Regulatory status

The applicability of bulk and intense sweeteners is determined by their regulatory status. Bulk and intense sweeteners require food additive approval in many countries. 

An important step and for some countries even a prerequisite before food additive approval is endorsement for food use by international scientific bodies like the JECFA or the European SCF. These committees evaluate the safety data, identify a no-observed-effect level and allocate an ADI, usually by applying a safety factor of 100 to the ADI. While numerical values have been allocated for all intense sweeteners, the ADIs for bulk sweeteners are normally not specified as any numerical limitation would not be reasonable for these substances. 

In the USA the available bulk sweeteners are listed under different provisions, like food additive, interim status, GRAS (Generally Recognised As Safe) or GRAS by self-determination or self-affirmation of the manufacturers. Intense sweeteners require food additive approval which includes a listing of the approved fields of use or may be a listing as a general purpose sweetener.32 

Beyond national approvals the Codex Alimentarius is developing a General Standard for Food Additives which will be the applicable basis for international trade. All and only sweeteners endorsed for food use by JECFA are/or will be listed in this standard. For bulk sweeteners the standard has progressed to permanent while the part dealing with intense sweeteners is still under discussion. 

For bulk sweeteners, which are often an important and sometimes the most important ingredient, any limitation would be unreasonable and often even render their use impossible. In the EU consumers are alerted of potential laxative effects by labelling of products containing more than 10% by weight of sugar alcohols. 

Valeriana officinalis L. is acceptable as an active ingredient in the listed products category of the Therapeutic Goods Administration 

Subterranean parts, powder, extract, and tincture are permitted as traditional tranquilizers The Health Protection Branch of Health Canada allows products containing valerian as a single medicinal ingredient in the form of crude dried root in tablets, capsules, powders, extracts, tinctures, drops, or tea bags intended to be used as sleeping aids/sedatives 

Valerian root (from Valeriana officinalis L.) has traditional use in symptomatic treatment of neurotonic conditions of adults and children, particularly in cases of minor sleep disturbances Commission E has approved valerian for restlessness and nervous disturbances of sleep Valerian is included in the General Sale List of the Medicines Control Agency and permitted in traditional herbal remedies as a sedative and to promote natural sleep 

Note Valerian consists of the dried rhizome and roots of Valeriana officinalis Linne (Fam. Valerianaceae). It has been employed as an antianxiety agent and sleep aid for more than 1000 years. The drug contains from 0.3 to 0.7% of an unpleasant-smelling volatile oil containing bornyl acetate and the sesquiterpenoids, valerenic acid, and acetoxyvalerenolic acid. Also present is a mixture of lipophilic iridoid principles known as valepotriates. These bicyclic monoterpenoids are quite unstable and occur only in the fresh plant or in material dried at temperatures under 40°C. Although the specific active principals of valerian have not been determined, it is possible that a combination of the sesquiterpenoids and the valepotriates may be involved. The drug may be administered as a tea prepared from 2 to 3 g of the dried herb or equivalent amounts of a tincture or extract may be employed. 

Valerian (as Valeriana officinalis L.) has official status (i.e., government approval in some capacity) in many countries throughout the world. In some cases, the status is based on traditional use rather than controlled trials. Table 65.2 shows the regulatory status of valerian. 

In the United States, CAS number 88-73-3, Benzene, l-chloro-2-nitro-, is listed on the Toxic Substances Control Act (TSCA) Non-Confidential Inventory with no Significant New Use Rule (SNUR) [38]. It has been designated as a High Production Volume (HPV) chemical [39]. In the European Union (EU), ONCB has been notified under REACH as an intermediate and as a chemical produced or imported at 100-1,000 tormes per armum. The REACH notifications refer to use as an intermediate in closed processes, and to use as a laboratory reagent [40]. In China, ONCB is listed on the Inventory of Existing Chemical Substances Produced or Imported in China (lESC) it is also listed in the Catalog of Hazardous Chemicals [41]. 

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Sweeteaer lateasity Developer and/or manufacturer Regulatory status... 

SheU material Regulatory status Chemical class Encapsulation process AppHcations... 

Enzymes are used as feed digestibiUty enhancers for chicken and pigs. They must comply with purity specifications comparable to food-grade enzyme specifications. European Community (EC) guidelines for the assessment of additives in animal nutrition are being revised to make them appHcable for enzymes. Upon completion of these guidelines, the regulatory status of feed enzymes will be estabUshed in EC directive 70/524/EEC. 

Technical Enzymes. When an enzyme is used for a technical appHcation, ie, industrial but nonfood and nonfeed, its regulatory status is determined by its properties as a naturally occurring substance. These properties determine the classification and consequent labeling in accordance with existing schemes for chemicals. It should be noted that enzymes are not Hsted as dangerous chemicals. 

In order to determine the regulatory status of an individual product you need to answer two key questions ... 

Hallagan, J.B., Allen, D.C., and Borzelleca, J.F., The safety and regulatory status of food, drug and cosmetic color additives exempt from certification. Food Chem.Tox-icoL, 33, 515, 1995. 

FIGURE 20.1 Regulatory status and number of Class I wells in the U.S. (From U.S. EPA, Assessing the Geochemical Fate of Deep-Well-Injected Hazardous Waste A Reference Guide, EPA/625/6-89/025a, U.S. EPA, Cincinnati, OH, June 1990.)... 

Figure 20.1 shows the number of Class I wells in the 1986 survey by state, divided into U.S. EPA regions, and also indicates the regulatory status of such wells in each state as of 1989. The map shows the heavy concentration of hazardous waste injection wells in three geologic basins Gulf Coast, Illinois Basin, and the Michigan Basin.1 3 ... 

Regulatory status In 1998, Lopez Canyon Sanitary Landfill received conditional approval for an ET cover, which required a minimum of 2 years of field performance data to validate the model used for the design. An analysis was conducted and provided the basis for final regulatory approval of the ET cover. The cover was fully approved in October 2002 by the California Regional Water Quality Control Board—Los Angeles Region. 

REGULATORY STATUS AND ENVIRONMENTAL PROPERTIES OF BROMINATED FLAME RETARDANTS UNDERGOING RISK ASSESSMENT IN THE EU DBDPO, OBDPO,... 

A conflict clearly exists between permanent confidentiality, available under the system of U.S. laws, and the eventual disclosure of identities of specialized chemical substances which had heretofore been undisclosed, but which are now affected by EINECS or by EEC s premarketing notification system. The rules are different the assumptions regarding disclosure are different. Perhaps the best solution a lawyer could offer is that member states should be willing to adjudicate individual cases of specific confidentiality needs. Inventories of existing substances are rules, adopted prospectively to announce to the world both the existence of a material and its regulatory status. Those rules can operate to accommodate both public and private needs. 

Hatcher, J. A. Slater, G. S. Regulatory Status of Silicones in the United States. In The Handbook of Environmental Chemistry Vol. 3 Antropogenic Compounds, Part H Chandra, G., Ed. Springer Berlin, 1997 Chapter 9, pp 241-266. 

Production, Import/Export, Use, Release, and Disposal. Because of the general confusion in the literature about the nomenclature for octylphthalate esters, historical information about the production and import/export of di- -octylphthalate is not readily available. These values generally must be estimated as a percentage of di(2-ethylhexyl)phthalate production or import/export. The compound is used principally as a plasticizer additive to plastics and PVC resins. It is also used as a dye carrier in plastics production and as a chemical intermediate (EPA 1993a HSDB 1995 Mannsville Chemical Products Corporation 1989 Sittig 1991). Limited information is available about releases of di-n-octylphthalate to environmental media. Even the TRI data, which comprise the most current information available, contain errors as a result of the nomenclature confusion (EPA 1993a Vista Chemical 1992). Data are available about the disposal and regulatory status of the compound (see Chapters 4 and 7). More information on the production and releases of di-ft-octylphthalate is needed to estimate potential exposure to the compound. 

Bioavailability, dissolution and stability study data Regulatory status in other countries Marketing information Proposed product monograph... 

Explain what is meant by biogenerics and the regulatory status with respect to approving these drugs. 

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