Page 334 - Industrial Ventilation Design Guidebook

290 CHAPTER 5 PHYSIOLOGICAL AND TOXICOLOGICAL CONSIDERATIONS

TABLE 5.12 Principal Assays in Genetic Toxicology

J. Pivotal assays
A. An assay for gene mutations
Salmonella/mammalian microsome assay (Ames test)
B. A mammalian assay for chromosome damage in vivo
Metaphase analysis or micronucleus assay in rodent bone marrow
II. Other assays offering an extensive database or unique endpoint
A. Assays for gene mutations
E. coli WP2 trytophan reversion assay
TK or HPRT forward mutation assays in cultured mammalian cells
Drosophila sex-linked recessive lethal assay
B. Cytogenetic analysis in cultured Chinese hamster or human cells
Assays for chromosome aberrations and micronuclei
Assays for aneuploidy
C. Other indicators of genetic damage
Assay for mitotic recombination in yeast and Drosophila
Assay for unscheduled DNA synthesis in cultured hepatocytes and
rodents
D. Mammalian germ cell assays
Mouse visible or electrophoretic specific-locus tests
Assays for skeletal and cataract mutations
Cytogenetic analysis and heritable translocation assays
DNA damage and repair in rodent germ cells
Dominant lethal assay
Source: Modified from Hoffmann, 1SI1

5.3.4.4 Target Organs
Organs as Targets of Chemical Compounds
Blood acts as the transport system for distribution of absorbed sub-
stances throughout the body. The distribution is often uneven. Adverse re-
sponses may occur if the concentration exceeds a critical concentration in the
target organ. As stated previously, the target organ is not necessarily the same
as the organ with the largest accumulation of the substance. Many corn-
pounds are stored in the skeleton and fatty tissue but critical effects usually
occur in other organs. Lipophilic organic materials are deposited in fatty tis-
sue, whereas some inorganic materials accumulate in the bones due to their
resemblance to calcium (e.g., lead) or their ability to bind with calcium (e.g.,
fluoride). 131 132
'
Water-soluble compounds are naturally easily transported in the blood.
Non-soluble compounds are usually transported bound to plasma proteins
(albumins). This binding is reversible in most cases but may vary remarkably.
The degree of protein binding may vary between 50% and 99%. The propor-
tion of the free (unbound) compound in the circulation is the amount of the
compound that can reach the tissues and thus the target organs. Very lipid-