Vinyl acetate monomer (VAM) is a key intermediate used in the making of a number of polymers and resins for adhesives, coatings, paints. Human data on the acute toxicity of vinyl acetate is not available. Based on the carcinogenic potential of vinyl acetate in the animals, the substance can have a cancer risk for humans. Carcinogenicity is thought to act via a secondary mechanism and the concern may only be relevant above threshold concentrations.

Ethyl acetate is a widely used synthetic solvent. It is used in cosmetics and considered to be safe. Ethyl acetate is cited as a direct and indirect food additive as detailed in the Code of Federal Regulations. Ethyl acetate is generally recognized as safe (GRAS) for use as a synthetic flavor and/or adjuvant; limitations on concentrations of use were not specified. Ethyl acetate was tested for in vitro in human breast cancer cell line and demonstrated considerable cytotoxicity.

Norgestomet is a synthetic derivative of progesterone with improved oral activity due to its 17α-acetate side chain. In veterinary medicine norgestomet is used for the synchronisation of oestrus in cattle. It is administered as a subcutaneous ear implant (containing 3 mg norgestomet; to be removed after 9 to 10 days), in combination with a single intramuscular injection containing 3 mg norgestomet and 5 mg oestradiol valerate. The injection is to be given immediately after application of the implant. Norgestomet is not used in human medicine. It is a steroidal progestin of the 19-norprogesterone group.

Zindoxifene (D 16726 or 5-acetoxy-2-(4-acetoxyphenyl)-1-ethyl-3-methylindole), is an antiestrogenic phenylindole with a high affinity for the estrogen receptor. Zindoxifene exerts inhibiting activity against tumors of prostatic and mammary origins both in vitro and in vivo. It was in phase I/II study for the treatment of advanced breast cancer. Zindoxifene development has been discontinued.

Levomethadyl acetate (LAAM) is a synthetic opioid agonist with actions qualitatively similar to morphine (a prototypic mu agonist) and affecting the central nervous system (CNS) and smooth muscle. Principal actions include analgesia and sedation. Tolerance to these effects develops with repeated use. An abstinence syndrome generally occurs upon cessation of chronic administration similar to that observed with other opiates, but with slower onset, more prolonged course, and less severe symptoms. LAAM exerts its clinical effects in the treatment of opiate abuse through two mechanisms. First, LAAM cross-substitutes for opiates of the morphinetype, suppressing symptoms of withdrawal in opiate-dependent individuals. Second, chronic oral administration of LAAM can produce sufficient tolerance to block the subjective “high” of usual doses of parenterally administered opiates. Since the introduction of levomethadyl in 1995, the manufacturer has received increasing reports of severe cardiac-related adverse events, including QT interval prolongation, Torsades de Pointes and cardiac arrest. Other cardiac-related adverse events have also been reported, including arrhythmias, syncope, and angina. These events led to the removal of levomethadyl from the European market in March 2001. A very small number of patients may benefit from levomethadyl, but the risk of continued distribution and use no longer outweighs the overall benefits.

Propanidid (Epontol) is an analgetically potent and shortterm anesthetic, widely used in the 1960s. It was originally introduced by Bayer in 1963. Epontol, an injectable emulsion formulation of propanidid, provided by Bayer, was withdrawn from the market in Great Britain in 1983 because of concern over anaphylactoid reactions. Thus, in spite of the fact that propanidid provides shorter and more predictable recovery times than propofol, it has not been accepted widely as an injectable anesthetic. Even though Cremophor EL has been shown to cause anaphylactic reactions in humans in several cases (both when given intravenously and orally), it is still debated whether or not propanidid itself may have contributed to the reactions. It has been argued that the toxic effects or reactions to propanidid (and Althesin) were due to the drugs themselves. Several cases of negative reactions have been recorded for different drugs using Cremophor EL as solubilizer. This suggest that the negative reactions were mainly caused by Cremophor and not by the drug substances themselves. Propanidid is presumed to work as a GABA receptor agonist.

PREDNISOLAMATE is a synthetic corticosteroid.

Alrestatin, an inhibitor of aldose reductase, was studied in clinical trials for the treatment of diabetes. But this study was discontinued, because of the high hepatotoxicity events.