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A bioassay using Pseudomonas fluorescens was affected by the sequence of exposure to pentachlorophenol (PCP) and 2,3,4,5-tetrachlorophenol (TCP). Surviving cells from standardized cell suspensions initially treated with PCP at concentrations ranging from 10 to 75 micrograms/ml, followed by removal of the toxicant, were not affected by a second dose of PCP at the same concentration. However, if the second dose was TCP, the test organism was sensitive to the second exposure. The most toxic sequence was an initial exposure to TCP followed by a second exposure to PCP. The response of the test organism to PCP and TCP was clearly dependent upon both the toxicant concentrations used and the sequence of toxicant addition.
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Epidemiological studies have revealed an increased risk of cancer, notably soft-tissue sarcomas and non-Hodgkin's lymphomas, in people occupationally exposed to chlorophenoxy herbicides, including those contaminated by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). We report here a historical cohort study of mortality in an international register of 18,910 production workers or sprayers from ten countries. Exposure was reconstructed through questionnaires, factory or spraying records, and job histories. Cause-specific national death rates were used as reference. No excess was observed in all-cause mortality, for all neoplasms, for the most common epithelial cancers, or for lymphomas. A statistically non-significant two-fold excess risk, based on 4 observed deaths, was noted for soft-tissue sarcoma with a standardised mortality ratio (SMR) of 196 and 95% confidence interval (Cl) 53-502; this was concentrated as a six-fold statistically significant excess, occurring 10-19 years from first exposure in the cohort as a whole (SMR = 606 [165-1552]) and, for the same time period, as a nine-fold excess among sprayers (SMR = 882 [182-2579]). Risks appeared to be increased for cancers of the testicle, thyroid, other endocrine glands, and nose and nasal cavity, based on small numbers of deaths. The excess of soft-tissue sarcomas among sprayers is compatible with a causal role of chlorophenoxy herbicides but the excess does not seem to be specifically associated with those herbicides probably contaminated by TCDD.
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A series of 22 chlorinated phenols was investigated for their uncoupling effect on Acer cell suspensions. All the studied molecules were able to enter the cell and had instantaneous uncoupling properties: pentachlorophenol was the best uncoupler of the series (the concentration required to uncouple by 50% was 5 microM), being 200-fold more effective than 3-Cl or 2-Cl phenol, which were the molecules having the lowest activity. The QSAR (quantitative structure-activity relationship) study gave good equations for the uncoupling activity with the steric and electronic parameters taken together. The electronic parameter sigma was always present with a positive sign, whereas A, the angular parameter, was always negative. The general steric parameters (sigma D, 1 chi v, MR) represented the third component of the equations and each of them played practically an equivalent role. Equations of quality (r greater than 0.9), which were statistically significant, could be obtained after four compounds in F (2,5-diCl phenol; 2,4,5-triCl phenol; 2,4-diCl 6-NO2 phenol; and 2-Cl 4,6-diNO2 phenol) had been excluded and when quadratic terms were not present. The best equation (r = 0.940) was obtained with sigma D, A, and sigma 1. The comparison of the significant equations with those previously established with isolated mitochondria led us to suppose that there were no selective limiting steps during the transfer of the studied compounds from the reaction medium to mitochondria inside the cells. The major difference between the uncoupling results obtained with isolated mitochondria and with cells was that the concentrations needed to uncouple by 50% were always higher in cells.
Acute static toxicity experiments have been performed under normoxic and hypoxic conditions. The test animals used were adults of the groundwater-adapted copepod Parastenocaris germanica. The animals originated from a sandy, gravelly phreatic aquifer of the Meuse valley in The Netherlands. Toxicants applied were pentachlorophenol, 3,4-dichlorophenol, zinc, and cadmium. The results were statistically evaluated by a log-logistic model. LC50 and LC5 values with 95% confidence limits were calculated. Response models of application under both oxygen conditions were compared. The influence of ambient oxygen concentration on sensitivity appeared to be very small; only in the case of pentachlorophenol were hypoxic and normoxic models slightly but significantly different. Comparisons with the sensitivity of other organisms are made and the results are discussed against the specific physiological adaptations of the organisms to groundwater conditions.
Industrial wastewater often contains a mixture of chemical substances and knowledge of joint action of toxicants is therefore important when the toxicity of an effluent is evaluated or reduction of the toxicity is needed. In this study, the joint action of three pairs of toxicants, selected on the basis of their expected different modes of toxic actions, was tested for inhibition of the growth of the bacteria Pseudomonas fluorescens: pentachlorophenol and aniline, the surfactants nonylphenolethoxylate and tetrapropylenebenzenesulfonate, and pentachlorophenol and 2, 4-dichlorophenol. The joint effect of pentachlorophenol and aniline did not differ significantly from additivity, whereas less than additive responses were observed for mixtures of nonylphenolethoxylate and tetrapropylenbenzenesulfonate. A more than additive response was observed for mixtures of pentachlorophenol and 2,4-dichlorophenol at some concentration levels, while at others additive responses were found. It was concluded that joint actions other than additivity may occur between commonly known toxic substances, and that the modes of toxic action of the substances studied can explain the different types of joint action observed in this study. Further, test strategy followed proved useful in the evaluation of the joint toxicity of binary mixtures.