Abstract  A series of systemic toxicity tests for various types of compounds are presented with illustrative data and discussed in regard to their relevance as potential screening tests for dental compounds and products. In developing and marketing a new dental material, it is important not only to ensure safety for the patient but also for the dentist, dental assistant, and laboratory worker who routinely handles and uses the product. Data are presented on a number of commercially available dental products as well as various chemical entities, which were tested by one or more of the methods described.

Abstract  Seventy-six compounds used as artificial flavouring substances in food products were studied for mutagenic properties by the use of the Salmonella/mammalian microsome test (Ames test), Basc test on Drosophila melanogaster and micronucleus test on mouse bone marrow. The following four compounds were mutagenic in Ames tests: ethyl nitrite, ethyl 3-phenylglycidate, 6-methylquinoline and musk ambrette. Of these, ethyl nitrite and musk ambrette also induced a significant (P ⩽ 0.01) increase in sex-linked recessive lethal mutations in Drosophila. Two further compounds, ethyl 3-methyl-3-phenylglycidate and 4-n-propylanisole, appeared weakly mutagenic in Drosophila only. The result with 4-n-propylanisole was judged to be of equivocal biological significance. None of the flavouring substances induced micronuclei, i.e. cytogenetic damage in the bone marrow of mice.

Abstract  Dibutyl Adipate, the diester of butyl alcohol and adipic acid, functions as a plasticizer, skin-conditioning agent, and solvent in cosmetic formulations. It is reportedly used at a concentration of 5% in nail polish and 8% in suntan gels, creams, and liquids. Dibutyl Adipate is soluble in organic solvents, but practically insoluble in water. Dibutyl Adipate does not absorb radiation in the ultraviolet (UV) region of the spectrum. Dibutyl Adipate is not toxic in acute oral or dermal animal toxicity tests. In a subchronic dermal toxicity study, 1.0 ml/kg day-1 caused a significant reduction in body weight gain in rabbits, but 0.5 ml/kg/day was without effect. In a study with dogs, no adverse effects were observed when an emulsion containing 6.25% Dibutyl Adipate was applied to the entire body twice a week for 3 months. Dibutyl Adipate was tested or dermal irritation using rabbits and mice and a none to minimal irritation was observed. Dibutyl Adipate at a concentration of 25 % was not a sensitizer in a guinea pig maximization study. Undiluted Dibutyl Adipate was minimally irritating to the eyes of rabbits and 0.1 % was nonirritating. A significant increase in fetal gross abnormalities was observed in rats given intraperitoneal injections of Dibutyl Adipate at 1.75 ml/kg on 3 separate days during gestation, but no effect was seen in animals given 1.05 ml/kg Dibutyl Adipate was as not genotoxic in either bacterial or mammalian test systems. Clinical patch tests confirmed the absence of skin irritation found in animal tests. Clinical phototoxicity tests were negative. Dibutyl Adipate at 0.1 % was not an ocular irritant in two male volunteers. In a clinical test of comedogenicity, Dibutyl Adipate produced no effect. The Cosmetic Ingredient Review (CIR) Expert Panel recognized that use of Dibutyl Adipate in suntan cosmetic products will result in repeated, frequent exposure in a leave-on product. The available data demonstrate no skin sensitization or cumulative skin irritation, no comedogenicity, and no genotoxicity. Combined with the data demonstrating little acute toxicity, no skin or ocular irritation, and no reproductive or developmental toxicity, these data form an adequate basis for reaching a conclusion that Dibutyl Adipate is safe as a cosmetic ingredient in the practices of use and concentrations as reflected in this safety assessment.

Abstract  HEEP COPYRIGHT: BIOL ABS. The toxicity to HeLa cells of 29 plasticizers was determined in the MIT(Metabolic Inhibition Test)-24 test system. The 7-day IC50 (median inhibitory concentration) for HeLa cells varied from 260 to 1.5 g/l. Phthalates, adipates, sebacates, azelates and phosphates with long carbon chain alcohols were very non-toxic to the cells, probably due to insolubility in water of the compounds, while the citrates, some phosphates and the 2 polymer plasticizers had a higher toxicity to the cells. A comparison of the HeLa cytotoxicity with the toxicity in vitro to other cells for 7 plasticizers showed a similarity of the cytotoxicity to all cell types. A comparison of the HeLa cytotoxicity for 20 plasticizers with i.p. lethal dosage in rodents demonstrated a rough similarity of values, suggesting a toxicity in rodents of the compounds by toxic interference of the agents with basal functions and structures of tissues (basal cytotoxicity). Tissue culture studies of the cytotoxic mechanisms of the plasticizers therefore could reveal modes of toxic action in vivo.

Abstract  Stabilizers (epoxidized linseed oil and epoxidized soybean oil) and plasticizers (acetyl tributyl citrate, diacetyl monolauryl glyceride and dibutyl sebacate) commonly used in polyvinylidene chloride (PVDC) films and extracts of such films were investigated for estrogenic and androgenic activity by means of estrogen receptor (ER) and androgen receptor (AR) competitive ligand-binding assays. Further, in in vivo experiments, ovariectomized Sprague-Dawley rats were observed for uterine wet weight change, uterine endometrium hyperplasia and vaginal mucosa cornification, following administration of each test compound or extract orally (0.5 or 500 mg/kg) or subcutaneously (0.5 or 100 mg/kg). No significant response or change was observed with any of the test compounds or extracts, either in vitro or in vivo. The results thus indicate that neither the stabilizers and plasticizers used in PVDC films, nor their extracts, exert sex-hormonal activity.

Abstract  The toxicology of Otto-Fuels-II (106602806), a mixture of propylene-glycol-dinitrate (6423434), 2-nitrodiphenylamine (119755), and dibutyl-sebacate (109433), was reviewed with regard to its adverse health effects, toxicokinetics, human exposures, chemical and physical data, and other characteristics. The health effects of Otto-Fuels-II exposure were discussed by route of exposure: inhalation, oral, and dermal. Specifically addressed were systemic, immunological, neurological, reproductive, developmental, genotoxic, and carcinogenic effects. The absorption and distribution of Otto-Fuels-II following inhalation, oral, and dermal exposure were reviewed as were its metabolism, excretion, and mechanisms of action. The relevance of Otto-Fuels-II exposure to public health, biomarkers of exposure and effects, interactions between Otto-Fuels-II and other chemicals, populations particularly susceptible to the adverse effects of Otto-Fuels-II, and methods to reduce toxic effects were described and discussed. Also presented and discussed were chemical and physical data on Otto-Fuels-II, its production, import, use, and disposal, the potential for human exposure as a result of environmental releases, its environmental persistence and estimated levels in air, water, soil, and other media, occupational exposures, populations with potentially high exposures, and methods for analysis in biological and environmental samples.

Abstract  Dibutyl sebacate was not an irritant on human skin but was a slight skin irritant in rabbits and guinea-pigs. There was some evidence of skin sensitization potential in workes exposed to the sebacate. Dibutyl sebacate caused effects on the kidneys and nerve function when inhaled by rodents, but was of low acute oral and injection toxicity. Studies involving repeated oral administration revealed no sites of orally treated rats was a decrease in pup growth. A limited feeding study generated no evidence of carcinogenicity in rats. Dibutyl sebacate did not induce chromosome damage in the bone marrow of mice treated by injection. It was not mutagenic in bacterial assays (including the Ames test) or in the fruit fly.