2,4(1H,3H)-Pyrimidinedione, 1-(3,5-di-O-acetyl-2-deoxy-.beta.-L-erythro-pentofuranosyl)-5-methyl-

Endpoint summary

Description of key information

The oral LD50 value of LDT600 C3 in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7.5.2009 - 26.5.2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: 8 - 9 weeks
- Fasting period before study: Animals were fasted overnight prior dosing until 3 h after application of the test substance.
- Housing: Animals were housed in groups of 3 in Macrolon cages (MIV type) with sterilized saw dust as bedding material and paper as cage enrichment.
- Diet: SSNIFF SM R/M-Z pelleted rodent diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 21.3
- Humidity (%): 40 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 7.5.2009
To: 21.5.2009
From: 12.5.2009
To: 26.5.2009

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1% in aqueous solution

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 groups of 3 females each

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Animals were observed periodically on Day 1 and once daily thereafter. Body weights were recorded on Days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred until the end of the observation period.

Clinical signs:

other: Hunched posture was noted in all animals immediately after dosing on Day 1.

Gross pathology:

No abnormalities were found at macroscopic postmortem examination of the animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of LDT600 C3 in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

Due to all technical measures to prevent contamination the exposure of the personnel is unlikely.
The following control measures have been identified as suitable control measures:
- Dust extraction units and laminar flow ventilation for charging/dischatging
- HVAC operates in all areas
- Regular maintenance is carried out on all ventilation installations.
- Respiratory protection equipment and personal protective equipment is specified
Process Safety Training regarding the use of control measures and the actions to be taken in the event of control measure failure is performed by the Process manager at the start of the production campaign and on a three-monthly basis thereafter.

The personal protective measure may be adapted appropriately when working in closed systems:
Respiration : Dust mask (tested in line with EN 149), approved respirator or airhood.
Filter : Combination filter
Eye : Wear approved safety glasses or visor
Hand : All KCL chemical protective gloves used on-site provide >8 hours protection
Additional protection : Wear chemical protective suit tested in line with EN 369/374-3

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because skin contact in production and/or use is not likely

Justification for type of information:

Due to all technical measures to prevent contamination the exposure of the personnel is unlikely.
The following control measures have been identified as suitable control measures:
- Dust extraction units and laminar flow ventilation for charging/dischatging
- HVAC operates in all areas
- Regular maintenance is carried out on all ventilation installations.
- Respiratory protection equipment and personal protective equipment is specified
Process Safety Training regarding the use of control measures and the actions to be taken in the event of control measure failure is performed by the Process manager at the start of the production campaign and on a three-monthly basis thereafter.

The personal protective measure may be adapted appropriately when working in closed systems:
Respiration : Dust mask (tested in line with EN 149), approved respirator or airhood.
Filter : Combination filter
Eye : Wear approved safety glasses or visor
Hand : All KCL chemical protective gloves used on-site provide >8 hours protection
Additional protection : Wear chemical protective suit tested in line with EN 369/374-3

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Due to all technical measures to prevent contamination the exposure of the personnel is unlikely.

The following control measures have been identified as suitable control measures:

- Dust extraction units and laminar flow ventilation for charging/dischatging

- HVAC operates in all areas

- Regular maintenance is carried out on all ventilation installations.

- Respiratory protection equipment and personal protective equipment is specified

Process Safety Training regarding the use of control measures and the actions to be taken in the event of control measure failure is performed by the Process manager at the start of the production campaign and on a three-monthly basis thereafter.

The personal protective measure may be adapted appropriately when working in closed systems:

Respiration : Dust mask (tested in line with EN 149), approved respirator or airhood.

Filter : Combination filter

Eye : Wear approved safety glasses or visor

Hand : All KCL chemical protective gloves used on-site provide >8 hours protection

Additional protection : Wear chemical protective suit tested in line with EN 369/374-3