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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
Study period:
Test start date: 06 December, 1989; Test end date: 27 December 1989; Study completion date: 21 February, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Reaction mass of 6-chloro-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium acetate and 6-bromo-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium acetate and 6-chloro-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium hydroxide
IUPAC Name:
Reaction mass of 6-chloro-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium acetate and 6-bromo-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium acetate and 6-chloro-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium hydroxide
Test material form:
solid
Specific details on test material used for the study:
- Substance identified as: FAT 31064/F
- Batch No.: EN 158496.82 / HEW 133/6
- Description: Powder
- Stability of test article: stable; expiration date: November 1994
- Stability of test article dilution: stable for at least 2 hours
- Safety Precautions: Gloves, goggles and face mask were sufficient to assure personnel health and safety.

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Han. (outbred, SPF-quality)
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: BRL, Biological Research Laboratories Ltd., Wolferstrasse 4, CH-4414 Füllinsdorf
- Initial body weight range: males: 196 - 199 g, females: 165 - 178 g
- Initial age: males: 9 weeks, females: 11 weeks

Husbandry:
Standard Laboratory Conditions.
Air-conditioned with 10-15 air changes per hour, and hourly monitored environment with temperature 22+/-3 °C, relative humidity 40-70 %, 12 hours artificial fluorescent light/12 hours dark, music/light period.
Diet: Pelleted standard Kliba 343, Batch 60/89 rat maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst) available ad libitum.
Water: Community tap water from Itingen.
Acclimatisation: One week under laboratory conditions, after veterinary examination.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Distilled
Details on oral exposure:
TEST ARTICLE PREPARATION
The test article was placed into a glass beaker on a tared Mettler PE 360 balance, and the vehicle, (bi-distilled water) was added. A weight by volume dilution was prepared using a homogenizer (Ultra-Turrax, Janke and Kunkel, D-7813 Staufen).
Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer (Janke and Kunkel, D-7813 Staufen). The preparation was made immediately prior to each dosing.

TREATMENT
The animals received a single dose of the test article on a mg/kg body weight base by oral gavage after being fasted for 12 to 18 hours (access to water was not interrupted). Food was again presented approximately three hours after dosing.
Application Volume/kg body weight: 10 mL at 2000 mg/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Mortality: Four times during test day 1, and daily during days 2 - 15.
- Body Weights: Test days 1 (pre-administration), 8 and 15.
- Clinical Signs: Each animal was examined for changes in appearance and behaviour four times during day 1, and daily during days 2-15. All abnormalities were recorded.
- Necropsies were performed by experienced prosectors. All animals were necropsied. The surviving animals were killed by intraperitoneal injection of sodium pentobarbitone.
Statistics:
The LOGIT-Model could not be applied to the observed rates of death. The toxicity was estimated without use of a statistical model.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
A female was found dead on day 6 after treatment.
Clinical signs:
other: The following systemic symptoms were observed: males - no systemic symptoms were observed. females - rales. The surviving female rats had recovered after 2 hours.
Gross pathology:
The following macroscopical organ changes were observed in the female found dead:
2000 mg/kg: dead - lungs: discoloration, dark red.
stomach: distended with gas.
liver: discoloration, black-brown.
sacrificed - no findings noted.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of FAT 31064/F was determined to be >2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test substance was evaluated in a study conducted according to OECD Guideline 401 and EU Method B.1. Wistar Han. (outbred, SPF-quality) rats were used for this experiment. A limit test was performed with the dose being 2000 mg/kg bw. A group of rats, containing 5 males and 5 females, was administered the test substance via oral gavage. A female was found dead on day 6 after treatment. No systemic symptoms were observed in treated males. Two out 5 females had rales. The surviving female recovered in 2 hours after treatment. No effect on body weight changes were seen. No deviations from normal morphology were seen in surviving animals at the necropsy. Based on these findings, the LD50 of the test substance was determined to be >2000 mg/kg bw.