Chemical Manufacture Section

Product innovation absorbs considerable resources in the fine chemicals industry, in part because of the shorter life cycles of fine chemicals as compared to commodities. Consequently, research and development (R D) plays an important role. The main task of R D in fine chemicals is scaling-up lab processes, as described, eg, in the ORAC data bank or as provided by the customers, so that the processes can be transferred to pilot plants (see Pilot PLANTS AND microplants) and subsequently to industrial-scale production. Thus the R D department of a fine chemicals manufacturer typically is divided into a laboratory or process research section and a development section, the latter absorbing the Hon s share of the R D budget, which typically accounts for 5 to 10% of sales. Support functions include the analytical services, engineering, maintenance, and Hbrary. 

The development section serves as an intermediary between laboratory and industrial scale and operates the pilot plant. A dkect transfer from the laboratory to industrial-scale processes is stiH practiced at some small fine chemicals manufacturers, but is not recommended because of the inherent safety, environmental, and economic risks. Both equipment and plant layout of the pilot plant mirror those of an industrial multipurpose plant, except for the size (typically 100 to 2500 L) of reaction vessels and the degree of process automation. 

Are you involved m the transport of dangerous substances by road (replaced by IND(G)234L) COSHH and Section 6 of the Health and Safety at Work Act Permit-to-work systems. (Chemical manufacturing)... 

A completed Form R must be submitted for each toxic chemical manufactured, processed, or otherwise used at each covered facility as prescribed in the reporting rule in 40 CFR Part 372 (published February 16,1988 in the Federal Register). These instructions supplement and elaborate on the requirements In the reporting rule. Together with the reporting rule, they constitute the reporting requirements. All references in these instructions are to sections in the reporting rule unless otherwise indicated. 

The route of entiy section describes the primary patluvay by which the chemical enters the body. There are tlu-ee principal routes of entry inlialation, skin, and ingestion. This section of the MSDS supplies the PEL. the TLV, and other e.xposure levels used or recommended by the chemical manufacturer. 

Catalytic transformations can be divided on the basis of the catalyst-type - homogeneous, heterogeneous or enzymatic - or the type of conversion. We have opted for a compromise a division based partly on type of conversion (reduction, oxidation and C-C bond formation, and partly on catalyst type (solid acids and bases, and biocatalysts). Finally, enantioselective catalysis is a recurring theme in fine chemicals manufacture, e.g. in the production of pharmaceutical intermediates, and a separate section is devoted to this topic. 

Modelling can at least facilitate the determination of the most effective scale-up program. Information from three fields is needed for modelling (1) chemical kinetics, (2) mass transfer, and (3) heat transfer. The importance of information for different processes has been qualitatively evaluated (see Table 5.3-5). Obviously, sufficiently accurate information on heat transfer is needed for batch reactors, which are of great interest for fine chemicals manufacture. Kinetic studies and modelling requires much time and effort. Therefore, the kinetics often is not known. Presently, this approach is winning in the scale-up of processes for bulk chemicals. The tools developed for scale-up of processes for bulk chemicals have been proven to be very useful. Therefore, the basics of this approach will be discussed in more detail in subsequent sections. 

The Chemical Manufacturers Association (CMA) had reached similar conclusions about a year ago and filed a petition with EPA suggesting that there was a strong case to be made for exemptive relief under Section 5 (h)(4) of TSCA for many polymers, site-limited intermediates, and chemicals produced in volumes of less than 25,000 pounds per year. (An examination of the effect of PMN costs at various prices and levels of production reveals that the PMN cost, as a percentage of total cost per pound of product, generally rises most rapidly as output falls below 25,000 pounds. See the Appendix for a more detailed discussion.) It is CMA s firm belief that exemption could be granted in terms that would operate to assure "no unreasonable risk" to the public in terms of either health or the environment. 

Monsanto s experience illustrates both the positive and negative impacts on one chemical company under TSCA sections 5 and 8. For a broader perspective, refer to the Chemical Manufacturers Association publication "The First Four Years of the Toxic Substance Control Act." - The authors views are also presented relative to EPA s management of information under section 10. 

Heiden, Edward J. Pittaway, Alan R. "A Critique of the EPA, Economic Impact of Analysis of Proposed Section 5 Notice Requirements", Chemical Manufacturers Association (March 16, 1981). 

CSB searched over 40 data sources for incidents that met its definition of a reactive incident (Section 2.1). The data search focused on recent incidents (since 1980) where the primary cause was related to chemical reactivity however, the 1980 cutoff is not intended to diminish the important lessons learned from prior incidents. The search covered both chemical manufacturing (i.e., raw material storage, chemical processing, and product storage) and other industrial activities involving bulk chemicals, such as... 

This section of this paper reports on a detailed study of the organic compounds in the Delaware River. Since most of our previous studies have dealt with isolated chemical plants on small rivers, we felt it would be instructive to study a complex river system surrounded by several large-scale chemical manufacturers. This would give us information on the effluents from several industrial dischargers, the relative persistence of chemical discharged from any single source, and the movement of these industrial chemicals in a major river ecosystem. 

F. X-ray Powder Difi action Search System. Compounds that fail to crystallize may still be examined by X-ray diffraction, because non-crystalline materials, as powders, give characteristic diffraction patterns. A collection of powder diffraction patterns proves to be a very effective means by which to identify materials and indeed, one of the very earliest search systems in chemical analysis was based upon such data by Hanawalt (21) over forty years ago. The importance of these data in TSCA can be seen by examining the TSCA Inventory regulations for treatment of confidential chemicals (22). Section 710.7 of these regulations indicates that EPA intends to rely on powder diffraction data to assure the validity and seriousness of a manufacturers request for treating information on a chemical as confidential. 

The magnitude of the effect of this scheduled phaseout on total carbon tetrachloride production is uncertain, since the Halogenated Solvents Industry Alliance estimates that only about 3% of the chemical manufactured in the U.S. is used in nonfeedstock applications (EPA 1991). Nevertheless, since the major current use of carbon tetrachloride is in the production of chlorofluorocarbons (see Section 4.3), and production of these chemicals has dropped significantly in recent years (C EN 1993) and is also scheduled for phase-out by 1996, a significant reduction in carbon tetrachloride production is expected during this decade. 

CMA. 1981. Report of the Chemical Manufacturers Association Ketones Program Panel, Chemical Manufacturers Association, Washington, DC. OTS Section 4 submission. Microfiche No. OTS0512076. 

CMA. 1984. Voluntary Testing Program under Section 4 of the Toxic Substances Control Act. Submission of Test Data. Volume III. Isophorone Mutagenicity Studies. Unpublished studies performed by Microbiological Associates, Bethesda, MD for Chemical Manufacturers Association, Washington, DC. OTS Section 4 submission. Doc. ID. 40-8455047. Microfiche No. OTS0507222. 

KEMI s list of toxics is one of the most important sources of information for retailers in deciding on their purchases. Recent versions of the KEMI list carry an explanatory section that encourages the user to make some sort of risk assessment of the listed substances rather than automatically deciding against a product because it contains one or more of the listed chemicals. However, according to information from the Swedish Chemicals Manufacturers Association, retailers purchasing departments... 

Polybrominated Biphenyls. Hypothyroidism was diagnosed in 4 of 35 men who were occupationally exposed to unspecified PBBs and/or decaBDE (Bahn et al. 1980). The cohort consisted of workers (mean age 35.9 years) who had been employed at a production plant for at least 6 weeks during a 52-month period during which PBBs and decaBDE were the only chemicals manufactured and who had volunteered for a comprehensive medical evaluation performed 3 months after the end of the 52-month period. There was no further description of exposure, and it was assumed to have occurred by both inhalation and dermal routes. As detailed in Section 3.2.1.2, the results of this study suggest that occupational exposure to PBBs, decaBDE, and/or bromine affected the thyroid, but the mixed chemical exposure and a lack of data on serum or tissue levels of the chemicals preclude attributing effects solely to any particular congener or mixture of congeners. 

Cheng et al. (1993) analysed mortality in 109 workers who had been employed for one year or longer since 1974 in the pentachlorophenol section of a chemical manufacturing plant in China. During follow-up to 1990, three deaths were recorded, of which one was from lung cancer. 

For information about chemical manufacturing processes, the main encyclopedic references are Kirk-Othmer (1978-1984), McKetta and Cunningham (1976-date) and Ullmann (1972-1983) (References, Section 1.2, Part B). The last of these is in German,... 

Toxic Substances Control Act (TSCA) Enacted in 1976, the TSCA provides the EPA with the authority to require testing and to regulate chemicals, both old and new, entering the environment. It was intended to supplement sections of the Clean Air Act, the Clean Water Act, and the Occupational Safety and Health Act that already provide for regulation of chemicals. Manufacturers are required to submit information to allow the EPA to identify and evaluate the potential hazards of a chemical prior to its introduction into commerce. The act also provides for the regulation of production, use, distribution and disposal of chemicals, toxicant See poison, toxicokinetics See pharmacokinetics. 

During preclinical development, the structure, physical and chemical characteristics, and stereochemical identity of the IND/CTA candidate are fully characterized. This information, for example, is required for the chemical manufacture and control (CMC) section of the IND. Appropriate bioanalytical methods are developed for the evaluation of pharmacokinetics, typically a series of studies focusing on absorption, distribution, metabolism, and excretion (ADME) in toxicology species, as well as systemic exposure and metabolism in toxicological and clinical studies. 

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