Extrapolating from toxicity data to occupational exposure limits: some considerations.

This paper evaluates procedures relevant to extrapolating from toxicity data in man and animals to Occupational Exposure Limits. It examines effects at or around the "No Observed Adverse Effect Level' (NOAEL) and the magnitude of safety factors which can be applied in developing occupational exposure limits for non-stochastic effects. The relationship between incidence of stochastic effect and occupational exposure limit is also discussed.     

过氧化甲乙酮毒性及职业接触限值研究进展

过氧化甲乙酮(MEKP)是世界上应用最为广泛的不饱和聚酯树脂固化剂,职业和非职业接触人数逐年增多,不断出现中毒的个案报道,目前我国尚未制定MEKP职业接触限值.该文就过氧化甲乙酮的毒性以及国外对其职业接触限值的研究情况作一简要综述,为制定过氧化甲乙酮的职业接触限值提供参考.     

Maternal occupational exposure to chemical substances and the risk of infants small-for-gestational-age.

BACKGROUND: The association between maternal occupational exposure to specific chemical substances (organic solvents, carbon tetrachloride, herbicides, chlorophenols, polychlorinated biphenyls, aromatic amines, lead and lead compounds, mercury and mercury compounds) and birth of small-for-gestational-age (SGA) infants was evaluated using data from a prospective cohort study of 3,946 pregnant women in West Germany from 1987 to 1988. METHODS: Occupational, medical, and psychosocial information was gathered through a questionnaire from pregnant women who were recruited between 15 and 28 gestational weeks. Exposure to chemical substances at the current workplace was assessed by a job-exposure matrix constructed by Pannett in 1985 and weighted for the number of working hours per week. Women not working at the time of the interview, women with multiple births, and women with stillbirths were excluded from analysis. Data were analyzed using dichotomous and polytomous logistic regression to control for age, smoking status, alcohol consumption, body mass index, and number of former births. RESULTS: The results of the dichotomous logistic regression analysis suggest that leather work might be associated with the birth of infants small-for-gestational-age through exposure to chlorophenols (P = 0.02) and aromatic amines (P = 0.05). In the polytomous logistic regression analysis, only the association between exposure to mercury and growth retardation reached statistical significance (P = 0.02); however, the power of the study is limited. Further adjustment for income, shift work, and heavy physical work had no substantial effect on the results. CONCLUSIONS: These findings suggest that maternal exposure to specific chemicals at work may be a risk factor for the birth of SGA infants.     

甲基异戊基甲酮毒性及职业接触限值的研究进展

<正>甲基异戊基甲酮(methyl isoamyl ketone,MIAK),又名甲基异戊基酮、5-甲基-2-己酮、5-甲基己-2-酮、异丁基丙酮、异庚酮,用作纤维素脂、丙烯酸类、聚乙烯醇缩甲醛树脂、乙烯共聚物等物质的溶剂[1],也是各种工业用品的原料。随着我国经济的快速发展,生产和使用MIAK的企业日益增多,由此导致接触MIAK的人数及其带来的职业病危害逐年增加。本文对MIAK相关的研究报道及接触限值的制定现状作一简要概述,为后续研究提供必     

Permissible limits for occupational exposure to toxic agents

Summary The author discusses the differences in approach between US and USSR in setting permissible limits for respiratory exposure to chemical agents in industry. One should clearly distinguish between basic facts, e.g. dose-response relationships ánd decisions taken in regard to acceptability of certain levels. The former are determined by differences in research methods: focused on cells and organs (US) or on organism with emphasis upon central nervous control (USSR). The latter are determined by differences in interpretation of biological changes in regard to health. It is of primordial importance to promote exchange of basic data; this would promote mutual understanding much more than trying to impose one's own choice of acceptability upon others. Ultimate agreement on decisions to be taken may only result through the way of reasoning based upon facts; it is not a matter of negotiation.     

Reducing occupational exposure to chemical carcinogens

Strategies for controlling occupational exposure to chemicalcarcinogens are set out in the European Union Carcinogens Directiveand in national legislation such as the British Control of SubstancesHazardous to Health Regulations. While such legislative requirementsmust apply to all occupational chemical carcinogens, it is arguedthat priority should be given to controlling those agents thatcontribute most to the cancer burden. Examples of possible strategiesto reduce exposure to two agents (diesel exhaust particulateand paint emissions) are discussed. It is concluded that thereare no real technical difficulties in controlling exposuresto chemical carcinogens; however, for many of the key agents,we need to change attitudes to the potential risks and clearlydemonstrate to employers and employees how to reduce the exposures.     

A system for predicting the acute toxicity of chemical substances

A method has been proposed to recognize and predict the range values of acute toxicity (LD50) and for this a system has been developed. The essence of the method is to gradually decrease the predictable toxicity ranges for the test substances in a stepwise manner while advancing within the formed predictive complexes. The transmission of information on the structure of compounds along this complex is determined by the preset logistic scheme along which narrower LD50 ranges are designated. The intervals are automatically set, by optimizing the recognition of the properties of compounds at the stage of formation of models (that recognize the set of signs). The predicting system includes two predicting complexes and contains a total of 30 mathematical models: for heterocyclic and carbocyclic compounds. Logistic schemes for passage of predictable compounds have been developed for each complex in accordance with the hierarchic organization of the elements that are constituents of the complex. The prediction significance is 70-90%.     

Occupational exposure limits for therapeutic substances

Few therapeutic substances have occupational exposure limits (OELs) set by regulatory bodies and reliance is often placed on in-house OELs derived from a formula based on the therapeutic dose. This mode of derivation relies on assumptions about pharmacokinetics, pharmacodynamics and risk acceptability which might not be soundly based for occupational health purposes. Pharmacodynamic evidence shows that occupational exposure to airborne therapeutic substances can be associated with a much higher risk of an adverse health effect especially on the lungs or skin than by their therapeutic administration. Pharmacokinetic studies indicate that for certain therapeutic substances occupational exposure by inhalation results in a more rapid and complete systemic absorption than a similar dose administered (usually orally) for therapeutic purposes. These and other considerations are used to develop a systematic strategy for deriving OELs for therapeutic substances. The first stage of this consists of a qualitative assessment and ranking of likely occupational health effects. This is based on pharmacological studies, analogy and specific workplace studies. Subsequently assessment of the relevant pharmacological data together with environmental monitoring and exposure-linked health surveillance provides the quantitative data for the setting of appropriate OELs.     

Organophosphate toxicity and occupational exposure

The ubiquitous organophosphates present a continuing health hazard in agriculture, public health eradication programmes and as chemical warfare agents. Despite significant progress in understanding the potential mechanisms of toxicity far beyond the commonly accepted mechanism of cholinesterase inhibition in intentional exposures, the precise health effects following occupational exposures are yet to be completely defined. A much greater understanding exists of the clinical features of organophosphate poisoning. These are characterized by a triphasic response involving an initial acute cholinergic phase, an intermediate syndrome (both associated with high mortality) and a disabling but non-lethal delayed polyneuropathy. The delayed polyneuropathy may occur in the absence of the cholinergic or intermediate phases. However, progress is still required in order to improve the quantification and assessment of occupational exposures and the implementation of appropriate preventive measures. Finally, evidence-based guidelines for appropriate or optimal therapeutic interventions following poisoning are required urgently and collaborative work with colleagues in developing countries, where the occurrence of organophosphate exposures is more frequent, may provide the answers.