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PubMed1993

In vivo differences between Asian, black and white in the stratum corneum barrier function.

The stratum corneum barrier function of Blacks, Caucasians and Asians were compared in vivo. A noninvasive technic, laser doppler velocimetry (LDV), was used to evaluate the cutaneous penetration of nicotinates by the determination of the lag time before vasodilatation induced by the application of those local vasodilator drugs. The study was performed on untreated skin and after removal of the stratum corneum by 12 strips. The influence of molecular weight and solubility of different nicotinates (methyl, ethyl, hexyl and vitamin E) were also studied on Japanese skin. Vasodilatation lag times assessed by LDV, with methyl nicotinate (MN), showed that skin permeability was more important in Asians (P < 0.01) and in Caucasians (P < 0.05) than in Blacks. Moreover Asian skin was significantly more sensitive to stripping (P < 0.05) than Black skin. A significant shorter lag time was obtained with small and hydrophilic nicotinates (methyl and ethyl) (P < 0.01) compared to a lipophilic one (hexyl). The alteration of the stratum corneum barrier function by stripping showed a more important modification with MN (P < 0.05) than with hexyl nicotinate. Consequently, this noninvasive method can evaluate the modifications of the stratum corneum barrier function and racial origin has to be taken into account in the determination of skin absorption.

Adult↗

PubMed1987

[Experimental studies of toxic effects of 1,3,5-trioxane and 1,3-dioxolane. I. Acute toxic effect].

The problems arising from occupational exposure to 1,2,3-trioxane and 1,3-dioxolane made it necessary to carry out complex studies on that issue. This paper is focussed on systemic and local effects of those compounds. The studies involved: 1) Determination of acute systemic toxic effects following intragastric administration of the test compounds (DL50) and inhalatory exposure (CL50) using the Litchfield and Wilcoxon method as well as determination of medium lethal dose (MDLder) following dermal administration of the test compounds after Deichmann and Le Blanca, 2) Determination of the intensity of acute primarily irritating effects upon skin and eye using the Draize et al method, as well as irritating effects under repeated exposure, 3) Determination of allergic effects using the Magnusson and Kligman method, as modified by B. Krysiak. The DL50 and CL50 values for 1,3,5-trioxane and 1,3-dioxolane come to 8.5 g/kg m.c. and 5.8 g/kg m.c. respectively, and CL50 greater than 26000 mg/m3 and 87000 mg/m3 of air. Of those two compounds only 1,3-dioxolane may be absorbed through intact skin. However, the medium lethal dose MDLder coming to 15 g/kg b.w. in the rabbit implies that the rate of skin absorption for that compound is too low to induce a severe poisoning. Locally, the compounds exhibit irritating effects upon the eyeball and eye protective apparatus. As regards the irritating effectus upon skin, only 1,3-dioxolane induces skin irritation under repeated exposure. Under experimental conditions, no dermatitis related to oversensitivity was found.

Acute Disease↗

PubMed2005

Enantioselective separation of the sunscreen agent 3-(4-methylbenzylidene)-camphor by electrokinetic chromatography: Quantitative analysis in cosmetic formulations.

3-(4-Methylbenzylidene)-camphor (MBC) is a chiral sunscreen agent used in cosmetic products. In this work, the enantioseparation of MBC has been performed by EKC and applied to the analysis of the MBC enantiomers in cosmetic creams. Different experimental conditions (type and concentration of the chiral selector, temperature, and sample solvent) have been optimized. Due to the neutral nature of this compound, anionic CD derivatives were investigated as chiral selectors. Carboxymethylated-beta-CD (CM-beta-CD) showed the highest chiral separation power, observing that a 15 mM concentration of this CD at a working temperature of 15 degrees C enabled to obtain the highest enantioresolution. However, under these conditions, tailing of peaks obtained for the enantiomers was observed. The addition of increasing concentrations of the neutral alpha-CD to CM-beta-CD at a 15 mM concentration in a 100 mM borate buffer at pH 9.0 improved the enantiomeric separation and decreased peak tailing. The use of DMF for the total dissolution of the cosmetic creams, and methanol:water (1:1 v/v) for appropriate dilution enabled to observe good shape and size for the peaks of the MBC enantiomers. After optimizing a method for the preconditioning of the capillary, the analytical characteristics of the chiral separation method for the analysis of MBC were investigated. Linearity, LODs and LOQs, precision (instrumental repeatability, method repeatability, intermediate precision), accuracy, and selectivity were evaluated. The method was applied to analyze MBC enantiomers contained in two commercial cosmetic creams containing racemic MBC and to study the skin absorption of this compound with time.

Camphor↗

PubMed1995

Papaverine topical gel for treatment of erectile dysfunction.

Intracavernous injection of vasoactive substances has been shown to be an effective means of treatment of organic erectile dysfunction. However, up to 50% of men eventually discontinue treatment often because of lack of spontaneity and needle phobia. This study was done as a phase I, placebo controlled, nonblinded investigation of the safety and efficacy of a topical papaverine gel in the treatment of erectile dysfunction. Of 20 men with organic impotence 17 completed the trial and 13 of these patients had spinal cord injuries. After application of a 15% and 20% papaverine base gel to the scrotum, perineum and penis, cavernous artery diameter was significantly increased (36%, p < 0.001) as assessed by color flow Doppler ultrasound. Peak systolic flow velocity increased 26%. Only 3 of 14 patients achieved an increase in cavernous artery diameter of 75% or more and 2 of 14 had a peak systolic flow velocity of 25 cm. per second or more after application of a topical base gel. Similar findings were present when only the patients with spinal cord injury were analyzed. The effect of a papaverine base in producing flow alterations to the penis is dose-dependent. A diminution in blood pressure was present at 15 and 30 minutes after application to the forearm, and the heart rate diminished from 68 to 62 beats per minute after application to the genitalia. No patient was symptomatic. Serum papaverine levels were not elevated over pre-application values. No hepatotoxic effects were demonstrated. Full clinical erections (mean duration 38.7 minutes) were present in 3 patients but were also present with the placebo preparation (mean duration 8.0 minutes). In conclusion, topical papaverine gel appears to be safe and well tolerated after application to the genitalia, and increases blood flow to the penis with a 15% and 20% base preparation. Minimal systemic absorption occurs and, thus, effects are probably from local absorption. Topical therapy appears to augment reflex erections in the spinal cord injury patient and may be especially beneficial in this population. Further investigation is warranted at higher concentrations or in combination with different skin absorption enhancers.

Administration, Cutaneous↗

PubMed2000

The 500 Dalton rule for the skin penetration of chemical compounds and drugs.

Human skin has unique properties of which functioning as a physicochemical barrier is one of the most apparent. The human integument is able to resist the penetration of many molecules. However, especially smaller molecules can surpass transcutaneously. They are able to go by the corneal layer, which is thought to form the main deterrent. We argue that the molecular weight (MW) of a compound must be under 500 Dalton to allow skin absorption. Larger molecules cannot pass the corneal layer. Arguments for this "500 Dalton rule" are; 1) virtually all common contact allergens are under 500 Dalton, larger molecules are not known as contact sensitizers. They cannot penetrate and thus cannot act as allergens in man; 2) the most commonly used pharmacological agents applied in topical dermatotherapy are all under 500 Dalton; 3) all known topical drugs used in transdermal drug-delivery systems are under 500 Dalton. In addition, clinical experience with topical agents such as cyclosporine, tacrolimus and ascomycins gives further arguments for the reality of the 500 Dalton rule. For pharmaceutical development purposes, it seems logical to restrict the development of new innovative compounds to a MW of under 500 Dalton, when topical dermatological therapy or percutaneous systemic therapy or vaccination is the objective.

Absorption↗

PubMed1997

Occupational exposure to polycyclic aromatic hydrocarbons in a graphite-electrode producing plant: biological monitoring of 1-hydroxypyrene and monohydroxylated metabolites of phenanthrene.

OBJECTIVE: The objective of this study was to assess external and internal exposure to polycyclic aromatic hydrocarbons (PAHs) of workers who are employed in a graphite-electrode producing plant. Additionally we wanted to contribute to the question of biological limit values in order to reduce exposure to tolerable levels. METHODS: At five different working places 12 stationary and 16 personal air measurements were carried out to determine the concentrations of phenanthrene, fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[a]pyrene and dibenz[a, h]anthracene in air. In addition, we investigated the excretion of 1-, 2 + 9-, 3- and 4-hydroxyphenanthrene and of 1-hydroxypyrene in the urine of 67 workers by a very sensitive and practical high-performance liquid chromatographic (HPLC) method with fluorescence detection; 2- and 9-hydroxyphenanthrene could not be separated with our analytical method. RESULTS: During the production of graphite electrodes significantly higher PAH exposures were found in the baking and impregnation area than in the crushing, graphitisation and conditioning area. The results of personal air measurements (mean values of the sum of eight PAHs) are: 29.3 (baking), 23.4 (impregnation), 5.2 (crushing), 1.3 (graphitisation) and 0.4 microgram/m3 (conditioning). Stationary air measurements yielded similar concentrations. Workers employed in the baking and impregnation areas excreted the highest amount of PAH metabolites in urine. The 1-hydroxypyrene concentrations (median) were: 23.4 (baking), 22.0 (impregnation), 9.6 (crushing), 1.8 (graphitisation) and 2.3 micrograms/g creatinine (conditioning). The corresponding concentrations of the sum of monohydroxylated phenanthrene metabolites (median) were: 23.1, 36.0, 10.4, 4.6 and 7.6 micrograms/g creatinine. Within the monohydroxylated phenanthrene metabolites 3-hydroxyphenanthrene predominates with a percentage of 43%. Our results showed that a benzo[a]pyrene concentration in air of 2 micrograms/m3 would lead to 1-hydroxypyrene concentrations in urine of 20-74 micrograms/g creatinine. That means that corresponding values in the literature which lie between 4.4 and 6.2 micrograms/g creatinine are due to other conditions of exposure and cannot be applied to graphite-electrode producing plants. CONCLUSIONS: Although to date there are no obligatory biological exposure limits for metabolites of PAHs in urine, it must be concluded that the internal PAH exposure is too high at some work places in this plant, as is generally the case in graphite-electrode producing plants. This is probably caused by skin absorption of PAHs. So for the prevention of health hazards by PAH, internal exposure must be measured using biological monitoring. Although it has not been possible to establish biological exposure limits for PAHs until now, we suggest a reduction in skin contact with these substances and thereafter use of the 90th percentile of the results of biological monitoring as "action levels" for corrective measures.

Air↗

PubMed1987

Dermal penetration of carbofuran in young and adult Fischer 344 rats.

Dermal penetration of carbofuran was determined in young (33 d) and adult (82 d) female Fischer 344 rats employing in vivo and in vitro methods. In vivo dermal penetration at 120 h was 43% for young and 18% for adult rats. The half-time for carbofuran skin penetration (in vivo) was 128 h for the young and 400 h for the adults. The young to adult ratio of dermal penetration was greater than 1 at all time points (average 2.9) and had a maximum of 4.2 at 24 h. Cumulative urinary excretion approached about 95% of the absorbed dose in both the young and adult animals at 120 h. Whole-body retention was slightly higher in adults. Kidney showed the highest tissue-to-blood concentration ratio (4.6 in adult, 2.3 in young). The ratio for the carcass was 2.8 in the adult and 2.4 in the young. The urine/blood concentration ratio was high, 435 in the adult and 573 in the young. The feces/blood ratio was 44 in the adult and 65 in the young. Skin absorption by the in vitro continuous-flow system was 41% for the young and 11% for the adult at 72 h, compared to 36% and 13% by the in vivo method. The static in vitro method gave consistently lower skin penetration values of 12% for the young and 8.8% for the adult. Differences in the kinetics of retention and excretion were observed between the young and adult animals.

Administration, Topical↗

PubMed1988

Bioavailability of topically administered steroids: a "mass balance" technique.

The percutaneous absorption of four steroids (hydrocortisone, estradiol, testosterone, and progesterone) has been measured in vivo in man under occluded and "protected" (i.e., covered, but non-occlusive) conditions. The experimental approach, involving simple modifications of standard radiochemical methodology, has enabled excellent "mass balance" and dose accountability to be achieved. Consequently, the utility of the procedure for the measurement of in vivo topical bioavailability can be inferred. In addition, because of the precision and accountability of the results, the technique offers a potential means to establish quantitative structure-penetration relationships for skin absorption in man. It was found that steroid absorption increased with increasing lipophilicity up to a point, but that penetration of progesterone (the most hydophobic analog studied) did not continue the trend and was at least partly rate-limited by slow interfacial transport at the stratum corneum-viable epidermis boundary. Comparison of data obtained from the occluded and "protected" experiments permitted the effect of occlusion (defined as the complete impairment of passive transepidermal water loss at the application site) to be assessed. Occlusion significantly increased percutaneous absorption of estradiol, testosterone, and progesterone but did not effect the penetration of hydrocortisone. A mechanism is proposed to explain why the absorption of the more lipophilic steroids is enhanced by occlusion but that of the most water-soluble (i.e., hydrocortisone) is not. It is suggested that the rate-determining role of the sequential steps involved in percutaneous absorption can be revealed by experiments of the type described using related series of homologous or analogous chemicals.

Absorption↗

PubMed1980

Induction of local epidermal papillomas and carcinoma by selected nitrosamines.

Weekly cutaneous application of N-nitrosobis (2-oxopropyl)amine (BOP) at a dose of 2 mg/application to the neck area resulted in the induction of local papillomas and carcinomas in 80% of Syrian hamsters as early as 19 weeks post-treatment. In addition, a few tumors of internal organs (predominantly in the liver) were also found. N-Nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), a common metabolite of BOP and BHP, was also found to be an epidermal carcinogen at a dose of 3.8 mg/application. N-Nitrosobis(2-hydroxypropyl)amine (BHP), however, failed to induce any epidermal lesions, when applied similarly at a much higher dose level (%) mg/animal/week). In contrast to BOP and HPOP, BHP induced a high incidence of tumors in internal organs, especially pancreatic cancer, which was the only induced tumor in 5 animals. Skin absorption studies demonstrated that BHP, but not BOP is rapidly absorbed and was detectable in the blood in concentrations of up to 5.5 mug/ml as early as 15 min after carcinogen administration. The possible reasons for the differing effects of BHP and BOP upon hamster skin are discussed.

Adenocarcinoma↗

PubMed1993

NTP Toxicology and Carcinogenesis Studies of p-Nitrophenol (CAS No. 100-02-7) in Swiss Webster Mice (Dermal Studies).

p-Nitrophenol is used in the production of acetaminophen, methyl and ethyl parathion insecticides, fungicides, and dyestuffs. Toxicology and carcinogenesis studies of p-nitrophenol (greater than 97% pure) were conducted by dermal application to male and female Swiss-Webster mice for 18 months. Dermal application was selected as the route of chemical administration because of possible skin absorption from p-nitrophenol-treated leather footwear. Genetic toxicology studies were conducted in Salmonella typhimurium, Chinese hamster ovary cells, and Drosophila melanogaster. 18-MONTH STUDIES: Groups of 60 Swiss-Webster mice of each sex received p-nitrophenol in acetone applied to the interscapular skin. Doses of 0, 40, 80, or 160 mg/kg p-nitrophenol were administered to mice 3 days per week for 78 weeks. At the end of the study, survival rates of mice receiving 0, 40, 80, or 160 mg/kg p-nitrophenol were 29/60, 17/60, 26/60, and 24/60 for males and 35/60, 26/60, 33/60, and 27/60 for females. Deaths after 60 weeks were caused by generalized amyloidosis and secondary kidney failure. The severity of amyloidosis was similar among dosed and control animals. At the end of the study, the final mean body weights of the dosed groups of each sex were similar to those of the controls. No biologically significant lesions were observed that were related to the dermal administration of p-nitrophenol. GENETIC TOXICOLOGY: p-Nitrophenol was not mutagenic in Salmonella typhimurium (strains TA100, TA1535, TA1537, and TA98) with or without exogenous metabolic (S9) activation, or in germ cells of male Drosophila melanogaster administered p-nitrophenol in feed or by injection. In Chinese hamster ovary cells, no induction of sister chromatid exchanges was observed with or without S9, but a significant increase in chromosomal aberrations occurred in trials conducted with S9. CONCLUSIONS: Under the conditions of these 18-month dermal studies there was no evidence of carcinogenic activity in male or female Swiss-Webster mice receiving 40, 80, or 160 mg/kg p-nitrophenol. Synonyms: 4-hydroxynitrobenzene, p-hydroxynitrobenzene, 4-nitrophenol, paranitrophenol, PNP, Niphen

Journal Article↗

PubMed2001

Control of chemical risks during the treatment of soil contaminated with chlorophenol, creosote and copper-chrome-arsenic-wood preservatives.

BACKGROUND: Exposure to chemicals in polluted soil was studied during the remediation of four polluted sites. They are sawmill areas contaminated with chlorophenols and polychlorinated dibenzo-p-dioxins and furanes (PCDD/F), wood impregnating plants contaminated with polycyclic aromatic hydrocarbons (PAH) from creosote oil, old gas works area contaminated with PAH, and a wood impregnation plant contaminated with copper-chromium-arsenic (CCA) preservative. METHODS: The exposure levels were determined by both air and biological monitoring. RESULTS: Air monitoring showed that the exposure levels were generally well below the current occupational exposure limits. The calculations indicated, however, that the lowest acceptable daily intake value recommended for PCDD/F by the U.S. Environmental Protection Agency was exceeded. Chlorophenol exposure was generally low. Exposure to volatile PAH was 0.038-0.884 mg/m(3) and that to particulate PAH was 0.004-0.183 mg/m(3). The biomonitoring results (urinary 1-pyrenol) suggested that some exposure occurs, probably through the contamination of hands or skin absorption. At the sites contaminated with CCA salts, no exposure limits were exceeded. CONCLUSIONS: The results generally suggest that the exposure of cleanup workers is generally below the current occupational exposure limits but that short-term high exposure cannot be excluded. There was also some indication of poor skin protection, which should be improved when soil contaminated with PAH and creosote oil is handled.

Arsenic↗

PubMedDate not supplied

Liposomes as alternative vehicles for sun filter formulations.

The aim of our study was to determine the influence of several types of liposomes with a different lipid composition on the percutaneous absorption of one conventional sun filter with a lipophilic character (ethyl hexyl methoxycinnamate) using both in vitro and in vivo methodologies. Three different liposomes were prepared with unsaturated and saturated phosphatidylcholine (PC, HPC), and with a wool lipid mixture (IWL) with a composition similar to that of the stratum corneum lipids. Results showed that the liquid crystalline state associated with PC liposomes plays a key role in enhancing skin penetration. when liposomes with a composition and structural organization similar to that of the stratum corneum lipids (HPC and IWL) are used, the skin penetration is retarded, suggesting a certain reinforcement of the stratum corneum barrier. These two types of liposomes could be regarded as alternatives to conventional oil/water emulsions in the formulations of lipidic sun filters. Finally, an acceptable correlation was obtained using both in vitro and in vivo methodologies to evaluate the corresponding skin absorption profile.

Animals↗

PubMed1998

Pharmacokinetics, formulation, and safety of insect repellent N,N-diethyl-3-methylbenzamide (deet): a review.

This review is intended to provide the reader with an overview of the all-purpose topical insect repellent N,N-diethyl-3-methylbenzamide (deet), with emphasis on its pharmacokinetics, formulation, and safety aspects. N,N-diethyl-3-methylbenzamide is effective against a variety of mosquitoes, flies, fleas, and ticks, and its protection efficacy depends on factors such as type of formulation, application pattern, physical activity of the user, environment, and species and feeding behavior of the insects. It offers an inexpensive and practical means of preventing the attack of biting insects and, more importantly, the transmission of vector-borne diseases. In both humans and animals, deet skin penetration and biodistribution are rapid and extensive, and metabolism and elimination appear to be complete. As evidenced by over 4 decades of human experience and rigorous animal testing, deet is generally safe for topical use if applied as recommended, although it has occasionally been related to side effects such as toxic encephalopathy, seizure, acute manic psychosis, cardiovascular toxicity, and dermatitis, along with a few cases of death due to extensive skin absorption. N,N-diethyl-3-methylbenzamide may compete in metabolism with and alter the biodistribution properties of other compounds to which a subject is simultaneously exposed, resulting in an added risk of side effects. The appropriate use of formulation techniques and new formulation excipients not only offers a way to extend the duration of protection, but also reduces deet skin penetration. In addition to extended repellency, minimal skin penetration of deet should be an important consideration in the evaluation of a deet formulation during new product development.

Animals↗

PubMed1990

Percutaneous absorption enhancing effect and skin irritation of monocyclic monoterpenes.

The percutaneous absorption promoting effect and skin irritancy of cyclic monoterpenes were investigated in rats and with rabbits, respectively. Ketoprofen (KPF) was applied to rat skin in gel ointments containing various cyclic monoterpenes. Plasma concentrations of KPF markedly increased with the addition of the hydrocarbons of cyclic monoterpenes such as trans-p-menthane and d-limonene, whereas no significant enhancing effect was observed in the cases of other terpenes such as l-menthol, l-menthone and 1,8-cineole. The lipophilicity of the enhancers seems the important factor in promoting penetration of KPF through the skin. The enhancing activity of d-limonene was found to be much higher than that of Azone. Irritancy of the hydrocarbons of cyclic monoterpenes and Azone to the skin was evaluated using a Draize scoring method with rabbits. No change was observed on the skin surface when ethanol containing 2% of the hydrocarbons was applied to the dorsal skin, though a slight edema and erythema were observed in the case of Azone. In particular, an obvious difference was observed in the erythema formation between Azone and the hydrocarbons of cyclic monoterpenes.

Animals↗

PubMed2001

Full-spectrum fluorescent lighting: a review of its effects on physiology and health.

BACKGROUND: Full-spectrum fluorescent lighting (FSFL) has been credited with causing dramatic beneficial effects on a wide variety of behaviours, mental health outcomes and physical health effects, as compared to other fluorescent lamp types. These effects are hypothesized to occur because of similarity between FSFL emissions and daylight, which is said to have evolutionary superiority over other light sources. METHOD: This review, covering the period 1941-1999, critically considers the evidence for direct effects of FSFL through skin absorption as well as indirect effects on hormonal and neural processes. CONCLUSIONS: Overall, the evidence does not show dramatic effects of fluorescent lamp type on behaviour or health, neither does it support the evolutionary hypothesis.

Arousal↗

PubMedDate not supplied

Airborne concentrations of toxic metals resulting from the use of low melting point lead alloys to construct radiotherapy shielding.

Determinations of airborne concentrations of lead, cadmium, bismuth, and tin were made above vessels containing a "fusible" lead alloy (158 degrees F melting point) commonly used for construction of radiotherapy blocks. Fume concentrations were determined by collection on a membrane filter and analysis by atomic absorption spectrophotometry. Samples were obtained for alloy temperatures of 200 degrees, 400 degrees, and 600 degrees F. In all instances, concentrations were much lower than the applicable occupational limits for continuous exposure. The results of this study indicate that the use of a vented hood as a means of reducing air concentrations of toxic metals above and near vessels containing low temperature melting point lead allows commonly used in construction of radiotherapy shields appears unjustifiable. However, proper handling procedures should be observed to avoid entry into the body via alternate pathways (e.g., ingestion or skin absorption). Transmission data of a non-cadmium containing lead alloy with a melting point of 203 degrees F was ascertained and is reported on.

Air↗

PubMed1973

Antihemophilic factor antigen. Localization in endothelial cells by immunofluorescent microscopy.

The tissue localization of antihemophilic factor (AHF, Factor VIII) has been determined by immunofluorescent studies using monospecific rabbit antibody to human AHF. Specific staining demonstrating AHF antigens has been identified in endothelial cells of a wide range of human tissues. The staining pattern was observed in endothelial cells of arteries, capillaries, and veins as well as the cells lining hepatic and splenic sinusoids. Specific fluorescence was limited to these endothelial cells in sections of kidney, liver, spleen, lymph node, cardiac and smooth muscle, thyroid, umbilical cord, and skin. Absorption studies established that the staining was specific for cells in which there were proteins that had AHF antigens. The demonstration of fluorescence within the cytoplasm of endothelial cells suggests that these cells synthesize proteins that have AHF antigens.

Animals↗

PubMed2006

In vivo near-infrared spectroscopy of rat skin tissue with varying blood glucose levels.

We have performed in vivo measurements of near-infrared rat skin absorption in the 4000-5000-cm(-1) spectral range (2.0-2.5-microm wavelength) during a glucose clamp experiment in order to identify the presence of glucose-specific spectral information. Spectra were collected during an initial 3-h period where the animal's blood glucose concentration was held at its normal value. The blood glucose level was then increased above 30 mM by venous infusion of glucose and held for 2 h, after which it was allowed to return to normal. Spectra were recorded continuously during the procedure and are analyzed to identify spectral changes associated with changes in glucose concentration. Because the change in absorbance due to an increase in glucose concentration is small compared to changes due to other variations (e.g., the thickness of the skin sample), a simple subtraction of absorbance spectra from the hyperglycemic and euglycemic phases is not instructive. Instead, a set of principal components is established from the euglycemic period where the glucose concentration is constant. We then examine the change in absorbance during the hyperglycemic period that is orthogonal to these principal components. We find that there are significant similarities between these orthogonal variations and the net analyte signal of glucose, which suggests that glucose spectral information is present. The analysis described here provides a procedure by which the analytical significance of a multivariate calibration can be evaluated.

Animals↗