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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017-11-30 to 2017-12-28
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:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001-12-17
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2015-06-05
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- State of aggregation: solid
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: dry, < 30°C

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-10 weeks

- Weight at study initiation: 158 - 177 g
- Fasting period before study: Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted).
- Housing: animals were kept in groups of three animals in IVC cages, type III H, polysulphone cages; bedding material: Altromin saw fibre bedding
- Diet (ad libitum, for exception refer to "fasting period before study" above): Altromin 1324 maintenance diet for rats and mice (Altromin Spezialfutter GmbH & Co. KG, Im Seelenkamp 20, 32791 Lage, Germany)
- Water (ad libitum): tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least 5 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C ± 3 °C
- Humidity: 55 ± 10%
- Air changes: 10x/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Source: Sigma-Aldrich Chemie GmbH, Riedstrasse 2, 89555 Steinheim, Germany
- Justification for choice of vehicle: this vehicle was chosen due to its non-toxic characteristics.
- Lot no.: MKCC0462
- Expiry date: 2018-01-31
Doses:
Starting dose (step 1): 300 mg/kg bw
Step 2: 2000 mg/kg bw
Step 3: 300 mg/kg bw
No. of animals per sex per dose:
9 female rats (3 animals/step)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
- Necropsy of survivors performed: yes, all animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. The animals which had to be sacrificed for ethical reasons or died spontaneously during the observation period were necropsied as soon as they were killed.
Statistics:
No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Results and discussion

Preliminary study:
not applicable
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
300 mg /kg bw: no animals died
2000 mg/kg bw: all animals died prematurely
Clinical signs:
300 mg/kg bw
after 0-30 min: slightly reduced spontaneous activity, prone position, slight ataxia, moderate piloerection, moving the bedding
after 30-60 min: prone position, moderate ataxia, moderate piloerection, moving the bedding, hunched posture, moderately reduced spontaneous activity, sunken flanks, slow movements
after 60-120 min: slightly reduced spontaneous activity, hunched posture, moderate piloerection, half eyelid-closure, slow movements, prone position, moderate ataxia, moderately reduced spontaneous activity, severely reduced spontaneous activity, sunken flanks
after 120-180 min: slight ataxia, moderate piloerection, moderately reduced spontaneous activity, half eyelid-closure, slightly reduced spontaneous activity, hunched posture
after 240 min-2d: slight ataxia, slight piloerection, slightly reduced spontaneous activity

2000 mg/kg bw
after 0-30 min: slightly reduced spontaneous activity, slight piloerection, hunched posture, prone position
after 30-60 min: severely reduced spontaneous activity, prone position, moderate ataxia, moderate piloerection, hunched posture, sunken flanks, half eyelid-closure
after 60-120 min: moderately reduced spontaneous activity, moderate ataxia, moderate piloerection, hunched posture
after 120-240 min: slightly reduced spontaneous activity, hunched posture, moderate piloerection, slight diarrhoea, slight ataxia
after 120-180 min: moderately reduced spontaneous activity, slight, moderate piloerection, hunched posture, moderate diarrhoea, moving the bedding, slight ataxia, prone position
after 240 min-2d: slightly reduced spontaneous activity, moderate ataxia, slight/moderate piloerection, slight/moderate diarrhoea, hunched posture, slow movements

Body weight:
All animals gained the expected body weight.
Gross pathology:
No specific gross pathological changes were recorded for any animal.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LD50 value: 300 < LD50 ≤ 2000 mg/ kg bw
According to the Regulation (EC) NO 1272/2008 and subsequent adaptations, the substance is classified as acute toxic via the oral route (Cat.4; H302).