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.

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.

The University of Pennsylvania Smell Identification Test (UPSIT) was administered, on a volunteer basis, to workers frequenting the cafeteria of the corporate offices of a major chemical manufacturing company to (1) establish the level of acceptance of self-administered olfactory testing within such a setting, (2) determine the percentage of the sample that reported or evidenced marked olfactory impairment, and (3) develop guidelines for the use of the UPSIT as a corporate medical surveillance tool. The initial acceptance of the testing program was high. Thus, 640 of the cafeteria visitors agreed to take the test (total work force in building less than 1,000). However, only 52% of the tests handed out were completed by the employees and returned to the test examiners, possibly reflecting the informal atmosphere in which they were distributed. Of the group returning the tests, seven employees reported having smell problems due to allergies or sinus disease. However, all of these employees had normal UPSIT scores. Three subjects (1% of the sample) evidenced marked olfactory dysfunction. Of these three, only one was aware of the problem before testing. On average, the corporate subjects significantly outperformed matched control subjects obtained from previous administrations of the UPSIT at health fairs and other public events, although the difference was less than half a point (37.89 v 37.53; P less than .004). As in previous studies, the test scores of women were slightly, but significantly, higher than those of men (respective means = 37.98 v 37.80, P less than .04).

Quantitative assessment of olfactory function in an industrial setting.

A 13-week subchronic study was conducted by administering hexachlorocyclopentadiene ( HCCP ) in corn oil by gavage to groups of ten male and ten female F344 rats at doses of 150, 75, 38, 19, 10 or 0 mg kg-1, and to groups of ten male and ten female B6C3F1 mice at doses of 300, 150, 75, 38, 19 or 0 mg kg-1. The doses were administered once a day, five days per week for 13 weeks. Chemically induced deaths occurred at 150 and 300 mg kg-1 in rats and at 300 mg kg-1 in mice. A significant (P less than 0.05) depression in mean body-weight change relative to controls was observed in male and female rats receiving greater than or equal to 38 and greater than or equal to 75 mg kg-1, respectively, and in male and female mice receiving 150 and 300 mg kg-1, respectively. There was a significant (P less than 0.05) increase in liver and kidney weight: brain weight ratios in the high-dose female rats (75 and 150 mg kg-1) and female mice at all doses (19-300 mg kg-1). HCCP caused proliferative and inflammatory changes of the epithelia in the forestomach of male rats, and male and female mice receiving greater than or equal to 38 mg kg-1 and in female rats receiving greater than or equal to 19 mg kg dose level. Nephrosis characterized by proximal tubular dilation, cytoplasmic vacuolization, cytomegaly, karyomegaly and anisokaryosis occurred in male and female rats and female mice receiving greater than or equal to 38 mg kg-1.

Toxicity of hexachlorocyclopentadiene: subchronic (13-week) administration by gavage to F344 rats and B6C3F1 mice.

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 ...

D. J. Alexander

Papers

Effects of inhalation exposure to hexachlorocyclopentadiene on rats and monkeys.