An investigation of the olfactory function of 731 workers at a chemical facility which manufacturers acrylates and methacrylates was undertaken using a standardized quantitative test. In a cross-sectional analysis of the data, no associations of chemical exposure with olfactory test scores were observed. A nested case-control study designed to evaluate the cumulative effects of exposure on olfactory function, however, revealed elevated crude exposure odds ratios (95% confidence interval) of 2.0 (1.1, 3.8) for all workers and 6.0 (1.7, 21.5) for workers who never smoked cigarettes. Logistic regression analysis, adjusting for multiple confounders, revealed exposure odds ratios of 2.8 (1.1, 7.0) and 13.5 (2.1, 87.6) in these same groups, respectively, and a dose-response relationship between olfactory dysfunction and cumulative exposure scores--semi-quantitative indices of lifetime exposure to the acrylates. The data also revealed decreasing exposure odds ratios with increasing duration since last exposure t...

Olfactory function in chemical workers exposed to acrylate and methacrylate vapors.

Male Swiss-Webster mice were exposed to naphthalene, 1-methyl-, 2-methyl-, 1-nitro- and 2-nitronaphthalene by intraperitoneal injection of peanut oil solutions over a dose range of 0.5-3.0 mmol kg-1 body weight. Treated mice were killed at times from 6 hours to 14 days post-treatment. Tissues were analyzed for cytotoxic effects by optical and electron microscopy, and for cell proliferation by autoradiography following in vitro labeling of lung slices with 3H-thymidine. The naphthalene derivatives varied widely in their cytotoxic effects. The most toxic was 1-nitronaphthalene with no mice surviving doses greater than 1 mmol kg-1. Naphthalene and 2-methylnaphthalene were about equally toxic, followed by 2-nitro- and 1-methylnaphthalene, in decreasing order of toxicity. In all cases the first evidence of cytotoxic effects was seen in the Clara cells of the bronchiolar epithelium, and, at the highest doses, toxic effects were found in the adjacent ciliated cells. Changes could be detected at the ultrastructural level at all doses, and within 6 hours after treatment. Only slight effects were seen in other cell types. Increased cell proliferation following chemical treatment was seen only in the bronchiolar epithelium, among cells tentatively identified as Clara cells or their precursors. Cytotoxic effects of naphthalene and its 1- and 2-methyl derivatives were confined to the lung, with minimal evidence of toxicity in the liver and kidney. The mononitronaphthalenes both produce small areas of centrizonal necrosis in the liver, but no discernible effects in the kidney. The experiments demonstrate the effect of small structural differences on the cytotoxicity of this group of environmental pollutants and also illustrate the sensitivity of the Clara cell as a target for xenobiotics.

Comparative cytotoxicity of naphthalene and its monomethyl‐ and mononitro‐derivatives in the mouse lung

We present four cases of fragile X premutation carriers with early neurological symptoms, including symptoms consistent with multiple sclerosis (MS) and fragile X-associated tremor/ataxia syndrome (FXTAS). Each patient had significant exposure to one or more environmental neurotoxicants that have documented neurotoxicity (i.e. hexachlorocyclopentadiene or C56, Agent Orange, and 2,4- or 2,6-toluene diisocyanate and dichlormate). We hypothesize that premutation carriers are a vulnerable group to neurotoxins because elevated mRNA in the premutation can lead to early cell death and brain disease, leading to neuropsychiatric and neurological symptoms consistent with FXTAS.

Early onset of neurological symptoms in fragile X premutation carriers exposed to neurotoxins

An assessment has been made of biochemical alterations in renal and hepatic functions of 73 male operators employed for an average of 8.2 years (range 0.5-23 years) in a chemical plant producing chlorinated hydrocarbons. Exposure to allyl chloride (AC), 1,3-dichloropropene (DCP), epichlorohydrin (ECH), and hexachlorocyclopentadiene (HEX) has regularly been determined by personal air monitoring since 1980. Although exposures to DCP and ECH were well below currently accepted maximum allowable concentrations (MACs), relatively high exposures to AC and HEX, occasionally exceeding the MAC, have been measured. The results of the kidney and liver function tests were compared with those of a control group comprising 35 men employed at the materials division and not occupationally exposed to chemicals. Biochemical alterations of liver function were assessed by determination in serum of alanine and aspartate aminotransferases (ALAT, ASAT), alkaline phosphatase (AP), total bilirubin (BIL), gamma-glutamyltranspeptidase (GGT), lactate dehydrogenase (LDH), and total bile acids (SBA). No differences between the exposed group and the control group were found. Nor were differences found in biochemical tests for renal tubular damage (urinary alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) and renal tubular function (urinary retinol binding protein (RBP). Total urinary protein and albumin excretion were measured to assess the integrity of the glomerulus. Urinary total protein did not differ between the groups, but urinary albumin, although within normal limits in both groups, was significantly higher (p < 0.02) in the exposed group. This difference in urinary albumin could not simply be explained by exposure to chlorinated hydrocarbons because albumin concentrations did not correlate with the duration of employment. It is concluded that long term exposure to concentrations of AC, DCP, ECH, or HEX below or near the current limit threshold value does not lead to clinically significant effects on kidney and liver.

https://oem.bmj.com/content/oemed/50/4/331.full.pdf

Effects of exposure to low concentrations of chlorinated hydrocarbons on the kidney and liver of industrial workers.

This chapter addresses upper airway physiology for the pediatric intensivist, focusing on functions that affect ventilation, with an emphasis on laryngeal physiology and control in breathing. Effective control of breathing ensures that the airway is protected, maintains volume homeostasis, and provides ventilation. Upper airway structures are effectors for all of these functions that affect the entire airway. Nasal functions include air conditioning and protective reflexes that can be exaggerated and involve circulatory changes. Oral cavity and pharyngeal patency enable airflow and feeding, but during sleep pharyngeal closure can result in apnea. Coordination of breathing with sucking and nutritive swallowing alters during development, while nonnutritive swallowing at all ages limits aspiration. Laryngeal functions in breathing include protection of the subglottic airway, active maintenance of its absolute volume, and control of tidal flow patterns. These are vital functions for normal lung growth in fetal life and during rapid adaptations to breathing challenges from birth through adulthood. Active central control of breathing focuses on the coordination of laryngeal and diaphragmatic activities, which adapts according to the integration of central and peripheral inputs. For the intensivist, knowledge of upper airway physiology can be applied to improve respiratory support. In a second part the mechanical properties of the respiratory system as a critical component of the chain of events that result in translation of the output of the respiratory rhythm generator to ventilation are described. A comprehensive understanding of respiratory mechanics is essential to the delivery of optimized and individualized mechanical ventilation. The basic elements of respiratory mechanics will be described and developmental changes in the airways, lungs, and chest wall that impact on measurement of respiratory mechanics with advancing postnatal age are reviewed. This will be follwowed by two sections, the first on respiratory mechanics in various neonatal pathologies and the second in pediatric pathologies. The latter can be classified in three categories. First, restrictive diseases may be of pulmonary origin, such as chronic interstitial lung diseases or acute lung injury/acute respiratory distress syndrome, which are usually associated with reduced lung compliance. Restrictive diseases may also be due to chest wall abnormalities such as obesity or scoliosis (idiopathic or secondary to neuromuscular diseases), which are associated with a reduction in chest wall compliance. Second, obstructive diseases are represented by asthma and wheezing disorders, cystic fibrosis, long term sequelae of neonatal lung disease and bronchiolitis obliterans following hematopoietic stem cell transplantation. Obstructive diseases are defined by a reduced FEV1/VC ratio. Third, neuromuscular diseases, mainly represented by DMD and SMA, are associated with a decrease in vital capacity linked to respiratory muscle weakness that is better detected by PImax, PEmax and SNIP measurements.

/pdf/the-respiratory-system-nobcv5a5x5.pdf

The Respiratory System

Hexachlorocyclopentadiene (Hex or C‐56) is a highly reactive intermediate used in the production of some insecticides, flame retardants, and resins. The present study was conducted to evaluate the inhalation toxicity of high‐purity Hex (97.7%) in rats and monkeys to provide information on the potential hazards of accidental exposure of workers to Hex vapors. Acute, range‐finding (14‐d), and subchronic (90‐d) inhalation studies were conducted with Sprague‐Dawley rats and subchronic (90‐d) inhalation studies were conducted with cynomolgus monkeys. Both acute and range‐finding studies with rats showed a steep dose‐response curve, and male rats were more sensitive than females. In the range‐finding study with rats the threshold of toxicity for Hex was 0.11–0.5 ppm. Histopathologic examination on rats in the 0.5 ppm group revealed lesions in the olfactory and bronchiolar epithelium and inflammatory exudate in the lumens of the respiratory tract; these changes were consistent with observed impaired respiratory ...

Effects of inhalation exposure to hexachlorocyclopentadiene on rats and monkeys.

The effects of inhalation of hexachlorocyclopentadiene (Hex) up to 14 wk on the terminal bronchioles of rats and monkeys was examined by electron microscopy. Exposed rats elicited a concentration‐related increase in the incidence of electron‐lucent inclusions in the bronchiolar Clara cells when compared to controls. The inclusions in the high‐concentration (0.2 ppm) group were round and more abundant than the rod‐shaped inclusions observed in the intermediate (0.05 ppm) and low‐concentration (0.01 ppm) exposure groups. No ultrastructural changes were observed that could be attributed to the inhalation of Hex vapor in exposed monkeys. The origin and significance of these inclusions is discussed in light of the literature.

C. J. Calo

Papers

Effects of inhalation exposure to hexachlorocyclopentadiene on rats and monkeys.

The Clara cell: an electron microscopy examination of the terminal bronchioles of rats and monkeys following inhalation of hexachlorocyclopentadiene.