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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:
From 14 september 1992 to 7 october 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: white powder
- Storage condition of test material: room temperature under silica gel

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, U.K.
- Age at study initiation: five to eight weeks old
- Weight at study initiation: males weighed 130-161 g, females weighed 125-146 g
- Fasting period before study: an overnight fasting immediately before dosing and for approximately two hours after dosing
- Housing: 5 by sex in solid-floor polypropylene cages with sawdust bedding
- Diet : ad libitum, rat and mouse expended diet No. 1, special Diet services Limited, Witham, essex, U.K.)
- Water : ad libitum
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-20
- Humidity (%): 46-67
- Air changes (per hr): 15
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 14 september 1992 To: 7 October 1992

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: no data







Doses:
5000 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: The animals were observed for death or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to dosing on Day 0 and on days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
No statistics were performed.

Results and discussion

Preliminary study:
1 animal/sex was tested at 5000 mg/kg bw. The female was found dead one day after dosing. Signs of systemic toxicity noted in the female were hunched posture, lethargy, decreased respiratory rate, ptosis and ataxia. Based on this information, a dose level of 5000 mg/kg bw was selected for the main study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed expected gain in body weight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
No data

Any other information on results incl. tables

 Table 7.2.1/2: Number of animals dead

 

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity(#/total)

Male

Female

Combined

Male

Female

Combined

5000

 0

 0

 0

 -

 0

 0

 0

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this test, the acute oral median lethal dose (LD50) of ITC 288/S was found to be greater than 5000 mg/kg body weight in the Sprague-dawley strain rat. Therefore no classification is required according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC).
Executive summary:

In an acute oral toxicity study (Tuffnell PP, 1992) a group of ten fasted animals (five males and five females) was given a single oral dose of the test material, as a solution in distilled water at dose level of 5000 mg/kg bodyweight. The animals were observed for 14 days after the day of dosing and were then killed for gross pathological examination. There were no deaths. No signs of systemic toxicity were noted during the study. Moreover, all animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy. Under the conditions of this test, the LD50 combined of ITC 288/S was found to be greater than 5000 mg/kg body weight. Based on the present results in males and females, ITC 288/S is not classified according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC).

This acute oral study is classified as acceptable. It satifies the guideline requirement for an acute oral study in the rats.