Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 208-536-9 | CAS number: 532-40-1
Oral, male rats: LD50 = 3710 mg/kg bw (RA CAS 67-03-8)
Justification for read-across
There are no reliable data available regarding acute toxicity for 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-1,3-thiazol-3-ium chloride (CAS 532-40-1). Read-across from an appropriate substance Thiamine, hydrochloride (CAS 67-03-8) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.5. Common functional groups, structural similarities and comparable toxicological properties (according to the joint consideration in Annex VI to CLP) of the source and target substance are the basis of read-across. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).
Acute oral toxicity
Acute toxicity of thiamine hydrochloride was tested in male CFE albino rats (Sprince et al., 1974).In this study several doses of 4, 6, 8, 10, 11, 12, 14 and 16 mM/kg bw were tested in 15 animals per dose. 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. Based on the results of this study a LD50 value of 11 mM/kg bw corresponding to 3701 mg/kg bw was derived.
Haley et al. (1948) investigated the source substances thiamine hydrochloride and thiamine mononitrate on its potential to exhibit toxicity after intravenous and intraperitoneal administration in mice, respectively. The determined LD50 values in mice were 329.8 mg/kg bw intraperitoneal for thiamine hydrochloride, and 387.3 mg/kg bw intraperitoneal and 84.24 mg/kg bw intravenous for thiamine mononitrate, respectively. In rabbits the intravenous lethal dose was determined to be 112.58 mg/kg bw for thiamine mononitrate and 117.45 mg/kg for thiamine hydrochloride. Symptoms by i.v. injections are hypotonia due to vasodilatation, bradycardia and respiratory arrhythmia leading to general neuromuscular inhibition. Death is caused by depression of the respiratory centre (Haley, 1948).
Besides these publications, further information was taken from the reports "Evaluation of the health aspects of thiamin hydrochloride and thiamin mononitrate as food ingredients" (FDA, 1978) and "Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Vitamin B1" (SCF, 2001). In the SCF Opinion, LD50 levels of a study from Bitsch (1997; as cited in SCF, 2001) were described to be 0.07-0.125 g/kg bw intravenous, 0.317-0.500 g/kg bw intraperitoneal and 3-15 g/kg bw orally in mice for thiamine hydrochloride. Lang (1979; as cited in SCF, 2001) quoted an oral LD50 of vitamin B1 of 3.0 g/kg bw for mice. The lethal i.v. for mice were 0.125 g/kg bw, for rats 0.25 g/kg bw, for rabbits 0.30 g/kg bw and dogs 0.35 g/kg bw (McCormick, 1988; as cited in SCF, 2001). In monkeys up to 0.60 g/kg bw was required to produce toxic symptoms (Gubler, 1991; as cited in SCR, 2001). According the FDA report, the oral LD50 values of thiamin were considered to be 2450 and 5000 mg/kg bw for mice, respectively, and 9500 mg/kg bw for rats. After oral administration with thiamin hydrochloride LD50 values of 3000, 5000, 6000 and 8224 mg/kg bw for mice were determined, respectively. The administration with thiamin mononitrate revealed LD50 values of 7000 mg/kg bw in mice.
The thiamine derivates thiamin hydrochloride (CAS 67-03-8) and thiamin mononitrate (CAS 532-43-4) did not exhibit acute oral toxicity. Therefore based on the analogue approach, 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-1,3-thiazol-3-ium chloride (CAS 532-40-1) is not considered to exhibit hazardous properties after single exposure.
According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-1,3-thiazol-3-ium chloride (CAS 532-40-1), data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.
The available data on acute oral toxicity from the source substances thiamin hydrochloride (CAS 67-03-8) and thiamin mononitrate (CAS 532-43-4) do not meet the criteria for classification according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.
Therefore, applying the RA-A approach, the target substance 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-1,3-thiazol-3-ium chloride (CAS 532-40-1) is also considered no to meet the classification criteria for acute oral toxicity.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again