statring dose 300 mg/kg bw in absence of any information on toxicity
Doses:
300 mg/kg bw 1 female
2000 mg/kg bw 1 female
300 mg/kg bw 4 additional females
No. of animals per sex per dose:
at 2000 mg/kg bw 1 female; at 300 mg/kg bw 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
mortality: twice daily (once in weekends)
clinical signs: 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days
bodyweight: day 0, 7 and 14
- Necropsy of survivors performed: yes
Statistics:
NA

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
1 female at 2000 mg/kg bw on day 1
Clinical signs:
none observed at 300 and 2000 mg/kg bw
at 2000 mg/kg bw: purple staining of urine
at 300 mg/kg bw: black/purple staining of faeces 4/5 females
Body weight:
at 2000 mg/kg bw: decreased by ca 10% within one day
at 300 mg/kg bw within normal ranges
Gross pathology:
at 2000 mg/kg bw: abnormally red lungs, dark liver, dark kidneys, dark purple coloured substance present in the stomach and purple colored staining of the small intestine
at 300 mg/kg bwno abnormalities observed

Applicant's summary and conclusion

Interpretation of results:
other: Category 4 based on CLP criteria
Conclusions:
The oral LD50 of the substance is between 300 and 2000 mg/kg bw
Executive summary:

In a fixed dose procedure female rats received a single dose of 2000 (1 female) and 300 mg/kg bw (5 females) by gavage. Rats were observed for 14 days thereafter. The female at 2000 mg/kg bw died within one day after dosing showing reduced body weight, purple staining of the urine and abnormally red lungs, dark liver, dark kidneys, dark purple coloured substance present in the stomach and purple colored staining of the small intestine. Females at 300 mg/kg did not show any effects on body weight, clinical signs and macroscopic investigations. The faeces of 4 of these females was purple stained. Based on these findings the oral LD50 of the substance is between 300 and 2000 mg/kg bw.