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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
- test substance was not administered by gavage but by feeding in a single dose for up to 6 hours and only 5 of six animals received the complete dose
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
- test substance was not administered by gavage but by feeding in a single dose for up to 6 hours and only 5 of six animals received the complete dose
GLP compliance:
yes (incl. certificate)
Remarks:
deviation: stability of the test substance in the formulation for administration was not determined. However, the test substance was formulated directly before administration.
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, Borchen, Germany
- Strain: HsdCpb:Wu
- Age at study initiation: approx. 10-12 weeks
- Weight at study initiation: 164-180 g
- Fasting period before study: 16-24 hours
- Housing: individual (for the period of administration); in groups (for 14-day observation period)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: feed
Details on oral exposure:
The individual dose for each animal was calculated on the base of the body weight at time of administration. To make the test compound flavorsome for the animals, the individual dose for each animal was carefully mixed with approximately 2 g chocolate hazelnut spread (Nutella®, Ferrero, 60624 Frankfurt, Germany).
For administration, food was withheld from the animals for approximately 16 - 24 h before administration of the test compound. The animals were feed again
approximately 2 h after the end of the period of administration. For the period of administration the animals were housed individually. The mixture was offered to the animals in stainless steel containers. Over the period of administration in 2 of 6 cases (animal no. 4 and 7) residuals of the test compound were mixed with additional chocolate hazelnut spread (approximately 1 g) and were offered to the animals again.
The period of administration did not exceed 6 hours. Residues were documented and judged: Only one animal (animal no. 8) did not consume the complete amount of test compound within the period of administration (Residue: 1 g oft he mixture).
Doses:
2000 mg/kg
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least once daily (clinical signs, mortality) or once weekly (weight gain)
- Necropsy of survivors performed: yes
Statistics:
Not specified.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LDLo
Effect level:
>= 2 000 mg/kg bw
Sex:
female
Dose descriptor:
other: LD50 cut-off
Effect level:
>= 5 000 mg/kg bw
Mortality:
All 6 animals survived the treatment.
Clinical signs:
No clinical signs were observed.
Body weight:
Body weight development was not affected.
Gross pathology:
No gross pathological findings were observed.

Other findings:
none

Applicant's summary and conclusion

Executive summary:

A single oral dose of 2000 mg /kg body weight was tolerated by female rats without mortalities, clinical signs, effects on weight gain and gross pathological findings. According to OECD guideline 423 the LD50 cut-off of the test material meeting the form described in Section 4.5 of the IUCLID dossier is > 5000 mg/kg bw for rats (Category 5 / unclassified of the Globally Harmonized Classification System).