Scientific basis for uncertainty factors used to establish occupational exposure limits for pharmaceutical active ingredients

Naumann, Bruce D.; Weideman, Patricia A.

doi:10.1080/10807039509380049

Cited by 69 publications

(24 citation statements)

References 45 publications

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“…For instance, the U.S. EPA (2002) recommends using "half log" (i.e., 10 0.5 or approximately 3) factors where uncertainty is reduced by the availability of multispecies pharmacokinetic or pharmacodynamic data. Others have advocated uncertainty factors that are derived on a compound-speciWc basis from supporting data ("data-derived factors"; Naumann and Weideman, 1995;Renwick, 1993;Silverman et al, 1999 or "chemical-speciWc adjustment factors"; IPCS, 2001). Table 2 describes our implementation of these concepts, incorporating the considerable amount of human and laboratory data available for APIs.…”

Section: Development Of Adismentioning

confidence: 99%

Human pharmaceuticals in US surface waters: A human health risk assessment

Schwab

Hayes

Fiori

et al. 2005

Regulatory Toxicology and Pharmacology

370

182

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Section: Development Of Adismentioning

confidence: 99%

Human pharmaceuticals in US surface waters: A human health risk assessment

Schwab

Hayes

Fiori

et al. 2005

Regulatory Toxicology and Pharmacology

370

182

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“…The International Programme on Chemical Safety (IPCS, 1994), however, recommended that the UF for interindividual differences should be split evenly (3.16 each for kinetics and dynamics), while the UF for interspecies variability remained 4.0 for kinetics and 2.5 for dynamics. Recently, Naumann and Weideman (1995) demonstrated that individual variability can be quantitated using kinetics and dynamics in order to reduce uncertainties when establishing OELs for pharmaceutical active ingredients. Furthermore, Naumann et al (1996) made specific recommendations on how kinetic and dynamic parameters can be used to replace default UFs with data-derived values.…”

Section: Subchronic-to-chronic Extrapolationmentioning

confidence: 99%

Assessing human health risks of chemicals and drugs: An overview

Suh

Abdel‐Rahman

1997

Human and Ecological Risk Assessment: An International Journal

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The risk assessment process for non-carcinogens involves extrapolation of toxicological animal data to humans by applying uncertainty factors (UF). A 10-fold UF is most commonly used to account for underlying variability in different areas of uncertainty. The purpose of this investigation is to evaluate whether the magnitude of the 10X UF can be reduced when pharmacokinetic and pharmacodynamic data are incorporated especially into interspecies extrapolation and interindividual variability. A compilation and comparison of kinetic and dynamic data between animal/human and sensitive human/human were made. The composite UFs were calculated using the highest ratios for available kinetic and dynamic data and default subfactors. When relevant kinetic and dynamic data are available, UFs are significantly reduced by replacing the default factors with actual data derived-values.

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“…For many years pharmaceutical companies established occupational exposure limits (OELs) for the active ingredients used in their products (Naumann and Weideman, 1995). The method used to establish OELs for pharmaceuticals parallels the method described originally by Lehman and Fitzhugh (1954).…”

Section: Introductionmentioning

confidence: 99%

“…The most common used formula for establishing OELs is that of Sargent and Kirk (1988 The trend in the pharmaceutical industry is to identify and develop more selective drugs of increasing potency. The process of drug development usually generates a large data sets on the physiological and pharmacological activity of the drug (Naumann and Weideman, 1995). The relationship between biological indicators and exposure or tissue burdens is determined by the pharmacokinetic and pharmacodynamic behavior of the chemical (Conolly, 1995).…”

Section: Introductionmentioning

confidence: 99%

Kinetic and dynamic data of analgesics and NSAIDs drugs reduce 10X uncertainty factors

Kadry¹,

Suh²,

Abdel‐Rahman

1997

Human and Ecological Risk Assessment: An International Journal

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The risk assessment process must use all available toxicological data and scientific evidence on the adverse effects of chemicals or drugs. The relationship between biological indicators and exposure or tissue burdens is determined by the pharmacokinetic and pharmacodynamic behavior of the chemical. The purpose of the present project was to investigate the use of pharmacokinetic and pharmacodynamic data in reducing the uncertainties in establishing exposure levels for some analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Five pharmaceuticals were evaluated, namely: naproxen, acetaminophen, aspirin, ibuprofen and ketoprofen. The pharmacokinetic and pharmacodynamic parameters in inter-and intra-species were evaluated. The composite factors for all the examined drugs were far less than 100. The present study indicated that the formation of data basis for different chemicals based on pharmacokinetic and pharmacodynamic behavior is important in setting up exposure levels, rather than the use of default uncertainty factors which are in many cases imprecise.

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Scientific basis for uncertainty factors used to establish occupational exposure limits for pharmaceutical active ingredients

Cited by 69 publications

References 45 publications

Human pharmaceuticals in US surface waters: A human health risk assessment

Human pharmaceuticals in US surface waters: A human health risk assessment

Assessing human health risks of chemicals and drugs: An overview

Kinetic and dynamic data of analgesics and NSAIDs drugs reduce 10X uncertainty factors

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