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Diss Factsheets

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: well-documented GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
other: directive 84/449/EEC
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl 1,3,3-trimethyl-2-methylidene-2,3-dihydro-1H-indole-5-carboxylate
EC Number:
700-424-2
Cas Number:
6872-10-2
Molecular formula:
C14 H17 N O2
IUPAC Name:
Methyl 1,3,3-trimethyl-2-methylidene-2,3-dihydro-1H-indole-5-carboxylate
Details on test material:
- Name of test material (as cited in study report): Carboxytrimethylbase, roh, feucht
- Lot/batch No.: Pt. 1 H
- Appearance: black powder (solid)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Borchen, Germany
- Strain: Bor: WISW (SPF Cpb)
- Age at study initiation: males approx. 8 and females approx. 10 weeks
- Weight at study initiation: mean weight for males 177 g, mean weight for females 171 g
- Fasting period before study: approx. 16 hours
- Housing: in groups (5 animals per Makrolon type III cage)
- Diet and water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 50 +/- 10%
- Air changes (per hr): 10 times
- Photoperiod (hrs dark / hrs light): 12 hrs light/ 12 hrs dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE: polyethylene glycol 400
- Application volume:10 ml/kg bw
- test substance formulation was prepared immediately before administration
Doses:
for males: 1000, 2000, 3100, 5000 mg/kg bw
for females: 1000, 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: 14 days
- Frequency of observations: On day of administration several times, thereafter 2 times per day (exception: on week-end once per day)
- Frequncy of weighing: Before administration and after 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
LD50 was determined computer-assisted according to the method of Rosiello (J. Tox. Environ. Health, 3, 1977, 797), modified by Pauluhn (report no. 11835, Bayer AG, 1983). This procedure is based on the Maximum-Likelihood-Method according to Bliss (J. Pharm. Pharmacol., 11, 1938, 192).

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
3 168 mg/kg bw
95% CL:
2 549 - 3 940
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Number of deaths at each dose/number of animals in dose group (time of deaths)
Male rats: 1000 mg/kg 0/5; 2000 mg/kg 1/5 (day 1); 3100 mg/kg 1/5 (day 1); 4000 mg/kg 4/5 (day 1); 5000 mg/kg 5/5 (day 1).
Female rats: 1000 mg/kg 0/5; 2000 mg/kg (0/5)
Clinical signs:
Clinical signs occurred approx. 1 hour after administration and were low to medium pronounced. All symptoms were resolved at least on Day 3 after administration.
Male rats:
- dose groups 2000 to 5000 mg/kg: poor general condition and sedation; dose group 3100 mg/kg: increased diuresis; dose groups 3100 and 4000 mg/kg: tremor; dose groups 3100 to 5000 mg/kg: abdominal position and piloerection; dose group 5000 mg/kg: bloody eye surroundings, bloody snouts. For one male of dose group 2000 mg/kg and all males of dose group 5000 mg/kg clonical cramps were observed.
Female rats:
- dose group 2000 mg/kg: poor general condition, piloerection, sedation
No symptoms were observed for males or females of dose group 1000 mg/kg.
Body weight:
Female rats of dose group 2000 mg/kg showed a marginally reduced body weight gain in the 1st and 2nd week.
Gross pathology:
Gross pathology of the male rats found dead: flattening of gastric mucosa, gastro-intestinal tract partially bloated and reddened or discoloured (violet-orange or violet), lungs strongly reddened, caecum hardened. For one animal of dose group 3100 mg/kg parts of the liver showed pale regions.
All animals sacrificed after the end of the study were found unobtrusive at necropsy.

Applicant's summary and conclusion

Executive summary:

A rat study according to directive 84/449/EEC (fulfilling OECD TG 401) was conducted under GLP with 5 animals per dose and with dose groups 1000, 2000, 3100 and 5000 mg/kg for males and 1000 and 2000 mg/kg for females.

Clinical signs (poor general condition, sedation, piloerection; for male rats also: increased diuresis, tremor, abdominal position, bloody snouts and eye surroundings; for one male clonical cramps) occurred approx. 1 hour after administration and were low to medium pronounced. All symptoms were resolved at least on Day 3 after administration. No clinical signs were observed for males or females of dose group 1000 mg/kg. Body weight gain was marginally reduced in the 1st and 2nd week post administration for females of dose group 2000 mg/kg. At necropsy the most prominent effects for rats found dead (only males) were observed in the gastro-intestinal tract (flattening of gastric mucosa, gastro-intestinal tract partially bloated and reddened or discoloured, caecum hardened). Also effects on lungs and for one animal on the liver were observed. Gross pathology was unobtrusive for all animals sacrificed at the end of the postobservation period.

The LC50 was 3168 mg/kg for male rats and > 2000 mg/kg for female rats.