In vitro mutagenicity of rubber chemicals and their nitrosation products

14 chemicals employed in rubber manufacture were assayed in the Salmonella reversion test with the strains TA98 and TA100. Mixed diaryl-p-phenylenediamines were weakly mutagenic in TA98 after metabolic activation; poly-p-dinitrosobenzene was active in TA98 without as well as with S9. After in vitro reaction with nitrite at low pH, mixed diaryl-p-phenylenediamines became directly mutagenic in both strains, whereas poly-p-dinitrosobenzene retained its activity unchanged. Furthermore, 4 of the remaining chemicals acquired mutagenic characteristics: in the presence of S9, N,N'-dimethylpentyl-p-phenylenediamine reverted TA98 and hexamethylenetetramine reverted both TA98 and TA100; N-isopropyl-N'-phenyl-p-phenylenediamine was mutagenic in TA98 with and without S9; N-nitrosodiphenylamine was active in both strains without S9 and weakly mutagenic in TA98 after metabolic conversion.     

Urinary cytology in workmen engaged in the petrochemical industry with reference to non-industrial risk factors

Summary Urine cytology was evaluated in 8,406 male workers of 8 petrochemical factories in western and northern Germany during the routine medical check-up performed by the department of industrial medicine of the respective factory. All relevant data referring to possible private and occupational risk factors were registered and evaluated. Four percent (n=358) of the 8,406 workers examined exhibited Pap 3/4 cytology. Urological examination did not reveal any bladder tumor in those workers with either a single Pap 4 or a repeated Pap 3 finding on cytology. Our study showed that deterioration of cell differentiation correlated significantly with age and cigarette smoking. Furthermore, a risk group (males above 40 years of age exposed to occupational chemicals, smokers, and coffee drinkers) differed from a non-risk group. Age and cigarette smoking seemed to be the determinant factors. No correlation could be adduced between any kind of industrial exposure and urine cytology.     

Purpuric contact dermatitis from black rubber chemicals

Black rubber chemicals are capable of causing an allergic contact dermatitis, in some cases associated with a purpuric capillaritis. A typical case of such a purpuric reaction is described in a man sensitive to black rubber chemicals.     

REPDOSE: A database on repeated dose toxicity studies of commercial chemicals--A multifunctional tool

A database for repeated dose toxicity data has been developed. Studies were selected by data quality. Review documents or risk assessments were used to get a pre-screened selection of available valid data. The structure of the chemicals should be rather simple for well defined chemical categories. The database consists of three core data sets for each chemical: (1) structural features and physico-chemical data, (2) data on study design, (3) study results. To allow consistent queries, a high degree of standardization categories and glossaries were developed for relevant parameters. At present, the database consists of 364 chemicals investigated in 1018 studies which resulted in a total of 6002 specific effects. Standard queries have been developed, which allow analyzing the influence of structural features or PC data on LOELs, target organs and effects. Furthermore, it can be used as an expert system. First queries have shown that the database is a very valuable tool.     

The comparative toxicogenomics database: a cross-species resource for building chemical-gene interaction networks.

Chemicals in the environment play a critical role in the etiology of many human diseases. Despite their prevalence, the molecular mechanisms of action and the effects of chemicals on susceptibility to disease are not well understood. To promote understanding of these mechanisms, the Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org/) presents scientifically reviewed and curated information on chemicals, relevant genes and proteins, and their interactions in vertebrates and invertebrates. CTD integrates sequence, reference, species, microarray, and general toxicology information to provide a unique centralized resource for toxicogenomic research. The database also provides visualization capabilities that enable cross-species comparisons of gene and protein sequences. These comparisons will facilitate understanding of structure-function correlations and the genetic basis of susceptibility. Manual curation and integration of cross-species chemical-gene and chemical-protein interactions from the literature are now underway. These data will provide information for building complex interaction networks. New CTD features include (1) cross-species gene, rather than sequence, query and visualization capabilities; (2) integrated cross-links to microarray data from chemicals, genes, and sequences in CTD; (3) a reference set related to chemical-gene and protein interactions identified by an information retrieval system; and (4) a "Chemicals in the News" initiative that provides links from CTD chemicals to environmental health articles from the popular press. Here we describe these new features and our novel cross-species curation of chemical-gene and chemical-protein interactions.     

Large effects from small exposures. II. The importance of positive controls in low-dose research on bisphenol A

Over six-billion pounds per year of the monomer bisphenol A (BPA) are used to manufacture polycarbonate plastic products, resins lining cans, dental sealants, and polyvinyl chloride plastic products. There are 109 published studies as of July 2005 that report significant effects of low doses of BPA in experimental animals, with many adverse effects occurring at blood levels in animals within and below average blood levels in humans; 40 studies report effects below the current reference dose of 50 microg/kg/day that is still assumed to be safe by the US-FDA and US-EPA in complete disregard of the published findings. The extensive list of significant findings from government-funded studies is compared to the 11 published studies that were funded by the chemical industry, 100% of which conclude that BPA causes no significant effects. We discuss the importance of appropriate controls in toxicological research and that positive controls are required to determine whether conclusions from experiments that report no significant effects are valid or false.     

Evaluation of contact sensitivity of rubber chemicals using the murine local lymph node assay

The sensitizing abilities of 4 rubber additives, tetramelhylthiuram disulfide (TMTD), 2-mercaplob-enzothiazole (MBT), V-isopropyl-N'-phenyl-p-phenylenediamine (IPPD) and zinc diethyldithiocar-bamate (ZDEC), were evaluated using the murine local lymph node assay. Exposure to IPPD induced a significant increase of lymph node cell proliferation in the draining lymph nodes even at a low concentration. Exposure to TMTD and MBT induced moderate proliferation responses, while ZDEC induced a weak proliferation even at the higher concentrations. The sensitizing potency of each chemical was described in terms of the concentration that increased lymph node cell proliferation by a factor of 2 over that in the vehicle-treated control group. The concentrations of IPPD, TMTD. MBT and ZDEC were 0.14%. 10%, respectively.