Skin toxicity

Health and Safety Factors. Phloroglucinol has low toxicity by ingestion. Prolonged severe overexposure may dismpt the thyroid function. High dust concentration may cause respiratory irritation the product is irritating to eyes and skin. Toxicity data include LD q oral (rat) = 5800 mg/kg ... 

Dermal Toxicity Dermal toxicity is the ability of a substance to poison people or animals by contact with the skin. Toxic materials absorb through the skin to various degrees depending on their chemical composition and whether they are dissolved in a solvent. Always wear proper personal protection equipment (PPE), such as gloves and aprons, when working with a toxic (or nontoxic) substance that can be absorbed through the skin. 

Docetaxel asthenia, peripheral neuropathy, alopecia, cardiovascular Fatigue, nausea, vomiting, skin toxicity, neuropathy, anemia, Mild (on administration days... 

Skin toxicity is determined by the penetration and transport of the compound being tested through the lipid matrix in the outer skin layers (the stratum corneum)... 

Continuous IV infusion of 5-FU is generally well tolerated but is associated with palmar-plantar erythrodysesthesia or hand-foot syndrome. This distinct skin toxicity can be acutely disabling, but it is reversible and not life threatening. IV bolus administration is associated with leukopenia, which is dose limiting and can be life threatening. Both methods are associated with a similar incidence of mucositis, diarrhea, nausea and vomiting, and alopecia. 

Monteiro-Riviere, N., Inman, A., and Riviere, J., Skin toxicity of jet fuels Ultrastructural studies and the effects of substance P, Toxicol. Appl. Pharmacol., 195, 339, 2004. 

Skin-Contact Toxicity Data for acute (short-term) exposures of the skin to corrosive and toxic liquids, solids, and gases are extremely limited, particularly where the consequences are severe or fatal injury and the available data may not be useful, from an engineering standpoint. For example, the skin toxicity of hydrogen peroxide to rats is stated as 4060 mg/kg, but the skin area and duration of exposure are not stated. Thus, it is not possible (with the available data) to estimate the relationship among percent of body surface exposed to a corrosive material, the concentration of the corrosive material, the duration of exposure (before removal of the corrosive material), and the severity of the effect. 

Sami, T. (2007) Skin toxicity seen in other DPP-4 inhibitors missing in Januvia IDA review. Pharmaceutical Approvals Monthly The Pink Sheet DAILY, 12, 29-30. 

Keywords Transdermal drug delivery Skin toxicity Microdialysis In vitro permeation In vitro penetration... 

Chapter 1 Models for Skin Absorption and Skin Toxicity Testing... 

Valdecoxib (Bextra Pfizer), a second COX-2 specific inhibitor NSAID was taken off the market a few months after Vioxx. In addition to a higher risk of serious skin toxicity, pahents given Vioxx after Coronary Bypass Surgery had a higher rate of myocardial infarchons. 

The surface area for different species can be calculated by empirically derived equations using a species-specific shape factor, which depends on the ration of weight to height (Voisin et al. 1990). According to Voisin et al. (1990), there are several limitations in the accuracy of conversions based on body surface area (1) the surface area appears to be difficult to estimate (2) some analyses have indicated that the exponent of 2/3 may be inaccurate (3) some physiological parameters are not so well related to body surface area (4) body surface area conversions are inaccurate when the mode of administration is different across species and (5) not aU types of toxicity correlate with body surface area, e.g., skin toxicity. 

Ethylene chlorohydrin is highly irritating to mucous membranes but produces little reaction on contact with rabbit skin. Toxic amounts can be absorbed through the skin without causing dermal irritation the dermal LDso for rabbits is 68 mg/l. This value extrapolated to humans suggests that a volume slightly more than a teaspoon could be lethal with prolonged contact. ... 

A randomized study comparing carboplatin/5-FU/radiotherapy vs radiotherapy in patients with locally advanced oropharyngeal carcinoma was recently reported by the French Group of Radiation Oncology for HNC (GORTEC) (54). Two hundred twenty-six patients were randomized to conventional radiotherapy or identical radiotherapy combined with three cycles of the 4-d regimen of carboplatin (70 mg/m2/d) and continuous infusion 5-FU (600 mg/m2/d) on d 1,22, and 43 of radiation. Increased mucositis was reported in the combined modality arm 67% vs 36%. No difference in skin toxicity was... 

A potentially fatal lung toxicity occurs in 10 to 20% of patients receiving bleomycin. Patients particularly at risk are those who are over 70 years of age and have had radiation therapy to the chest. Rarely, bleomycin also may cause allergic pneumonitis. Bleomycin skin toxicity is manifested by hyperpigmentation, erythematosus rashes, and thickening of the skin over the dorsum of the hands and at dermal pressure points, such as the elbows. Many patients develop a low-grade transient fever within 24 hours of receiving bleomycin. Less common adverse effects include mucositis, alopecia, headache, nausea, and arteritis of the distal extremities. 

The popular movie Erin Brockovich, although focusing on the power industry, is an example of how the popular media can simplify the public s perception of chemical exposure. In Erin Brockovich the chemical of concern was hexavalent chromium, Cr +. Hexavalent chromium is listed as a carcinogen by EPA, but complicated questions dealing with exposure (drinking, inhalation, absorption through skin), toxicity levels, and specific health effects were lost in Hollywood s version. 

The toxicology of triethanolamine has been reviewed (Knaak et al., 1997). In general, rather high doses of triethanolamine are well tolerated by rats and mice. Major sites of toxicity in rats and mice are liver and kidney, while skin toxicity occurs after dermal application, especially when undiluted triethanolamine is applied. 

FU remains the most widely used agent in the treatment of colorectal cancer, both as adjuvant therapy and for advanced disease. It also has activity against a wide variety of solid tumors, including cancers of the breast, stomach, pancreas, esophagus, liver, head and neck, and anus. Major toxicities include myelosuppression, gastrointestinal toxicity in the form of mucositis and diarrhea, skin toxicity manifested by the hand-foot syndrome, and neurotoxicity. 

Bleomycin Oxygen free radicals bind to DNA causing single- and double-strand DNA breaks Hodgkin s and non-Hodgkin s lymphoma, germ cell cancer, head and neck cancer Allergic reactions, fever, hypotension Skin toxicity, pulmonary fibrosis, mucositis, alopecia... 

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