Abstract  2-Bromopropane and hydrochlorofluorocarbons (HCFCs), whose toxicity has scarcely been known, have recently been introduced as main substitutes for chlorofluorocarbons (CFCs). A major corporation in Korea replaced CFCs with 2-bromopropane and this actually led 23 Korean workers to be the world's first 2-bromopropane intoxication victims. Out of 25 female workers in the tactile switch assembling section, 17 (68%) were diagnosed as having ovarian failure. Two affected female workers showed marked pancytopenia with markedly hypoplastic marrow. In the same section, two out of eight male workers showed azoospermia and four some degree of oligospermia. The above toxicity of 2-bromopropane was reproduced in experimental animal studies. Recently, health effects of HCFC 123, including toxic hepatitis, have been reported by several authors. The principle of replacement of toxic substances with non-toxic or less toxic chemicals is important in risk management, but substances still poorly known should not be confused with non-toxic or less toxic substances. Measures aimed at reducing exposure to chemicals with known toxicity rather than using new unknown alternatives may be a rational and effective approach to risk management.

Abstract  The National Institute for Occupational Safety and Health (NIOSH) conducted a field study at an aerospace component manufacturing plant where n-propyl bromide (nPB) was used as a vapor degreasing solvent. Workers' breathing zone and exhaled breath concentrations of nPB and isopropyl bromide (iPB), and urinary metabolite concentrations of bromide and propyl mercapturic acid were measured. n-Propyl bromide has been marketed to replace ozone depleting solvents 1,1,I-trichloroethane and freons®, as well as suspect carcinogens trichloroethylene and methylene chloride; chemicals that were commonly used in industry. Very little data are currently available to evaluate human exposure to nPB. However, there is concern that nPB may be a hematological, reproductive, or neurological toxin, based on analogy to other brominated-propanes, animal toxicity studies, and a limited number of case studies. Full-shift exposure to nPB in air samples collected in workers' breathing zones ranged from 0.19 to 2.6 parts per million (ppm). All of the workers were exposed to nPB at levels below the American Conference of Governmental Industrial Hygienist (ACGIH) Threshold Limit Value® (10 ppm) as well as the industrial guideline of 25 ppm published by the EPA in their proposed rulemaking to accept nPB under the Clean Air Act. Isopropyl bromide was not detected in either the air or breath samples. Exhaled breath concentrations of n-propyl bromide ranged from ND to 0.13 ppm and ND to 0.38 ppm, respectively, for pre-shift samples and post-shift samples. Average urinary bromide concentrations were approximately 77% higher for workers than for unexposed control subjects who were not employed by the company. Twenty-four hour average propyl mercapturic acid concentrations measured in urine specimens from workers were over an order of magnitude higher than that measured in control samples. Dermal absorption may have contributed to some of the workers' exposure in addition to inhalation exposure. Workers with the lowest breathing zone concentrations of nPB had urinary metabolite levels similar to those measured in control specimens. At this time, the health significance of these levels of urinary metabolites is unclear. Recommendations include, but are not limited to, substitution of nPB solvents with a less toxic solvent (if feasible), periodic exposure monitoring, use of gloves that are impermeable to nPB, and routine medical examinations.

Abstract  Data from National Health and Nutrition Examination Survey for the years 2011-2012 were used to evaluate variability in the observed levels of 20 urinary metabolites of volatile organic compounds (VOCs) by age, gender, and race/ethnicity among children aged 6-11 years. Exposure to environmental tobacco smoke was positively associated with the levels of selected metabolites of acrylonitrile, 1,3-butadiene, cyanide, and propylene oxide in a dose-response manner. Levels of the selected metabolites of acrolein, acrylonitrile, 1,3-butadiene, styrene, toluene, and xylene decreased with increase in age. Levels of 1-bromopropane decreased with number of rooms in the house but the reverse was true for 1,3-butadiene, carbon-disulfide, and N,N-dimethylformamide. Levels of most of the 20 metabolites did not vary with gender. Non-Hispanic white children had higher adjusted levels of N-Acetyl-S-(3,4-dihydroxybutyl)-l-cysteine (DHBMA), N-Acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC), and phenylglyoxylic acid (PGA) than non-Hispanic black children. Non-Hispanic white children had statistically significantly higher adjusted levels of N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine (GAMA), trans, trans-Muconic acid (MU), and N-Acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC) than non-Hispanic Asian children but statistically significantly lower levels of N-Acetyl-S-(n-propyl)-l-cysteine (BPMA) than non-Hispanic Asian children. Non-Hispanic Asian children had the lowest levels of 13 of the 20 metabolites among four major racial/ethnic groups but highest levels for three metabolites. For selected metabolites of acrolein, acrylamide, acrylonitrile-vinyl chloride-ethylene oxide, benzene, 1,3-butadien, crotonaldehyde, cyanide, ethylbenzene-styrene, and toluene, children had statistically significantly higher levels than nonsmoking adults. These results demonstrate how vulnerable children are to being exposed to harmful chemicals like VOCs in their own homes.

Abstract  This document presents the scope of the risk evaluation to be conducted for 1-BP. If a hazard, exposure, condition of use or potentially exposed or susceptible subpopulation has not been discussed, EPA, at this point in time, is not intending to include it in the scope of the risk evaluation. As per the rulemaking, Procedures for Chemical Risk Evaluation Under the Amended Toxic Substances Control Act (TSCA), with respect to conditions of use in conducting a risk evaluation under TSCA, EPA will first identify “circumstances” that constitute “conditions of use” for each chemical. While EPA interprets this as largely a factual determination—i.e., EPA is to determine whether a chemical substance is actually involved in one or more of the activities listed in the definition—the determination will inevitably involve the exercise of some discretion.

Abstract  We examined the biological consequences of bi-stranded clustered damage sites, consisting of a combination of DNA lesions, such as a 1-nucleotide gap (GAP), an apurinic/apyrimidinic (AP) site, and an 8-oxo-7,8-dihydroguanine (8-oxoG), using a bacterial plasmid-based assay. Following transformation with the plasmid containing bi-stranded clustered damage sites into the wild type strain of Escherichia coli, transformation frequencies were significantly lower for the bi-stranded clustered GAP/AP lesions (separated by 1bp) than for either a single GAP or a single AP site. When the two lesions were separated by 10-20bp, the transformation efficiencies were comparable with those of the single lesions. This recovery of transformation efficiency for separated lesions requires DNA polymerase I (Pol I) activity. Analogously, the mutation frequency was found to depend on the distance separating lesions in a bi-stranded cluster containing a GAP and an 8-oxoG, and Pol I was found to play an important role in minimising mutations induced as a result of clustered lesions. The mutagenic potential of 8-oxoG within the bi-stranded lesions does not depend on whether it is situated on the leading or lagging strand. These results indicate that the biological consequences of clustered DNA damage strongly depend on the extent of repair of the strand breaks as well as the DNA polymerase in lesion-avoidance pathways during replication.

Abstract  Human infants can discover words directly from unsegmented speech signals without any explicitly labeled data. Current machine learning methods cannot efficiently estimate language model (LM) and acoustic model (AM) and discover words directly from continuous human speech signals in an unsupervised manner. To solve this problem, we propose an integrative generative model that combines an LM and an AM into a single generative model called the hierarchical Dirichlet process hidden LM (HDP-HLM). The HDP-HLM is obtained by extending the hierarchical Dirichlet process hidden semi-Markov model (HDP-HSMM) proposed by Johnson et al. An inference procedure for the HDP-HLM is derived using the blocked Gibbs sampler originally proposed for the HDP-HSMM. This procedure enables the simultaneous and direct inference of LM and AM from continuous speech signals. Based on the HDP-HLM and its inference procedure, we develop a novel machine learning method called nonparametric Bayesian double articulation analyzer (NPB-DAA) that can directly acquire LM and AM from observed continuous speech signals. By assuming HDP-HLM as a generative model of observed time series data, and by inferring latent variables of the model, the method can analyze latent double articulation structure, i.e., hierarchically organized latent words and phonemes, of the data in an unsupervised manner. We also carried out two evaluation experiments using synthetic data and actual human continuous speech signals representing Japanese vowel sequences. In the word acquisition and phoneme categorization tasks, the NPB-DAA outperformed a conventional double articulation analyzer and baseline automatic speech recognition system whose AM was trained in a supervised manner. The main contributions of this paper are as follows: 1) we develop a probabilistic generative model that integrates LM and AM, i.e., HDP-HLM; 2) we derive an inference method for this, and propose the NPB-DAA; and 3) we show that the NPB-DAA can discover words directly from continuous human speech signals in an unsupervised manner.

Abstract  Low frequency of green plant production and albinism limits the use of isolated microspore culture (IMC) in cereal breeding programs. The present study was conducted in triticale and bread wheat IMC to increase the production of green plants and minimize albinism. NPB-99 + 10% Ficoll induction medium was supplemented with mitochondrial or plastid antioxidants, in a completely random design, to evaluate their contribution to successful microspore embryogenesis and green plant production. Each group of antioxidants was tested independently: first in triticale and then validated in various spring wheat genotypes. While the response differed by wheat genotype, induction medium supplemented with proline (10 mM) yielded a greater number of embryos/embryo-like structures and green plants in both triticale and wheat. No differences were found with respect to albinism in triticale or wheat except for the cv. Sadash. Among plastid antioxidants tested, glutathione (2 mu M) proved to be the best antioxidant to increase embryo and green plant production. Salicylic acid also helped to reduce the number of albino plants in triticale and the wheat genotype SWS366. Overall, induction medium supplemented with proline or glutathione enhanced microspore embryogenesis in both triticale and wheat and increased the number of green plants in the recalcitrant genotypes.