Registration Dossier

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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
435-030-7
EC Name:
-
Cas Number:
26452-81-3
Molecular formula:
C5H5N2OCl
IUPAC Name:
435-030-7
Test material form:
other: solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: Males: 354 - 418 g; Females 222 - 238 g
- Fasting period before study: overnight
- Housing: Max 5 rats per cage, sexes separately, in cages suitable for animals of this strain and the weight range expected during the course of the study.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: ≥5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): ≥15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg

Doses:
500 mg/kg
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 and weighing: Prior to the dosing, all rats were examined to ensure that they were physically normal and exhibited normal activity. The animals were observed for signs of systemic toxicity at least twice following dosing on day 1. Subsequent observations were made daily, up to day 15. The animals were weighed prior to fasting on the day before dosing (day 0), immediately before dosing (day 1) and on days 8 and 15.
- Necropsy of survivors performed: yes; macroscopic examination

Results and discussion

Preliminary study:
Following a dose of 2000 mg/kg in one female animal, the animal was killed in extremis approximately 5 hours after dosing on day 1. There were no macroscopic abnormalities at examination post mortem.
Following a dose of 500 mg/kg in one female animal, the animal showed signs of evident toxicity, with complete recovery by day 6.
Effect levels
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
500 mg/kg bw
Based on:
test mat.
Mortality:
Following a dose of 500 mg/kg, none of the animals died.
Clinical signs:
There were signs of evident toxicity in all animals. These signs included decreased activity, piloerection, (signs of) salivation, subdued behaviour and reduced breathing rate in all animals. Upward curvature of the spine was observed in all female animals and 2 of the male animals. In 3 out of 5 males and 3 out of 5 females, lacrymation was observed in both eyes. Miosis, sides pinched in and stained with urine were observed in 1 animal only. All animals had completely recovered by day 4.
Body weight:
All animals showed an initial weight loss due to the pre-dose fast. All the males and two of the females showed an overall weight gain during the study. Three females showed a slight overall weight loss.
Gross pathology:
There were no treatment-related findings at examination post mortem.
One male had red areas in the thymus. This is considered to be a spontaneous finding which is incidental to treatment.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The highest fixed dose of test substance administered in this test without causing any lethality (ie the discriminating dose-level), was 500 mg/kg to male and female rats.
Executive summary:

In this GLP compliant fixed dose oral toxicity study, performed according to OECD guideline 420, Alpk:APrSD (Wistar-derived) rats were administered the test substance by oral gavage followed by a 14 -day observation period. In a sighting phase, single female animals received a single oral dose of 2000 or 500 mg/kg of test substance and were assessed daily for 6 days for any signs of systemic toxicity. Following a dose of 2000 mg/kg, the animal was killed in extremis on day 1. Following a dose of 500 mg/kg, the animal showed signs of evident toxicity, with complete recovery by day 6. From the results of the sighting phase of the study, a single fixed dose level of 500 mg/kg was selected for the main phase of the study. A group of five male and five female rats was dosed once and assessed daily for 14 days for any signs of systemic toxicity. Their body weights were recorded at intervals throughout the study. At the end of the study all the animals were killed and subjected to a macroscopic examination. Following a dose of 500 mg/kg, none of the animals died. There were signs of evident toxicity in all animals, with complete recovery by day 4. All the males and two of the females showed an overall body weight gain during the study. Three females showed a slight overall weight loss. There were no treatment-related abnormalities at examination post mortem. In conclusion, the highest fixed dose of the test substance administered in this test without causing any lethality (i.e. the discriminating dose-level), was 500 mg/kg to male and female rats.