Clinically relevant safety issues associated with St. John's wort product labels

<p>Abstract</p> <p>Background</p> <p>St. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA.</p> <p>Methods</p> <p>Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings.</p> <p>Results</p> <p>Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of <it>a priori </it>safety issues included on a product label was 1.91 (range 0–8) for 23.9% completeness.</p> <p>Conclusion</p> <p>The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements.</p

Fate of Carbaryl, l-Naphthol, and Atrazine in Seawater

The fate of carbaryl, l-naphthol, and atrazine was determined under light and dark conditions in filter-sterilized and raw (unfiltered) seawater. Carbaryl was hydrolyzed in the dark, quantitatively, to l-naphthol with a half-life of 24 hr at pH 7.9 or 23 hr at pH 8.2 (24°C). Naphthol was stable in the dark in sterile seawater, but was degraded to undetectable levels in 96 hr in raw seawater. In artificial sunlight, carbaryl degraded with a half-life of 5 hr and l-naphthol was completely degraded after 2 hr. No further degradation products were observed for either compound. Atrazine was stable under light and dark conditions in sterile seawater; however, in raw seawater, it was degraded by 23% after 96 hr. These data suggest that atrazine may be stable enough in seawater to permit exposure of susceptible marine life, while, in the presence of sunlight, carbaryl and l-naphthol would rapidly dissipate to undetectable levels

Potential risk to human skin cells from exposure to dicloran photodegradation products in water

Exposure to sunlight and certain pesticides can induce phototoxic responses. Long- and short-term exposure to the photoactivated pesticides can cause a variety of skin diseases. However, assessment of pesticide phototoxicity on human skin is difficult. In the present study, human skin keratinocytes were cultured in several forms: monolayer cell sheet, three-dimensional culture, and keratinocyte-fibroblast co-culture. A common fungicide, dicloran (DC, 2,6‑dichloro‑4‑nitroaniline), was irradiated with simulated sunlight for 2 (DC-PD-2h) and 4 (DC-PD-4h) hours. Dicloran, and two purified intermediate photodegradation products, 2‑chloro‑1,4‑benzoquinone (CBQ) and 1,4‑benzoquinone (BQ), were applied in toxicity tests independently with the keratinocyte culture models. The cell migration, cell differentiation, pro-inflammatory molecule production, and dermal fibroblast cell activation were all measured in the keratinocytes treated with the chemicals described above. These parameters were used as references for dicloran phototoxicity assessment. Among all tested chemicals, the DC-PD-4h and BQ demonstrated elevated toxicities to the keratinocytes compared to dicloran based on our results. The application of DC-PD-4h or BQ significantly delayed the migration of keratinocytes in monolayer cell sheets, inhibited the keratinocyte differentiation, increased the production of pro-inflammatory molecules by 3D keratinocyte culture, and enhanced the ability of 3D cultured keratinocytes in the activation of co-cultured dermal fibroblast cells. In contrast, dicloran, DC-PD-2h, and CBQ showed minimal effects on the keratinocytes in all assays. The results suggested that the four-hour photodegraded dicloran was likely to induce inflammatory skin diseases in the natural human skin. The 1,4‑benzoquinone, which is the predominant degradation product detected following 4 h of irradiation, was the main factor for this response. Photoactivation increased the risk of skin exposed to dicloran in nature. Our models provided an efficient tool in the assessment of toxicity changes in pesticide following normal use practices under typical environmental conditions

Breakdown Rates of Tulip-poplar Leaves in Streams Draining Suburban Watersheds

Proceedings of the 2001 Georgia Water Resources Conference, April 26 and 27, 2001, Athens, Georgia.Leaf litter inputs are an integral part of stream food webs. Changes to this basic food resource from natural or anthropogenic causes can have repercussions at higher trophic levels. Stormwater runoff from residential lawns transports pesticides and fertilizers to stream ecosystems. This study measures leaf breakdown rates in two suburban streams in Peachtree City, Georgia, and considers if fungicide or nutrient concentrations have impacted those rates. Leaf breakdown rates in these suburban streams were compared with breakdown rates in two reference streams. We analyzed stream temperature and concentrations of ammonium, nitrate, soluble reactive phosphorus, and selected pesticides. Relationships between these parameters and breakdown rates of tulip-poplar leaves (Liriodendron tulipifera L.) were examined. Surprisingly, nitrate, ammonium and hydroxychlorothalonil (a fungicide degradation product) concentrations were somewhat higher in the reference streams. Leaf breakdown rates for the first seven weeks were similar in three streams and lower in one of the reference streams. Differences in nutrient and pesticide concentrations were not consistent and could not explain observed differences in leaf breakdown rates.Sponsored and Organized by: U.S. Geological Survey, Georgia Department of Natural Resources, Natural Resources Conservation Service, The University of Georgia, Georgia State University, Georgia Institute of TechnologyThis book was published by the Institute of Ecology, The University of Georgia, Athens, Georgia 30602-2202. The views and statements advanced in this publication are solely those of the authors and do not represent official views or policies of The University of Georgia, the U.S. Geological Survey, the Georgia Water Research Institute as authorized by the Water Resources Research Act of 1990 (P.L. 101-397) or the other conference sponsors

The Effects of a Golf Course on Leaf Litter Breakdown Rates in a Georgia Piedmont Stream

Proceedings of the 2001 Georgia Water Resources Conference, April 26 and 27, 2001, Athens, Georgia.Golf courses apply heavy loads of fertilizer and a variety of pesticides, including fungicides, herbicides, and insecticides, to maintain both impeccable greens and aesthetically pleasing fairways and fringes. The primary purpose of this study is to determine if these practices have an impact upon leaf litter breakdown rates in a stream draining a suburban Atlanta golf course. Liriodendron tulipifera leaf packs were placed in a reference reach upstream of the golf course and in a study reach, just below a tributary draining a green. Mass of leaf material remaining in leaf packs was determined incrementally, and the logarithmic leaf breakdown rate (k) was calculated for each reach. Fine sediment accumulation in packs, and concentrations of NO₃, NH₄, soluble reactive phosphorous (SRP), chlorothalonil, and its metabolite in the water were measured. Similar leaf breakdown rates were found for each reach, although the study reach had somewhat higher concentrations of NO₃₋N and OH-chlorothalonil.Sponsored and Organized by: U.S. Geological Survey, Georgia Department of Natural Resources, Natural Resources Conservation Service, The University of Georgia, Georgia State University, Georgia Institute of TechnologyThis book was published by the Institute of Ecology, The University of Georgia, Athens, Georgia 30602-2202. The views and statements advanced in this publication are solely those of the authors and do not represent official views or policies of The University of Georgia, the U.S. Geological Survey, the Georgia Water Research Institute as authorized by the Water Resources Research Act of 1990 (P.L. 101-397) or the other conference sponsors