Registration Dossier

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other: GLP compliant guideline study, available as unpublished report. No restrictions, fully adequate for assessment

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994
Reference Type:
other: Amendment to the report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Qualifier:
according to
Guideline:
other: Acute Toxic Class Method (ATC Method) by E. Schlede, U. Mischke, R. Roll, D. Kayser: A National Validation Study of the Acute-Toxic-Class Method - An Alternative to the LD50 Test. Arch. Toxicol. 66: 455-470 (1992).
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): Asta-C9-Diol-Natrium
- Physical state/appearance: liquid, red-brown
- Storage conditions: Refrigerator, exclusion of light.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: DR. K. Thomae GMBH, Biberach, FRG
- Age at study initiation: young adult animals
- Weight at study initiation: 150g - 300g (+- 20 % of the mean weight).
- Fasting period before study: at least 16 hours
- Housing: Single housing in stainless steel wire mesh cages, type DK-III (Becker & co., Castrop-Rauxel, FRG). No bedding in the cages.
- Diet: Kliba-Labordiaet 343, Klingentalmuehle AG, Kaiseraugst, Switzerland, ad libitum.
- Water: Tap water ad libitum
- Acclimation period: At least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): Fully airconditioned rooms
- Photoperiod (hrs dark / hrs light): 12 / 12 ( 6.00 a.m. - 6.00p.m. / 6.00 p.m. - 6.00 a.m.)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 gram per 100 mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Aqueous formulation corresponds to the physiological medium
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Bodyweight determination: Individual body weights shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period).
- Recording of signs and symptoms: Several times on the day of administration, at least once each workday for the individual animals
- General observation and mortality: Twice each workday and once on Saterdays, Sundays and on public holidays for general observations and for any dead or moribound animals.
- Necropsy of survivors performed: yes, at the last day of the observation period. Withdrawal of food at least 16 hours before killing withe CO2; then necropsy with gross pathology examination. Necropsy of all animals that died before as early as possible.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
Male animals: In all animals discoloured urine (orange) was observed on day 1
Female animals: All animals showed Impaired general state (H0 - H4), Dyspnoea (H0 - H4) and Piloerection (H1- H4). One animal showed signs of staggering (H0 - H3) and two animals showe signs of twitching (H0). H= hour
Body weight:
- Male animals: Mean bodyweight before application was 180 gram, after 7 days 248 gram and after 13 days 283 gram.
- Female animals: Mean bodyweight before application was 179 gram, after 7 days 212 gram and after 13 days 217 gram.
Gross pathology:
No pathologic findings noted

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
Under the conditions of this study the oral LD50 in male and female Wistar rats is above 2000 mg/kg bw.
Executive summary:

In a GLP compliant study performed according to EU method B.1, and modified according to the acute toxic class method, three Wister rats per sex were given a single oral dose of test material preparation in aqua bidest. at a dose level of 2000 mg/kg body weight. Signs of reaction to treatment noted in the female animals comprised impaired general state, dyspnea, staggering and twitching. In the male animals only orange discolored urine could be observed. The female animals appeared normal 1 day after application The expected body weight gain has been observed in the course of the study. No mortality occurred. No abnormalities were noted at necropsy of animals sacrificed at the end of the study (14 days). Under the conditions of this study the range of mortality after oral application was found to be greater than 2000 mg/kg body weight for male and female animals.