2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Protection against Acetaldehyde Toxicity in the Rat by L-Cysteine, Thiamin and L-2-Methylthiazolidine-4-carboxylic Acid

Author:

Sprince, H. et al.

Year:

1974

Bibliographic source:

Agents Actions. 4(2):125-130

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The oral LD50 values were obtained by the Litchfield-Wilcoxon method after oral intubation of the test substance in 15 male CFE albino rats using 8 dose levels ranging from 4 up to 16 mM/kg bw.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Thiamine hydrochloride

EC Number:

200-641-8

EC Name:

Thiamine hydrochloride

Cas Number:

67-03-8

Molecular formula:

C12H17N4OS.ClH.Cl

IUPAC Name:

3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium chloride hydrochloride

Test animals

Species:

rat

Strain:

other: CFE albino rat

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Carworth Farms
- Age at study initiation: 90 ± 5 days
- Weight at study initiation: 365 ± 20 g
- Fasting period before study: Animals were fasted overnight prior to administration.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

physiological saline

Details on oral exposure:

VEHICLE
- Amount of vehicle: 1 - 2.5 mL (total)

Doses:

4, 6, 8, 10, 11, 12,14 and 16 mM/kg bw

No. of animals per sex per dose:

15

Control animals:

yes

Details on study design:

The oral LD50 values were obtained by the Litchfield-Wilcoxon method.

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

3 710 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 3710 mg/kg bw, calculated from 11.0 mM/kg bw (according to Sprince et al., 1974)

Mortality:

Death occurred within 15 - 45 minutes after intubation from respiratory failure.

Clinical signs:

Marked tremors developed within 5 - 10 minutes, persisting for another 5 - 10 minutes and were followed by a characteristic jumping behavior for about 1 - 3 minutes. Soon thereafter, the animals became limp.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008

Conclusions:

CLP: not classified