• Biomedical Science Letters
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• v.22 no.4
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• pp.140-149
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• 2016

All pesticides must be assessed strictly whether safe or not when agricultural operators are exposed to the pesticides in farmland. A pesticide is commonly regarded as safe when estimated dermal absorption amount is lower than the acceptable operator's exposure level (AOEL). In this study, dermal absorption rate of chlorpyrifos, a widely used organophosphate insecticide, was investigated using rat dermal tissue model. Chlorpyrifos wettable powder solved in water (250, 500 and 2,500 ppm) was applied to freshly excised rat dermal slices ($341{\sim}413{\mu}m$ thickness) on static Franz diffusion cells at $32^{\circ}C$ for 6 hours. After exposure period of 6 hours, and then washing-at residual amount of chlorpyrifos was analyzed in dermal tissues, tape strips, washing solution, washing swabs of receptor bottles and receptor fluids at 1, 2, 4, 8 and 24 hours. Chlorpyrifos was only detected in dermal tissue but not found in receptor fluid at each concentration and time point, and the absorption rate of 250, 500 and 2,500 ppm was 2.36%, 1.96% and 1.69%, respectively. The estimated exposure level of chlorpyrifos was calculated as 0.012 mg/kg bw/day. The health risk for farmers in this condition is a level of concern because the estimated exposure level is 12 times higher than AOEL 0.001 mg/kg bw/day. However, actual health risk will be alleviated than estimated because absorbed chlorpyrifos is not permeated into internal body system and only retained in skin layer.

• Biomedical Science Letters
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• v.22 no.4
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• pp.199-206
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• 2016

Pesticides are widely used to prevent loss of agricultural production but extensive exposure can induce health problems to pesticide operators. This study was performed to evaluate the health risk of highly produced pesticides used in fruit growing farm land by comparison of estimated exposure level with AOEL using KO-POEM program. AOEL was driven based on NOAEL of each pesticide evaluated by JMPR, EFSA or KRDA. In calculation of exposure level, types of formulation, dilution factors, spraying duration and motor type and exposure protection device were allocated according to actual condition of use. Dermal absorption rate was differently applied among EFSA default values (25% or 75%), general default value (10%) or real test result values to know the plausibility of default values and safety of pesticide to operators in outline. Twenty pesticide ingredients (fungicides and insecticides) were produced more than 30 tons per year, which were mancozeb, chlorothalonil, imidaclopirid and etc in order. Dermal absorption rates obtained from studies were various from 0.07 to 81% but mostly under 10%. The estimated exposure levels showed big differences more than 10 times higher when using EFSA default rate and up to 5 times higher when using general rate of 10% comparing using rates of test results. Mancozeb, chlorthalonil, diazinon and chlorpyrifos presented still higher exposure level than AOEL even when using test absorption rate from study, which suggests that re-evaluation of AOEL or dermal exposure absorption rate or strict management are required for health protection of operators who use those four pesticides in farm land.

• Archives of Craniofacial Surgery
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• v.20 no.1
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• pp.10-16
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• 2019

Background: Physicians tend to overcorrect when applying the acellular dermal matrix for reconstructive option because of volume decrement problem after absorption comparing with initial volume. However, there are no studies on the exact volume decrement and absorption rate with commercial products in South Korea. To figure out absorption rate of acellular dermal matrix product in South Korea (Megaderm), authors designed this experiment. Methods: Nine mice were used and randomly divided into three groups by the time with sacrificing. The implant (Megaderm) was tailored to fit a cuboid form ($1.0cm{\times}1.0cm$ in length and width and 2.0 mm in thickness). A skin incision was made at anterior chest with blade #15 scalpel with exposing the pectoralis major muscle. As hydrated Megaderm was located upon the pectoralis major muscle, the skin was sutured with Ethilon #5-0. After the surgical procedure, each animal group was sacrificed at 4, 8, and 12 weeks, respectively, for biopsies and histological analysis of the implants. All samples were stained with routine hematoxylin and eosin staining and Masson's trichrome staining and the thickness were measured. A measurements were analyzed using Friedman test. Statistically, the correlation between thicknesses of Megaderm before and after implantation was analyzed. Results: After sacrificing the animal groups at postoperative 4, 8, 12 weeks, the mean tissue thickness values were $2.10{\pm}1.03mm$, $2.17{\pm}0.21mm$, and $2.40{\pm}0.20mm$ (p= 0.368), respectively. The remaining ratios after absorption comparing with after initial hydrated Megaderm were 82.7%, 85.4%, and 94.5%, respectively. In histopathological findings, neovascularization and density of collagenous fiber was increased with time. Conclusion: Author's hypothesis was absorption rate of implant would be increased over time. But in this experiment, there is no statistical significance between mean absorption thickness of implant and the time (p= 0.368). Also it can be affected by graft site, blood supply, and animals that were used in the experiment.

• Journal of Environmental Health Sciences
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• v.45 no.1
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• pp.9-17
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• 2019

Objectives: This study examined the safety of tattoo ink by analyzing the phenol contents in tattoo inks and its risk assessment of selected phenol. Methods: A sample of 30 tattoo inks was purchased, the phenol contents were analyzed, and a risk assessment on dermal exposure from tattooing was carried out. Hazard identification was collected from toxicity data on systemic effects caused by dermal exposure to phenol, and the most sensitive toxicity value was adopted. Exposure assessment ($Exposure_{phenol}$) was calculated by applying phenol contents and standard exposure factors, while dose-response assessment was based on the collected toxicity data and skin absorption rate of phenol, assessment factors (AFs) for derived no-effect level ($DNEL_{demal}$). In addition, the risk characterization was calculated by comparing the risk characterization ratio (RCR) with $Exposure_{phenol}$ and $DNEL_{dermal}$ Results: The phenol concentration in the 30 products was from 1.4 to $649.1{\mu}g/g$. The toxicity value for systemic effects of phenol was adopted at 107 mg/kg. $Exposure_{phenol}$ in tattooing was from 0.000087 to 0.040442 mg/kg. $DNEL_{dermal}$ was calculated at 0.0072 mg/kg (=toxicity value 107 mg/kg ${\div}$ AFs 650 ${\times}$ skin absorption rate 4.4%). Thirteen out of 30 products showed an RCR between 1.02 and 5.62. The RCR of all red inks was above 1. Conclusions: Phenol was detected in all of the 30 tattoo inks, and the RCR of 13 products above 1 indicates a high level of risk concern, making it necessary to prepare safety management standards for phenol in tattoo inks.

• Archives of Plastic Surgery
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• v.35 no.3
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• pp.248-254
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• 2008

Purpose: Human acellular dermal matrix(ADM) is widely used in the treatment of congenital anomalies and soft tissue deficiencies. But it is rapidly degraded in the body and does not provide satisfactory results. There is a need to improve collagen fiber stability through various methods and ultimately regulate the speed of degradation. Methods: The ADMs were added with various cross-linking agents called glutaraldehyde, dimethyl 3,3'-dithiobispropionimidate to produce cross-linked acellular dermal matrices. 1,4-butanediol diglycidyl ether solution was applied with a pH of 4.5 and 9.0, respectively. The stability of cross-linked dermal matrix was observed by measuring the shrinkage temperature and the degradation rates. The cross- and non-cross linked dermis were placed in the rat abdomen and obtained after 8, 12 and 16 weeks. Results: The shrinkage temperature significantly increased and the degradation rate significantly decreased, compared to the control(p<0.05). All of cross-linked dermises were observed grossly in 16 weeks, but most of non-cross linked dermis were absorbed in 8 weeks. Histologically, the control group ADM was found to have been infiltrated with fibroblasts and most of dermal stroma were transformed into the host collagen fibers. However, infiltration of fibroblasts in the experiment was insignificant and the original collagen structure was intact. Conclusion: Collagen cross-linking increases the structural stability and decreases degradation of acellular dermis. Therefore, decrease in body absorption and increase in duration can be expected.

• Journal of Pharmaceutical Investigation
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• v.26 no.4
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• pp.315-321
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• 1996

It has been indicated that problems associated with insulin iontophoresis are low bioavailability, slow absorption rate and the use of high dosage. Pretreatment of skin as a method of solving these problems was used in alloxan-induced diabetic white rabbits. Skins were treated with skin needle, electric razor, knife razor and scotch tape. Transport data shows that insulin delivery was enhanced significantly by the treatment which disrupt the barrier properties of stratum corneum. The data also shows that insulin absorption lasted for several hours after the cessation of iontophoresis. The degree of skin treatment was estimated by measuring the electrical resistance of skin. When the skins were treated with skin needle and electric razor, the standard deviations of resistance were small, which suggests the possibility of uniform delivery of insulin. The dermal responses after the invasive delivery were evaluated in accordance with OECD Guideline. It seems that electrical resistance of the skin correlate well with the dermal irritation.

• Toxicological Research
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• v.17 no.1
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• pp.7-9
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• 2001

The quantitative assessment of the penetration of organic solvents through skin is necessary for the evaluation of health hazards in occupational environments. We investigated the rate of dermal penetration when mixed or single forms of organic solvents were placed into a diffusion cell in vitro or into an experimental animal in vivo. The diffusion rates of methanol. toluene, and styrene were 6.07, 0.129, and 0.046 mg/$cm^2$/h, respectively. When skin was exposed to the mixed solvent of methanol and toluene, the penetration rate of toluene did not change significantly (0.110 mg/$cm^2$/h). However, the rate of methanol penetration increased to 43.90 mg/$\textrm{cm}^2$/h. The penetration rate of methanol also increased significantly to 54.69 mg/$cm^2$/h by mixing it with styrene. The concentration of methanol in the blood was monitored during the epicutaneous exposure in rats. The blood concentration of methanol was increased by mixing methanol with toluene as seen in the in vitro experiments. These results showed that the penetration rate of organic solvents would be enhanced by mixing them with other solvents.

• Toxicological Research
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• v.17 no.4
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• pp.317-323
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• 2001

The skin penetration rate of methidathion in vitro and pharmacokinetics of methidathion in vivo were studied with male Sprague-Dawley rats by dermal treatment. The in vitro skin penetration rates for Sprague-Dawley rats of methidathion technical (50 mg, 100 ${mu}ell$) and emulsifable concentrate (EC,40mg, 100${mu}ell$) were determined as 18.4 $\mu\textrm{g}$/c $m^2$/h (RSD : 6.5) and 18.5 $\mu\textrm{g}$/c $m^2$/h (RSD : 3.2), respectively. Dose-related systemic exposure (AUC) was observed in rats after dermal treatment. The corresponding AUC, $T_{max}$, $C_{max}$, and $T_{1}$2/ of methidathion in plasma were 1.5$\mu\textrm{g}$.hr/ml, 6 h, 0.10 $\mu\textrm{g}$/ml, and 16 h, for 116mg/kg doses, 3.2 $\mu\textrm{g}$. hr/ml, 8 h, 0.12 $\mu\textrm{g}$/ml, and 23 h, for 232 mg/kg doses and 10 $\mu\textrm{g}$. hr/ml, 12 h, 0.32 $\mu\textrm{g}$/ml, and 20 h, for 1,160 mg/kg doses respectively. The urinary excretion of methidathion, estimated wing an equation derived from the in vitro skin penetration study was 0.24~0.35% of the absorbed dose. The concentration of methidathion in kidney was higher than that in liver. Dose-dependent absorption and excretion of methidathion without saturation was observed under in vivo experimental condition.n.n.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.572-577
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• 2001

The feasibility of skin penetration was studied for aspalatone (AM, acetylsalicylic acid maltol ester), a novel antithrombotic agent. In this studys hairless mouse dorsal skins were used as a model to select composition of vehicle and AM. Based on measurements of solubility and partition coefficient, the concentration of PC that showed the highest flux for AM across the hairless mouse skin was found to be 40%. The cumulative amount permeated at 48 h, however, appear inadequate, even when the PC concentration was employed. To identify a suitable absorption enhancer and its optimal concentration for AM, a number of absorption enhancers and a variety of concentration were screened for the increase in transdermal flux of AM. Amongst these, linoleic acid (LOA) at the concentration of 5% was found to have the largest enhancement factor (i.e., 132). However, a further increase in AM flux was not found in the fatty acid concentration greater than 5%, indicating the enhancement effect is in a bell-shaped currie. In a study of the effect of AM concentration on the permeation, there was no difference in the permeation rate between 0.5 and 1% for AM, below its saturated concentration. At the donor concentration of 2%, over the saturated condition, the flux of AM was markedly increased. A considerable degradation of AM was found during permeation studies, and the extent was correlated with protein concentrations in the epidermal and serosal extracts, and skin homogenates. In rat dorsal skins, the protein concentration decreased in the rank order of skin homogenate > serosal extract > epidermal extract. Estimated first order degradation rate constants were $6.15{\pm}0.14,{\;}0.57{\pm}0.02{\;}and{\;}0.011{\pm}{\;}0.004{\;}h^{-1}$ for skin homogenate, serosal extract and epidermal extract, respectively. Therefore, it appeared that AM was hydrolyzed to some extent into salicylmaltol by esterases in the dermal and subcutaneous tissues of skin. taken together, our data indicated that transdermal delivery of AM is feasible when the combination of PC and LOA is used as a vehicle. However, since AM is not metabolically stable, acceptable degradation inhibitors may be nervessary to fully realize the transdermal delivery of the drug.

• Biomolecules & Therapeutics
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• v.9 no.4
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• pp.298-306
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• 2001

To develop a novel transdermal delivery system of loxoprofen (LP), a potent antiinflammatory and analgesic agent, the effects of vehicle composition and drug loading dose on the skin permeation property were investigated. And in vivo skin absorption property studied by analysing the $C_{max}$ and AUC was investigated after applying the developed plaster systems on rabbit back skin. Addition of isopropyl myristate (IPM) and IPM-diethylene glycol monoethyl ether (DGME) cosolvent in the plaster showed higher permeation rates than those from propylene glycol laurate-DGME cosolvent systems. As the concentration of LP in the plaster increased from 0.56 mg/$\textrm{cm}^2$ to 1.19 mg/$\textrm{cm}^2$, the drug release and skin permeation rates increased linearly. At loading dose of 1.19 mg/$\textrm{cm}^2$, the flux reached 35.6 $\mu$g/$\textrm{cm}^2$/hr. New LP plasters showed a good adhesive property onto skin, and showed no crystal formation. The AU $C_{0-24hr}$ and $C_{max}$ after dermal application of LP plaster (60 mg/70 $\textrm{cm}^2$) were found to be 6951$\pm$230 ng.hr/ml and 400$\pm$44 ng/ml, respectively. And the plasma concentration maintained above 300 ng/ml up to 24 hr period. In the carrageenan-induced rat paw edema test, LP plaster showed similar inhibition rate with marketed ketoprofen (Ketoto $p^{R}$) plaster.aster.r.