The activities of INRS in the classification and labeling of glycol ethers.

Glycol ethers are a complex family of more than 30 substances that exhibit a wide range of toxicological properties. This complexity can lead to confusion over which are of real concern and which do not pose significant hazards. Also, many have not been reviewed under the European hazard classification and labelling scheme. Following a major study carried out in France, a number of glycol ethers were identified for review under the classification scheme. This process is now substantially complete and revised classification proposals made and agreed at the European level. When these changes are enacted, the classification of all the commercially important glycol ethers and glymes will reflect their known toxicological hazards.

Interdependence of polymorphonuclear neutrophils and macrophages stained for N-acetyl-beta-glucosaminidase in lavage effluents from toluene diisocyanate-exposed rat lungs.

Male Sprague-Dawley rats were exposed to toluene diisocyanate (TDI) concentrations between 0.082 and 1.087 ppm for 4 h, and pulmonary lavage was carried out 24 h after initiation of the exposure. Cells recovered from the lavage effluents of TDI-exposed rat lungs were identified and counted, then pulmonary macrophages (PMs) resulting from cytocentrifuged preparations were examined for N-acetyl-beta-glucosaminidase (NAG) cytochemical staining. Exposure to TDI led to a parallel and concentration-dependent increase in the number of polymorphonuclear neutrophils (PMNs) and the proportion of PMs stained for NAG, suggesting that the same primary event initiates the two cell responses.

Testing natural indigo for genotoxicity.

The genotoxicity of indigo has been assessed by two short-term tests. The mutagenicity of natural indigo was compared with that of synthetic indigo. Both chemicals were tested using the standard procedure of the Salmonella/microsome mutagenicity test as described by Ames. The substance exhibits mutagenicity towards strains TA1538 and TA98 when S9 preparations of rat liver induced with Aroclor 1254 were present in the medium. The clastogenic potential was evaluated by the micronucleus test in the bone marrow of male mice. The test compound was administered twice with an interval of 24 h, the animals were killed 30 h and 54 h after the first treatment. When the test compound was given by oral gavage as two equal dosages of 0.1, 1 and 1.2 g/kg body weight, no statistically significant increase in the percentage of polychromatic erythrocytes with micronuclei was observed for any group treated with natural indigo.

Mutagenicity of nitrosodiethanolamine on Salmonella typhimurium.

Nitrosodiethanolamine was examined in the Ames assay for bacterial mutagens. In absence of S9 activation a mutagenic effect was found.

To what extent are biomonitoring data available in chemical risk assessment?

1. Chemical risk assessment integrates the identification of hazards and the human exposure levels which can be established from external and/or internal exposure data. 2. The availability of biomonitoring and metabolism animal data, the skin penetration ability, and the existence of atmospheric threshold limit values were examined for twelve substances of the European first list of priority existing substances. This investigation was focused on workplace exposures and on urinary biomarkers of exposure. Appropriate biomonitoring data appeared to be available for two substances: styrene and trichloroethylene. Some biomonitoring research has been conducted on acrylonitrile, buta-1,3-diene, cyclohexane, 1,4-dichlorobenzene, hydrogen fluoride, 2-(2-methoxyethoxy)ethanol, however additional studies could be usefully carried out. No biomonitoring data are available for alkanes, C10-13, chloro; benzene, C10-13-alkyl derivatives; bis(pentabromophenyl)ether; diphenylether, octabromo-derivative. 3. It was concluded that in some cases, biomonitoring data are either lacking or scarce. This is rather surprising since the selection of the substances of the priority list was based on high tonnage, widespread use, extent of human exposure, and toxicological concern. The development of biomonitoring information could be helpful in assessing individual or population chemical exposure whatever the source and route, and would result in both more realistic and more accurate risk assessments.

Mutagenicity of 4,4'-methylene-bis-(2-chloroaniline) "MOCA" and its N-acetyl derivatives in S. typhimurium.

4,4'-methylene-bis-(2-chloroaniline) ("MOCA") and two identified urinary N-acetyl and N,N'-diacetyl derivatives were tested in a Salmonella/mammalian microsome assay. No mutagenic activity was observed without rat liver S9 mix activation. In the presence of rat liver S9 mix, the chemicals were mutagens, but the mutagenicity of N-acetyl derivatives to strain TA100 was reduced when compared to that of "MOCA", and a greater amount of S9 was required to exhibit the mutagenicity of the N,N'-diacetyl-"MOCA". These data suggest that N-acetylation does not account for the mutagenic effectiveness of "MOCA".