Evaluation of a community intervention programme for preschool behaviour problems.

OBJECTIVES: To evaluate an early intervention project focused on improving child prereading skills and parent behaviour-management skills, for 4-year-old children in the western suburbs of Melbourne (Victoria, Australia). METHODOLOGY: Following screening of a large sample of preschoolers, four groups were constructed: (i) children receiving a phonological skills-based prereading package in their normal preschool programme; (ii) children whose parents attended six sessions of child behaviour management skill training; (iii) children who received both interventions; and (iv) a control group. Pre-, post-, 1 and 2 year follow-up measures were taken to assess effects on child behavioural and learning adjustment. RESULTS AND CONCLUSIONS: This community based intervention resulted in positive effects, despite being of low intensity, in achieving significantly less hyperactive/distractable behaviour in children from the combined intervention group at 2 years postintervention. Anxiety problems were also reduced at the post-treatment phase. The prereading package did not demonstrate any effects on reading skills and was deemed to be insufficiently intensive to affect a population of disadvantaged preschoolers. This universal-type of intervention was well accepted by the community, but there is need for further effort to increase recruitment of families of at-risk children into such programmes.

The preparation of anthraquinone used in the National Toxicology Program cancer bioassay was contaminated with the mutagen 9-nitroanthracene.

Commercial anthraquinone (AQ) (9,10-anthracenedione) is produced by at least three different production methods worldwide: oxidation of anthracene (AQ-OX), Friedel-Crafts technology (AQ-FC) and by Diels-Alder chemistry (AQ-DA), with the final product varying in color and purity. AQ-OX begins with anthracene produced from coal tar and different lots can contain various contaminants, particularly the mutagenic isomers of nitroanthracene. AQ has been reported to be negative in a variety of genotoxicity tests including numerous Ames Salmonella mutagenicity assays. In addition, we report that AQ-DA is negative in the Salmonella-Escherichia coli reverse mutation assays, the L5178Y mouse lymphoma forward mutation assay, for inducing chromosomal aberrations, polyploidy or endoreduplication in Chinese hamster ovary cells, and in the in vivo mouse micronucleus assay. Further, a previous 18 month bioassay conducted with AQ administered to male and female B6C3F(1) and (C57BL/6xAKR)F(1) mice reported no induction of cancer. Thus, it was somewhat unexpected that in a long-term study conducted by the National Toxicology Program (NTP) AQ-OX induced a weak to modest increase in tumors in the kidney and bladder of male and female F344/N rats and a strong increase in the livers of male and female B6C3F(1) mice. In the studies reported here, a sample of the AQ-OX used in the NTP bioassay was shown to be mutagenic in the Ames tester strains TA98, TA100 and TA1537. Addition of an S9 metabolic activation system decreased or eliminated the mutagenic activity. In contrast, the purified NTP AQ-OX as well as the technical grade samples AQ-FC and AQ-DA were not mutagenic in the Ames test. The chemical structure of AQ does not suggest that the parent compound would be DNA reactive. Therefore, a mutagenic contaminant was present in the NTP bioassay sample that is either directly mutagenic or can be activated by bacterial metabolism. Analytical studies showed that the primary contaminant 9-nitroanthracene (9-NA) was present in the NTP AQ-OX at a concentration of 1200 p.p.m., but not in the purified material. The 9-NA and any other contaminants that might have been present in the NTP AQ-OX induced measurable mutagenicity at 9-NA concentrations as low as 0.15 microg/plate in tester strain TA98, indicating potent mutagenic activity. On the basis of revertants per microgram, 9-NA was more potent than benzo[a]pyrene (B[a]P) and was about equally as potent as the 2-nitrofluorene run concurrently as positive controls. TD(50) quantitative carcinogenicity potency estimates indicate that a carcinogen of a potency in the range between B[a]P and dimethylnitrosamine would be required to produce the observed carcinogenic response at the levels of the contaminants found in the test sample. While recognizing that there are limitations in extrapolating mutagenic potency to potential carcinogenic potency, these estimates do indicate that it is plausible that the 9-NA contaminant might have been responsible for all of the tumor induction observed in the NTP study. In fact, in the absence of reliable cancer data, the genetic toxicology profile indicates that AQ would not be a genotoxic carcinogen. Thus, no conclusion as to the carcinogenic activity of AQ can be made at this time.

Pharmacokinetics and hepatic disposition of bis[1-(ethoxycarbonyl)propyl]5-acetylamino-2,4,6-triiodoisophthalate in rats and isolated perfused rat livers.

Bis[1-(Ethoxycarbonyl)propyl]5-acetylamino-2,4,6- triiodoisophthalate+ (NC 68183) was designed as a new computed tomography imaging agent. The purpose of this study was to determine the pharmacokinetics and metabolism of NC 68183 in conscious rats and in the isolated perfused rat liver. Animals were i.v. dosed at 69 and 690 mg of iodine/kg. Blood samples were collected at 5, 15, 30, and 60 min, and 7 days after dosing. Tissue samples (liver, kidney, and spleen) were taken at 60 min and 7 days after dosing. NC 68183 was cleared from blood in first order kinetics following an i.v. administration of 69 mg I/kg. The volume of distribution (Vss) at steady state and elimination half-life (t(1/2)) were estimated as 24 ml and 11 min. The clearance of NC 68183 from blood was changed to zero-order kinetics following administration of 690 mg/kg, and its elimination rate was 16 microg I/ml.min. The liver and spleen were the only tissues to have the nanoparticle residue at day 7 following administration. NC 68183 (75 mg of agent, 35 mg of I) was injected into the isolated perfused rat liver system. Bile flow increased from 1.0 to 1.3 microl/min/g liver following administration. The biliary excretion rate maximum was estimated as 11 microg/min/g liver. The metabolite was identified using liquid chromatography/mass spectrometry as a monocarboxylic acid product, which exclusively excreted into the bile in a soluble iodinated metabolite. Pharmacokinetics data suggested that NC 68183 primarily resides in the blood pool following an i.v. administration with a plasma half-life appropriate for blood pool imaging.