Median metabolites

Actual exposure of the hands was reduced by approximately 95% and 87% for applicators and harvesters, respectively, wearing gloves. Respiratory exposure did not differ significantly between the two trials and was estimated to contribute approximately 4% to the excreted amount of metabolite in urine. Median IPP excretion was reduced 42% and 38% for applicators and harvesters, respectively. IPP excretion of the harvesters was strongly correlated with... 

A decrease in the amplitude of the sensory nerve action potential has also been observed in a group of 20 asymptomatic workers exposed to -hexanc (Pastore et al. 1994). The subjects of this study were selected on the basis of urinary levels of the n-hexane metabolite 2,5-hexanedione (See Sections 2.3 and 2.7) exceeding 5 mg/L and compared to a group of unexposed laboratory workers. Mean years worked was 8.13 (range, 1.5—23 years). Sensory and motor nerve conduction velocities and distal latencies were normal in all nerves tested. However, significant decreases were found in sensory nerve action potential amplitude in the median, sural, and ulnar nerves. Neither the level of 2,5-hexanedione in urine nor age correlated with the changes in amplitude however, there was a significant correlation between years worked and amplitude. 

Both clinical and experimental studies have provided evidence that 5-HT can also regulate dopamine turnover. Thus several investigators have shown that a positive correlation exists in depressed patients between the homovaniUic acid (HVA), a major metabolite of dopamine, and 5-HIAA concentrations in the CSF. In experimental studies, stimulation of the 5-HT cell bodies in the median raphe causes reduced firing of the substantia nigra where dopamine is the main neurotransmitter. There is thus convincing evidence that 5-HT plays an important role in modulating dopaminergic... 

In urine, OPFR metabolites have been detected, but the median concentrations of the diaryl and dialkyl phosphates remained mostly below the quantification limit. Ranges of concentrations of dialkyl and diaryl phosphates are shown in Table 4. In the study of Schindler et al. [302, 303], the detection frequency was highest for BCEP (50%), followed by DPP (30%), BCPP (12%), and DBP (3%). Di-w-cresyl and di-/7-cresyl phosphate were not found in any sample, probably due to lower exposure in the indoor environment. Reemtsma et al. [304] found also monoaryl and alkyl phosphates in human urine, of which the monobutyl phosphate was the... 

Table 7 Levels (I median/range concentrations expressed in pg/L of sample II median/range creatinine adjusted concentrations expressed in pg/g) of phthalates, substitutes, and their metabolites from human fluids samples...

Table 6 Selected biomonitoring data on phthalate metabolites exposure in different countries (median, range or 95th percentile), expressed in pg/L, found in different population... 

The EDI of phthalates in China, Germany, Taiwan, and US populations are shown in Table 7. The calculation was based on phthalate metabolite (primary and secondary) concentrations, the model of David [137] and the excretion fractions according to various authors [23,28,143,144]. DEHP median values are very close or clearly exceed the TDIs and RfD values (Table 4). The median values for the rest of PAEs are below levels determined to be safe for daily exposures estimated by the US (RfD), the EU and Japan (TDI) (Table 4). However, the upper percentiles of DBP and DEHP urinary metabolite concentrations suggested that for some people, these daily phthalate intakes might be substantially higher than previously assumed and exceed the RfD and TDIs. 

The major urinary metabolite of di(2-ethylhexyl) adipate, 2-ethylhexanoic acid, has been shown to be an appropriate marker for biological monitoring of dietary di(2-ethylhexyl) adipate intake (Loftus etal., 1993, 1994). A limited population study in the United Kingdom was undertaken to estimate the daily intake of di(2-ethylhexyl) adipate following intake of a mean dose of 5.4 mg di(2-ethylhexyl) adipate presented with food. The study involved the determination of the urinary metabolite, 2-ethyl-hexanoic acid (24-h mine sample) in 112 individuals from five geographical locations. A skewed distribution with a median value for the daily intake of 2.7 mg was determined (Loftus et al., 1994). This value is about one third of the indirectly estimated maximum intake of 8. 2 mg per day. The probability of a daily intake in excess of 8.2 mg in the limited population (112 individuals) was calculated to be 3% (Loftus etal, 1994). 

An expected ratio of 6-MMPR to 6-TGN is considered a value between 5 and 25. When 6-TG is applied, 6-TGN levels in children using a median 6-TG dose of 41.8 mg/m /d have been described more than 7-fold higher in comparison to those on a median 6-MP dose of 54.3 mg/m /d (111). Thus, expected 6-TGN concentrations under 6-TG exposure range from approximately 500 to 5000pmol/8 x 10 RBC (lll).T as discrepancy may be explained by the fact that in RBC, 6-TGN are generated far more efficiently from 6-TG than from 6-MP. However there are several open questions as to whether thiopurine metabolite levels in RBC are comparable with leukocytes under treatment of childhood leukemia (125) or whether a substantial part of 6-TGN measured in RBC under 6-MP therapy derives from the metabolism in other tissues via a subsequent uptake in RBC (126). 

The guanosine analog penciclovir, the active metabolite of famciclovir, is available for topical use. Penciclovir cream (1%) is effective for the treatment of recurrent herpes labialis (Table 49-1). When applied within 1 hour of the onset of prodromal symptoms and continued every 2 hours during waking hours for 4 days, median time until healing was shortened by 17 hours compared with placebo. Adverse effects are uncommon, although application site reactions occur in about 1%. 

A group of 30 male Swiss mice was treated with undiluted epoxybutene, the initial monoepoxide metabolite of butadiene, by skin application at a dose of 100 mg three times per week for life. The median survival time was 237 days and four skin tumours were observed (Van Duuren et al., 1963). [The Working Group noted that this incidence was similar to that in control groups that were either administered solvents or left untreated]... 

Azathioprine and 6-mercaptopurine have a serum half-life of less than 2 hours however, the active metabolites, 6-thioguanine nucleotides, are concentrated in cells resulting in a prolonged half-life of days. The prolonged kinetics of 6-thioguanine nucleotide results in a median delay of 17 weeks before onset of therapeutic benefit from oral azathioprine or 6-mercaptopurine is observed in patients with inflammatory bowel disease. 

The medians and ranges of the hypothetical dissolution data for the metabolite XYZ1234 obtained by de-convolution are listed in Table 32. 

In general, most of the herbicides are only moderately to slightly toxic to fish, having median tolerance limits (Tim) generally above 1 p.p.m. A few, however, exhibit Tims well below 1 p.p.m. When fed to dairy and meat animals at dietary concentrations of several parts per million, the herbicides, in general, are not excreted in milk and do not accumulate in tissues. While this seems to be the case for the herbicide per se, the metabolites of many of the herbicides have not been fully investigated. 

After daily oral doses of 4 g to 9 subjects, steady-state serum concentrations of 37 to 92 pg/ml (median 50) for total sulphapyridine and its metabolites,... 

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