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CUPRESSACEAE(Cypress family)
The 130 species of principally evergreen coniferous trees and shrubs in 19 genera are of cosmopolitan distribution. Several species provide useful timber, including the incense cedar (Calocedrus decurrens Florin), Lawson's cypress (Chamaecyparis lawsoniana Parl.), the Monterey cypress (Cupressus macrocarpa Hartw.), alerce (Tetraclinis articulata Masters), and the red cedar (Juniperus virginiana L.). The incense cedar and red cedar are both used to make pencils. The fruit of the common juniper (Juniperus communis L.) is used for flavouring gin; oil of cade, which is used in dermatological preparations, is produced by the destructive distillation of prickly juniper wood (Juniperus oxycedrus L.); savin oil is produced from Juniperus sabina L.; sandarac resin, which was formerly used as a pill varnish, is derived from Tetraclinis articulata Masters. Generally, timbers derived from members of this family should be regarded as potentially hazardous to the skin. Quinones such as thymoquinone, and tropolones such as β- and γ-thujaplicin appear to be the principal contact allergens, but podophyllotoxin and other dermatologically active compounds have also been found in members of the family. Foliage, too, may be responsible for contact dermatitis. Occupational asthma may occur in woodworkers.
Fitzgerald et al. (1957) reported the presence of desoxypodophyllotoxin in the leaves of this species. See also Podophyllum peltatum L. (fam. Podophyllaceae). According to Maiden (1921), an itch can occur in those cutting Callitris whilst the trees are laden with pollen. Cleland (1925) notes that the wood of Callitris can produce dermatitis. The timber of commerce comes mainly from Callitris glauca R.Br. (Boas 1947).
Aynehchi (1971) reported the presence of desoxypodophyllotoxin, otherwise known as silicicolin, in the leaves and stems of this species (see also Podophyllum L., fam. Podophyllaceae). Brecknell & Carman (1978, 1979) found several sesquiterpene lactones including columellarin, a potentially allergenic guaianolide (see also Compositae), in the heartwood.
This species yields valuable timber. Incense cedar and Virginian pencil cedar (probably Juniperus virginiana L.) are both officially recognised causes of dermatitis in the German pencil industry (Koelsch 1931). Calnan (1972) described cases of dermatitis from cedar wood pencils: a male carpenter and floor layer developed dermatitis affecting the groins, buttocks, thighs, legs, and feet. From time to time he developed patches of an exudative dermatitis behind his ear which he attributed to holding a pencil there. The dermatitis on his feet followed a period of work sawing wood. Patch tests were positive to the wood of a pencil. In the case of a female clerk, aged 48 year, dermatitis affecting the right hand and middle and ring fingers was reported. Patch tests were positive to the wood of her pencil. In the case of the carpenter, patch tests were positive to ethereal, aqueous, and ethanolic extracts of the heartwood of Libocedrus decurrens. In both cases, patch tests were positive to thymoquinone and thymoquinol and, in the case of the clerk, to carvacrol. These compounds are known to occur in the heartwood (Zavarin & Anderson 1955a, Anderson et al. 1963). Other dermatologically active compounds have also been found in the heartwood, including γ-thujaplicin (Zavarin & Anderson 1955b, 1956, Anderson et al. 1963) which was studied by Bleumink et al. (1973b) in a case of western red cedar (Thuja plicata Donn ex D.Don — see below) allergy, and β-thujaplicin (Zavarin & Anderson 1956), the contact allergenic properties of which were studied by Ito (1964). In addition, the cytotoxic lignan desoxypodophyllotoxin has been isolated from the leaves and stems (Kupchan et al. 1967) — see Podophyllum L., fam. Podophyllaceae.
Prosser White (1934) noted that healing was troublesome and prolonged if a spicule [= ?] entered the skin. Several authors report that the foliage of this tree can produce dermatitis, and the wood can cause asthma in wood-workers (Rasch 1923/24, Schonwald 1929, Stier 1929, Hausen 1970). Woods & Calnan (1976), however, found that none of the literature cited by Hausen (1970) provided convincing evidence for contact dermatitis. The powerful resinous odour of the newly-cut wood was said to cause troublesome diuresis in saw mill workers (Sargent 1896). The pollen can cause pollinosis (Wodehouse 1971). Fitzgerald et al. (1957) reported the presence of desoxypodophyllotoxin in the leaves of this species. Only traces of β-thujaplicin and no other tropolones have been found in the heartwood (Zavarin & Anderson 1956, Zavarin et al. 1959).
This species yields carvacrol (Watt & Breyer-Brandwijk 1962), one of the elicitors of Calocedrus decurrens allergy. No thujaplicins could be detected (Zavarin & Anderson 1956).
This species, known locally in Japan as chyabohiba, was found to contain sesamin (Masumura 1955). Sesamin is known for its role in sesame oil (Sesamum indicum L., fam. Pedaliaceae) dermatitis. The presence of β-thujaplicin has been reported in this species (Zavarin et al. 1959). The contact allergenic properties of this compound were investigated by Ito (1964).
Zavarin & Anderson (1956) and Zavarin et al. (1959) reported the presence of tropolones, including β- and γ-thujaplicin, in the heartwood of this species. Enzell (1960), on the other hand, could not detect any tropolones in their material. The role of γ-thujaplicin in western red cedar (Thuja plicata Donn ex D.Don — see below) allergy was investigated by Bleumink et al. (1973b). The contact allergenic properties of β-thujaplicin were demonstrated by Ito (1964).
A male aged 40 years, who was contact sensitive to zinc oxide plaster containing colophony, developed dermatitis from planting this species (Hindson et al. 1982). This is a genus of between 15 and 20 species found in the region of the Mediterranean, the Sahara, Asia, and North America. β-Thujaplicin, the contact allergenic properties of which have been investigated by Ito (1964), has been found in the majority of species (Zavarin et al. 1967, Zavarin et al. 1959), including:
Both γ-thujaplicin and β-thujaplicinol, which have been found to be elicitors of Thuja plicata dermatitis (Bleumink 1973b), have been demonstrated to occur in the heartwood of the following species (Zavarin et al. 1967):
In addition, β-thujaplicinol, but not γ-thujaplicin, has been detected in: This species is a native of Greece and Crete, but is commonly planted for ornament in the Mediterranean region. The wood can cause dermatitis (Hausen 1970). The presence of β-thujaplicin and carvacrol in the heartwood of this species was reported by Enzell & Erdtman (1957). See Calocedrus decurrens Florin and Thuja plicata Donn ex D.Don. A man who was contact sensitive to Dalbergia L.f. (fam. Leguminosae) showed transient erythema from a patch test with cypress wood (Lewith 1929). The pungent smell of cypress wood causes headaches in carpenters (Ramazzini 1713). Cypress oil, a fragrance raw material derived from this taxon by steam distillation of the leaves, was found to be moderately irritating to rabbit skin when applied under occlusion for 24 hours. At a dilution of 5% in petrolatum, it was found to be non-irritant to human skin in a 48 hour closed patch test. No sensitising nor phototoxic effects could be demonstrated (Opdyke 1978, p. 699). Zavarin et al. (1967) reported the presence of β-thujaplicin in the heartwood. The contact allergenicity of this compound has been demonstrated on guinea pigs (Ito 1964).
The wood is irritant to the respiratory tract (Orsler 1973) and has caused allergic contact dermatitis (Oleffe et al. 1974, Oleffe et al. 1975a, Oleffe et al. 1975b, Oleffe et al. 1975c). The genus Fitzroya Hook.f. ex Lindl. is now considered to be monotypic. The tree grows naturally in southern Argentina and southern Chile (Mabberley 1997). Some 60 species are found in the Northern Hemisphere. A commercially available Juniperus extract (Hollister-Stier Laboratories) frequently (14/26) produced irritant patch test reactions (Mathias et al. 1979). The leaves of some species can cause punctate erythema or linear papules on the hands, wrists, forearms, and ankles of persons who weed or work amongst juniper shrubs. The reaction seems to be a mechanical effect, but an eczematous reaction sometimes observed may be a reaction from self-medication. Patch tests produced equivocal or negative results (Mitchell JC — unpublished observation). Hjorth (1968) recorded a positive patch test reaction to juniper. Juniper wood can produce dermatitis and respiratory symptoms in wood-workers (Orsler 1973). Juniper, either smoked or used in tea, can produce euphoric, stimulant, or hallucinogenic effects (Anon 1979). β-Thujaplicin, the contact allergenic properties of which were investigated by Ito (1964), has been detected in trace amounts in the heartwood of some species (Zavarin et al. 1959), including:
See also Calocedrus decurrens Florin above. A phytochemical investigation of the heartwood demonstrated the presence of thymoquinone, carvacrol, and β-thujaplicin (Runeberg 1960a). Positive patch test reactions to both of these compounds have been observed (see Calocedrus decurrens Florin and Thuja plicata Donn ex D.Don). Carvacrol, β-thujaplicin and other tropolones, and derivatives of thymoquinone have been reported to occur in the heartwood of this species (Zavarin et al. 1959, Pilo & Runeberg 1960). See also Calocedrus decurrens Florin. Juniper oil rubbed onto the skin produces a burning sensation with slight reddening, and even blistering if occluded (Nothnagel 1870). Externally, oil of juniper berry is skin irritant (Nadkarni 1976). Rothe et al. (1973) found juniper berry oil to be an occupational allergen to the skin and respiratory tract. Lord (1933) described oil of cadeberry, a combination of green Barbados tar (obtained from seepage from coral) and oil of juniper berry. He noted that it was almost entirely non-irritant to the skin, but that one occasionally saw infants who seemed to be definitely sensitive to it. β-Thujaplicin, the contact allergenic properties of which were investigated by Ito (1964), has been detected in trace amounts in the heartwood of this species (Zavarin et al. 1959). See also Calocedrus decurrens Florin. Hartwell et al. (1953) and Fitzgerald et al. (1957) reported the presence of podophyllotoxin in this species. (See Podophyllum peltatum L., fam. Podophyllaceae). This species can have irritant properties (Behl et al. 1966). When smoked, this juniper has strongly hallucinogenic properties (Siegel 1976). Wood cutters in Texas, where the pollen is a common cause of pollinosis (Wodehouse 1971), have developed dermatitis from J. mexicana. The aromatic oil of the tree, or lichens on the bark have been suggested as the causative agents (Morton 1977a). The fragrance raw material cedarwood oil Texas is derived from J. mexicana by steam distillation of the wood. No irritant, sensitising, nor phototoxic effects could be demonstrated with the oil in a variety of test procedures (Opdyke 1976, p. 711). Sax (1975) reported that the oil possesses slight activity as a local irritant or allergen. Irritant and probably allergic dermatitis can result from application of oil of cade derived from the wood of this tree by destructive distillation (White 1887, Gougerot & Blamoutier 1922, Nelson 1932, Lord 1933, Grolnick 1938a, Greenberg & Lester 1954). Acneiform eruptions can also result from the use of oil of cade (White 1887). Carvacrol and β-thujaplicin have been reported from the heartwood of this species (Runeberg 1960b). Positive patch test reactions to these compounds have been observed (see Calocedrus decurrens Florin). The wood can cause dermatitis, conjunctivitis, and rhinitis in wood-workers (Piorkowski 1944, Watt & Breyer-Brandwijk 1962). Piffard (1881) recorded that "the twigs cause inflammation of the skin". Harrison (1906) included savin in a list of drugs, applied externally or taken internally, which may cause dermatitis. According to Stuart (1979), savin has a long history as a stimulant veterinary drug in Europe, and was applied to the wounds and ulcers of animals. As a human medicine it is now only used externally, if at all (because of its toxicity), as a stimulant dressing for blisters, wounds, and ulcers, and to remove warts. Savin oil, obtained by steam distillation of the plant material, is a violent irritant both internally and externally (Todd 1967). If applied to the skin, it can produce erythema and blistering (Fasal 1926). The species and also J. sabina var. tamariscifolia yield podophyllotoxin (Hartwell et al. 1953, Fitzgerald et al. 1957), the irritant properties of which are well known (see Podophyllum peltatum L., fam. Podophyllaceae). Podophyllotoxin has been reported from this species (Hartwell et al. 1953, Fitzgerald et al. 1957). See also Podophyllum peltatum L., fam. Podophyllaceae. Hartwell et al. (1952) reported the isolation of silicicolin, a lignan, from the heartwood of this species. This was subsequently shown to be desoxypodophyllotoxin (Hartwell & Schrecker 1954). See also Podophyllum peltatum L., fam. Podophyllaceae.
Carvacrol and β-thujaplicin have been reported from both of these species (Runeberg 1960c, 1960d). Positive patch test reactions to these compounds have been observed (see Calocedrus decurrens Florin). Incense cedar and Virginian pencil cedar (probably Juniperus virginiana L.) are both officially recognised causes of dermatitis in the German pencil industry (Koelsch 1931). The leaves were used in an ointment for their irritant and rubefacient properties (White 1887). The fragrance raw material known as cedarwood oil Virginia, red cedarwood oil, or oil cedar is obtained from this species by steam distillation of the sawdust. The principal constituents are cedrene, thujopsene, and cedrol. The oil was found to be moderately irritating to rabbit skin when applied under occlusion for 24 hours. On mouse skin, and at a dilution of 8% in petrolatum on human skin in a 48 hour closed patch test, the oil was non-irritant. No sensitising nor phototoxic effects could be demonstrated (Opdyke 1974, p. 845). However, the use of toilet preparations containing cedarwood oil followed by exposure to sunlight is sometimes a cause of dermatitis (Bray 1937, Greenbaum 1934). Pigmentation may follow the topical application of cedarwood oil (del Vivo 1930, Sandler 1939). Podophyllotoxin has been reported to occur in this species (Hartwell et al. 1953, Fitzgerald et al. 1957). See also Podophyllum peltatum L., fam. Podophyllaceae. β-Thujaplicin, the contact allergenic properties of which have been investigated by Ito (1964), has been reported to occur in the heartwood of this species. See also Calocedrus decurrens Florin. The leaves and branches of this species and of Thuja occidentalis L. can produce dermatitis in gardeners (Genner & Bonnevie 1938, Schwartz et al. 1957). Contact dermatitis from the leaf of Thuja orientalis was reported by Zubiri & Obras-Loscertales (1970).
In NW Moroccan traditional medicine, the leaves of this plant mixed with henna leaves (Lawsonia inermis L., fam. Lythraceae) are powdered and kneaded with water to make a hair tonic for external application (Merzouki et al. 2000). The heartwood of this species is known to contain several dermatologically active compounds including thymoquinone, carvacrol, and β- and γ-thujaplicins (Erdtman & Rennerfelt 1949, Chow & Erdtman 1962). Calnan (1972) and Woods & Calnan (1976) were probably referring to this species and to this earlier literature when they asserted that Callitris articulata Vahl [sic] contains thymoquinone. See also Calocedrus decurrens Florin, Thuja plicata Donn ex D.Don. Five species are to be found in China, Japan, and North America. An irritant and possibly a sensitiser is present in Thuja leaves (Sachs 1926, McCord 1962, Schwartz et al. 1957). This species can excite irritation of the skin by contact (Maiden 1909b). The name white cedar is applied to this species and to Chamaecyparis thyoides Britton and Calocedrus decurrens Florin. The plant, or a decoction of it irritates and inflames the skin like Juniperus sabina L. (Cantani 1876). Felter & Lloyd (1898), citing Howe (1880; Eclectic Medical Journal, p. 331) record that "A tincture of fresh leaves of thuja will, locally applied, according to my experience, remove warts from the face and hands, condylomata about the nates, but will not destroy swiftly growing venereal warts. It will deaden fungous granulations, and utterly destroy them in some instances. But the best action of the drug is in overcoming the growing and spreading progress of epithelioma. I have seen it repress and overcome fungoid and ulcerous epitheliomata in an astonishingly happy manner." Citing Howe further, they record that "Thuja comes highly recommended as a dressing for sloughing wounds, ulcers, bedsores, senile and other forms of gangrene, serving a useful purpose in overcoming the horrible stench arising therefrom. It may likewise be used in carcinomatous ulcerations. Some even claim that it has power to check the latter disorder, but in all probability, this is claiming too much for the drug. It is frequently valuable to restrain hemorrhages occasioned by malignant growths." References in the more recent literature to the use of preparations of Thuya occidentalis for the removal of warts and fungoid growths (for example: Wren 1975) evidently relate to Howe's observations. The tree can produce dermatitis in gardeners (Genner & Bonnevie 1938, Schwartz et al. 1957). Several men working with white cedar developed dermatitis of the hands; another man had pharyngitis and bronchitis, but no dermatitis (Sachs 1926). The fragrance raw material cedar leaf oil or oil thuja (also known as oil of arbor-vitae or oil of white cedar) is derived from this species by steam distillation of the fresh branch ends and leaves. The oil was found to be moderately irritating to rabbit skin when applied under occlusion for 24 hours. A 4% dilution in petrolatum was not irritant to human skin in a 48 hour closed patch test. No sensitising properties could be demonstrated in 25 human volunteers; no phototoxic effects have been reported (Opdyke 1974, p. 843).
Bleumink et al. (1973b) investigated a woodworker with acute dermatitis of the face, hands, and arms. He reacted to patch tests with western red cedar and to aqueous and ethanolic extracts prepared from it. Several other woods were also tested but gave negative results. Positive reactions to γ-thujaplicin (which is 5-isopropyltropolone), β-thujaplicinol (which is 7-hydroxy-4-isopropyltropolone), thymoquinone, and to methyl-p-benzoquinone, but not to β-thujaplicin (all 1% in ethanol) were also observed. Thymoquinone was noted to be both an irritant and a potent elicitor of allergic contact dermatitis. Seventy six cases of dermatitis from the sawdust were reported by Ishizaki et al. (1973). Conjunctivitis, urticaria, rhinitis, and asthma were also observed. A patient who exhibited positive patch tests reactions to extracts of both western red cedar and incense cedar (Calocedrus decurrens Florin) was reported by Calnan (1972). A joiner who had dermatitis showed positive patch test reactions to Thuja plicata and oak (Quercus L., fam. Fagaceae), negative to some other woods (Woods & Calnan 1976). "Cedar poisoning", a form of allergic contact dermatitis sometimes presented by forest workers, results from exposure to lichens and liverworts which grow on the trees (Tan & Mitchell 1968, Mitchell et al. 1972a). An ethyl acetate extract but not a diethyl ether extract of wood from a tree identified only as "western cedar" and "red cedar" growing in the forests of Oregon, USA, but probably this species, exhibited a high degree of sensitisation in guinea pigs (Suskind 1967). The wood dust can produce allergic respiratory symptoms in wood-workers (Chan-Yeung 1982, Brooks et al. 1981, Mue et al. 1975, Mitchell & Chan-Yeung 1974, Chan-Yeung et al. 1973, Pickering et al. 1972, Mitchell 1970, Gandevia & Milne 1970, Gandevia 1970, Milne & Gandevia 1969, Doig 1949). The responsible agent is plicatic acid. Asthma has also been reported in persons working with urea formaldehyde / western red cedar particle board (Cockcroft et al. 1982). The main symptoms in 1320 persons with reactions to western red cedar, and the rate of occurrence were (Yasue 1973): asthma 3.6%; nasal inflammation 5.6%; urticaria 3.1%; skin infection 3.0%; conjunctivitis 5.1%. A number of persons living in houses built of western red cedar after the 1923 Tokyo earthquake developed "beisugi asthma" (Hausen 1970). The wood can cause dermatitis and respiratory symptoms in wood-workers (Ito 1963, Komatsu 1964, Yasue 1973). The contact sensitiser is β-thujaplicin (Ito 1964). The fragrance raw material hibawood oil is obtained from the sawdust and trunk wood shavings of this tree by steam distillation. It was found to be moderately irritating to rabbit skin when applied under occlusion for 24 hours. At a dilution of 12% in petrolatum, it was non-irritant to human skin in a 48 hour closed patch test. No sensitising nor phototoxic properties could be detected (Opdyke 1979, p. 817). Contact dermatitis from timbers is usually attributable to contamination of the skin during machining. Handling of solid wood rarely induces dermatitis, but Calocedrus (and also Dalbergia L.f., fam. Leguminosae) used for pencils, etc. may do so (Calnan 1972). Thymoquinone is very irritant in high concentration, and may be so at 1%; a concentration of 0.1% is recommended for patch testing (Calnan 1972, Hausen 1981). Bleumink & Nater (1974b) observed a positive patch test reaction to thymoquinone (0.1%). β-Thujaplicin, which is also known as hinokitiol, is used in Japan in hair tonics for its bactericidal properties. A male aged 60 years, who had dermatitis of the face, scalp, and hands associated with the use of such a lotion showed positive patch test reactions to β-thujaplicin (0.1% in ethanol) as well as to pyridoxine-3,4-dioctanoate (0.001% in ethanol), pyridoxine hydrochloride (1% in petrolatum), and 10% aqueous propylene glycol (Fujita & Aoki 1983). Primin was found not to be an elicitor in cases of tropolone (γ-thujaplicin and β-thujaplicinol) and thymoquinone allergy (Bleumink et al. 1973b). References
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