Dutch Group

The second experiment (Feron et al. 1995a, Groten et al. 1997) was a 4-week oral/inhalatory study in male Wistar rats in which the toxicity of combinations of nine compounds was examined (Table 10.6) in a complex design. The study comprised a main study and a satellite study. In the main study, the rats were simultaneously exposed to mixtures of aU nine chemicals. The satellite study was designed as a fractionated two-level factorial study in which the rats were simultaneously exposed to combinations of maximally five compounds at their LOAEL these 16 combinations of 9 factors (9 chemicals) jointly comprise a 1/32 fraction of a complete study. 

Toxicological Studies of Chemicals with Different Target Organs and/or Modes of Action 

Stannous chloride 100 330 1,000 3,000 Body weight, blood, liver 

In the main study, a number of effects were observed at the LOAEL and, based on the toxicity data of the individual compounds, most of these effects were expected. A few effects seen in the toxicity studies with the individual compounds had disappeared in the combination, whereas some effects not seen in the range-hnding studies with the individual compounds appeared in the combination. Only minor treatment related effects were observed in the NOAEL. 

Eor most of the endpoints studied in the satelhte groups, the factorial analysis revealed main effects of the individual compounds and interactions (cases of nonadditivity) between the compounds. 

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Mont Cenis [Named after a coal mine in the Ruhr] An early ammonia synthesis process, basically similar to the Haber-Bosch process but using coke-oven gas. Operated by The Royal Dutch Group at Ymuiden, The Netherlands, since 1929. 

However, the Dutch group around Victor Feron (Groten et al. 2001, Feron and Groten 2002, Jonker et al. 2004), as well as US-EPA (1999, 2000b) and the Agency for Toxic Substances and Disease Registry (ATSDR 2004) have suggested approaches that cover also chemicals that differ in their modes of action. 

As regards complex mixtures, the Dutch group initially recommended a two-step approach (see Figure 10.5) first to identify the n (e.g., 10) most risky chemicals in the mixture, and then to perform hazard identification and risk assessment of the defined mixture of the (10) priority chemicals using procedures appropriate for simple, defined mixtures (Feron et al. 1995a,b, 1998 Cassee et al. 1998. 

Thanks to the perfecting of chemical, physical, and enzymic methodologies during the past few years (for reviews, see Refs. 8,10,13,14, 17,27, and 28), the structures of glycans have been determined by the dozen (for reviews, see Refs. 8, 10, 11, 13, 14, 16, 17, and 29-34). In particular, the development by our laboratory, in association with the Dutch group of J. F. G. Vliegenthart, of a process based uniquely on permethylation and 360-MHz, n.m.r. spectroscopy (see later) allows the rapid determination of glycan structures of the N-acetyl-lactosa-minic type (see Fig. 3). 

DUTCH group. A comparison of two doses of aspirin (30mg vs. 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. The Dutch TIA Trial Study Group. N Engl J Med I 991 325 1261-1266. 

A few years after van de Hulst s prediction, scientists in Holland began to prepare an experiment to determine whether, in fact, this spectral transition with its wavelength of 21 cm could be detected from hydrogen atoms located in the depths of space. Unfortunately, a fire in their apparatus set them back and, with the passage of time, their opportunity for the original discovery was lost. As we shall see, however, fate eventually smiled on the Dutch group. 

In the meantime Japanese and Dutch groups also made determinations of K, i. Segawa and Sugai (1983) concluded that bovine, human, and caprine a-Iactalbumins prepared by ordinary methods contain 1.1-1.3 Ca(II) ions per protein molecule and that the removal of the calcium destabilizes the tertiary structures in these proteins. They concluded, on the basis of changes in CD ellipticity, that values for these proteins are, respectively, 2.5 x 10 M S3.0 x 10 M, and 2.8 x 10 M . Later, Hamano et al. (1986), using a calcium-sensitive electrode, determined, in 0.06 M Tris buffer (pH 7.8-8.5) in the presence of varying concentrations of NaCl. They found for Ca(II) and Na(I) to be 2.2 ( 0.5) x 10 and 99 ( 33) M respectively, at pH 8.0 and 37°C. 

An opposite approach was taken by the Dutch group of Korf [123,124]. In order to achieve a (near) quantitative in vivo recovery, they proposed an... 

From analysis of third sites for different sweeteners, inter-class relationships have been developed by a Dutch group for the sweet classes oximes, nitroanilines, sulphamates, dipeptides and isocoumarins104. 

In our opinion, the best example of transformation of water-insoluble substances in micellar systems is the work of a Dutch group [65] on the reduction of steroid hormones. 

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