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Genotoxic chlorinated hydrocarbons?
Information Section--FdChem.
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weight/day for both species(150 ppm for rats, and 200 ppm for rabbits), based on decreased water consumption and a reduction in maternal body weight gain. No convincing reproductive effects were seen even at the maximum tested concentrations, providing doses of 27 mg/kg body weight for rats and 29 mg/kg body weight for rabbits (Heindel et al., Fundamaental and Applied Toxicology 1996,30, 162). Genotoxic chlorinated hydrocarbons? An in vitro assay, using genetically engineered human cells with metabolic (cytochrome P-450) competence, demonstrated the induction of micronuclei (an indicator of chromosome damage) by 14 of the 15 tested materials, mainly chlorinated hydrocarbons, including carbon tetrachloride, 1-chlorohexane, 1,2dichloroethylene, methylene chloride, tetrachloroethylene and toluene. 2,3-Dichlorobutane and 1,1,2-trichloroethane, which produced aneuploidy (on this occasion a reduced number of chromosomes), were said by the investigators to “warrant a high priority for testing in germ cells” (Doherty et al., Mutagenesis 1996, 11, 247). Subcbronic biphenyl
toxicity
of
2,2’,4,4’,5,5’-hexachloro-
PCB 153 (2,2’,4,4’,5,5’-hexachlorobiphenyl) produced clear pathological changes in the liver and thyroid and decreasedthe biogenic amine levelsin the brain when given in the diet to rats for 13 wk at a level of 5 ppm and above. Indications of mild effects at these same sites were still present at the lowest tested concentration of 0.05 ppm. Nevertheless the investigators felt disposed to describe 0.5 ppm as the NOAEL (equivalent to 34 pg/kg body weight/day) (Chu et al., Journal of Applied Toxicology 1996, 16, 121). Lead and nervous system cancer A higher than expected incidence of cancer of the nervous system associated with occupational exposure to lead has been reported by Finnish investigators. The cancer status of a cohort of over 20,000 workers was checked for a 12-yr period. RRs for nervous system cancer were 1.6 (95% CI 0.7-3.8) and 1.8 (95% CI 0.6-5.8) for groups with blood lead measurements of between 1.Oand 1.9 pmol/litre and 2.0 pmol/litre or more, respectively, compared with those with blood lead less than 1.0 pmol/litre. Corresponding RRs rose to 3.0 (95% CI 0.8-11; based on six cases)and 5.6 (95% CI 1.4-23; based on four cases)in workers aged over 44 yr. A nested case-control study of 26 of the men with cancer of the nervous system and 200 matched non-cancer controls revealed increased odds ratios with increasing blood lead levels, due largely to an increase in gliomas (Anttila et al., Journal of Occupational and Environmental Medicine 1996, 38, 131).
Toxic.
Vol. 34, No. 9
Diesel exhaust not carcinogenic in mice Diesel exhaust has been shown previously to induce lung cancer in rats exposed by inhalation, but not in Syrian hamsters treated similarly. In a recently reported US study, CD-l mice exposed to whole diesel exhaust at soot concentrations of 0.35, 3.5 and 7.1 mg/m’ for 7 hr/day, 5 days/wk for 2 yr-an exposure regimen that proved carcinogenic in a parallel study with rats-failed to develop an increased incidence of lung tumours. “Although rodents serve as useful indicators of potential human carcinogenic hazards, it is not yet clear which, if any, rodent specieshave lung neoplastic responsesthat are useful for quantitative predictions of human lung cancer risk from chronic inhalation of poorly soluble, respirable particles” (Mauderly et al., Fundamental and Applied Toxicology 1996, 30, 233). Lead and the kidney In a study of 151 young Rumanian children (aged 3-6 yr) living near a lead smelter, the Dutch investigators claim to have provided the first evidence of “an effect of environmental lead exposure on renal integrity in children”. Mean blood lead levels (which ranged from around 150 to 440 pg/litre in four groups of children who lived at varying distances from the smelter) were found to be correlated with the urinary activity of the enzyme N-acetyl-p-D-glucosaminidase, an indirect indicator of kidney injury (Verberk et al., Archives of Environmental Health 1996, 51, 83).
Nonylphenol oestrogenicity to trout Nonylphenol was oestrogenic to rainbow trout even at the lowest tested water concentration of 10 ppb. Oestrogenic activity was indicated by the induction of a protein, vitellogenin, by the fish. The lethal concentration of nonylphenol to trout under similar conditions was around 150 ppb (Lech et al., Fundamental
and Applied
Toxicology
1996, 30, 229).
Passivesmoking-lung complications in children under anaesthesia Adult patients who smoke can suffer breathing complications while under general anaesthesia. Investigators from Boston, USA have studied whether similar problems can occur in children who are exposed to environmental tobacco smoke (ETS). Laryngospasm-resulting in obstruction of the airways and an inability to breath-was assessedin 310 patients (aged 3 months to 9 yr) undergoing a surgical procedure involving halothane anaesthetic. Laryngospasm developed in nine of 96 (9.4%) children from households where there was exposure to smoke, but in only two of 214 patients (0.9%) without ETS exposure (RR 10, 95% CI 2.2-45.6; P < 0.001) (Lakshmipathy et al., Anesthesia et Analgesie 1996, 82, 724).
928
weight/day for both species(150 ppm for rats, and 200 ppm for rabbits), based on decreased water consumption and a reduction in maternal body weight gain. No convincing reproductive effects were seen even at the maximum tested concentrations, providing doses of 27 mg/kg body weight for rats and 29 mg/kg body weight for rabbits (Heindel et al., Fundamaental and Applied Toxicology 1996,30, 162). Genotoxic chlorinated hydrocarbons? An in vitro assay, using genetically engineered human cells with metabolic (cytochrome P-450) competence, demonstrated the induction of micronuclei (an indicator of chromosome damage) by 14 of the 15 tested materials, mainly chlorinated hydrocarbons, including carbon tetrachloride, 1-chlorohexane, 1,2dichloroethylene, methylene chloride, tetrachloroethylene and toluene. 2,3-Dichlorobutane and 1,1,2-trichloroethane, which produced aneuploidy (on this occasion a reduced number of chromosomes), were said by the investigators to “warrant a high priority for testing in germ cells” (Doherty et al., Mutagenesis 1996, 11, 247). Subcbronic biphenyl
toxicity
of
2,2’,4,4’,5,5’-hexachloro-
PCB 153 (2,2’,4,4’,5,5’-hexachlorobiphenyl) produced clear pathological changes in the liver and thyroid and decreasedthe biogenic amine levelsin the brain when given in the diet to rats for 13 wk at a level of 5 ppm and above. Indications of mild effects at these same sites were still present at the lowest tested concentration of 0.05 ppm. Nevertheless the investigators felt disposed to describe 0.5 ppm as the NOAEL (equivalent to 34 pg/kg body weight/day) (Chu et al., Journal of Applied Toxicology 1996, 16, 121). Lead and nervous system cancer A higher than expected incidence of cancer of the nervous system associated with occupational exposure to lead has been reported by Finnish investigators. The cancer status of a cohort of over 20,000 workers was checked for a 12-yr period. RRs for nervous system cancer were 1.6 (95% CI 0.7-3.8) and 1.8 (95% CI 0.6-5.8) for groups with blood lead measurements of between 1.Oand 1.9 pmol/litre and 2.0 pmol/litre or more, respectively, compared with those with blood lead less than 1.0 pmol/litre. Corresponding RRs rose to 3.0 (95% CI 0.8-11; based on six cases)and 5.6 (95% CI 1.4-23; based on four cases)in workers aged over 44 yr. A nested case-control study of 26 of the men with cancer of the nervous system and 200 matched non-cancer controls revealed increased odds ratios with increasing blood lead levels, due largely to an increase in gliomas (Anttila et al., Journal of Occupational and Environmental Medicine 1996, 38, 131).
Toxic.
Vol. 34, No. 9
Diesel exhaust not carcinogenic in mice Diesel exhaust has been shown previously to induce lung cancer in rats exposed by inhalation, but not in Syrian hamsters treated similarly. In a recently reported US study, CD-l mice exposed to whole diesel exhaust at soot concentrations of 0.35, 3.5 and 7.1 mg/m’ for 7 hr/day, 5 days/wk for 2 yr-an exposure regimen that proved carcinogenic in a parallel study with rats-failed to develop an increased incidence of lung tumours. “Although rodents serve as useful indicators of potential human carcinogenic hazards, it is not yet clear which, if any, rodent specieshave lung neoplastic responsesthat are useful for quantitative predictions of human lung cancer risk from chronic inhalation of poorly soluble, respirable particles” (Mauderly et al., Fundamental and Applied Toxicology 1996, 30, 233). Lead and the kidney In a study of 151 young Rumanian children (aged 3-6 yr) living near a lead smelter, the Dutch investigators claim to have provided the first evidence of “an effect of environmental lead exposure on renal integrity in children”. Mean blood lead levels (which ranged from around 150 to 440 pg/litre in four groups of children who lived at varying distances from the smelter) were found to be correlated with the urinary activity of the enzyme N-acetyl-p-D-glucosaminidase, an indirect indicator of kidney injury (Verberk et al., Archives of Environmental Health 1996, 51, 83).
Nonylphenol oestrogenicity to trout Nonylphenol was oestrogenic to rainbow trout even at the lowest tested water concentration of 10 ppb. Oestrogenic activity was indicated by the induction of a protein, vitellogenin, by the fish. The lethal concentration of nonylphenol to trout under similar conditions was around 150 ppb (Lech et al., Fundamental
and Applied
Toxicology
1996, 30, 229).
Passivesmoking-lung complications in children under anaesthesia Adult patients who smoke can suffer breathing complications while under general anaesthesia. Investigators from Boston, USA have studied whether similar problems can occur in children who are exposed to environmental tobacco smoke (ETS). Laryngospasm-resulting in obstruction of the airways and an inability to breath-was assessedin 310 patients (aged 3 months to 9 yr) undergoing a surgical procedure involving halothane anaesthetic. Laryngospasm developed in nine of 96 (9.4%) children from households where there was exposure to smoke, but in only two of 214 patients (0.9%) without ETS exposure (RR 10, 95% CI 2.2-45.6; P < 0.001) (Lakshmipathy et al., Anesthesia et Analgesie 1996, 82, 724).