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The REACH Regulation represents a major piece of chemical legislation in the EU and requires manufacturers and importers of chemicals to assess the safety of their substances. The classification of substances for their hazards is one of the crucial elements in this process. We analysed the effect of REACH on classification for human health endpoints by comparing information from REACH registration dossiers with legally binding, harmonised classifications. The analysis included 142 chemicals produced at very high tonnages in the EU, the majority of which have already been assessed in the past. Of 20 substances lacking a harmonised classification, 12 chemicals were classified in REACH registration dossiers. More importantly, 37 substances with harmonised classifications for human health endpoints had stricter classifications in registration dossiers and 29 of these were classified for at least one additional endpoint not covered by the harmonised classification. Substance-specific analyses suggest that one third of these additional endpoints emerged from experimental studies performed to fulfil information requirements under REACH, while two thirds resulted from a new assessment of pre-REACH studies. We conclude that REACH leads to an improved hazard characterisation even for substances with a potentially good data basis.

A 61-year-old woman was found unconscious by her husband. The emergency doctor detected hypoglycemia (blood glucose 1.7 mmol/l). This was the first such event, the patient had not been known to have diabetes mellitus. At admission the physical examination and the laboratory findings revealed no abnormalities.A fasting test was aborted shortly after the start because of the onset of neurological symptoms. An insulinoma was excluded by detecting suppressed levels of insulin and C-peptide. Computed tomography of the abdomen revealed a mesenteric tumour of 9 cm in diameter, which was identified immunhistologically as a grade 1 follicular lymphoma (FL). After exclusion of endocrinological causes the recurrent hypoglycaemia was diagnozed as part of a paraneoplastic syndrome associated with a non-islet cell tumour hypoglycaemia (NICTH) with a newly diagnosed FL.Specific medication with the CD20 antibody rituximab (375 mg/m2, once per week for a total of four cycles) was initiated. There were no further episodes of hypoglycaemia. After one year the patient remains free of any symptoms.After exclusion of any endocrinological reasons for hypoglycemia, differential diagnosis should include NICTH as paraneoplastic syndrome. In rare cases a hematological malignancy may be the underlying disease. The specific treatment of this disease likewise represents the causal treatment of NICTH.

Problems of frequency-specific objective assessment of hearing threshold by means of auditory brainstem response (ABR) have been discussed recently. While a number of workers have recommended methods of selective masking to improve the frequency specificity, others believe that frequency-specific potentials can also be obtained without masking. In this context, the effects of rise-decay time and high-pass masking on ABRs were investigated.ABRs were recorded in normal-hearing subjects and patients with high and low frequency hearing loss by means of surface electrodes between the vertex and the ipsilateral mastoid. The frequency of the stimulus was 1 kHz, and the rise-decay time 1 ms (1-0-1) or 2 ms (2-0-2). High-pass filtered noise (cutoff frequency 1.5 kHz; filter slope 250 dB/octave) was employed for masking. Particular attention was paid to the problem of efficient masking.In normal-hearing subjects under the influence of high-pass masking compared to non-masked ABRs, longer mean latencies and diminished means of the amplitudes of wave V were found, with differences in the near-threshold domain being less pronounced. Similar results were observed in patients with high frequency hearing loss. In patients with low frequency hearing loss, the influence of high-pass masking was especially marked distinctly near to threshold. Furthermore, latency and amplitude differences of wave V of the 1-0-1 and the 2-0-2 stimuli were determined from the ABRs obtained with and without high-pass masking. The differences between the latency differences of both stimuli in the suprathreshold range (70 dB nHL) only were statistically significant.The results are suggestive of an inadequate frequency specificity of unmasked stimuli in the suprathreshold range. Evaluation of the latencies revealed for both rise-decay times a similar frequency specificity near the threshold and a higher frequency specificity of the longer stimulus in the suprathreshold range.

To study the putative precursor proteins (PreA4 695 , PreA4 751 , and PreA4 770 ) of Alzheimer's disease A4 amyloid protein, polyclonal and monoclonal antibodies were raised against a recombinant bacterial PreA4 695 fusion protein. These antibodies were used to identify the precursors in different cell lines as well as in human brain homogenates and cerebrospinal fluid (CSF). The precursors are tyrosine-sulfated, O- and N-glycosylated membrane proteins and have half-lives of 20–30 min in cells. Cells express the polypeptides at their surface but also secrete C-terminal truncated proteins into the medium. These proteins are also found in CSF of both Alzheimer's disease patients and normal individuals. The proteins are derived from their cognate membrane-associated forms by proteolysis and have apparently lost the cytoplasmic and the transmembrane domains. Since the latter contributes to the A4 amyloid sequence, it seems possible that this proteolytic cleavage represents the first step in the formation of A4 amyloid deposits.