Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2-22 June 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Yellow to brown, aromatic liquid
- Storage: At +10°C to +25°C under inert gas, kept in a tightly closed container and stored in a dry place, protected from heat and direct sunlight.

Test animals

Species:
rat
Strain:
other: Crl: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: No data
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 165-167 g
- Fasting period before study: 16 hours
- Housing: Individually in MAKROLON cages (type III plus) with granulated textured wood bedding material
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany); discontinued approximately 16 hours before administration
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2 June 2016 To: 22 June 2016

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1 g/mL
- Amount of vehicle (if gavage): 5 mL/kg bw
- Justification for choice of vehicle: Corn oil was chosen as vehicle as it is known not to produce toxic effects.
- Lot/batch no. (if required): MKBQ9948V, SIGMA ALDRICH Chemie GmbH, 82024 Taufkirchen, Germany
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw
Doses:
5000 mg/kg bw (limit dose)
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. During the follow-up period, changes of skin and fur, eyes and mucous membranes, respiratory and circulatory function, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: yes (macroscopic)
- Other examinations performed: No histopathology was carried out as no macroscopic findings were noted at necropsy.
Statistics:
No statistical analysis was performed.

Results and discussion

Preliminary study:
The LD50 was greater than 5000 mg/kg bw therefore no main test was carried out.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No statistical analysis needed
Mortality:
No animal died prematurely.
Clinical signs:
There were no clinical signs of toxicity.
Body weight:
All animals gained the expected body weight.
Gross pathology:
No pathological findings were noted at necropsy.
Other findings:
Not applicable

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an OECD guideline study, conducted to GLP, the acute oral LD50 of “Karstedt concentrate” was found to exceed 5000 mg/kg bw in female rats.
Executive summary:

The acute oral toxicity of “Karstedt concentrate” was assessed in female rats, in a study conducted according to OECD Test Guideline 425 and to GLP.

 

Initially, one female received a single (limit) dose of 5000 mg/kg bw by oral gavage. As the animal survived, the test item was administered to an additional two animals. No mortality or pathological changes were apparent at the limit dose following the 14-day observation period while growth was unaffected. The study authors conclude that the acute oral median lethal dose (LD50) of the test material in females rats exceeds 5000 mg/kg bw.

 

Based on the results of this study, “Karstedt concentrate” does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).