Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to OECD guideline and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): trans-tilidin Oxalat, Erstabtrennung
- Test substance No: 10/0345-1
- Homogeneity: The test substance was homogenous by visual inspection.
- Analytical purity: > 99.5%
- Purity test date: > 99.5%
- batch No.: LV 8/10
- physical state/colour: solid / white
- Storage conditions: room temperature
- Storage stabilityl: The stability under storage conditions over the study period was guarenteed by the sponsor, and the sponsor
holds this responsibility.
- Other: pH-value: ca. 3 (undiluted test substance, moistened with water)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany.
- Age at study initiation: young adult animals (female animals approx. 9-11 weeks)
- Weight at study initiation: 190 - 198 g
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diet Services, 67122 Altrip, Germany
- Water (e.g. ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
300 mg/kg bw: 6 females
2000 mg/kg bw: 3 females
Control animals:
no

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Mortality:
All animals of the 300 mg/kg bw dose group survived.
All animals of the 2000 mg/kg bw dose group died.
Clinical signs:
Clinical observation in the 2000 mg/kg bw test group revealed impaired and poor general state, dyspnoea, staggering, abdominal position, ataxia, twitching, chromodacryorrhea, exophthalmos, flat respiration, high stepping gait and salivation from hour 0 up to hour 5 after administration.

In the first 300 mg/kg bw test group impaired general state, dyspnoea, staggering and exophthalmos were observed from hour 1 up to day1 in all three animals at the latest. Furthermore, piloerection, exsiccosis and reduced feces were observed in one animal at study day 1 after administration.

In the second 300 mg/kg bw test group impaired and poor general state, dyspnoea, ataxia, staggering, abdominal position, exophthalmos, piloerection, reduced feces, exsiccosis and salivation was observed from hour 0 until study day 2 at the latest.
Body weight:
The mean body weight of the surviving animals increased throughout the study period within the normal range.
Gross pathology:
At necropsy two animals that died in the 2000 mg/kg bw test group showed dark red spotted discoloration in all lobes of the lung. Two animals showed gaseous stomach, filled with liquid content and two animals were found to have red discoloration of content in the small intestine and red discoloration of the small intestine. There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
moderately toxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of this study the mean lethal dose of trans-tilidin-Oxalat, Erstabtrennung after oral administration was found to be greater than 300 mg/kg bw and less than 2000 mg/kg bw in rats.

Based on the results of this study, the test substance trans-tilidin-Oxalat, Erstabtrennung has to be classified Acute Tox Cat 4 (Directive 1272/2008 of CLP) and R22 (67/548/EWG).