Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2005-11-28 to 2006-04-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Cross-reference
Reason / purpose for cross-reference:
reference to other 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
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
December 17, 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2004/73/EC
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sokalan PG B62

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Age at day 0: 8-12 weeks.
Acclimatization: 5 days.
Weight: 170-180 g.
Housing:
Animals were housed (single housing) in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 - 24°C for temperature and of 30 - 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study .
Supplier: Laboratory Animal Services, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
As suggested by the OECD guideline nulliparous and nonpregnant female animals were used for the test, because there
is no indication that male animals are likely to be more sensitive to the acute effects of the test substance.
Day / night rhythm : 12 h/ 12 h(6.00 a .m. - 6 .00 p.m. / 6.00 p.m. - 6 .00 a.m.)
Type of cage : Stainless steel wire mesh cages, type DK-III (Becker & Co ., Castrop-Rauxel, FRG)
Feeding: Kliba-Labordiät (Maus / Ratte Haltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
Drinking water: Tap water ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
Administration 1: 5000 mg/kg; 1 animal; Administration 2: 5000 mg/kg; 2 animals
Doses:
5000 mg/kg in 0.5% CMC (cleaned sodium carboxymethylcellulose)-solution (20 ml/kg; 25 g/100 ml)
No. of animals per sex per dose:
Administration 1: 1 female
Administration 2: 2 females
Control animals:
no
Details on study design:
Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
Time of day of administration : In the morning
Observation period : At least 14 days.
Body weight determination: Individual body weights shortly before administration (day 0) , weekly thereafter and at the end of the study.
Signs and symptoms: Recording of signs and symptoms several times on the day of
administration, at least once each workday for the individual animals ; these records are maintained with the raw data .
Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays .
Pathology: Necropsy with gross-pathology examination on the last day of the observation period after killing by C02-inhalation .
Statistics:
not applicable

Results and discussion

Preliminary study:
no preliminary study
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: unspecific and reversible clinical signs observed
Mortality:
No mortality occurred.
Clinical signs:
Clinical observation revealed impaired general state, dyspnoea and piloerection. Findings were observed from hour 1 until including hour 5 after administration.
Body weight:
The body weights increased throughout the study period.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals examined at the end of the observation period.

Any other information on results incl. tables

Individual weight of female animals (g)

Weightday

0

7

14

cage 432

170

192

213

cage 436

176

195

204

cage 437

183

203

217

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study, the median lethal dose (LD50) of 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate after oral administration was found to be greater than 5000 mg/kg body weight in rats.
Executive summary:

In an acute oral toxicity study, groups of fasted young Wistar rats (1 respectively 2 females) were given a single oral dose of 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate in CMC-solution at a limit dose of 5000 mg/kg bw and observed for 14 days.

Single doses of 5,000 mg/kg body weight of test material preparations in 0.5% CMC-solution in doubly distilled water were given to three fasted female animals (stepwise procedure starting with one animal and supplementing two additional animals).

No mortality occurred. Clinical observation revealed impaired general state, dyspnoea and piloerection . Findings were observed from hour 1 until including hour 5 after administration. The body weights increased throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the observation period.

Under the conditions of this study the median lethal dose of 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate after oral administration was found to be greater than 5000 mg/kg body weight in rats .