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Description of key information

Two studies have been conducted to assess the oral toxicity of the test substance: Dosing by gavage of the test substance, suspended in water for irrigation, to groups of 10 male and female mice to determine toxic effects from oral exposure to the substance, showed no toxicity up to a dosage of 1000 mg/kg body weight. Further testing in a group of 10 female mice demonstrated that the test substance has a very low order of acute oral toxicity, with a LD50 value in excess of 5 g/kg. No reaction to treatment or macroscopic damage to tissue were observed at that dose level.

A single study was conducted where dermal exposure of rats to the test substance at a concentration of 3400mg/kg did not result in apparent toxicity or skin irritation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
No guideline was specified. Dosing by gavage of the test substance, suspended in water for irrigation, to groups of 10 male and female mice to determine toxic effects from oral exposure to the substance.
GLP compliance:
no
Limit test:
yes
Species:
mouse
Strain:
other: CRH (Glaxo Group Research Limited, Harefield Breeding Unit)
Sex:
male/female
Details on test animals and environmental conditions:
Weight range: 16-20g.
Not starved prior to treatment
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Irrigation water
Details on oral exposure:
Material was formulated as a suspension in Water for Irrigation, using a Silverson blender, and dosed by gavage at a dose volume of 1ml/20g, to groups of 10 male and 10 female mice.
Doses:
1ml suspension / 20 g of animal
1000 mg/kg
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
Observation period: 14 days
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No animals died due to ingestion of the test material.
Clinical signs:
Nothing abnormal detected
Body weight:
Nothing abnormal detected
Gross pathology:
No significant lesions were seen at autopsy although Kidneys of 5 males and 6 females were slightly pale. These tissues were submitted for histopathological examination and were found to be microscopically normal.
Interpretation of results:
study cannot be used for classification
Conclusions:
'Trityl DMF solvate' has a low order of acute oral toxicity in mice with an LD50 value in excess of 1000 mg/kg. No signs of toxicity were seen at that dose level.
Executive summary:

Dosing by gavage of the test substance, suspended in water for irrigation, to groups of 10 male and female mice to determine toxic effects from oral exposure to the substance, showed no toxicity up to a dosage of 1000 mg/kg body weight.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
No test guideline was mentioned in the study report. Material was formulated as a suspension in deionised water, using a Silverson blender, and dosed by gavage at a dose volume of 1ml/20g, to groups of 10 mice.
GLP compliance:
no
Specific details on test material used for the study:
Material was supplied by Dr PA Wilkinson (Greenford) and was stored at 4C before use. Material is intermediate in the synthesis of ceftazidine.
Species:
mouse
Strain:
other: CRH (Glaxo Group Research breeding unit, Harefield)
Sex:
female
Details on test animals and environmental conditions:
weight range: 16-20g
Not starved before treatment
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionised water
Details on oral exposure:
Material was formulated as 10% w/v suspension in deionised water and dosed by gavage.
Doses:
1ml / 20g
No. of animals per sex per dose:
10 female
Control animals:
not specified
Details on study design:
Observation period of 7 days
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mice were found dead
Clinical signs:
No signs of toxicity were observed in the test animals
Body weight:
No effects mentioned
Gross pathology:
All mice were killed at the end of the observation period and examined macroscopically. All tissues appeared normal and none were submitted to histopathological examination.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance has a very low order of acute oral toxicity to female mice with LD50 value in excess of 5 g/kg. No reaction to treatment or macroscopic damage to tissue were observed at that dose level.
Executive summary:

Dosing by gavage of the test substance, suspended in water for irrigation, to groups of 10 mice to determine toxic effects from oral exposure to the substance, showed no toxicity at a dosage of 5000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May-June 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
No guideline is mentioned in the study report. Percutaneous administration of 1 g substance per rat took place.
The rats were tested in accordance with the method used in an older documented report (internal report number 77TM7 of 28 January 1977)
GLP compliance:
no
Remarks:
The study was conducted prior to the requirement for GLP for such studies
Test type:
other: Percutaneous administration of 1 g substance per rat took place.
Limit test:
yes
Specific details on test material used for the study:
The material was supplied by Dr P.A. Wilkinson (Greenford) and was stored at 4C before use. It is an intermediate in the synthesis of ceftazidime.
Species:
rat
Strain:
Sprague-Dawley
Remarks:
(SDG)
Sex:
male
Details on test animals and environmental conditions:
Male SDG rats weighing 290 to 292 were used. They were obtained from the Glaxo Group Research Ltd., breeding unit (Harefield). The rats were housed singly.
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Duration of exposure:
7 day observation period
Doses:
A dose of 1 g/rat was used throughout. (3.4 g/kg body weight)
No. of animals per sex per dose:
3
Control animals:
no
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 3 400 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred
Clinical signs:
No signs of local or systemic effects toxity were shown.
Body weight:
Not specified
Gross pathology:
Not specified
Other findings:
No irritation (erythema or oedema) was observed
Interpretation of results:
GHS criteria not met
Conclusions:
"**1132/4 DMF" has a low order of percutaneous toxicity in the rat with values greater than 3.4 g/kg bw.
Executive summary:

Three male SDGrats were percutaneously exposed to 1 kg/rat of 1132/4 DMF to determine acute toxicity and irritation through the dermal route. There were no mortalities and no local or systemic toxicity was observed. Finally, the substance was not found to be irritant to skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
3 400 mg/kg bw

Additional information

Justification for classification or non-classification

The substance has been tested in mice by oral gavage at 1000 and 5000 mg/kg bw, no toxicity was observed. Additionally, percutaneous testing with the substance in rats established that the LD50 exceeds 3400 mg/kg bw, with no apparent toxicity or irritation resulting from the exposure. From the results above, it can be predicted that inhalation exposure of test animals would not result in toxicity by that route upto the limit dose of 5mg/ L/4 hours.

Accordingly, the classification criteria for acute toxicity according to 1272/2008/EC are not met.