The duration of toxicity studies required to support repeated dosing in clinical investigation — a clinician’s opinion

1994 ◽  
pp. 75-83
Author(s):  
Kurt Suter
Keyword(s):  
Clinical Investigation ◽  
Toxicity Studies ◽  
Repeated Dosing

Biokinetics in repeated-dosing in vitro drug toxicity studies

2015 ◽  
Vol 30 (1) ◽  
pp. 217-224 ◽  
Author(s):  
Nynke I. Kramer ◽  
Emma Di Consiglio ◽  
Bas J. Blaauboer ◽  
Emanuela Testai
Keyword(s):  
Drug Toxicity ◽  
Toxicity Studies ◽  
Repeated Dosing

Reproductive toxicity testing of pharmaceutical compounds to support the inclusion of women in clinical trials

1997 ◽  
Vol 16 (5) ◽  
pp. 239-246 ◽  
Author(s):  
Chris Parkinson ◽  
Kate E Thomas ◽  
Cyndy E Lumley
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Animal Studies ◽  
Clinical Investigation ◽  
Reproductive Toxicity ◽  
Toxicity Testing ◽  
Toxicity Tests ◽  
Toxicity Studies ◽  
Important Concern ◽  
The Usa

1 The potential for toxicity to reproduction and the developing fetus is an important concern requiring attention during the development of new medicines. However, there are differences in the opinions of the regulatory authorities in Europe, Japan and the USA regarding the nature and amount of data from reproductive toxicity tests that should be available at the various stages of clinical development. 2 Forty-one companies or their subsidiaries from Eur ope, Japan and the USA provided data for a ques tionnaire-based study, carried out in 1994, to ascertain the practices of pharmaceutical companies and their views on an ideal approach to the timing of reproduc tion and development toxicity studies in relation to clinical investigation. 3 Differences were identified in the stage of drug development at which animal studies were completed, the sequence of completion of specific studies, and the extent of reproduction testing completed to support the inclusion of women in clinical trials. 4 A harmonised, but flexible, guideline, encompassing the timing of reproductive toxicity studies in relation to clinical trials, would permit better integration between clinical and non-clinical studies in an international drug development programme.

Acute, Subchronic, and Developmental Toxicological Properties of Lubricating Oil Base Stocks

2014 ◽  
Vol 33 (1_suppl) ◽  
pp. 110S-135S ◽  
Author(s):  
Walden E. Dalbey ◽  
Richard H. McKee ◽  
Katy Olsavsky Goyak ◽  
Robert W. Biles ◽  
Jay Murray ◽  
...  
Keyword(s):  
Vacuum Distillation ◽  
Developmental Toxicity ◽  
Reproductive Organs ◽  
Lubricating Oil ◽  
Hydrogen Treatment ◽  
Toxicity Studies ◽  
Developmental Effects ◽  
Polycyclic Aromatic ◽  
Repeated Dosing ◽  
Additional Refining

Lubricating oil base stocks (LOBs) are substances used in the manufacture of finished lubricants and greases. They are produced from residue remaining after atmospheric distillation of crude oil that is subsequently fractionated by vacuum distillation and additional refining steps. Initial LOB streams that have been produced by vacuum distillation but not further refined may contain polycyclic aromatic compounds (PACs) and may present carcinogenic hazards. In modern refineries, LOBs are further refined by multistep processes including solvent extraction and/or hydrogen treatment to reduce the levels of PACs and other undesirable constituents. Thus, mildly (insufficiently) refined LOBs are potentially more hazardous than more severely (sufficiently) refined LOBs. This article discusses the evaluation of LOBs using statistical models based on content of PACs; these models indicate that insufficiently refined LOBs (potentially carcinogenic LOBs) can also produce systemic and developmental effects with repeated dermal exposure. Experimental data were also obtained in ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and seven dermal developmental toxicity studies with sufficiently refined LOBs (noncarcinogenic and commonly marketed) in which no observed adverse effect levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d with dermal exposures, typically the highest dose tested. Results in both oral and inhalation developmental toxicity studies were similar. This absence of toxicologically relevant findings was consistent with lower PAC content of sufficiently refined LOBs. Based on data on reproductive organs with repeated dosing and parameters in developmental toxicity studies, sufficiently refined LOBs are likely to have little, if any, effect on reproductive parameters.

The timing of toxicity studies in relation to clinical investigation

1994 ◽  
Vol 74 ◽  
pp. 60
Author(s):  
C. Parkinson ◽  
K. Thomas ◽  
N. McAuslane ◽  
C.E. Lumley
Keyword(s):  
Clinical Investigation ◽  
Toxicity Studies

Acute, 14-Day Repeated Dosing, and 90-Day Subchronic Toxicity Studies of Potassium Picloram

1986 ◽  
Vol 7 (3) ◽  
pp. 464-470
Author(s):  
JOHNNIE R. HAYES ◽  
LYMAN W. CONDIE ◽  
JOSEPH F. BORZELLECA
Keyword(s):  
Subchronic Toxicity ◽  
Toxicity Studies ◽  
Repeated Dosing

Acute, 14-Day Repeated Dosing, and 90-Day Subchronic Toxicity Studies of Carbon Tetrachloride in CD-1 Mice

1986 ◽  
Vol 7 (3) ◽  
pp. 454-463 ◽  
Author(s):  
JOHNNIE R. HAYES ◽  
LYMAN W. CONDIE ◽  
JOSEPH F. BORZELLECA
Keyword(s):  
Carbon Tetrachloride ◽  
Subchronic Toxicity ◽  
Toxicity Studies ◽  
Repeated Dosing
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