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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: study done under GLP and acc. 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 (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Nadide
EC Number:
200-184-4
EC Name:
Nadide
Cas Number:
53-84-9
Molecular formula:
C21H27N7O14P2
IUPAC Name:
nadide
Details on test material:

- Physical state: off-white crystalline powder
- 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: 8-9 weeks old
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: 5 Days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 ml/kg) body weight
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: days 1 (pre-administration, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Dy 15.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
Hunched posture was observed for three females on Day 1.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the
same age and strain.
Gross pathology:
Dark red or red brown foci on the kidneys were noted for two females.

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-Nicotinamide-adenine Dinucleotide II (nadide) 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-Nicotinamide-adenine Dinucleotide II (nadide) 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:

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

nadide 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.

Dark red or red brown foci on the kidneys were noted for two females.

The oral LD50value of nadide 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-Nicotinamide-adenine Dinucleotide II (nadide) does not have to be classified and has no obligatory labelling requirement for acute oral toxicity.