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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from supporting substance. Similar to OECD guideline 420, but main study should have followed up non toxic dose of 50 mg/kg with test at 300 mg/kg.
Justification for type of information:
See attached justification document
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
see attached justification document
Reason / purpose:
read-across source
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
yes
Remarks:
Non toxic dose of 50 mg/kg should be followed by test at 300 mg/kg
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
other: Liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Zeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, UK
- Age at study initiation: young adults
- Weight at study initiation: 202-247 g(m) 191-211 (f)
- Fasting period before study: up to 24 hours
- Housing: 5 rats per cage, separate sexes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 55 +/- 15
- Air changes (per hr): 25-30
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: not available (July-August 1995)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Deionised Water
Doses:
Preliminary study: 50, 200, 500 mg/kg (corrected for water content of 26.1%)
Main study: 50 mg/kg (corrected for water content of 26.1%)
No. of animals per sex per dose:
Preliminary sighting study: 3 (female)
Main study: 5 (male)
Main study: 5 (female)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 3 times during fist 24 hours, then once or twice daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Preliminary study:
Species/strain: Rat (Wistar)
200 mg/kg bw: Evident toxicity: No; Mortality: No
500 mg/kg. Mortality: Yes, day 2
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
50 mg/kg bw
Based on:
other: test substance corrected for water content of 26.1%
Sex:
male/female
Dose descriptor:
LD0
Effect level:
200 mg/kg bw
Based on:
other: test substance corrected for water content of 26.1%
Mortality:
Preliminary study: 500 mg/kg: 1/1 (f)
Main study: 50 mg/kg: 1/10 (f) but not conidered due to treatment.
Clinical signs:
Signs of toxicity:
There were no signs of evident toxicity at any time point.
Body weight:
No effect.
Gross pathology:
Effects on organs:
No treatment-related macroscopic findings were observed.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The minimum lethal dose of the test substance was 500 mg/kg. The test substance is considered Acute category 4 (harmful) according to the criteria of EC Reg. 1272/2008.
Executive summary:

ITC 826 concentrate was tested for acute oral toxicity using the fixed dose procedure. In a preliminary study, single animals received a single oral dose of 50, 200 or 500 mg/kg (corrected for water content) and were assessed daily for signs of systemic toxicity. There was no mortality or clinical signs at 50 mg/kg. No mortality and slight clinical signs were observed at 200 mg/kg. The female dosed at 500 mg/kg was found dead on day 2.

A single fixed dose level of 50 mg/kg was selected for the main study. A group of 5 males and 5 females was dosed. Animals surviving to the end of the study were killed. All animals were subjected to a macroscopic post-mortem examination.

here were no signs of evedent toxicity at 50 mg/kg. One femal rat was found dead on day 5 but this mortality was considered incidental to treatment since no clinical abnormalities were present in this animal prior to death.

The discriminating dose level was 50 mg/kg. The minimum lethal dose was 500 mg/kg..