Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2005-12-19 to 2006-12-05
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 402 (Acute Dermal Toxicity)
Version / remarks:
February 24, 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
92/69/EEC
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes
Test type:
standard acute 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:
male/female
Details on test animals or test system and environmental conditions:
Test animals: Rat / Wistar / HanRcc:WIST(SPF)
The female animals were nulliparous and non-pregnant
Age at day 0 : Male: 8 - 10 weeks; Female: 12 - 14 weeks.
Acclimatization: 5 days.
Body weight at day 0 : Male: 283 g; Female: 225 g.
Housing:
The 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.
Day-Night-Rhythm: 12 h/ 12 h (6.00 a .m. - 6.00 p .m. / 6.00 p.m. - 6.00 a .m.)
Drinking water: ad libitum.
Supplier: RCC Ltd Laboratory Animal Services, Wölferstrasse 4, CH- 4414 Füllinsdorf, Switzerland

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
CMC (carboxymethyl cellulose)
Details on dermal exposure:
Route of application:
Single application to the clipped epidermis (dorsal and dorsolateral parts of the trunk) ; covering of the application site with a semi-occlusive dressing (the bandage consists of four layers absorbent gauze (Ph. Eur. Lohmann GmbH & Co. KG) and Fixomull stretch (adhesive fleece, Beiersdorf AG)) for 24 hours, afterwards removal of the dressing . Rinsing of the application site with warm water.
Clipping of the fur: About 24 hours before the beginning of the study . Rinsing of the application site with warm water. Application area: 40cm2 (corresponds to at least 10% of the body surface).
Duration of exposure:
24 h
Doses:
5000 mg/kg in 0.5% CMC-solution
(Application amount: 10 g/kg; Concentration: 50 g/100 ml)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Observation period: At least 14 days.
Body weights determination: Individual body weights shortly before application (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 application, at least once each workday for the individual animals ; these records are maintained with the raw data.
Scoring of skin findings: Individual readings 30 - 60 minutes after removal of the semiocclusive dressing (day 1), as a rule weekly thereafter and at the end of the study (last day of the observation period).
Assessment of skin findings: According to Draize, J .H . (1959) : Appraisal of the safety of chemicals in foods, drugs and cosmetics . The association of food and drug officials of the United States Austin, Texas.
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 with C02.
Statistics:
The binomial test (Snedecor G .W ., Cochran W .G . (1989), Statistical methods, 8th ed ., Iowa State University Press/Ames) was used.

Results and discussion

Preliminary study:
No preliminary test.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Unspecific and reversible clinical signs were 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.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of a study according to OECD 402, the acute dermal median lethal dose (LD50) of 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate after dermal application was found to be greater than 5000 mg/kg body weight in male and female rats.
Executive summary:

In an acute dermal toxicity study according to OECD guideline 402, a single dose of 5000 mg/kg body weight of a test material preparation (purity: 92.4 weight-%; dose volume 10 g/kg bw) in 0.5% CMC-solution in doubly distilled water was applied in five male and five female animals to ca. 10% of the clipped skin (dorsal and dorsolateral parts of the trunk) and covered by a semi-occlusive dressing for 24 hours.

No mortality occurred. No systemic clinical observations or skin effects were noted in the animals. The mean body weights of the animals increased throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Under the conditions of this study, the acute dermal median lethal dose (LD50) of 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate after dermal application was found to be greater than 5000 mg/kg body weight in male and female rats.