Toxicology of Industrial Compounds

to 50 ng g −1 haemoglobin (Figure 6.5). No macromolecular adducts were
detectable in the rats treated with the two diarylide pigments. The limits of
determination would correspond to a daily DCB dose of 0.3–0.5 mg kg −1
body weight, indicating that DCB was not liberated from the pigments at a
determination limit of 0.3% of the DCB equivalents, whereas the
bioavailability of DCB in the rats treated with the azo dye could clearly be
confirmed.
Formation of glycidaldehyde from glycidylethers
Bisphenol A diglycidylether (BPADGE) is widely used as component of
epoxy resins. The chemical reactivity of this class of compounds is a
prerequisite for their technical use, and accounts for the sensitising,
mutagenic and in some cases carcinogenic properties of many epoxy resin
monomers. It was suggested that the metabolic inactivation of BPADGE by
hydrolysis of epoxides may form an equilibrium with its metabolic
activation by oxidative dealkylation of the intact glycidyl side chain
followed by the release of glycidaldehyde. Cutaneous treatment of mice
with glycidaldehyde led to the formation of one major epidermal DNA
adduct which was identified as HMEdA
(hydroxymethylethenodeoxyadenosine, Steiner et al., 1992a). This cyclic
deoxyadenosine adduct is strongly fluorescent and can be quantified by
fluorescence measurements.
In order to investigate the formation of glycidaldehyde from BPADGE,
mice were treated with BPADGE (2 mg) and the fluorescent
glycidaldehydeDNA adducts formed in epidermal DNA were compared
with those obtained after treatment with glycidaldehyde (2 mg). After 24–
96 h epidermal DNA was isolated, enzymatically digested to the
deoxynucleoside-3'-monophosphates and analysed for the presence of
HMEdA by HPLC with fluorescence detection (excitation at 231 nm,
emission at 420 nm). In glycidaldehyde treated mice 166 adducts per 10 6
nucleotides could be detected after an exposure time of 24 h (Figure 6.6)
whereas with epidermal DNA from BPADGE treated mice 0.2– 0.8
adducts per 10 6 nucleotides were found. This adduct level would be equal
to a dose of 10 µg glycidaldehyde, indicating that, at the most, 1.1% of the
glycidaldehyde moiety in BPADGE were bioavailable for DNA-adduct
formation (Steiner et al., 1992b).
Determination of reactive compounds in unknown
mixtures
P.SAGELSDORFF 83
A challenging task is the analysis of reactive metabolities in unknown
mixtures of different compounds. In order to assess the impact of chemical
pollution on aquatic organisms, rainbow trouts were continuously exposed