Disulfide oil hazard assessment using categorical analysis and a mode of action determination.

Diethyl and diphenyl disulfides, naphtha sweetening (Chemical Abstracts Service [CAS] # 68955-96-4), are primarily composed of low-molecular-weight dialkyl disulfides extracted from C4 to C5 light hydrocarbon streams during the refining of crude oil. The substance, commonly known as disulfide oil (DSO), can be composed of up to 17 different disulfides and trisulfides with monoalkyl chain lengths no greater than C4. The disulfides in DSO constitute a homologous series of chemical constituents that are perfectly suited for a hazard evaluation using a read-across/worst-case approach. The DSO constituents exhibit a common mode of action that is operable at all trophic levels. The observed oxidative stress response is mediated by reactive oxygen species and free radical intermediates generated after disulfide bond cleavage and subsequent redox cycling of the resulting mercaptan. Evidence indicates that the lowest series member, dimethyl disulfide (DMDS), can operate as a worst-case surrogate for other members of the series, since it displays the highest toxicity. Increasing the alkyl chain length or degree of substitution has been shown to serially reduce disulfide toxicity through resonance stabilization of the radical intermediate or steric inhibition of the initial enzymatic step. The following case study examines the mode of action for dialkyl disulfide toxicity and documents the use of read-across information from DMDS to assess the hazards of DSO. The results indicate that DSO possesses high aquatic toxicity, moderate environmental persistence, low to moderate acute toxicity, high repeated dose toxicity, and a low potential for genotoxicity, carcinogenicity, and reproductive/developmental effects.

Determining the Safety of Maltogenic Amylase Produced by rDNA Technology.

A maltogenic amylase produced by a genetically engineered Bacillus subtilis was studied to evaluate its safety in the food industry. First, the safety of the component parts used in the cloning process, i.e. the host organism ( B. subtilis ), the donor organism ( Bacillus stearothermophilus ) and the construction process, were evaluated. This evaluation indicated that the final construct should be regarded as a safe source for maltogenic amylase when manufactured according to current Good Manufacturing Practices. Additional experimental safety testing was carried out to confirm this conclusion. In a 13-week oral toxicity study rats tolerated the maltogenic amylase at dietary levels of 5% without toxicologically significant adverse reaction. Lack of mutagenic potential was confirmed in bacterial mutagenic as-says with Salmonella typhimurium and in an in vivo cytogenetic study in rat bone marrow cells. In an acute inhalation study with 4 h of exposure to rats, no death occurred at the highest dose level, i.e, 1.59 mg/L. The test material was non-irritating to skin and did not product eye injury in rabbits. A skin sensitization study in guinea pigs was negative. Antibiotic activity tests indicated that the microorganism did not produce antibiotics. Results indicated that maltogenic amylase should be generally recognized as safe for use in production of maltose syrups, and confirmed the conclusion drawn from the safety evaluation of the component parts used in the cloning process.