Topical toxicity studies

Only a few in vivo dermal toxicity studies have been reported so far. Huczko and Lange [50] evaluated the potential of raw CNTs to induce skin irritation by conducting two routine dermatological tests (patch test on 40 volunteers with allergy susceptibilities and Draize rabbit eye test on four albino rabbits). Koyama etal. [51] showed the biological responses to four different types of carbon nanotubes (SWNTs, two types of MWNTs with different diameters, and cup-stacked carbon nanotubes) after their subcutaneous implantation in mice. Both tests [50, 51] showed no or poor irritation effects. However, the in vitro studies in epidermal cell lines exposed to CNTs, and also a more recent report on the toxic outcomes of topical exposure of mice to SWNTs [46], have raised concerns over these assessments. Clearly, this is an area requiring further scientific evaluation. 

In subacute toxicity studies only the highest rifaximin dose (i.e. 100 mg/kg, corresponding to 25 times the therapeutic dose in humans) induced mild toxic effects (like, for instance, acute gastroenteritis) connected to the topical GI action of the drug [59, 255], A dose-dependent increase of the total cholesterol value was recorded in female animals [255], most likely due to an alteration of biliary acid metabolism consequent to the antibiotic effect on gut flora [256]. 

In a follow-up study in mice, exposure to DEA, via drinking water or by topical application, caused dose-dependent toxic effects in the liver (hepatocellular cytological alterations and necrosis), kidney (nephropathy and tubular epithelial necrosis in males), heart (cardiac myoqn e degeneration), and skin (site of application ulceration, inflammation, hyperkeratosis, and acanthosis). Doses ranged from 630 to 10,000 ppm in the drinking water and from 80 to 12 50 mg/kg in the topical application study. 

In 2-week and 13-week toxicity studies topical administration of MEKP (as a 45% solution in dimethyl phthalate) to both rats and mice resulted in a spectrum of necrotic, inflammatory, and regenerative skin lesions limited to the application site. Lesions considered secondary to the dermal lesions included increased hematopoiesis in the spleen in rats and mice and increased myeloid hyperplasia of the bone marrow in mice. 

National Toxicology Program Toxicity Studies of Methyl Ethyl Ketone Peroxide in Dimethyl Phthalate Administered Topically to P344/N Rats and B6C3P1 Mice. National Toxicology Program Toxicity Report Series. Vol 18, pp 1-58. US Department of Health and Human Services, Public Health Service, National Institutes of Health, 1993... 

National Toxicology Program (1992) Toxicity Studies of Diethanolamine (CAS No. 111-42-2) Administered Topically and in Drinking Water to F344/NRats and B6C3F Mice (Tech. Rep. Ser. No. 20 NIH Pubhcation No. 92-3343), Department of Health and Human Services, Research Triangle Park, NC... 

Additional considerations for topically (dermal, intransal, introral, ophthalmic, rectal or vaginal) or pulmonary adminstered excipients are ocular irritation, sensitisation, oral or parenteral route toxicity studies additional considerations for injectable excipients are an in vitro hemolysis study, measurement of creatinine kinase and protein binding evaluation where appropriate new excipients should also be examined for photosafety. 

The use of chemical extractants for the assessment or prediction of agricultural crop plant contents, plant growth or health and the estimation of the likelihood of plant or animal (consuming the fodder plant) deficiency or toxicity has been a major topic of study in agricultural laboratories for almost half a century, although... 

Animal toxicity studies have shown no evidence of phototoxicity or tumor occurrence when bronopol is applied to rodents topically or administered orally and there is no in vitro or in vivo evidence of mutagenicity this is despite the demonstrated potential of bronopol to liberate nitrite on decomposition, which in the presence of certain amines may generate nitrosamines. Formation of nitrosamines in formula-... 

Dimethylacetamide is used in pharmaceutical preparations as a solvent in parenteral formulations and is generally regarded as a nontoxic material when used as an excipient. Animal toxicity studies indicate that dimethylacetamide is readily absorbed into the bloodstream following inhalation or topical application. Repeated exposure to dimethylacetamide may be harmful and... 

Animal toxicology a summary along with acute, long-term, reproduction, local toxicity and mutagenic/carcinogenic data. There are detailed requirements of toxicity studies in terms of time, dose, route of administration, which are beyond the scope of this article. Reproduction study requirements are also specified in terms of fertility studies, terato-genecity studies and perinatal studies. Local toxicity is limited to preparations intended for topical use. 

For detailed information on safety assessment of vaccines (prophylactic and therapeutic), readers are referred to reviews on this topic (Lebron et al. 2005 Sun et al. 2012 Matsumoto et al. 2014). SP for bacterial- or mammalian cell-derived oligonucleotides is typically evaluated during repeat-dose toxicity studies (Dixit et al. 2010 Kim et al. 2014) however, recommendations and strategies that can be used to assess these unique agents have been developed by the SP subcommittee of the Oligonucleotide Safety Working Group (Schubert et al. 2012 Berman et al. 2014). 

Christian MS, Mitala JJ, Powers WJ, McKenzie BE, Latriano L (1997) A developmental toxicity study of tretinoin emollient cream (Renova) applied topically to New Zealand white rabbits. J Amer Acad Dermatol 36 (6 Pt 2) S67-S76... 

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