Additive dose method

A new additive dose method is proposed to obtain the age directly without extrapolating the growth curve.1115 The experimental growth curve at the artificial irradiation dose rate gives simply the defect production efficiency (G-value) from the initial growth and the interaction distance, d, between spins from the saturation behaviour. The latter involves the effect of magnetic dipolar and exchange interactions of similar and dissimilar spins and also destabilization of a spin in a distorted area by a local lattice distortion. 

Fig. 9.12 The additive dose method. The magnitude of the intercept on the horizontal axis gives an estimate of the unknown dose. The figure is reproduced from [H. Gustafsson,...

The guidance document offers a comparison of TG 420 (Fixed Dose Method), TG 423 (Acute Toxic Class Method), and TG 425 (Up-and-Down Procedure). The purpose of this Guidance Document is to provide information to assist with the choice of the most appropriate Guideline to enable particular data requirements to be met while reducing the number of animals used and animal suffering. The Guidance Document also contains additional information on the conduct and interpretation of test guidelines 420, 423, and 425. 

An additional general method to reduce bypass is through vacuum deaeration. Miller9 performed experiments on a low-density active blend with and without vacuum deaeration, while holding all other parameters constant, and quantified the bypass for each trial. With the vacuum deaeration engaged, the bypass rate was 2% as compared to the control rate of over 20%. He also observed that the powder feed was uneven and the compact quality was not uniform. Most units are equipped with this capability and it should be considered to minimize bypass for low-dose products. However, vacuum deaeration can cause potency loss, unless the collected material is recirculated to the feed system. 

It is clear that the main focus in developing REACH has been related to at what level (i.e. production volume) requirements for certain relatively simple standard tests will come into force for hazard identification and dose-response assessment of single chemical substances. Little or no effort has been focused on the actual relevance of the ecotoxicological tests that should provide data for these crucial regulatory processes. As mentioned above, it has traditionally been a slow process for scientists to influence the regulatory framework, although thousands of scientific papers have presented additional test methods (e.g. reproduction tests, tests for endocrine disruption, molecular and biochemical analyses, population genetics, etc.) to improve our ability to protect ecosystems. 

The critical study (Bucci and Parker 1992) involved a relevant route of exposure (oral) for determining an RfD. Rats were administered GB by oral gavage, a route of administration that exaggerates the exposure that would normally occur from methods resulting in a slower rate of delivery (e.g., in feed or water). However, the study was subchronic in duration (13 weeks) rather than chronic (104 weeks), and ChE measurements varied and did not show a consistent dose-response relationship across ChE types and genders. Thus, the subcommittee believes that the study was too short in duration and that the results were too variable to form an ideal basis for determining a LOAEL. In addition, the methods used to measure ChE were not ideal (see Appendix G). However, in the absence of other well-conducted studies, the subcommittee agrees with ORNL that the study by Bucci and Parker (1992) is the most appropriate of the available studies for derivation of the RfD for GB. 

When this method is used for permeation studies, suitability of the methodology should be demonstrated, including determination of permeability relative to that of a reference compound whose fraction of dose absorbed has been documented to be at least 85%, as well as use of a negative control. Supportive data can be provided by the following additional test methods ... 

EPA used the relative potency factor (RPF) method in its cumulative hazard assessment of the OPs. The RPF method is based on the assumption of dose additivity, Dose additivity is the agency s assumption when evaluating the joint risk of chemicals that are toxicologically similar and act at the. same target site (EPA, 2001c). Briefly, with the RPF approach, the toxic potency of each chemical is first determined. One chemical, called the index chemical, is then selected. The index chemical provides the basis for comparison. Relative potency is determined by converting the toxic potency of each chemical into toxic equivalents of the index chemical. 

Although the effects of these reduced contraceptive steroids levels on ovulation were not assessed, it is likely that they could result in reduced efficacy. The manufacturer therefore recoimnends that alternative or additional contraceptive methods should be used during, and for 2 months (UK advice) or one month (US advice) after, aprepitant use. This seems a sensible precaution. No studies have been done on the effect of a single 40-mg dose of aprepitant 40 mg, as licensed in the US for postoperative nausea and vomiting. However, the US manufacturer states that the timing of the dose may cause contraceptive failure and the same guidance, as stated above, should be used. ... 

The tablets may be crushed and the resulting powder used as a source of active ingredient following a low dose method (see Sects. 4.5.1 and 4.6.1). Addition of a glidant is generally not necessary, because it is already present in the tablet. The final product also contains excipients from the original dosage form, which would have not been necessary if a preparation from the pure active substance was considered. 

The Association for Official Analytical Methods (AOAC) has approved the mouse bioassay [183] as a standard method for the screening of PSTs in seafood. It involves the intraperitoneal injection of 1 ml acid extract into a 20 g mouse, and the recording of symptoms and time to death. One mouse unit (MU) is defined as the toxin amount that kills a 20 g mouse in 15 min, which is equivalent to 0.18 mg saxitoxin. An obvious drawback of this method is animal cruelty. In addition, this method is not specific for PSTs, and it is prone to interference from substances that are imrelated to PSTs. Also the dose-response relationship is not always linear. 

The methods of ED determination described above involve the measurement of many subsamples. Several separate subsamples, or aliquots, are used for measurement of each point on the growth curve, so that between 20 and 60 aliquots are used for each ED determination. An alternative to such multiple aliquot methods is to make all the measurements on a single aliquot. The methods used are very similar to those for multiple aliquots, with both additive dose and regenerative measurements possible. 

In integration (continuous addition) dyeing, the use of different dosing methods produces different dye transfer profiles however, the difference in terms of DDF between the dosing methods is less than 5%. 

Internal Radiation The contractor s internal assessment revealed the new criteria for an internal dosimetry program were not stated in plant documentation. Additionally, a method or procedure to identify workers who meet the criteria did not exist, and a complete evaluation of all contributions to internal dose was required. 

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