Percutaneous absorption of organic solvents

Organic solvents pass the cutaneous barriers and may quickly be absorbed in substantial amounts, such that several solvents have "skin" denotations in lists of occupational exposure limit values. Solvents may be absorbed from liquids, upon direct skin contact, and in some cases also from contact with vapors. Environmental factors such as temperature, humidity, vehicle, and ventilation influence absorption. Absorption rates vary considerably; several amphiphilic solvents are absorbed at high rates. Since solvents are volatile, unoccluded repeated exposures result in less absorption than does continuous contact, and adequate ventilation may reduce absorption considerably. Risk assessments of skin absorption of organic solvents have benefited from calculation of quantitative structure-activity relationships based on log P(o/w), which enables skin absorption to be calculated with reasonable accuracy.     

The use of experimental studies to reveal suspected neurotoxic chemicals as occupational hazards: acute and chronic exposures to organic solvents.

The nervous system differs from many other body organs by its central control of vital functions and its low regeneration capacity. Organic solvents have, as a group, been suspected to have neurotoxic effects. Because of their similar physical properties and the fact that in industrial uses, they are often present in various mixtures, organic solvents have also been regarded, unfortunately, to induce common neurotoxic effects. However, it is evident from experimental studies using specified exposure conditions that different organic solvents have very diverse neurotoxic effects and also that the toxic mechanism may differ between acute and chronic exposure. No specific method used to describe a neurotoxic effect or single toxic response can be used for the overall occupational risk assessment of all organic solvents. Each solvent has to be considered as having its own unique toxic effects.     

Renal disorders induced by organic solvents

Organic solvents are a class of chemical substances that are widely used in large volume in various manufacturing plants. Due to their high lipophilicity, organic solvents may produce physicochemical damage to renal glomeruli and tubuli. Many reports have been published abroad, though only a few in Japan, on organic solvent-induced nephropathy such as Goodpasture syndrome, a form of renal damage mediated by anti-basement membrane antibodies. This article reviews the epidemiological studies published in the literature and stresses that organic solvent exposure is one of the etiological factors involved in the development of chronic nephropathy. At present in Japan there are 60,000 patients with terminal renal failure undergoing hemodialysis, 50,000 young men placed under observation each year for abuse of organic solvents, and one million workers exposed to organic solvents in factories. Attention should be focused on the occurrence of renal damage due to organic solvents in Japan.     

Exposure to organic solvent mixture and hearing loss: literature overview

The chemical sector is the third largest industry in Europe. There is increasing evidence from epidemiological and clinical studies that occupational exposures to organic solvents may have detrimental effect on hearing. Most of the literature data concern one of the three following types of exposure to industrial solvents: mixed solvent exposure (the most common type); styrene-only exposure; and toluene-only exposure. This paper overviews the effects of industrial exposure to a mixture of organic solvents on hearing, with special regard to the dose-response relationship. Although the existing data make it difficult to derive a correlation between solvent concentration and hearing outcome, the current occupational exposure limits for solvents seem to be inadequate with respect to the effect that solvents may have on the auditory system.     

Parental occupational exposures and risk of childhood cancer: a review

We reviewed the literature in order to summarize the present knowledge on the association between parental occupational exposures to chemicals and the risk of childhood malignancy. The 32 studies pertaining to this topic were evaluated by considering various study qualities such as sample size, specificity of outcome, confounding, exposure specificity, and control selection. When evaluating the findings from any epidemiologic study, the potential sources of bias have to be considered. The selection of subjects, misclassification of exposure or outcome, and confounding from extraneous factors can contribute to a biased estimate of effect. Studies done to minimize these potential biases will be more valid, and these studies should be given the most weight when parental occupational exposures are evaluated as risk factors for childhood malignancy. We conclude that the preponderance of evidence supports the hypothesis that occupational exposure of parents to chemicals increases the risk of childhood malignancy. The parental occupational exposures implicated in childhood malignancy risk are exposure to chemicals including paints, petroleum products, solvents (especially chlorinated hydrocarbons) and pesticides, and exposure to metals. The available data do not allow the identification of specific etiologic agents within these categories of compounds. Future epidemiologic and toxicologic studies should be designed to pursue these leads.     

Uses of and exposure to trichloroethylene in U.S. industry: a systematic literature review

This article describes a systematic review of the industrial hygiene literature for uses of trichloroethylene (TCE) in industry for the exposure assessment of two population-based case control studies of brain cancer in the United States. Papers and reports that address uses of and exposures to TCE were identified from MEDLINE, TOXLINE, NIOSHTIC, the NIOSH Health Hazard Evaluation database (keywords: chlorinated solvents and trichloroethylene), and in other reviews. This search was complemented by reviewing the reference lists from the identified literature. The collected information was systematized by the Standard Industrial Classification (SIC) system, and measurement data reported in the literature were summarized in a database. TCE use was extensive from the early 1920s through the 1970s mainly as a degreasing agent in metal-fabricating operations. After the 1970s it became less popular because of environmental concerns. TCE historically has had a multitude of uses in many other industries, e.g., dry cleaning, textile, electronics, leather, and rubber. Also, many products like adhesives, drugs, paints, inks, and various industrial products have contained TCE. It was banned as a food additive and in cosmetics in 1977. The arithmetic mean (AM) of the measurements across all industries and decades was 38.2 ppm. The highest personal and area air levels were reported in vapor degreasing (AM of 44.6 ppm). Most TCE measurements were performed in the 1950s, 1970s, and 1980s. The data described here could be used by exposure assessors as is to identify the presence and approximate levels of exposure. Using the same information as a basis should increase the reliability of the assessments, making it easier to compare both the exposure assessment methods and the epidemiologic results across different studies.     

A dermal model for spray painters. Part II: estimating the deposition and uptake of solvents

The contribution of dermal exposure to the total body burden of a given chemical is difficult to assess. However, it is possible that as regulatory pressures lead to reductions in inhalation exposure, the proportion of uptake via the dermal route will increase. This study brings together recent work in the field of dermal exposure to provide a model to estimate both exposure and uptake of solvents through the skin. Using spray painters as an example, the process of modelling exposure is described from identifying the determinants of exposure through to calculating the flux of solvent through the stratum corneum and thus the total dermal uptake. Results from a range of exposure scenarios are presented and areas requiring further research and validation are highlighted. The model should allow the estimation of combined dermal and inhalation exposure to solvents in both current work situations and retrospective epidemiological studies. Furthermore, it is envisaged that the model may provide the basis for generic assessment of dermal exposure and uptake.     

Health care of workers engaged in waste water treatment. 1) The exposure conditions to organic solvents in workers engaged in waste water treatment

In the investigation of the exposure conditions to organic solvents of workers in 35 waste water treatment facilities, it was found that these workers treated various kinds of solvents. Almost all of the facilities treated chloroform, acetone, n-hexane, methanol and carbon tetrachloride. The average exposure concentration of the workers was, however, low. Exposure concentration to organic solvents (chloroform, xylene and carbon tetrachloride) was evaluated in one of the facilities. The average concentration of the respective solvents in the workers did not exceed the threshold limit value of Japan, but the concentration calculated on the basis of combined exposure exceeded the threshold limit value. On the other hand, high concentrations of organic solvents were detected in the room where the solvents were introduced but not in the working rooms, indicating that the workers engaged in waste water treatment were mainly exposed to organic solvents in the former room where they sorted and mixed the solvents and placed them in the incinerator. In conclusion, improvement in working conditions and health care for workers engaged in waste water treatment facilities should be made in order to prevent workers from becoming intoxicated by organic solvents.     

Botanical solvents

Botanical, or plant-derived, solvents such as turpentine, pine oils, and various essential oils are used as environmentally acceptable alternatives to traditional solvents and degreasing agents. This article focuses on three lesser-known botanical solvents: limonene, oleic acid, and linoleic acid. Although data are limited, limonene, linoleic acid, and oleic acid are likely of low toxicity. Mild skin irritation may occur from exposure to these compounds, and oxidation products of limonene may produce dermal sensitization. Limonene, and possibly linoleic and oleic acids, may have irritative and bronchoconstrictive airway effects; however, data are scant and more studies are required.     

Occupational exposure and defects of the central nervous system in offspring: review.

A study of published work was carried out in a search for evidence of a causal role for parental occupational exposure in the origin of structural and functional defects of the central nervous system (CNS) in children. Studies that consider this topic are scarce and mostly refer to broad categories of exposures and effects. Non-occupational studies referring to environmental exposure of humans and studies on experimental animals were also reviewed. The studies on animals provided straightforward evidence about morphological and behavioural abnormalities resulting from some agents used occupationally. The studies on humans yielded a scala of defects that could be ascribed to exposure to high doses of various agents in the environment. Evidence for a causal role of occupational exposure has not been found, but a highly probable influence on the developing CNS is hypothesised for lead, methyl mercury, and ionising radiation. Parental occupational exposure to cadmium, organic solvents, anaesthetics, and pesticides may also play a part in causing defects of the CNS. Well designed future research is needed to test the above hypotheses.     

Occupational exposure and defects of the central nervous system in offspring: review

A study of published work was carried out in a search for evidence of a causal role for parental occupational exposure in the origin of structural and functional defects of the central nervous system (CNS) in children. Studies that consider this topic are scarce and mostly refer to broad categories of exposures and effects. Non-occupational studies referring to environmental exposure of humans and studies on experimental animals were also reviewed. The studies on animals provided straightforward evidence about morphological and behavioural abnormalities resulting from some agents used occupationally. The studies on humans yielded a scala of defects that could be ascribed to exposure to high doses of various agents in the environment. Evidence for a causal role of occupational exposure has not been found, but a highly probable influence on the developing CNS is hypothesised for lead, methyl mercury, and ionising radiation. Parental occupational exposure to cadmium, organic solvents, anaesthetics, and pesticides may also play a part in causing defects of the CNS. Well designed future research is needed to test the above hypotheses.     

Effects of industrial solvents on hearing and balance: a review

Industrial hearing loss has generally been associated with noise exposure, but there is a growing awareness that industrial solvents can have an adverse effect on the auditory and vestibular systems in man. Both animal experiments and human studies point to an ototoxic effect of industrial solvents, as well as some central auditory and vestibular disturbances. This review examines the research from the last four decades in an attempt to get an overview of the available evidence. Research shows that industrial solvents are ototoxic in rats. The majority of the solvents studied cause a loss of auditory sensitivity in the mid-frequencies in rats, affecting outer hair cells in the order OHC 3 > OHC 2 > OHC 1 . Inner hair cells are generally unaffected. Spiral ganglion cells are most vulnerable to trichloroethylene. Simultaneous exposure to solvents and noise results in a synergistic effect; the pattern of trauma mirrors that due to solvent exposure rather than noise, but is more enhanced. There is a critical level when synergy occurs. The effects of solvents on the vestibular system are neurotoxic and influence the vestibulo-oculomotor system in both animals and humans; humans also present with problems in postural sway. There is a strong suggestion from human studies that solvents are ototoxic in man, but findings show that both the peripheral and central auditory pathways can be affected. Hearing losses can be in the high frequency region or can affect a wider range of frequencies. Hearing loss and balance disturbances can occur at levels below permitted levels of exposure. The synergistic effect of combined exposure to solvents and noise has also been noted in humans, resulting in greater hearing losses than would be expected from exposure to noise and solvents alone. The findings from both human and animal studies indicate that exposure to industrial solvents or to industrial solvents and noise can have an adverse effect on hearing and balance. The implications for industry and hearing conservation are far reaching.     

Percutaneous absorption of solvent vapors in man

It is known from industrial experience and experimental studies that percutaneous absorption of concentrated liquid solvents may be considerable and even hazardous if large enough areas of skin are exposed for long periods of time. Percutaneous penetration of xylene, styrene, toluene, 1,1,1-trichloroethane and tetrachloroethylene vapors at ambient air concentrations of 600 ppm for 3.5 h was studied in a dynamic exposure chamber with a restricted number of human volunteers. Although the small number of exposed persons precluded conclusive quantitation of absorption and valid intercompound comparisons, aromatic solvents and tetrachloroethylene appear to penetrate skin much more readily than 1,1,1-trichloroethane. Skin penetrating properties of solvents seem, under the circumstances, to be associated primarily with lipid solubility. It was approximated that percutaneous exposure (total body surface) to 600 ppm of xylene vapor for 3.5 h corresponded to an equally long inhalation exposure of less than 10 ppm. Similar percutaneous exposure to 1,1,1,-trichloroethane corresponded to an inhalation exposure of only 0.6 ppm. Disease-affected skin may display altered permeability characteristics, and one volunteer with atopic dermatitis exhibited a more than three times larger absorption of xylene vapor when compared to subjects with normal skin. It may be concluded that in the work environment percutaneous absorption of solvent vapors from the surrounding air through undamaged skin is likely to be insignificant.     

Effects of exposure to mixed organic solvents on blood pressure in non-smoking women working in a pharmaceutical company

Some studies suggest that exposure to industrial solvents can affect blood pressure. The objective of this study was to investigate the effect of a mixture of organic solvents on blood pressure in women working in a pharmaceutical company in Iran. Four hundred and thirty-three women were included in the study. Women working in packing units (group 1) were not exposed to the mixture of organic solvents, women in new laboratory units (group 2) were exposed to the mixture within the permitted range and women working in old laboratory units (group 3) were exposed to the mixture above the permitted limit. We compared systolic and diastolic blood pressures (SBP & DBP) and prevalence of hypertension and pre-hypertension among groups. The results revealed a significant difference in SBP and pre-hypertension (p<0.001) and hypertension (p<0.05) prevalence between the exposed and the control group, but DBP did not differ significantly. Logistic regression analysis showed a significant association between hypertension and exposure to mixed solvents. Odds ratio for hypertension in the group 2 and group 3 (exposed) workers was 2.36 and 3, respectively, compared to controls. Our results suggest that exposure to a mixture of organic solvents may increase SBP and hypertension and pre-hypertension prevalence in drug manufacture workers. Therefore, more attention should be paid to workers that work in such settings by periodically measuring blood pressure and implementing accurate and comprehensive programs to reduce exposure to organic solvents.     

The practice of systematic reviews. III. Evaluation of methodological quality of research studies]

The methodological quality of the primary studies included in a systematic review may influence its results and final conclusions. Methodological quality may be defined in various ways. Partially because of this there are many different assessment lists. The most important dimension of quality is internal validity, defined as the confidence that the design, performance and report of a trial prevent or reduce systematic errors (bias) in the outcomes. For only a limited number of internal validity items a relationship with bias has been proven in empirical studies: concealment of randomisation and blinding of patients and outcome assessors. Preferably, quality should be assessed by at least 2 assessors independently. There is no consensus whether assessment should be done blinded for authors, journal, results and conclusions. Internal validity can be incorporated into statistical pooling in various ways: as a selection criterion, to be used as weight or to hierarchically order studies in a presentation. Well-designed comparative studies are needed to provide clearer guidelines for methodological assessment in the future.     

Assessment of methods and results of reproductive occupational epidemiology: spontaneous abortions and malformations in the offspring of working women

Epidemiological studies relating occupational exposures of working women to spontaneous abortions and malformation are reviewed and some methodological considerations are presented. The reproductive epidemiology is less developed than epidemiology in general and seems to involve some specific problems. The ascertainment of exposure and of outcome may be problematic. The exposures may be reported differently by the women depending on the outcome of the pregnancy; thus confirmation of exposure from an independent data source would be an asset. The recognition of spontaneous abortions by women is variable and this should be considered in the study design. An access to medical records could provide objective data on the outcome, but it may introduce other types of asymmetries. The types of occupational exposures of the women, suggested to carry a risk of spontaneous abortions, include anesthetic agents, laboratory work, copper smelting, soldering, and chemical sterilization using ethylene oxide and glutaraldehyde. Maternal employment in laboratories and exposure to solvents has been linked to a risk of congenital malformations in the offspring in five studies. Data on the teratogenic effects of anesthetic gases has been conflicting. In one study, employment in copper smelting was associated with malformations in the offspring.     

Studies of transferrin in serum of workers exposed to organic solvents.

Earlier studies have shown that determination of the serum concentration of different forms of transferrin (isotransferrins) may be used to detect hepatic effects caused by alcohol abuse. The isotransferrin variant with an isoelectric point of 5.7 has been compared with the total amount of serum transferrin in order to study hepatic effects caused by occupational exposure to organic solvents. Eighteen workers from a paint industry were tested before and after their holiday and compared with two different groups, a total of 60 subjects. The solvent workers had significantly higher values both before and after their holiday. This suggests that the effects on the liver caused by organic solvents are similar to those caused by alcohol abuse and that this is a long term effect. The level of exposure to organic solvents was below the Swedish threshold limit values.     

Studies of transferrin in serum of workers exposed to organic solvents

Earlier studies have shown that determination of the serum concentration of different forms of transferrin (isotransferrins) may be used to detect hepatic effects caused by alcohol abuse. The isotransferrin variant with an isoelectric point of 5.7 has been compared with the total amount of serum transferrin in order to study hepatic effects caused by occupational exposure to organic solvents. Eighteen workers from a paint industry were tested before and after their holiday and compared with two different groups, a total of 60 subjects. The solvent workers had significantly higher values both before and after their holiday. This suggests that the effects on the liver caused by organic solvents are similar to those caused by alcohol abuse and that this is a long term effect. The level of exposure to organic solvents was below the Swedish threshold limit values.     

某鞋厂347例接触混合有机溶剂作业工人肝脏B超检查结果分析

目的 探讨长期低浓度接触混合有机溶剂对制鞋作业工人肝脏的影响。 方法 对生产车间使用甲苯、苯、二氯乙烷、正己烷等混合有机溶剂的某鞋业工厂347名工人(接触组)和工厂无毒物接触史后勤人员321人(对照组)进行肝脏B超检查,比较两组检查结果。 结果 生产车间使用的有机溶剂的时间加权平均浓度均未超过职业接触限值。接触组弥漫性肝回声音改变、肝大的检出率均高于对照组,上述指标在两组间比较,差异均有统计学意义(χ2=27.8、12.5,P<0.05)。将两组各分成6个工龄段,弥漫性肝回声改变的检出率在工龄大于等于2年(4个工龄段)的两组员工间比较,差异均有统计学意义(χ2=8.9、10.2、10.2、10.5,P<0.05),两组的异常检出率均随着工龄的增加而升高。 结论 较长时间接触混合有机溶剂对作业工人肝脏可能存在慢性损害,应注意预防。