Biomedical subjects
C Winder
Publications and source records attributed to C Winder.
The experimental administration of lead to rats in neuropathological and behavioural studies.
The experimental investigation of the effects of lead have been studied for nearly 20 years. In that time, a variety of neurobiological processes have been reported to be altered following ingestion of lead. Most routes of administration and a bewildering number of doses have been employed to administer lead to experimental animals. However, inadequate characterization of dose regimes has impaired understanding of any effects, and their correlation to conditions of human exposure. As an index of lead burden, blood lead remains the most reliable means of assessing recent lead absorption. It is clear that a large number of model systems and dosing regimes do not address the problems of human clinical or subclinical lead intoxication. It is also clear from brain lead measurements in experimental animals that lead is selectively sequestered into specific areas of the control nervous system.
The effect of perinatal lead administration on the ontogeny of striatal enkephalin levels in the rat.
The effect of administration of lead in the maternal drinking water from conception to weaning on enkephalin levels in the developing rat striatum was studied between 10 and 100 days after birth. Concentrations of 300 and 1000 ppm Pb produced no overt toxicity in terms of effects on body and brain weight. However, marked differences in striatal enkephalins were observed. In lead-dosed animals enkephalin content was up to 50% lower at 10 and 21 days postpartum, and in addition lead appeared to delay the attainment of adult levels of this opioid neurotransmitter. Measures at later time points indicated that the effects of lead on enkephalin are reversible. The results suggest that lead depresses and delays the ontogeny of the enkephalinergic system within the striatum.
Lead neurotoxicity: a review of the biochemical, neurochemical and drug induced behavioural evidence.
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Low-level lead exposure alters morphine antinociception in neonatal rats.
Administration of lead (at 300 and 1000 ppm) in the maternal drinking water from conception to weaning impaired the antinociceptive activity of morphine in 10-day-old neonatal rats. Blood lead levels in these animals were below 50 microgram/100 ml in the high lead dose group and below 35 microgram/100 ml in the low lead dose group. The differences in the antinociceptive potency of morphine between normal and lead-exposed animals were not observed at later time points (21 and 30 days). It is suggested that lead disrupts the development of opioid receptor systems in the central nervous system and that this disruption occurs early in development.
The interaction between lead and catecholaminergic function.
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Minireview: the health implications of water treatment with ozone.
Ozone is a highly efficient disinfectant which may have significant advantages in water treatment compared to chlorine. It has, however, been shown that mutagenic and possibly carcinogenic byproducts may be produced under certain conditions of ozonation. Light chlorination following ozonization may meet the highest standards of disinfection. In addition the destruction of much of the organic matter by prior ozone treatment may well result in less harmful chlorinated and brominated products in the finished water. In many cases ozone treatment alone may suffice. It would be desirable to test with long term in vivo experiments which of the alternatives produces the best combination of microbiologically clean and pleasant water with minimum mutagenic and carcinogenic effect.
Teratogenicity, toxicity and perinatal effects of cadmium.
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Dose response relationships during perinatal lead administration in the rat: a model for the study of lead effects on brain development.
Pregnant rats were dosed with 300, 600, 1000, 2000, 3000 or 4000 ppm inorganic lead through their drinking water during pregnancy and during lactation until 21 days post partum. An effect on live litter size was noted at the higher doses as was an increased tendency for sperm positive females to fail to produce a litter. Dose related responses were seen in the offspring for brain weight, body weight, body length and blood lead at birth and at age 21 days. In neonates from the dose groups above 1000 ppm Pb these 3 indices of growth indicated that there was an effect of lead on nutrition. The 300 ppm, 600 ppm and 1000 ppm dose groups showed no significant dose related effects for body length or brain weight and only slight effects on body weight. These low dose groups gave average blood lead values of 39.8 micrograms/100 ml blood, 54.6 micrograms/100 ml blood and 85.4 micrograms/100 ml blood respectively in the 21-day old neonates. These values correspond to blood lead values in children with so called "subclinical lead poisoning" and we suggest the use of this regime as a model to investigate effects of lead on development of the nervous system.
Frequency and occurrence of LD50 values for materials in the workplace.
The main routes of occupational exposure for chemicals encountered in occupational environments are by skin contact and by inhalation. Acute toxicity data were collected for all chemicals with Australian Exposure Standards. For the 582 chemical entities, data were available as follows: oral toxicity (364, 63%), dermal toxicity (154, 26%) and inhalational toxicity (171, 29%). No acute toxicity data were available for 177 of these chemicals (177, 30%). Chemicals with data for more than one acute toxicity test were limited to: oral/dermal (151, 26%), oral inhalation (131, 23%), dermal/inhalation (73, 13%) and oral/dermal/inhalation (70, 12%). Analysis of subsets of groups of chemicals indicated that toxicity data were available for many pesticides and organic chemicals, but not for inorganic chemicals. The lack of acute inhalational and dermal toxicity data for chemicals used extensively enough to warrant exposure standards is at variance with the amount of toxicity information for other categories of chemicals (e.g. agricultural chemicals, therapeutic substances and food additives). This may also indicate scant regard given to toxicological information in the exposure standard setting process.
Effect of lead exposure on dopaminergic D2 receptor binding in the 21-day-old rat.
The effect of lead on dopaminergic D2 receptor binding, as measured by butaclamol-displaceable [3H]domperidone binding, was studied in the 21-day-old lead-dosed rat. Maternal rats were dosed with 300 ppm and 1000 ppm Pb in drinking water from conception to weaning as previously described [1]. Samples of limbic forebrain and striatum were taken from 21-day-old offspring and assayed for dopamine D2-receptor binding, as outlined by Lazareno and Nahorski [2]. There was a significant (P less than 0.05) decrease in body weight in the animals from which limbic forebrain samples were taken. There were no other significant effects of lead on body- or brain weight. Dopaminergic D2 receptor binding was unaffected by lead administration. These preliminary findings show that dopamine D2 receptor binding is not affected by lead at the doses and exposures used.
Integrating OHS, environmental, and quality management standards.
A number of ideas, concepts and systems have emerged over the past 50 years, attempting to offer insights into improving the effectiveness of contemporary management. Many of these have become part of the management landscape. With the continuing publication of standards for (among others) quality, environment and safety management of Integrated Management Systems (IMS) offers efficiencies in management processes that are intuitively logical but on occasion, frustratingly illusive. The development of an IMS is sometimes carried out for the wrong reasons, and often with unforeseen consequences. The establishment of an IMS should not be taken lightly and should include lengthy design, considered consultation, flexible redesign, and staged implementation. However, once in place, an IMS offers the potential of a unifying approach for dealing with management systems.
Using benchmarking to improve organizational communication.
Best practice refers to those practices that lead to superior performance in a company or enterprise relative to industry or international leaders. Benchmarking of those activities that are critical to organizational performance is an important part of the identification and implementation of best-practice approaches. This article looks at communication as one aspect in the development of best practice in the management of safety, environment, and quality. A number of barriers to effective communication are identified, and benchmarks for the evaluation of organizational communication are suggested.
Integrating training systems for occupational health and safety, quality and environmental management.
Quality, occupational health and safety, and environmental issues are three key areas that, along with productivity and service, must be managed effectively. Organizations face the need to develop integrated systems for the management of these areas. As organizations increasingly need to seek efficiencies, one field in which such integration can bring considerable gains is training. The present paper examines how the requirements for training in different areas overlap and how an integrated training program may be developed.
The morphological effects of lead on the developing central nervous system.
The pathological changes found in the central nervous system of lead-exposed humans and laboratory animals are reviewed. Data in man relate to relatively high exposure levels. In human childhood lead encephalopathy, which occurs with blood lead levels in the range 100-800 micrograms Pb/100 ml, oedema, vacuolation, haemorrhage and reactive glial changes appear to be secondary to microvascular lesions. No primary neuronal lesions have yet been clearly identified. Neurological signs and a pathological picture closely resembling that seen in human lead encephalopathy are obtained in young lead-exposed rats with blood lead levels above 500 micrograms Pb/100 ml. Oedema and haemorrhage, cyst formation, reactive glial changes and nerve cell alterations are observed consequent to changes in capillary endothelial cells and basement membranes. High-level lead exposure in rats also produces disturbances in myelinated axons and may affect neural network formation in the central nervous system. With intermediate lead levels (200-500 microgram Pb/100 ml blood), vascular changes and their sequelae are not seen, but nutritional effects occur which may produce neuropathological changes. Data from recent studies on developing rats with low blood levels (up to 100 microgram Pb/100 ml) appear to show effects of lead on maturing and differentiated nerve cell populations. The relevance of these changes to human subclinical lead intoxication remains to be seen. However, the overall correspondence of findings in lead-poisoned man and rat would make further investigation in this area appear necessary.
Lead, reproduction and development.
Lead remains a significant occupational health and public health problem. Excessive lead exposure, not only to men exposed at work, but also from lead based paint in older housing and from soil, still persists in the community. From the perspective of human reproduction, lead is known to cause a number of adverse outcomes in both men and women. Reported effects in men include reduced libido, effects on spermatogenesis (reduced motility and numbers, increased normal morphology), chromosomal damage, infertility, abnormal prostatic function and changes in serum testosterone. Most of these effects have been seen in lead exposed workers, and some are at levels presently considered 'acceptable'. Effects in women include infertility, miscarriage, premature membrane rupture, pre-eclampsia, pregnancy hypertension and premature delivery. Again, recent research findings indicate that lead may be toxic at levels previously thought to have no effect. The evidence implicating a possible teratogenic effect of lead is much less clear. While there is some indication of an association of lead with the production of anomalies, any dose-response relationship or causal mechanism has yet to be established. Therefore, while lead does affect human reproduction, the question: Is lead a teratogen? is yet to be answered.
Integrating quality, safety, and environment management systems.
Internationally consistent ISO standards are in use, or are being developed, for quality systems, environmental management, and occupational health and safety. These standards outline a model for the management of quality, environment or safety. In many respects the process of developing management systems for these matters contains a number of common elements, including obtaining commitment from senior management; instituting consultative mechanisms; developing a policy; identifying components of the management program; resourcing, implementing, and reviewing the program; and integrating the program into the organization's strategic plan. The necessity of developing separate management systems for different organizational aspects is wasteful and inefficient. Better management systems will be developed if they are integrated into a single management structure.
Integration of occupational health and safety, environmental and quality management system standards.
Occupational health and safety, environmental, and quality (SEQ) issues are commonly managed by three separate departments within organizations. Because of a number of commonalities in the three management systems, there could be a degree of overlap that might lead to inefficiencies. By integrating these three management systems into one SEQ system, the duplication of effort could be minimized and the health and safety, environmental, and quality issues could be managed by one common proactive approach. The draft Australian standard for an occupational health and safety (OHS) management system and the internationally accepted standards for environmental (ISO 14001) and quality (ISO 9001) management systems were analyzed to identify all requirements of the three management systems and integrate this into one SEQ management system standard.