Adenosine 5'-(trihydrogen diphosphate), 2'-(dihydrogen phosphate), 5'→5'-ester with 3-(aminocarbonyl)-1-β-d-ribofuranosylpyridinium hydroxide, inner salt, disodium salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: test report performed under GLP and according to OECD guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Adenosine 5'-(trihydrogen diphosphate), 2'-(dihydrogen phosphate), 5'→5'-ester with 3-(aminocarbonyl)-1-β-d-ribofuranosylpyridinium hydroxide, inner salt, disodium salt

EC Number:

246-129-8

EC Name:

Adenosine 5'-(trihydrogen diphosphate), 2'-(dihydrogen phosphate), 5'→5'-ester with 3-(aminocarbonyl)-1-β-d-ribofuranosylpyridinium hydroxide, inner salt, disodium salt

Cas Number:

24292-60-2

Molecular formula:

C21H28N7O17P3.2Na

IUPAC Name:

Adenosine 5'-(trihydrogen diphosphate), 2'-(dihydrogen phosphate), 5'→5'-ester with 3-(aminocarbonyl)-1-β-d-ribofuranosylpyridinium hydroxide, inner salt, disodium salt

Details on test material:

- Physical state: white powder
- Analytical purity: 98%
- Storage condition of test material: in refrigerator (2-8°C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 9 - 10 weeks old
- Housing: 3 animals per cage
- Diet (e.g. ad libitum): ad libitium
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days before start of treatment nuder laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0°C
- Humidity (%): 40 - 70 %
- Air changes (per hr): 15 per hr
- Photoperiod : 12 hrs dark/12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Dose level (volume): 2000 mg/kg (10 mL/kg) body weight

Doses:

Single dose: 2000 mg/kg b.w.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the
guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the
dose groups.
Observations:
Mortality/Viability Twice daily.

Body weights Days 1 (pre-administration), 8 and 15).

Clinical signs At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).

Necropsy At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
Descriptions of all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality occurred

Clinical signs:

other: hunched poster was observed for three females on Day 1

Gross pathology:

No macroscopic abnormalities were noted

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of b-NADP, Disodium salt 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.

Based on these results, b-NADP, Disodium salt does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

Executive summary:

Assessment of acute oral toxicity with b-NADP, Disodium salt in the rat (Acute Toxic Class Method).

 The study was carried out based on the guidelines described in: OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method" 

b-NADP, Disodium salt was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). 

No mortality occurred.

 Hunched posture was observed for three females on Day 1.

 The body weight gain shown by the animals over the study period was considered to be normal.

 No macroscopic abnormalities were noted.

  The oral LD50value of b-NADP, Disodium salt in Wistar rats was established to exceed 2000 mg/kg body weight.