οΈο Commonwealth of Australia 2002
Effects on Laboratory Mammals and In Vitro Test Systems
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- 10.2Irritation and sensitisation
10.Effects on Laboratory Mammals and In Vitro Test Systems10.1Single exposureThe acute toxicity of d limonene in rodents is fairly low after oral, intraperitoneal, subcutaneous, and intravenous administration, based on the magnitude of the LD50 values (Table 10.1). LD50 values were approxi mately 5 g/kg bw for the oral administration of d limonene or d/l limonene to rats and for dermal application of d/l limonene to rabbits and 6 g/kg bw for oral administration to mice *(Tsuji et al., 1974; *Tsuji et al., 1975b; *Opdyke, 1978). Studies on the acute inhalation toxicity of limonene were not identified. Table 10.1 - Acute toxicity of limonene
a Calculated from ml/kg body weight. Effects observed following the acute exposure of rodents to limonene include increased bile flow at 85 mg/kg bw *(Kodama et al., 1976), inhibition of S 3 hydroxy 3 methylglutaryl CoA reductase activity at 409 mg/kg bw *(Clegg et al., 1980), enzyme induction at 600 and 1200 mg/kg bw *(Ariyoshi et al., 1975), and decreased motor activity, hypothermia and potentiation of hexobarbital induced sleep at 3 ml/kg bw *(Tsuji et al., 1974). 10.2Irritation and sensitisationd Limonene is considered a skin irritant *(Cronin, 1980; *Fischer, 1986). The skin irritancy of limonene in guinea pigs *(Klecak et al., 1977) and rabbits *(Lacy et al., 1987; *Okabe et al., 1990) is considered moderate and low, respectively. In an in vivo study of rabbit skin irritation, d limonene was ranked 3.5 of 8 on the basis of the primary irritation index *(Bagley et al., 1996); effects were graded according to OECD Test Guideline 404 *(OECD, 1981c). In a study in rabbits, d limonene caused irritation to the eyes *(Tsuji et al., 1974). Airborne d- and l- limonene produced sensory irritation in mice over a 30 min period (Larsen et al., 2000). The estimated NOEL was 100 ppm (556 mg/m3), and the d- isomer was considered more potent. The RD50 values (exposure concentration decreasing respiratory rate by 50%) of d-limonene was estimated to be 1076 ppm (5983 mg/m3) and for l-limonene 1467 ppm (8156 mg/m3), based on the first 10 min of the exposure period. Pulmonary irritation and general anaesthetic effects were absent below 1600 ppm (8896 mg/m3). Mild bronchoconstriction was seen above 1000 ppm (5560 mg/m3). An earlier study (Kasanen et al., 1999) estimated the RD50 of limonene enantiomers to be between 1279 ppm and 4663 ppm (7111 mg/m3 and 25 926 mg/m3), based on testing of other terpenes and mixtures. Although d limonene was once considered the main allergen in citrus fruits, data from more recent studies in animals have revealed air oxidized d limo nene, rather than unoxidized d limonene, to be the sensitising agent. When limonene (unspecified form and unknown purity of the test material) was tested in four different sensitisation assays with guinea pigs (Open Epicutaneous Test, Maximization Test, Draize's Test, and a test with Freund's Complete Adjuvant), it was sensitising in all but Draize's Test *(Klecak et al., 1977). In another study in mice, d limonene did not induce sensitisation *(Maisey & Miller, 1986). Hydro peroxides and other oxidation products of d-limonene formed on exposure to the air have proved to be potent contact allergens when tested with Freund's Complete Adjuvant in guinea pigs, whereas unoxidized d-limonene did not cause any sensitisation (Karlberg et al., 1991; Karlberg et al., 1992). It has been suggested that limonene has a quenching effect (inhibition of the sensitising capacity of another substance) on the induction of skin sensitisation to citral. No effect was found in trials on guinea pigs or in the murine local lymph node assay (LLNA) (European Union, 2000). Directory: data -> assets -> word doc -> 0019 0019 -> Commonwealth of Australia 2000 0019 -> Rail safety news issue 6 β October 2011 0019 -> Social and economic benefits of improved adult literacy: Towards a better understanding Robyn Hartley Jackie Horne 0019 -> From: Virginia Holt [mailto: (personal contact details deleted) 0019 -> By Yvonne Hillier Introduction 0019 -> Communications alliance 0019 -> Allocations Manual Homeless with Support Category 0019 -> Inquiry into Vulnerable Road Users Inquiry into Vulnerable Road Users Download 1.1 Mb. Share with your friends:
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