Toxicological evaluation of peroxy sulfonated oleic acid (PSOA) in subacute and developmental toxicity studies.

Peroxy sulfonated oleic acid (PSOA) is a new coupler used in sanitizing solutions primarily for the food and beverage industry. The toxicity of PSOA was evaluated in a 28-day repeat dose study according to OECD 407 guidelines with a 14-day recovery period and a developmental toxicity study according to OECD 414 guidelines. In both studies, PSOA was administered once daily via gavage at 0, 5, 15 and 50 mg/kg/day to Sprague-Dawley rats. Due to its corrosive properties, the highest test concentration was restricted to 0.5%. No findings related to PSOA administration were observed for the 28-day repeat-dose study and the NOEL is 50 mg/kg/day. Additionally, no impairment of the mucous membranes of the gastrointestinal tract was observed up to 0.5%, which is considered the NOEC in terms of local toxicity. For the developmental study, an embryo-fetal NOEL of 50 mg/kg/day was identified and the maternal NOEL is considered to be 15 mg/kg/day, based on slight reductions in maternal body weight and food consumption, as well as a modest increase in the incidence of clinical observations at the high dose. These findings demonstrate that PSOA appears to have minimal potential to induce toxicity associated with repeat-dose or developmental exposures.

Assessment of reproductive toxicity under REACH.

The European REACH regulation requires the evaluation of reproductive toxicity in screening tests according to OECD TG 421 and 422 for substances above the tonnage level of 10 tons/year. The overall aim of this paper is to increase flexibility in combination with a reduced number of experimental animals. Therefore, in contrast to the existing approach the registrant should have the possibility to file a dossier for a substance at the level of 10 tons/year and above also on the basis of data from a developmental toxicity study (OECD TG 414) plus a full-scale subacute toxicity study (OECD TG 407 according to the 1995 protocol). The proposed new test strategy takes into account overall considerations of duty of care and animal welfare. It enables an assessment of developmental toxicity on a definitive instead of a screening level. Registrants should be allowed to select between these two options, either the existing approach (OECD TG 421/407 and alternatively TG 422) or the approach proposed in this paper (OECD TG 407 plus TG 414).

Nephrotoxicity of 4-cycloocten-1-carbaldehyde.

Natural and synthetic chemicals are often used in the fragrance industry. A toxicological profile of the synthetic fragrance booster, 4-cycloocten-1-carbaldehyde, was generated using a test program including the following methods: acute oral toxicity, acute dermal toxicity, acute skin and eye irritation, skin sensitization, subchronic toxicity, and mutagenicity. The substance was strongly irritating to the skin but only weakly irritating to the eye. It gave a clear indication of having skin-sensitizing properties. Based on the comprehensive data from a mutagenicity test battery, 4-cycloocten-1-carbaldehyde was assessed to be nonmutagenic. Although its acute toxicological profile shows no toxicity after oral or dermal application, 4-cycloocten-1-carbaldehyde displays a complex toxicological response after repeated dosing over 13 weeks. 4-Cycloocten-1-carbaldehyde or its metabolites show clear nephrotoxic properties focusing on tubular cells of the kidney. In view of these data no no-effect level can be derived from this study with 4-cycloocten-1-carbaldehyde. A broad interaction of the test substance with various tissue types and cell parameters together with severe and irreversible organic defects even at low doses leads to the conclusion that 4-cycloocten-1-carbaldehyde is unsuitable for the intended use in industrial fragrance formulations.

Assessment of the acute pulmonary toxicity of lamp oil aspiration in the isolated perfused rat lung.

Mainly among children incidental ingestion of conventional lamp oils (paraffin oil) is responsible for casual intoxications with severe pulmonary toxicity and fatal consequences. On the basis of the isolated blood-free perfused rat lung we developed a model to study the acute toxic effects of lamp oil. Three oils were studied: conventional paraffin lamp oil (kinematic viscosity 1.62 10(-6) m(2)/sec), the methyl ester Edenor ME C12 70 (2.7 10(-6) m(2)/s) and another ester Edenor LPL (4.5 10(-6) m(2)/s). The oils were instilled into the trachea of isolated rat lungs and the changes in lung mechanics (tidal volume, pulmonary compliance and pulmonary conductance) as well as edema formation (increase in lung weight) studied. Instillation of as little as 10 microl paraffin oil caused complete failure of lung functions within 20 min and even 2 microl caused noticeable edema. Similar results were obtained with Edenor ME C12 70, which appeared to be even more toxic than paraffin oil, while Edenor LPL was less toxic. We conclude that tracheal instillation of oils into isolated perfused rat lungs may be a useful model to study the toxicity of lamp oils in vitro. Our findings further suggest that Edenor LPL may be a safer alternative for use as a lamp oil than paraffin oil.