A dramatic increase in the rate of contact allergy caused by MI in cosmetics is occurring in Belgium. Notwithstanding the recent recommendation to discontinue the use of MI in leave-on cosmetics, safer use concentrations should also be determined for rinse-off products. Close monitoring of MI sensitization in the near future will be necessary, and the highest test concentrations reported for MI and MCI/MI should be included in the baseline series.

Chinese hamster ovary (CHO) cells in culture are known to consume large amounts of nutrients and divert most of them toward byproducts, some of which, including lactate and ammonia, are known to be toxic in nature. Glucose limitation strategies can successfully control lactate accumulation in fed-batch cultures yielding higher peak cell densities and titers. Interestingly, even in such optimized cultures, cell growth slows and eventually stops, indicating the emergence of other factors that negatively affect cell growth. In this study, we employed omics techniques to identify and quantify nine compounds that are intermediates or byproducts of amino acid metabolism, and accumulate in fed-batch cultures. Treatment with these compounds either individually or in a combined fashion resulted in partial or complete cell growth inhibition. Careful control of selected amino acid concentrations between one-half and one millimolar during the growth phase of fed-batch cultures reduced accumulation of the inhibitory metabolites and allowed for higher peak cell densities and increased productivity. Biotechnol. Bioeng. 2017;114: 1779-1790. © 2017 Wiley Periodicals, Inc.

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We have reviewed our patch test results for preservative allergy from 1982 to 1993. 8 preservatives were included: formaldehyde, 2-bromo-2-nitropropane-1,3-diol (Bronopol(TM)), quaternium-15 (Dowicil 200TM), imidazolidinyl urea (Germall 115TM), diazolidinyl urea (Germall IITM), parabens, 5-chloro-2methyl-isothiazolin-3-one (Kathon CG(TM)) and 1,2-dibromo-2,4-dicyanobutane (one of the constituents of Euxyl K 400TM). Whereas the allergy rate to formaldehyde is quite stable, there is a slight increase in the imidazolidinyl urea allergy rate. Quaternium-15's rate is decreasing and 5-chloro-2-methyl-isothiazolin-3-one plus 2-methyl-isothiazolin-3-one's rate, after a rapid rise, seems to have stabilized. Although very important constituents of cosmetics, preservatives not only induce allergies on the face but also on the hands, and, as expected, the allergy rate in men and women generally differs. Among the 5 formaldehyde-releasers, there are some favoured simultaneous reactions: quaternium-15 and formaldehyde, and diazolidinyl urea and imidazolidinyl urea. Concomitant reactions between 1-bromo-2-nitropropane-1,3-diol and formaldehyde are not common, and those between 2-bromo-2-nitropropane-1,3-diol and diazolidinyl urea, and formaldehyde are not very common. This supports the hypothesis that allergic reactions to the Germalls are directed toward the initial molecule rather than to formaldehyde.

Background: In the 2010s an epidemic of allergic contact dermatitis to methylisothiazolinone (MI) occurred in Europe. European authorities banned the use of methylisothiazolinone in leave-on cosmetics in 2017 and limited its use in rinseoff products in 2018. Objectives: To investigate the sensitization rate to MI in Belgium between January 2014 and December 2019, and to assess cosensitizations to octylisothiazolinone (OIT) and benzisothiazolinone (BIT) in MI-sensitized patients. Methods: A retrospective study of patch test results with MI, OIT, and BIT observed in patients attending five Belgian hospitals.Results: Overall, 560 of 10 029 patients (5.58%) had a positive patch test reaction to MI, and its sensitization rate decreased from 7.9% in 2014 to 3.1% in 2019. Rinse-off cosmetics, paints, and detergents were the most prevalent sensitization sources in recent years. Simultaneous reactions readily occurred to OIT, and, surprisingly, and increasingly, also to BIT.Conclusions: Contact allergy to MI in Belgium has reached a pre-epidemic level, reflecting the impact of recent regulatory measures. Leave-on cosmetics, in contrast to rinse-off products, have almost disappeared as sensitization sources in Europe.Paints and detergents also remain problematic. The remarkably high number of patients (co)sensitized to BIT should be a focus of future research.