Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08-03-2017 to 29-03-2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
17 Dec 2001
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan:WIST
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS Limited, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 163 - 185g (main study)
- Fasting period before study: overnight fast immediately before and approx. 3 -4 hours after dosing
- Housing: in groups of up to four in suspended solid-floor polypropylene cages with woodflakes
- Diet: free access to food (2014C Teklad Global Rodent diet)
- Water: free access to main drinking water
- Acclimation period: at least 5 days

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Doses:
300 mg/kg
2000 mg/kg
No. of animals per sex per dose:
2000 mg/kg: 1 animal (sighting study)
300 mg/kg: 1 animal (sighting study)
300 mg/kg: 5 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Morbidity and mortality checks twice daily, once daily at weekend and public holidays; weighing on days 0, 7 and 14 d or at death
- Necropsy of survivors performed: yes
- Clinical observations: 30 min, 1, 2, 4 h afer dosing, then daily up to 14 d

Results and discussion

Preliminary study:
Sighting study: In the absence of toxicity at a dose level of 300 mg/kg tested in one animal, an additional animal was treated with 2000 mg/kg. At this dose level, the signs of systemic toxicity noted were hunched posture, lethargy, noisy and labored respiration, pilo-erection and dehydration. The tested animal was killed for humane reasons, 1 day after dosing.
Due to mortality and signs of systemic toxicity in the "main test" a group of five animals was tested with 300 mg/kg.

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Dose level - 2000 mg/kg (sighting study): the animal was killed 1 day after dosing, due to the occurrence of clinical signs of toxicity that were considered likely to exceed the severity limit.
Dose level - 300 mg/kg: no death
Clinical signs:
Dose level - 2000 mg/kg (sighting study): Signs of systemic toxicity noted were hunched posture, lethargy, noisy and labored restiration, pilo-erection and dehydration
Dose level - 300 mg/kg: No signs of systemic toxicity noted during the observation period.
Body weight:
Dose level - 2000 mg/kg (sighting study): at 0d: 185g; at Death: 164g
Dose level - 300 mg/kg: at 0d (mean): 170g; at 14d (mean): 187g; Animals showed expected gains in body weight over the observation period except for one animal, which showed expected gain in body weight during the first week but body weight loss during the second week.
Gross pathology:
Necropsy:
Dose level - 2000 mg/kg (sighting study): Gaseous stomach and test item present in the stomach
Dose level - 300 mg/kg: No abnormalities

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (CLP - Category 4).
Executive summary:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (CLP - Category 4).