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Testing bergamot oil for phototoxicity
Natural products-FFtl
446
Costtier. Torirol.
disease, including diabetes mellitus. and the chronic consumption of large quantities of cassava has previously been reported in the malnourished populations of Southern India and Nigeria (Cited in F.C.7: 1975. 13. 157). A similar relationship has also been noted by Davidson (cited above) in Zambia. In regions where cassava is the major dietary component and undernourishment is common. there was a prevalence rate of 1.1% new cases of diabetes. This contrasted markedly with the remainder of the country where maize is the staple food and diabetes is uncommon. The recognized clinical syndromes of chronic cassava toxicity, including degenerative neurological disease and endemic goitre (ibid 1967. 5, 125), appear to be attributable to cyanogenetic glycosides present in the crop; these are hydrolyzed to hydrocyanic acid by the endogenous enzyme linamarase when the plant tissue is damaged. Among the wide range of methods traditionally used for the detoxication of cassava is one in which the roots are grated, fermented and roasted into flour. The product is known as gari. The second paper reports that the assay of 500 random samples of gari being sold in Nigerian markets showed that only a very small proportion (0.4”/0) contained no cyanide. There was no significant difference between the mean concentrations of total (glycosidebound plus non-glycosidic) cyanide and of free (nonglycosidic) cyanide (8.0 f 6.9 and 7.2 k 5.8 mg HCN/kg, respectively), which indicated that virtually all the residual cyanide content of commercial gari could be in the free form. Of the samples analysed. 82% contained less than 10 mg HCN/kg.
Vol. 18. no. 4
parallel between the degrees of reaction in the guineapig and in man to different concentrations of 5-MOP. although the volunteers seemed to be slightly more sensitive than the guinea-pigs. The lowest doses effective in the guinea-pig were 25”,, bergamot oil (80 ppm 5-MOP) with SSL irradiation and 0.312”, bergamot oil (IOppm 5-MOP) with LUVL. In man. the minimal doses augmenting pigmentation were 1.25”” with SSL and 0.15°,0 with LUVL. Very similar results were also obtained from readings of the human skin at 24 hr. but at each dose level the effect was slightly more marked at 8 days. Thus in both guinea-pig and man, phototoxicity was some eight times greater when LUVL was used than with SSL and seemed to depend essentially on long ultraviolet radiation. For a given degree of phototoxic reaction there was apparently, in the guinea-pig, an inverse relation between the concentration of bergamot oil and the quantity of irradiation energy attributable to LUVL. In man the situation was less clear and a greater involvement of ultraviolet rays in the 29(X320 nm range seems likely. Nevertheless this work suggests that the guinea-pig is a particularly appropriate experimental model for studying the phototoxic potential of psoralencontaining products to which man may be exposed.
Primrose
and rosewood
sensitizers
Schulz, K. H.. Garbe. I.. Hausen. B. M. & Simatupang, M. H. (1979). The sensitizing capacity of naturally occurring quinones. Experimental studies in guinea pigs. II. Benzoquinones. Arch Dem. Res. 264. 275.
Testing
bergamot
oil for
phototoxicity
Girard, J., Unkovic, J., Delahayes, J. et Lafille. C. (1979). Etude experimentale de la phototoxicite de l’essence de Bergamote. Correlations entre l’homme et le cobaye. Dermatologica 158. 229. The phototoxic effect of bergamot oil. which is frequently used in perfumes, has been ascribed to the furocoumarin bergapten (5-methyl-psoralen; 5-MOP). a common though not invariable component of the oil (Cited in F.C.T. 1978, 16, 507). Close correlation has now been reported between the phototoxic effects elicited in human volunteers and in guinea-pigs by a sample of bergamot oil containing 3200ppm 5-MOP. Guinea-pigs were treated with various dilutions of the oil. in ethanol, applied in doses of 4 PI/cm2 to depilated skin. The applications were followed 1 hr later by irradiation with a minimal erythema-inducing dose either of solar-simulating light (SSL; wavelength 290 nm and longer) or of light in the long ultraviolet range (LUVL; 320 nm and longer) and augmentation of erythema was assessed 24 hr after the irradiation. The effects were compared with the augmented pigmentation of forearm skin in adult volunteers similarly treated with the bergamot oil and exposed to the same types of irradiation, the test sites being assessed for augmented pigmentation 8 days after irradiation with the minimal dose causing immediate pigment darkening. With both types of irradiation, there was a clear
An eczematous dermatitis has been reported (Cired 1968.6. 678) in people handling Machaerium a substitute for Rio rosewood containing R-3,4-dimethoxydalbergione (R-5.6-dimethoxy-2-(1’phenylallyl)-l.4-benzoquinone). In view of the apparent increase in the incidence of sensitization to ornamental woods, further details of the sensitizing capacity of dalbergiones and related benzoquinones and naphthoquinones are of interest. Five of seven benzoquinone derivatives tested in guinea-pigs for sensitizing capacity gave positive results. These were primin, mansonone A. 4-methoxydalbergione racemate, R-3,4-dimethoxydalbergione and S-4,4’-dimethoxydalbergione. Primin (2-methoxy6-pentyl-1.4-benzoquinone from the primrose, Primula ohcorlica) was the most powerful. eliciting allergic reactions in concentrations of 0.5-0.2 mM in three of ten animals. Next came R-3,4-dimethoxydalbergione from M. sclerorylorl and mansonone A (l.Zdioxy-3,8-dimethyl-5-isopropyl-5,6.7,8-tetrahydronaphthalene from Mamorlia altissirua). Two compounds from Dalbrrgia rligra, 4-methoxydalbergione and S-4,4’-dimethoxydalbergione. were weaker sensitizers No sensitization was elicited by 2,6-dimethoxy- I .4-benzoquinone or rapanone (2,5-dihydroxy-6-tridecyl-l.4-benzoquinone) in these experiments. Allergic cross-sensitization was demonstrated in guinea-pigs sensitized with mansonone A and challenged with five related naphthoquinones. all derived from Mansonia altissima. in F.C.T. sclerosylo~~.
446
Costtier. Torirol.
disease, including diabetes mellitus. and the chronic consumption of large quantities of cassava has previously been reported in the malnourished populations of Southern India and Nigeria (Cited in F.C.7: 1975. 13. 157). A similar relationship has also been noted by Davidson (cited above) in Zambia. In regions where cassava is the major dietary component and undernourishment is common. there was a prevalence rate of 1.1% new cases of diabetes. This contrasted markedly with the remainder of the country where maize is the staple food and diabetes is uncommon. The recognized clinical syndromes of chronic cassava toxicity, including degenerative neurological disease and endemic goitre (ibid 1967. 5, 125), appear to be attributable to cyanogenetic glycosides present in the crop; these are hydrolyzed to hydrocyanic acid by the endogenous enzyme linamarase when the plant tissue is damaged. Among the wide range of methods traditionally used for the detoxication of cassava is one in which the roots are grated, fermented and roasted into flour. The product is known as gari. The second paper reports that the assay of 500 random samples of gari being sold in Nigerian markets showed that only a very small proportion (0.4”/0) contained no cyanide. There was no significant difference between the mean concentrations of total (glycosidebound plus non-glycosidic) cyanide and of free (nonglycosidic) cyanide (8.0 f 6.9 and 7.2 k 5.8 mg HCN/kg, respectively), which indicated that virtually all the residual cyanide content of commercial gari could be in the free form. Of the samples analysed. 82% contained less than 10 mg HCN/kg.
Vol. 18. no. 4
parallel between the degrees of reaction in the guineapig and in man to different concentrations of 5-MOP. although the volunteers seemed to be slightly more sensitive than the guinea-pigs. The lowest doses effective in the guinea-pig were 25”,, bergamot oil (80 ppm 5-MOP) with SSL irradiation and 0.312”, bergamot oil (IOppm 5-MOP) with LUVL. In man. the minimal doses augmenting pigmentation were 1.25”” with SSL and 0.15°,0 with LUVL. Very similar results were also obtained from readings of the human skin at 24 hr. but at each dose level the effect was slightly more marked at 8 days. Thus in both guinea-pig and man, phototoxicity was some eight times greater when LUVL was used than with SSL and seemed to depend essentially on long ultraviolet radiation. For a given degree of phototoxic reaction there was apparently, in the guinea-pig, an inverse relation between the concentration of bergamot oil and the quantity of irradiation energy attributable to LUVL. In man the situation was less clear and a greater involvement of ultraviolet rays in the 29(X320 nm range seems likely. Nevertheless this work suggests that the guinea-pig is a particularly appropriate experimental model for studying the phototoxic potential of psoralencontaining products to which man may be exposed.
Primrose
and rosewood
sensitizers
Schulz, K. H.. Garbe. I.. Hausen. B. M. & Simatupang, M. H. (1979). The sensitizing capacity of naturally occurring quinones. Experimental studies in guinea pigs. II. Benzoquinones. Arch Dem. Res. 264. 275.
Testing
bergamot
oil for
phototoxicity
Girard, J., Unkovic, J., Delahayes, J. et Lafille. C. (1979). Etude experimentale de la phototoxicite de l’essence de Bergamote. Correlations entre l’homme et le cobaye. Dermatologica 158. 229. The phototoxic effect of bergamot oil. which is frequently used in perfumes, has been ascribed to the furocoumarin bergapten (5-methyl-psoralen; 5-MOP). a common though not invariable component of the oil (Cited in F.C.T. 1978, 16, 507). Close correlation has now been reported between the phototoxic effects elicited in human volunteers and in guinea-pigs by a sample of bergamot oil containing 3200ppm 5-MOP. Guinea-pigs were treated with various dilutions of the oil. in ethanol, applied in doses of 4 PI/cm2 to depilated skin. The applications were followed 1 hr later by irradiation with a minimal erythema-inducing dose either of solar-simulating light (SSL; wavelength 290 nm and longer) or of light in the long ultraviolet range (LUVL; 320 nm and longer) and augmentation of erythema was assessed 24 hr after the irradiation. The effects were compared with the augmented pigmentation of forearm skin in adult volunteers similarly treated with the bergamot oil and exposed to the same types of irradiation, the test sites being assessed for augmented pigmentation 8 days after irradiation with the minimal dose causing immediate pigment darkening. With both types of irradiation, there was a clear
An eczematous dermatitis has been reported (Cired 1968.6. 678) in people handling Machaerium a substitute for Rio rosewood containing R-3,4-dimethoxydalbergione (R-5.6-dimethoxy-2-(1’phenylallyl)-l.4-benzoquinone). In view of the apparent increase in the incidence of sensitization to ornamental woods, further details of the sensitizing capacity of dalbergiones and related benzoquinones and naphthoquinones are of interest. Five of seven benzoquinone derivatives tested in guinea-pigs for sensitizing capacity gave positive results. These were primin, mansonone A. 4-methoxydalbergione racemate, R-3,4-dimethoxydalbergione and S-4,4’-dimethoxydalbergione. Primin (2-methoxy6-pentyl-1.4-benzoquinone from the primrose, Primula ohcorlica) was the most powerful. eliciting allergic reactions in concentrations of 0.5-0.2 mM in three of ten animals. Next came R-3,4-dimethoxydalbergione from M. sclerorylorl and mansonone A (l.Zdioxy-3,8-dimethyl-5-isopropyl-5,6.7,8-tetrahydronaphthalene from Mamorlia altissirua). Two compounds from Dalbrrgia rligra, 4-methoxydalbergione and S-4,4’-dimethoxydalbergione. were weaker sensitizers No sensitization was elicited by 2,6-dimethoxy- I .4-benzoquinone or rapanone (2,5-dihydroxy-6-tridecyl-l.4-benzoquinone) in these experiments. Allergic cross-sensitization was demonstrated in guinea-pigs sensitized with mansonone A and challenged with five related naphthoquinones. all derived from Mansonia altissima. in F.C.T. sclerosylo~~.