• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.59-66
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• 1994

The objective of this study was to determine the influence of drug lipophilicity on the extent of ocular and systemic absorption following topical solution instillation in the pigmented rabbit. ${\beta}-Blockers$ of various lipophilicity were chosen as model drugs, $25\;{\mu}l$ of a 15 mM drug solution in isotonic pH 7.4 buffer was instilled, and ocular tissue and plasma drug concentrations were monitored. Ocular absorption was apparently increased in all eye tissues, but non-corneal absorption ratio was decreased by increasing of drug lipophilicity. Systemic bioavailability was ranged from 61% for atenolol to 100% for timolol, and at least 50% of the systemically absorbed drug reached the blood stream from the nasal mucosa. Occluding the nasolacrimal duct for 5 min reduced the extent of systemic absorption of timolol and levobunolol, but did not do so for atenolol and betaxolol. Taken together, the ocular absorption of topically applied ophthalmic drugs would be modest for lipophilic drugs. By contrast, the systemic bioavailability would be modest for drugs at the extremes of lipophilicity, and the nasal contribution to systemically absorbed drug diminished with increasing of drug lipophilicity.

• International Journal of Safety
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• v.8 no.1
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• pp.18-23
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• 2009

Due to dermal exposure to hazardous chemicals causing potential adverse health symptoms through skin absorption, dermal monitoring has had an important role in assessing such exposure. This paper overviews comparatively a number of studies of dermal monitoring with different methodologies such as surface monitoring, skin wiping, skin washing, adhesive methods and tape stripping, fluorescence and infrared spectroscopy, skin patches, pads and clothing, video exposure monitoring and dermal exposure assessment toolkits and models. However, there is a lack of information on the relationship between exposure levels and adverse health symptoms. Therefore, more specific strategies for dermal exposure monitoring should be developed and standardized with further development of biological and ocular monitoring.

• Journal of Pharmaceutical Investigation
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• v.26 no.1
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• pp.43-53
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• 1996

The objective of this study was to determine whether 4-phenylazobezyloxycarbonyl-Pro-Leu-Gly-Pro-D-Arg (Pz-peptide), an enhancer of hydrophilic solute permeability in the intestine, could elevate the paracellular permeability of hydrophilic drugs across cornea and conjunctiva in the rabbit. The in-vitro penetration of hydrophilic drugs (mannitol, atenolol) and lipophilic drug (propranolol) across the rabbit cornea and conjunctiva was studied either in the presence or absence of 3 mM Pz-peptide. Drug penetration was evaluated using the modified Ussing chamber. The conjunctiva was more permeable than the cornea to all drugs. Pz-peptide showed enhanced effects on the drug transport across cornea and conjunctiva in a concentration dependent manner. Effects or ion transport inhibitor on the mannitol penetration were then investigated. Mannitol penetration was not changed by serosal addition of $100\;{\mu}M$ ouabain, suggesting that $Na^+/K^+$ ion tranporter was not involved in the Pz-peptide induced elevation of paracellular drug permeability. Furthermore, effects of Pz-peptide and EDTA on the transport of atenolol and propranolol into the ocular tissues or blood circulation after its administration into both eyes were investigated. EDTA showed enhanced effect on propranolol transport into the ocular tissues, but Pz-peptide did not show significant difference. Systemic absorption of propranolol by the addition of EDTA or Pz-peptide was not changed. On the other hand, EDTA and Pz-peptide elavated the atenolol transport into the ocular tissues. The transport of atenolol into the blood circulation was also enhanced by the addition of EDTA, but no effect was observed by the addition of Pz-peptide. The above findings suggest that Pz-peptide would be used as an paracellular pathway enahncer of hydrophilic drugs into the eye, without affecting the systemic absortion of topically applied opthalmic drugs.

• Journal of the Korean Society of Safety
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• v.24 no.6
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• pp.72-78
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• 2009

Exposure to HDI(hexamethylene di-isocyanate) commonly used in vehicle crash repair workshops remains a leading cause of occupational asthma. Although skin and eye contamination are considered as absorption routes, there are no occupational exposure standards for skin and ocular exposure. This is the reason why there are more empirical data should be provided. Therefore this study was to determine contamination levels of HDI on the skin, eyes, work surfaces, respirators and eye protectors. There was evidence of contamination on a variety of work surfaces, for example, door handles, bench top and spray gun, etc. A high proportion(47~80%) of skin wipe samples from neck, forehead, back hand, palm and wrist was positive for HDI contamination, even though spray time was relatively brief. The contamination levels from spraying inside spray booth were generally higher than outside booth due to poor work practices and inappropriate personal protective use like safety gloves. Apprentices had higher exposure levels than the qualified painters, likely due to lack of the recognition of safety and hygiene. The extent of contamination inside the PPE might provide an indication of the potential for respiratory & skin exposure and ocular exposure. Eye fluid samples from 4 out of 14 workers had the positive detection of HDI contamination, due to poor work practices like no or inappropriate eye protection. Considering the potential for dermal & ocular exposure to contribute to possible health symptoms including respiratory sensitization, the empirical data point to a need for improving work practices and appropriate PPE selection, use and maintenance.

• Journal of Food Hygiene and Safety
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• v.24 no.4
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• pp.352-356
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• 2009

The purpose of this study was to introduce the toxicological study review to evaluate the safety of PDMS on the 69th JECFA meeting. Polydimethylsiloxane is a polymer and its ADI was established at 23rd JECFA meeting in 1979. The ADI was maintained although the specification was expanded at its 26th, 29 th, 37 th meetings. Recently, it was reported that PDMS with low molecular weight and viscosity has high absorption rate and different toxicity, so it was submitted at 69th meeting. Toxicological studies of PDMS were submitted from the sponsor and additional information is collected from a document searching. The toxicological studies were reviewed in accordance with the 'Guidelines for the preparation of toxicological working papers for the Joint FAO/WHO Expert Committee on Food Additives'. In the available acute, sub-chronic and chronic toxicity studies on PDMS, dose-related increases in incidence and severity of ocular lesions(corneal crystal, inflammation of the corneal epithelium etc.) were consistently observed after oral dosing. It seems to be a local irritant effect, but the mechanism by which the ocular lesions arose is unclear, although the lack of absorption of PDMS indicates that it is unlikely to be a direct systemic effect. Consequently, the relevance of the ocular lesions for food use of PDMS could not be determined. The ADI of PDMS was re-established from 0-1.5 mg/kg bw/day to 0-0.8 mg/kg bw/day by applying additional safety factor 2 based on its ocular toxicity. The result of 0-0.8 mg/kg bw/day is a temporary ADI until further data are provided to 2010.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.247-255
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• 1994

As a series of safety studies of DA-3030, a new rhO-CSF, its local irritancy was examined in the rabbits after the following treatment; application into the conjunctival sac of the eye(single), subcutaneous injection(single), intramuscular injection(single), and intravenous injection(8-day repeated). In addition, paravenous irritation of DA-3030 was investigated in mice. The results obtained were as follows. 1. In the result of ocular irritation test, 0.03% solution of DA-3030 could be considered as a non-irritating material. 2. The local irritation of DA-3030 by an injection of 0.5mι of its solution subcutaneously or intramuscularly was negligible and not so much different from that of saline. 3. In the vascular irritancy test, macro- and microscopic observations revealed that the irritating activity of DA-3030 in blood vessels was not different from that of saline when they were injected once a day into vein retroauricularis of rabbits for 8 days.4. The paravenous administration of DA-3030 did not induce any abnormal changes at injection sites except mild swelling in 1 mouse at 3 hours after injection which was thought to be due to slow absorption. The above-mentioned results suggest that DA-3030 has no irritating activity when injected through intravenous or subcutaneous route for clinical practice as 0.03% solution.

• Journal of Korean Ophthalmic Optics Society
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• v.12 no.1
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• pp.23-33
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• 2007

It has been reported high concentrations of zinc and taurine in ocular tissue, especially the retina-choroid, and the presence of physiological levels of zinc and taurine in these tissues seem essential for their normal function. In addition, several studies have reported temperature as another effector to the visual sensitivity. But, in spite of many studies, there are still remained many questions about their function and correlation in visual adaptation system. The purpose of present study was to clarify these points using electroretinogram(ERG) recording and absorption spectra scanning, before and after zinc and taurine treatments and hypothermic-effect in bullfrog(Rana catesbeiana) which is one of the poikilothermal animal. The optimal zinc concentration used in this study was determined $10^{-4}M$ while the optimal taurine concentration was 10-5 M, and temperature change for hypothermic-effect went through '$25^{\circ}C {\rightarrow}0^{\circ}C{\rightarrow}25^{\circ}C$'. In ERG recording, it is obtained that dark-adapted threshold became elevated and b-wave amplitudes was increased with zinc and taurine treatment and hypothermic-effect. In absorption spectra scanning, there is distinct absorbance increment over the whole spectral range(400~750 nm) after zinc and taurine treatment and hypothermic-effect. Furthermore there are some synergism effects between zinc and taurine as well as between zinc and hypothermic-effect as a result of co-treatment, respectively.

• Journal of Photoscience
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• v.7 no.3
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• pp.115-121
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• 2000

Although there are high concentrations of zinc and taurine in ocular tissue, their exact role and correlation in the visual process are not clear. The purpose of present study was to clarity this point using electroretinogram (ERG) recording and spectrophotometer measurements before and after zinc and taurine treatment in bullfrog's eye. The optimal zinc concentration used in this study was 10$^{-2}$ M ZnCl$_2$120 ${mu}ell$/12$m\ell$ ringer solution while the optimal turine concentration was 10$^{-2}$ M taurine 12${mu}ell$/12$m\ell$ ringer solution. For the effects of zinc and taurine on the retinal function, the changes of ERG parameters (especially threshold and b-wave) and absorption spectra were observed before and after treatment. It is noteworthy that high concentrations of zinc and taurine present in the retinal pigment epithelium and the retina. Our results indicate that dark-adapted ERG threshold became elevated and the peak amplitude of b-wave was increased with zinc and taurine treatment. Furthermore there are some synergism effects between zinc and taurine as a result of co-treatment. In spectral scan, absorbance increment due to zinc and taurine treatment was shown over the whole range of spectral range (300-750 nm) with some differences in absorbance increment depending on the case of treatment. As the results of above we believe that zinc and taurine, which are abundant in the retinal pigment epithelium and the retina particularly, may be essential factors for visual process, have some synergism with each other and be required to improve the visual sensitivity during visual adaptation.

• Journal of Korean Ophthalmic Optics Society
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• v.9 no.2
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• pp.381-389
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• 2004

To investigate changes of multi-purpose solutions for soft contact lens(MPS) depending on using period or keeping temperature, we evaluate four brands of MPS. No significant difference was seen in protein deposit removing efficacy after samples had used for 24 weeks and kept at $4^{\circ}C$, $20^{\circ}C$ or $30^{\circ}C$. The pH values of the samples of 4 brands measured weekly over the 24 week testing period. The initial average pH value of samples were 7.0, 7.5, 7.6 or 8.2. One brand of MPS was in the range of the threshold for ocular awareness, which is outside the zone of 6.6 ~ 7.8. During the testing period, the pH value were decreased in using period-dependent manner. At the 24th week, the average pH values of samples turned to 6.6, 7.2, 7.2 or 7.7. However, the difference of keeping temperature was not associated with decreased levels of pH values. After 24 weeks, one of total 36 samples was contaminated by bacteria. Furthermore, the change of components was shown after 24 weeks in the analysis using thin layer chromatography and the analysis of UV absorption pattern. The results of our study provides that the keeping temperature of MPS is not the important factor of changes of MPS, but the using period of MPS can cause contact lens wearers discomfort.