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Objective: To test a kurtosis-adjusted cumulative noise exposure (CNE) metric for use in evaluating the risk of hearing loss among workers exposed to industrial noises. Specifically, to evaluate whether the kurtosis-adjusted CNE (1) provides a better association with observed industrial noise-induced hearing loss, and (2) provides a single metric applicable to both complex (non-Gaussian [non-G]) and continuous or steady state (Gaussian [G]) noise exposures for predicting noise-induced hearing loss (dose-response curves)., Design: Audiometric and noise exposure data were acquired on a population of screened workers (N = 341) from two steel manufacturing plants located in Zhejiang province and a textile manufacturing plant located in Henan province, China. All the subjects from the two steel manufacturing plants (N = 178) were exposed to complex noise, whereas the subjects from textile manufacturing plant (N = 163) were exposed to a G continuous noise. Each subject was given an otologic examination to determine their pure-tone HTL and had their personal 8-hr equivalent A-weighted noise exposure (LAeq) and full-shift noise kurtosis statistic (which is sensitive to the peaks and temporal characteristics of noise exposures) measured. For each subject, an unadjusted and kurtosis-adjusted CNE index for the years worked was created. Multiple linear regression analysis controlling for age was used to determine the relationship between CNE (unadjusted and kurtosis adjusted) and the mean HTL at 3, 4, and 6 kHz (HTL346) among the complex noise-exposed group. In addition, each subject's HTLs from 0.5 to 8.0 kHz were age and sex adjusted using Annex A (ISO-1999) to determine whether they had adjusted high-frequency noise-induced hearing loss (AHFNIHL), defined as an adjusted HTL shift of 30 dB or greater at 3.0, 4.0, or 6.0 kHz in either ear. Dose-response curves for AHFNIHL were developed separately for workers exposed to G and non-G noise using both unadjusted and adjusted CNE as the exposure matric., Results: Multiple linear regression analysis among complex exposed workers demonstrated that the correlation between HTL3,4,6 and CNE controlling for age was improved when using the kurtosis-adjusted CNE compared with the unadjusted CNE (R = 0.386 versus 0.350) and that noise accounted for a greater proportion of hearing loss. In addition, although dose-response curves for AHFNIHL were distinctly different when using unadjusted CNE, they overlapped when using the kurtosis-adjusted CNE., Conclusions: For the same exposure level, the prevalence of NIHL is greater in workers exposed to complex noise environments than in workers exposed to a continuous noise. Kurtosis adjustment of CNE improved the correlation with NIHL and provided a single metric for dose-response effects across different types of noise. The kurtosis-adjusted CNE may be a reasonable candidate for use in NIHL risk assessment across a wide variety of noise environments.

Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is identification of children who may be uniquely susceptible to Hg toxicity because of genetic predisposition. We examined the possibility that common genetic variants that are known to affect neurologic functions or Hg handling in adults would modify the adverse neurobehavioral effects of Hg exposure in children. Three hundred thirty subjects who participated as children in the recently completed Casa Pia Clinical Trial of Dental Amalgams in Children were genotyped for 27 variants of 13 genes that are reported to affect neurologic functions and/or Hg disposition in adults. Urinary Hg concentrations, reflecting Hg exposure from any source, served as the Hg exposure index. Regression modeling strategies were employed to evaluate potential associations between allelic status for individual genes or combinations of genes, Hg exposure, and neurobehavioral test outcomes assessed at baseline and for 7 subsequent years during the clinical trial. Among boys, significant modification of Hg effects on neurobehavioral outcomes over a broad range of neurologic domains was observed with variant genotypes for 4 of 13 genes evaluated. Modification of Hg effects on a more limited number of neurobehavioral outcomes was also observed for variants of another 8 genes. Cluster analyses suggested some genes interacting in common processes to affect Hg neurotoxicity. In contrast, significant modification of Hg effects on neurobehavioral functions among girls with the same genotypes was substantially more limited. These observations suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children, particularly boys, with genetic variants that are relatively common to the general human population. These findings advance public health goals to identify factors underlying susceptibility to Hg toxicity and may contribute to strategies for preventing adverse health risks associated with Hg exposure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Mercury (Hg) is neurotoxic and children may be particularly susceptible to this effect. A current major challenge is identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. This study examined the hypothesis that genetic variants of catechol-O-methyltransferase (COMT) that are reported to alter neurobehavioral functions that are also affected by Hg in adults might modify the adverse neurobehavioral effects of Hg exposure in children. Five hundred and seven children, 8-12 yr of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings. Subjects were evaluated at baseline and at seven subsequent annual intervals for neurobehavioral performance and urinary Hg levels. Following the clinical trial, genotyping assays were performed for single-nucleotide polymorphisms (SNPs) of COMT rs4680, rs4633, rs4818, and rs6269 on biological samples provided by 330 of the trial participants. Regression-modeling strategies were employed to evaluate associations between allelic status, Hg exposure, and neurobehavioral test outcomes. Similar analysis was performed using haplotypes of COMT SNPs. Among girls, few interactions for Hg exposure and COMT variants were found. In contrast, among boys, numerous gene-Hg interactions were observed between individual COMT SNPs, as well as with a common COMT haplotype affecting multiple domains of neurobehavioral function. These findings suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children with common genetic variants of COMT, and may have important implications for strategies aimed at protecting children from the potential health risks associated with Hg exposure.

Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is the identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. We examined the hypothesis that genetic variants of metallothionein (MT) that are reported to affect Hg toxicokinetics in adults would modify the neurotoxic effects of Hg in children. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings. Subjects were evaluated at baseline and at 7 subsequent annual intervals for neurobehavioral performance and urinary Hg levels. Following the completion of the clinical trial, we performed genotyping assays for variants of MT isoforms MT1M (rs2270837) and MT2A (rs10636) on biological samples provided by 330 of the trial participants. Regression modeling strategies were employed to evaluate associations between allelic status, Hg exposure, and neurobehavioral test outcomes. Among girls, few significant interactions or independent main effects for Hg exposure and either of the MT gene variants were observed. In contrast, among boys, numerous significant interaction effects between variants of MT1M and MT2A, alone and combined, with Hg exposure were observed spanning multiple domains of neurobehavioral function. All dose-response associations between Hg exposure and test performance were restricted to boys and were in the direction of impaired performance. These findings suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children with relatively common genetic variants of MT, and may have important public health implications for future strategies aimed at protecting children and adolescents from the potential health risks associated with Hg exposure. We note that because urinary Hg reflects a composite exposure index that cannot be attributed to a specific source, these findings do not support an association between Hg in dental amalgams specifically and the adverse neurobehavioral outcomes observed., (© 2013.)

This study examined: (1) the value of using the statistical metric, kurtosis [β(t)], along with an energy metric to determine the hazard to hearing from high level industrial noise environments, and (2) the accuracy of the International Standard Organization (ISO-1999:1990) model for median noise-induced permanent threshold shift (NIPTS) estimates with actual recent epidemiological data obtained on 240 highly screened workers exposed to high-level industrial noise in China. A cross-sectional approach was used in this study. Shift-long temporal waveforms of the noise that workers were exposed to for evaluation of noise exposures and audiometric threshold measures were obtained on all selected subjects. The subjects were exposed to only one occupational noise exposure without the use of hearing protection devices. The results suggest that: (1) the kurtosis metric is an important variable in determining the hazards to hearing posed by a high-level industrial noise environment for hearing conservation purposes, i.e., the kurtosis differentiated between the hazardous effects produced by Gaussian and non-Gaussian noise environments, (2) the ISO-1999 predictive model does not accurately estimate the degree of median NIPTS incurred to high level kurtosis industrial noise, and (3) the inherent large variability in NIPTS among subjects emphasize the need to develop and analyze a larger database of workers with well-documented exposures to better understand the effect of kurtosis on NIPTS incurred from high level industrial noise exposures. A better understanding of the role of the kurtosis metric may lead to its incorporation into a new generation of more predictive hearing risk assessment for occupational noise exposure.

Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is the identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. We examined the hypothesis that CPOX4, a genetic variant of the heme pathway enzyme coproporphyrinogen oxidase (CPOX) that affects susceptibility to mercury toxicity in adults, also modifies the neurotoxic effects of Hg in children. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings in children. Subjects were evaluated at baseline and at 7 subsequent annual intervals for neurobehavioral performance and urinary mercury levels. Following the completion of the clinical trial, genotyping assays for CPOX4 allelic status were performed on biological samples provided by 330 of the trial participants. Regression modeling strategies were employed to evaluate associations between CPOX4 status, Hg exposure, and neurobehavioral test outcomes. Among girls, few significant CPOX4-Hg interactions or independent main effects for Hg or CPOX4 were observed. In contrast, among boys, numerous significant interaction effects between CPOX4 and Hg were observed spanning all 5 domains of neurobehavioral performance. All underlying dose-response associations between Hg exposure and test performance were restricted to boys with the CPOX4 variant, and all of these associations were in the expected direction where increased exposure to Hg decreased performance. These findings are the first to demonstrate genetic susceptibility to the adverse neurobehavioral effects of Hg exposure in children. The paucity of responses among same-age girls with comparable Hg exposure provides evidence of sexual dimorphism in genetic susceptibility to the adverse neurobehavioral effects of Hg in children and adolescents., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To complete a systematic review of emergency department (ED) practices for reducing hemolysis in blood samples sent to the clinical laboratory for testing., Results: A total of 16 studies met the review inclusion criteria (12 published and 4 unpublished). All 11 studies comparing new straight needle venipuncture with IV starts found a reduction in hemolysis rates, [average risk ratio of 0.16 (95% CI=0.11-0.24)]. Four studies on the effect of venipuncture location showed reduced hemolysis rates for the antecubital site [average risk ratio of 0.45 (95% CI=0.35-0.57]., Conclusions: Use of new straight needle venipuncture instead of IV starts is effective at reducing hemolysis rates in EDs, and is recommended as an evidence-based best practice. The overall strength of evidence rating is high and the effect size is substantial. Unpublished studies made an important contribution to the body of evidence. When IV starts must be used, observed rates of hemolysis may be substantially reduced by placing the IV at the antecubital site., (© 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Autism (AUT) is a complex neurodevelopmental disorder that, together with Asperger's syndrome and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), comprises the expanded classification of autistic spectrum disorder (ASD). The heterogeneity of ASD underlies the need to identify biomarkers or clinical features that can be employed to identify meaningful subtypes of ASD, define specific etiologies, and inform intervention and treatment options. Previous studies have shown that disordered porphyrin metabolism, manifested principally as significantly elevated urinary concentrations of pentacarboxyl (penta) and coproporphyrins, is commonly observed among some children with ASD. Here, we extend these observations by specifically evaluating penta and coproporphyrins as biological indicators of ASD among 76 male children comprising 30 with validated AUT, 14 with PDD-NOS, and 32 neurotypical (NT) controls. ASD children (AUT and PDD-NOS) had higher mean urinary penta (P < 0.006) and copro (P < 0.006) concentrations compared with same-aged NT children, each characterized by a number of extreme values. Using Receiver Operating Characteristic curve analysis, we evaluated the sensitivity and specificity of penta, copro, and their combined Z-scores in ASD detection. The penta sensitivity was 30% for AUT and 36% for PDD-NOS, with 94% specificity. The copro sensitivity was 33% and 14%, respectively, with 94% specificity. The combined Z-score measure had 33% and 21% sensitivity for AUT and PDD-NOS, respectively, with 100% specificity. These findings demonstrate that porphyrin measures are strong predictors of both AUT and PDD-NOS, and support the potential clinical utility of urinary porphyrin measures for identifying a subgroup of ASD subjects in whom disordered porphyrin metabolism may be a salient characteristic., (© 2012 International Society for Autism Research, Wiley Periodicals, Inc.)

Background: Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU)., Objectives: This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism., Methods: This exploratory study enrolled 278 children 2-12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism., Results: Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received., Conclusions: These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent.

A functional polymorphism in the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) is reported to affect mood and behavior in humans. In this study, the effects of 5-HTTLPR polymorphism on neurobehavioral and mood domains that are known to be affected by elemental mercury (Hg degrees ) exposure in human subjects were examined. The Behavioral Evaluation for Epidemiologic Studies (BEES) test battery was administered concurrently with urine and buccal-cell collections for 164 male dentists (DD) and 101 female dental assistants (DA) with occupational exposure to Hg degrees for an average of 19 and 10 yr, respectively. Geometric mean urinary mercury (Hg) levels in DD and DA were 2.52 (2.22) microg/L and 1.98 (1.98) microg/L, respectively. Corresponding indices of chronic occupational Hg degrees exposure, weighted for historical exposure, were 1212 (1877) and 316 (429). 5-HTTLPR status was 40% and 20% wild type, 40% and 56% single allelic substitution, and 20% and 24% double allelic substitution for the two genders. DD and DA were evaluated separately. Regression analyses controlled for age, premorbid intelligence, frequency of alcohol per week, and education. 5-HTTLPR polymorphism was associated with 5 behavioral measures in DD and with 12 behavioral measures in DA. Mood scores were more consistently associated with the variant in both groups. The strongest evidence for an additive effect for urinary Hg and 5-HTTLPR polymorphism in both groups was for tests of Finger Tap(Alternate) and Hand Steadiness(Factor1). Other significant additive effects that were less consistent across groups were also observed. These results add to the growing evidence of genetic determinants of mood and behavior that potentially increase susceptibility to Hg toxicity in humans.

Associations were evaluated between a functional single nucleotide polymorphism (Val158Met) in the gene encoding the catecholamine catabolic enzyme catechol O-methyltransferase (COMT), dental mercury exposure, and self-reported symptoms and mood among 183 male dentists and 213 female dental assistants. Self-reported symptoms, mood, and detailed work histories were obtained by computerized questionnaire. Spot urine samples were collected and analyzed for mercury concentrations to evaluate recent exposures, whereas a chronic mercury exposure index for all subjects was created from the work histories. COMT polymorphism status was determined using a polymerase chain reaction (PCR)-based assay. Scores for current, recent, and chronic self-reported symptom groups and six self-reported mood factors were evaluated with respect to recent and chronic mercury exposure and COMT polymorphism status. Multiple regression analysis controlled for age, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Separate evaluations were conducted for dentists and dental assistants. No consistent patterns of association between either urinary mercury concentration or the chronic index of mercury exposure and any category of symptoms were observed. However, consistent and significant associations were found between increased symptoms and the COMT polymorphism involving the double allelic substitution (full mutation) compared to subjects with no substitutions. Associations with mood were limited to polymorphism status among female dental assistants, and were observed for four of six mood factors and overall mood score. These findings extend evidence of genetic factors potentially affecting human susceptibility to the toxic effects of mercury and other environmental chemicals.

The associations between a polymorphism of the serotonin transporter gene (5-HTTLPR), dental mercury exposure, and self-reported symptoms were evaluated among 157 male dentists and 84 female dental assistants. Self-reported symptoms and detailed work histories were obtained by computerized questionnaire. Spot urine samples were collected and analyzed for mercury concentrations to evaluate recent exposures, whereas a chronic mercury exposure index was created from the work histories. 5-HTTLPR polymorphism status was determined using a polymerase chain reaction (PCR)-based assay. Scores for current, recent, and chronic self-reported symptom groups were evaluated with respect to recent and chronic mercury exposure and 5-HTTLPR polymorphism status. Multiple regression analysis controlled for age, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Analyses were restricted to Caucasian subjects due to the highly skewed distribution of the 5-HTTLPR polymorphism. Separate evaluations were conducted for dentists and dental assistants. In contrast to previous reports, no consistent associations were found between either urinary mercury concentration or the chronic index of mercury exposure and any category of symptoms. However, both significant and consistent associations were observed between increased symptoms and the 5-HTTLPR polymorphism involving two copies of the short or "s" allele (full mutation), but not with the polymorphism involving only one copy (heterozygous), demonstrating a gene-dose relationship for symptom reporting. These findings suggest that within this restricted population increased symptoms of depression, anxiety, and memory are associated with the 5-HTTLPR polymorphism among both males and females.

Mercury (Hg) exposure in various forms remains a persistent public health concern in many parts of the world. In previous studies, we have described a biomarker of mercury exposure characterized by increased urinary concentrations of specific porphyrins, pentacarboxyporphyrin (5-CP) and coproporphyrin (4-CP), and the atypical keto-isocoproporphyrin (KICP), based on selective interference with the fifth (uroporphyrinogen decarboxylase, UROD) and sixth (coproporphyrinogen oxidase, CPOX) enzymes of the heme biosynthetic pathway. Whereas this response occurs in a predictable manner among approximately 85% of subjects with Hg exposure, an atypical porphyrinogenic response (APR) has been observed in approximately 15% of Hg-exposed persons, in which the three porphyrins that are affected by Hg, i.e., 5-CP, 4-CP and, KICP, are excreted in substantial excess of that predicted on the basis of Hg exposure alone. This APR has been attributed to a specific polymorphism in exon 4 of the CPOX gene (CPOX4). In the present study, we sought to further confirm the hypothesis that the observed changes in porphyrin excretion patterns might serve as a biomarker of Hg exposure and potential toxicity by statistically modeling the cascading effects on porphyrin concentrations within the heme biosynthetic pathway of Hg exposure and CPOX4 polymorphism in a human population with long-term occupational exposure to elemental mercury. Our results are highly consistent with this hypothesis. After controlling for precursor porphyrin concentrations, we demonstrated that 5-CP and 4-CP are independently associated with Hg concentration, while KICP is associated only with the CPOX4. An unpredicted association of Hg with heptacarboxyporphyrin (7-CP) may indicate a previously unidentified point of mercury inhibition of UROD. These findings lend further support to the proposed utility of urinary porphyrin changes as a biomarker of exposure and potential toxicity in subjects with mercury exposure. Additionally, these findings demonstrate the successful application of a computational model for characterizing complex metabolic responses and interactions associated with both toxicant exposure and genetic variation in human subjects.

We previously described a polymorphism in exon 4 of the gene encoding the heme biosynthetic pathway enzyme, coproporphyrinogen oxidase (CPOX4), which significantly modifies the effect of mercury exposure on urinary porphyrin excretion in humans. Here, we examined potential consequences of this polymorphism ("CPOX4") on performance within neurobehavioral domains, symptoms, and mood that are known to be affected by elemental mercury (Hg degrees ) exposure in human subjects. A behavioral test battery was administered on the day of urine and buccal cell collections for 194 male dentists (DDs) and 233 female dental assistants (DAs) occupationally exposed to Hg degrees for an average of 19 and 10 years, respectively. Subjects had no history of health disorders and were employed for a minimum of 5 years in the dental profession. Respective mean urinary mercury (HgU) levels in DDs and DAs were 3.32 (4.87) microg/l and 1.98 (2.29) microg/l. Corresponding indices of chronic occupational Hg degrees exposure, weighted for historical exposure, were 27.1 (20.6) and 15.2 (12.3). The frequencies of the homogygous common (A/A), heterozygous (A/C), and homozygous polymorphic (C/C) genotypes were 75%, 23% and 2% for DDs and 73%, 25%, and 2% for DAs, respectively. DDs and DAs were evaluated separately. Regression analyses controlled for age, premorbid intelligence, alcohol consumption, and education. Statistically significant associations with HgU (p<0.05) were found for nine measures among DDs (BEES Digit SpanForward and Backward, WMS-R Visual ReproductionN Correct, BEES Symbol DigitRate, BEES Finger TappingDom/Non-dom, and Alternate Partialed, Hand SteadinessFactor1, and BEES Tracking), and eight measures among DAs (BEES Digit SpanForward, BEES Symbol DigitRate, BEES Pattern Discrimination Rate, BEES Trailmaking B, BEES Finger TappingDom/Non-dom, and Alternate Partialed, Hand SteadinessFactor1, and Vibration SensitivityHits). CPOX4 status was associated with four measures in DDs (BEES Spatial SpanForward, BEES Pattern MemoryN Correct, BEES Symbol DigitRate, and BEES VigilanceHit) and five measures in DAs (BEES Digit SpanForward, WMS-R Visual ReproductionsN Correct, BEES Symbol DigitRate, BEES Simple and Choice Reaction TimeMove. Both groups experienced an additive effect (no interaction term) for HgU and the CPOX4 polymorphisms on the DigitRate whereas DAs also had additive effects for BEES Digit SpanForward and for Beck's Depression factor 'Worthlessness'. These exploratory findings suggest that the CPOX4 polymorphism may affect susceptibility for specific neurobehavioral functions associated with mercury exposure in human subjects.

Potential cognitive and motor effects from exposure to elemental mercury (Hg(0)) were examined in the presence and absence of a polymorphism (Val66Met) in brain-derived neurotrophic factor (BDNF). A group of 194 male dentists (DDs) and 233 female dental assistants (DAs) were occupationally exposed to mercury and had no history of kidney or nervous system disorders. Acute exposure was measured using spot urinary Hg (HgU) concentrations (average 3.32 and 1.98 microg/l, respectively) and indices of chronic occupational exposure (26.3 and 14.9 years, respectively, weighted for historical exposures). The BDNF status was 68% and 66% wild type, 26% and 30% single substitution, and 5% and 4% full mutation for DDs and DAs, respectively. DDs and DAs were evaluated separately. Regression analyses controlled for age, premorbid intelligence, alcohol consumption, and education. Statistically significant adverse associations with HgU (p<.05) were found for nine measures among DDs (Digit Span (Forward), Digit and Spatial Span(Backward), Visual Reproduction, Finger Tapping(Dominant, Alternate, and Alternate Partialed), Hand Steadiness, and Tracking), and eight measures among DAs (Digit Span(Forward), Visual Reproduction, Pattern Discrimination(Rate), Symbol Digit(Rate), Trailmaking B, Finger Tapping(Dominant and Alternate Partialed), and Hand Steadiness). The BDNF status was associated with four measures in DDs and three measures in DAs. Joint effects were found for Finger Tapping(Alternate and Alternate Partialed) in DDs and Hand Steadiness and Trailmaking B in DAs. Joint effects were additive in all cases. Performance on verbal intelligence and reaction time were not associated with either HgU or BDNF status. A test of threshold effect for the association of Hand Steadiness with HgU demonstrated no lower boundary in both DDs and DAs. No associations were observed with estimates of chronic mercury exposure. Our findings are applicable to exposure levels of the general population and identify a potentially vulnerable group with a BDNF polymorphism.

Previous studies have demonstrated highly specific urinary porphyrin profile (UPP) changes in response to mercury (Hg) exposure in animals and human subjects and have defined the biochemical etiology of this effect as selective alteration of the heme pathway enzymes, uroporphyrinogen decarboxylase (UROD), and coproporphyrinogen oxidase (CPOX) by Hg in the kidney. Ongoing validation studies in a population of dental practitioners with low-level occupational Hg exposure have demonstrated the predicted UPP change among approximately 85% of subjects. This study focused on the genetic etiology of an atypical porphyrinogenic response (APR) seen among the remaining 15% of Hg-exposed subjects, characterized by excess excretion of 4- and 5-carboxyl porphyrins and also of the atypical ketoisocoproporphyrin (KICP). Automated DNA-sequencing-based assays were developed to examine the 7 exons and flanking intron-exon boundaries of the CPOX gene. Among several polymorphisms identified, an A814C variant in exon 4 encoding a N272H substitution was found to be predominant among subjects with the APR. Studies suggest that this variant CPOX preferentially converts the upstream 5-carboxylporphyrin (5-CP) to KICP. By partially inhibiting the 5- to 4-decarboxylation step of UROD, Hg promotes 5-CP accumulation, accounting for e xcess KICP excretion and the APR in Hg-exposed subjects carrying the variant CPOX gene. This finding represents the first report of a polymorphism in a human gene that modifies the effect of Hg on a biological process. The APR might serve as a biomarker of both Hg exposure and susceptibility to Hg toxicity.

Recent reports have described neurobehavioral impairments in human subjects carrying a V66M polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF). Inasmuch as ventral nervous system (CNS) deficits associated with this BDNF polymorphism are similar to those observed among subjects with chronic exposure to elemental mercury (Hg degrees ), we examined the potential effect of this BDNF polymorphism on symptoms and mood in an established cohort of dental practitioners with chronic low-level Hg degrees exposure. Self-reported symptoms and mood were obtained by computerized questionnaire from 193 male dentists (DTs) and 230 female dental assistants (DAs). Spot urine samples were analyzed for mercury concentrations to evaluate recent exposure. Detailed work histories were obtained to calculate chronic indices of Hg degrees exposure. Buccal cell samples were obtained to identify the V66M polymorphism of BDNF. Scores for 11 current and 12 recent and chronic symptom groups, along with six mood factors, were evaluated with respect to recent and chronic Hg degrees exposure and BDNF polymorphism. Multiple regression analysis controlled for age, race, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Separate evaluations were conducted for DTs and DAs. Twenty-three associations between recent or chronic Hg degrees exposure and BDNF status and self-reported symptoms were observed with p < 0.10. All but three were in the expected direction (symptom scores increasing with Hg degrees exposure or BDNF polymorphism), and all but six were among DAs. All eight correlations between chronic exposure indices and recent and chronic symptoms among DAs were in the expected direction. All seven associations between BDNF and symptoms were in the expected direction and split between DTs and DAs. All three associations with mood factors were among DAs and in the expected direction. These results indicate that among DAs very low levels of occupational Hg degrees exposure are associated with increased symptoms. The BDNF polymorphism is also associated with increased symptom and mood scores. Notably, Hg degrees and BDNF polymorphism were additive with respect to their associations with the same symptom group.

The Behavioral Evaluation for Epidemiology Studies test battery uses touch-screen technology and novel methodologies to enhance neurobehavioral assessment. Scores generally show differential stability from the first trial with individual test reliabilities at or above .80 when normalized to a 3-min. administration. Six highly reliable (r > or = .87) factors were identified that cover functions known to be sensitive to neurotoxicants and physical exposures. These results strongly support recommendation of the new test battery for use in repeated-measures epidemiologic studies where first trial stability is desired.

There is limited and conflicting evidence regarding the exposure-response relationship between exposure to crystalline silica and silicosis; the level of risk to current workers remains uncertain. We conducted an epidemiologic investigation of 1,809 workers in the diatomaceous earth industry, where exposures to crystalline silica are primarily to the cristobalite form. On the basis of the median of three independent readings, 81 (4.5%) workers were judged to have opacities on chest radiographs (small opacities, profusion >= 1/0, and/or large opacities). Age-adjusted relative risk of opacities increased significantly with cumulative exposure to crystalline silica. The concentration of respirable crystalline silica to which workers were exposed (highly correlated with period of hire) was an important determinant of risk after accounting for cumulative exposure. For workers with an average exposure to crystalline silica of <= 0.50 mg/m3 (or hired >= 1950), the cumulative risk of opacities for a cumulative exposure to crystalline silica of 2.0 mg/m3-yr was approximately 1.1%; for an average exposure > 0.50 mg/m3 (or hired < 1950), the corresponding cumulative risk was 3.7%. These findings indicate an exposure-response relationship between cumulative exposure to crystalline silica and radiographic opacities; moreover, the relationship was substantially steeper among workers exposed at the highest average concentrations of crystalline silica.

Potential toxicity from exposure to mercury vapor (Hg(o)) from dental amalgam fillings is the subject of current public health debate in many countries. We evaluated potential central nervous system (CNS) toxicity associated with handling Hg-containing amalgam materials among dental personnel with very low levels of Hg(o) exposure (i.e., urinary Hg <4 microg/l), applying a neurobehavioral test battery to evaluate CNS functions in relation to both recent exposure and Hg body burden. New distinctions between subtle preclinical effects on symptoms, mood, motor function, and cognition were found associated with Hg body burden as compared with those associated with recent exposure. The pattern of results, comparable to findings previously reported among subjects with urinary Hg >50 microg/l, presents convincing new evidence of adverse behavioral effects associated with low Hg(o) exposures within the range of that received by the general population.

A Across-study design was used to evaluate the sensitivities of five psychomotor tasks previously used to assess preclinical effects of low-level Hg0 (urinary < or =55 microg/l). Pooling dental professional subject populations from six studies conducted over the last 6 years, a larger study population was obtained with a high degree of uniformity (N = 230). The five psychomotor tests were: Intentional Hand Steadiness Test (IHST); Finger Tapping: The One-Hole Test: NES Simple Reaction Time (SRT); and Hand Tremor. Multivariate analyses were conducted following the hierarchical analysis of multiple responses (HAMR) approach. First, multiple scores of each test were combined into a single-factor (or related summary) variable and its reliability was estimated. Second. multiple regression analyses were conducted including log-transformed [Hg0]U levels, age, gender, and alcohol consumption in each model. Computed were both B and bu, the magnitudes of the log-Hg0 standardized coefficient. respectively uncorrected and corrected for dependent variable attenuation due to unreliability. Results indicated remarkable differences in the effects of relative level of Hg0 on psychomotor performance. Significant associations were found for the IHST factor (B = 0.415, p < 10(-6)), followed by finger tapping, which was relatively meager and insignificant (B 0.141, p = 0.17). The IHST results hold the greatest occupational relevance for dental professionals who rely on manual dexterity in restorative dentistry. Further, this statistical approach is recommended in future studies for condensation of multiple scores into summary scores with enhanced reliabilities useful in correcting for attenuation relationships (B(u)s) with exposure levels.

Quantitative estimates of dust exposure in a diatomaceous earth (DE) mining and milling operation have been derived based on air sampling records for the period 1948-1988. A total of 6395 records was included in the analysis. Conversion of results obtained by particle counting, expressed as millions of particles per cubic feet (mppcf) of gravimetrically from a filter cassette and expressed as mg m-3 total, were converted to mg m-3 respirable dust using a conversion factor derived from data obtained during the same periods at the plant. Conversion factors were calculated as the average difference of means on the log scale in order to provide stable and consistent conversions and as a ratio of arithmetic means so that the results could be compared with similar studies. After converting the available data to mg m-3 respirable dust, geometric mean (geometric standard deviation) concentrations were 0.37 (2.43) during the 1950s and 0.17 (2.35) during later periods. Exposures were estimated using two linear models, one estimating the changes in concentration over time, and the other providing job-specific mean exposures during the more recent period. Extrapolation of the estimates to periods prior to the availability of any data was done using a subjectively-determined scaling factor. The average estimated respirable dust concentrations for 135 jobs were 3.55 (+/-1.25), 1.37 (+/-0.48), 0.47 (+/-0.16) and 0.29 (+/-0.10) mg m-3 prior to 1949, 1949-1953, 1954-1973 and 1974-1988, respectively. Despite the limitations of the available data, the estimation procedures used are expected to provide reasonable quantitative estimates of silica-containing dust exposure for subsequent exposure-response analyses.

The potential carcinogenicity of crystalline silica to humans remains a controversial issue. The authors conducted an historical cohort mortality study of 2,342 male workers exposed to crystalline silica, predominantly cristobalite, in a diatomaceous earth mining and processing facility in California. During the years 1942-1994, mortality excesses were detected for nonmalignant respiratory diseases (NMRD) (standardized mortality ratio = 2.01, 95% confidence interval (CI) 1.56-2.55) and lung cancer (standardized mortality ratio = 1.29, 95% CI 1.01-1.61). NMRD mortality rose sharply with cumulative exposure to respirable crystalline silica; allowing for a 15-year latency, the rate ratio for the highest exposure stratum (> or = 5.0 mg/m3-years) was 5.35 (95% CI 2.23-12.8). The rate ratio for lung cancer reached 2.15 (95% CI 1.08-4.28) in the highest exposure category. These associations were unlikely to have been confounded by smoking or asbestos exposure. The findings indicate a strong dose-response relation for crystalline silica and NMRD mortality. The lung cancer results, although less convincing, add further support to an etiologic role for crystalline silica.

A retrospective cohort study evaluated the risk of lung cancer in aerospace workers with minimum of 6 months' employment in jobs with chromium [VI] exposure (n = 2429). Standardized incidence ratios (SIR) estimated the risk of lung cancer by duration of employment in chromate-exposure jobs and cumulative exposure based on industrial hygiene and work-history data. The overall SIR for lung cancer was 0.8 (observed [Obs] = 15). Lung cancer risk was inversely related to estimates of cumulative chromate exposure and duration of employment as a painter. Although based on few cases, an elevated lung cancer risk was found in subjects who had worked for 5 or more years as a chrome plater or surface processor tank tender (Obs = 2, SIR = 1.9) and sander/masker or polisher (Obs = 3, SIR = 2.7). A clear association was not observed between chromate exposure and the risk of lung cancer in this population of workers.

We have added 14 years of mortality follow-up to a previously studied cohort of 18,446 white and 4,546 nonwhite male workers in the Florida phosphate industry. Follow-up was performed for the years 1949-1992. Based on comparisons with national rates, lung cancer standardized mortality ratios (SMR) were slightly elevated among white (SMR = 1.19; 354 observed) and nonwhite males (SMR = 1.13; 105 observed). However, no lung cancer excesses were found relative to local county rates (SMR = 0.98 for whites, SMR = 0.94 for nonwhites). Based on internal analyses of lung cancer mortality, using Poisson regression modeling, there were no associations of lung cancer with cumulative exposures to total dust, silica, or acid mists. There were weak trends of lung cancer risk with alpha and gamma radiation among white males, but no associations with radiation in nonwhites. No relation was found between acid mist exposures and laryngeal cancer. We conclude that there have not been large excesses of lung cancer or other diseases related to workplace exposures in this cohort.

Objective: To evaluate the potential for confounding from asbestos exposure, primarily chrysotile, on the relation between crystalline silica and mortality from lung cancer among diatomaceous earth (diatomite) workers., Methods: A reanalysis of a cohort mortality study of diatomite workers was performed to take into account quantitative estimates of asbestos exposure. The reanalysis was limited to a subset of the original cohort, comprising 2266 white men for whom asbestos exposure could be reconstructed with greatest confidence. Comparisons between mortality from lung cancer (standardised mortality ratios (SMR)) were made between rates for 1942-87 for United States white men, and workers cross classified according to cumulative exposures to crystalline silica and asbestos. Comparisons of internal rates, involving Poisson regression modeling, were conducted for exposure to crystalline silica, with and without adjustment for asbestos exposure. Exposures were lagged by 15 years to take into account disease latency., Results: There was an overall excess of lung cancer (SMR 1.41; 52 observed). The SMRs for four categories of increasing crystalline silica among the workers not exposed to asbestos were 1.13, 0.87, 2.14, 2.00. An SMR of 8.31 (three observed) was found for workers with the highest cumulative exposure to both dusts. Internal analysis, after adjustment for asbestos exposure, yielded rate ratios for categories of exposure to crystalline silica: 1.00 (reference), 1.37, 1.80, and 1.79., Conclusions: Asbestos exposure was not an important confounder of the association between crystalline silica and mortality from lung cancer in this cohort. Although based on a small number of deaths from lung cancer, the data suggest possible synergy between these exposures. An extended follow up of this cohort is in progress and should enable better assessments of independent and combined effects on risk of lung cancer.

Neurobehavioral studies often employ test batteries and confront issues of multiple testing and comparability between batteries. We have organized our battery of 12 tests into areas of neurobehavioral function to reduce the number of reported results, provide greater statistical power, and improve interpretability of the results. We explored several different organizational and statistical methods of creating summary scores including a priori groupings based upon clinical experience and factor analysis. We compared the sensitivity of these summary scores to performance changes associated with exposure to styrene in the manufacture of reinforced plastics. Our results demonstrated dramatic increases in power to detect exposure related changes compared to using individual test scores. Furthermore, the various methods provided generally compatible and comparable results. We encourage other neurobehavioral investigators to pursue and refine this approach.

Exposure thresholds for health effects associated with elemental mercury (Hg degree) exposure were examined by comparing behavioral test scores of 19 exposed (mean urinary Hg = 36 micrograms/l) with those of 20 unexposed dentists. Thirty-six micrograms Hg/l is 7 times greater than the 5 micrograms Hg/l mean level measured in a national sample of dentists. To improve the distinction between recent and cumulative effects, the study also evaluated porphyrin concentrations in urine, which are correlated with renal Hg content (a measure of cumulative body burden). Subjects provided an on-site spot urine sample, were administered a 1-h assessment consisting of a consent form, the Profile of Mood Scales, a symptom and medical questionnaire, and 6 behavioral tests: digit-span, symbol-digit substitution, simple reaction time, the ability to switch between tasks, vocabulary, and the One Hole Test. Multivariate regression techniques were used to evaluate dose-effects controlling for the effects of age, race, gender and alcohol consumption. A dose-effect was considered statistically significant below a p value of 0.05. Significant urinary Hg dose-effects were found for poor mental concentration, emotional lability, somatosensory irritation, and mood scores. Individual tests evaluating cognitive and motor function changed in the expected directions but were not significantly associated with urinary Hg. However, the pooled sum of rank scores for combinations of tests within domains were significantly associated with urinary Hg, providing evidence of subtle preclinical changes in behavior associated with Hg exposure. Coproporphyrin, one of three urinary porphyrins altered by mercury exposure, was significantly associated with deficits in digit span and simple reaction time.(ABSTRACT TRUNCATED AT 250 WORDS)

Study Design: This study covered a large, population-based cohort of workers in the Washington State workers' compensation system who received lumbar fusion between August 1, 1986 and July 31, 1987 to determine work disability status, reoperation rate, and patient satisfaction., Objectives: To use predictors of outcome of lumbar fusion to design clearer clinical guidelines for lumbar fusion in injured workers., Methods: Logistic regression analysis was used to determine the predictors of work disability and risk of reoperation after fusion., Results: The lumbar fusion incidence rate was 41.7/100,000 workers a year (n = 388 patients). Overall, 68% were work disabled and 23% required further lumbar spine surgery 2 years post-fusion. Five markers of severity predicted worse work disability outcome (older age at injury, longer time from injury to fusion, increased increased time on work disability before fusion, increased number of prior low back operations, and increased number of levels fused). Even after adjusting for these variables, receiving instrumentation with fusion doubled the risk of reoperation. Most patients reported that back pain (67.7%) was worse and overall quality of life (55.8%) was no better or worse than before surgery., Conclusions: Outcome of lumbar fusion performed on injured workers was worse than reported in published case series. Prospective studies should be conducted to determine the biologic indications that might lead to improved outcomes in this disabled population.

Objectives: Brain trauma is a major cause of disability in the United States, especially among young adults. Work-related brain trauma cases represent a subpopulation that may be amenable to intervention efforts, but largely because of unavailability of data, this group has not previously been studied., Methods: Washington State workers' compensation data were used to identify brain trauma cases and to describe incidence rates with respect to age, gender, and industrial classification. Cause of injury was evaluated for industrial classifications with numerous cases., Results: Washington State workers experienced 301 brain traumas over a 3-year period (9.4/100,000 full-time equivalent workers per year). One third of all traumatic brain injury claims were concentrated among seven industrial classifications. Cause of injury was highly correlated with specific industrial classifications., Conclusions: This study demonstrates the usefulness of diagnosis-related group codes to identify cases of traumatic brain injury. These injuries are concentrated among a few industries, with a dominant specific cause for each industry. This suggests that intervention methods may be efficiently introduced to reduce traumatic brain injuries in the workplace.

In order to determine if exposure to carcinogens in fire smoke increases the risk of cancer, we examined the incidence of cancer in a cohort of 2,447 male firefighters in Seattle and Tacoma, (Washington, USA). The study population was followed for 16 years (1974-89) and the incidence of cancer, ascertained using a population-based tumor registry, was compared with local rates and with the incidence among 1,878 policemen from the same cities. The risk of cancer among firefighters was found to be similar to both the police and the general male population for most common sites. An elevated risk of prostate cancer was observed relative to the general population (standardized incidence ratio [SIR] = 1.4, 95 percent confidence interval [CI] = 1.1-1.7) but was less elevated compared with rates in policemen (incidence density ratio [IDR] = 1.1, CI = 0.7-1.8) and was not related to duration of exposure. The risk of colon cancer, although only slightly elevated relative to the general population (SIR = 1.1, CI = 0.7-1.6) and the police (IDR = 1.3, CI = 0.6-3.0), appeared to increase with duration of employment. Although the relationship between firefighting and colon cancer is consistent with some previous studies, it is based on small numbers and may be due to chance. While this study did not find strong evidence for an excess risk of cancer, the presence of carcinogens in the firefighting environment warrants periodic re-evaluation of cancer incidence in this population and the continued use of protective equipment.

A cohort mortality study was conducted among workers from two plants in the diatomaceous earth mining and processing industry in California. Diatomaceous earth consists of the skeletal remains of diatoms. Exposure to amorphous (non-crystalline) and crystalline silica in the form of quartz results from open pit mining and exposure to crystalline silica (principally cristobalite) occurs in the processing of the material. Lung cancer and non-malignant respiratory diseases have been the health outcomes of greatest concern. The main study cohort included 2570 white men (533 Hispanic and 2017 non-Hispanic workers) who were employed for at least 12 months cumulative service in the industry and who had worked for at least one day during the follow up period, 1942-87. Vital status was ascertained for 91% of the cohort and death certificate information was retrieved for 591 of 628 (94%) identified deaths. The all causes combined standardised mortality ratio (SMR) was slightly increased (SMR = 1.12; 628 observed) compared with rates among US white males. The principal contributors to this excess were increased risks from lung cancer (SMR = 1.43; 59 observed) and non-malignant respiratory disease (NMRD) excluding infectious diseases and pneumonia (SMR = 2.59; 56 observed). The excess of lung cancer persisted when local county rates were used for comparison (SMR = 1.59). Internal rate comparisons by Poisson regression analysis were conducted to assess potential dose-response relations for lung cancer and NMRDs. Mortality trends were examined in relation to duration of employment in dust exposed jobs and with respect to an index of cumulative exposure to crystalline silica. The crystalline silica index was a semiquantitative measure that combined information on duration of exposure, differences in exposure intensity between jobs and calendar periods, the crystalline content of the various product mixes, and the use of respiratory protection devices. Increasing gradients of risk were detected for lung cancer and NMRD with both exposure indices. The relative risk trends for lung cancer and NMRD with crystalline silica exposure lagged 15 years were respectively: 1.00, 1.19, 1.37, and 2.74, and 1.00, 1.13, 1.58, and 2.71. Based on a review of available but limited data on cigarette smoking in the cohort and from application of indirect methods for assessing confounding variables, it seems unlikely that smoking habits could account for all of the association between exposure to dust and lung cancer. The intense and poorly controlled dust exposures encountered before the 1950s were probably the most aetiologically significant contributors to risks from lung cancer and NMRDs. The absence of an excess of lung cancer among workers hired since 1960, and the finding of no deaths attributed to pneumoconiosis as an underlying cause of death among workers hired since 1950 indicate that exposure reductions in the industry during the past 40 years have been successful in reducing excess risks to workers. Further mortality follow up of the cohort and the analysis of radiographic data will be needed to determine conclusively the long term patterns of disease risks in this industry.

Studies of cancer incidences among occupational cohorts are rarely performed in the United States because of incomplete registration and a limited time period available for follow-up. This study used data from concurrent studies of cancer mortality and incidence among a cohort of 4,528 fire fighters and police officers employed by the cities of Seattle and Tacoma, Washington, between 1944 and 1979 to examine the relative advantages of tumor registry and death certificate information. As expected, an increased ability to study relatively common cancers with low fatality rates was demonstrated using incidence data. The most dramatic example was seen for bladder cancer. Twenty-four bladder cancers had been diagnosed among the study cohort between 1974 and 1989, whereas only two deaths were attributed to this malignancy. The standardized incidence ratio for bladder cancer was 1.05 (95% confidence interval 0.67-1.55), whereas the corresponding standardized mortality ratio was 0.46 (95% confidence interval 0.05-1.65). The observed relative risk estimates for rapidly fatal cancers were similar using the two sources of information, and no increase in precision was observed. Of 142 persons in the registry area who died of cancer during the study period, 20 (14%) had a different site listed on the death certificate than was identified by the registry. Approximately 7% of the potential person-years of follow-up were lost due to migration out of the registry area; loss to follow-up was greater among older and short-term workers, but did not exceed 13% of the person-years. Population-based tumor registries can be a useful resource in the investigation of occupational cancer in the United States, especially for the study of cancers with high survival rates.

Occupational and environmental diseases are underrecognized. Among the barriers to the successful diagnosis, treatment, and prevention of these conditions are inadequate consultative and information resources. We describe the 10-year clinical and training experiences of an academically affiliated referral center that has as its primary goal the identification of work-related and other environmental diseases. The University of Washington Occupational and Environmental Medicine Program has evaluated 6,048 patients in its diagnostic and screening clinics. Among the 2,841 seen in the diagnostic clinics, 1,553 (55%) had a work-related condition. The most prevalent diagnoses included asbestos-related lung disease (n = 603), toxic encephalopathy (n = 160), asthma (n = 119), other specific respiratory conditions (n = 197), carpal tunnel syndrome (n = 86), and dermatitis (n = 82). The clinics serve as a training site for fellows in the specialty training program, primary care internal medicine residents, residents from other medical specialties, and students in industrial hygiene, toxicology, and occupational health nursing. The program serves two additional important functions: providing consultative services to community physicians and training specialists and other physicians in this underserved area of medicine.

To explore whether exposure among firefighters to fire smoke could lead to an increased risk of cancer, lung disease, and heart disease, the mortality of 4546 firefighters who were employed by the cities of Seattle and Tacoma, WA and Portland, OR for at least one year between 1944 and 1979 were compared with United States national mortalities and with mortality of police officers from the same cities. Between 1945 and 1989, 1169 deaths occurred in the study population and 1162 death certificates (99%) were collected. Mortality due to all causes, ischaemic heart disease, and most other non-malignant diseases was less than expected based upon United States rates for white men. There was no excess risk of overall mortality from cancer but excesses of brain tumours (standardised mortality ratio (SMR) = 2.09, 95% confidence interval (95% CI) 1.3-3.2) and lymphatic and haematopoietic cancers (SMR = 1.31, 95% CI = 0.9-1.8) were found. Younger firefighters (< 40 years of age) appeared to have an excess risk of cancer (SMR = 1.45, 95% CI 0.8-2.39), primarily due to brain cancer (SMR = 3.75, 95% CI 1.2-8.7). The risk of lymphatic and haematopoietic cancers was greatest for men with at least 30 years of exposed employment (SMR = 2.05, 95% CI 1.1-3.6), especially for leukaemia (SMR = 2.60, 95% CI 1.0-5.4).

Background: There is growing evidence that many children are injured while engaged in agricultural work. However, little specific information on farm work-related injuries among minors is available, probably because employment or workers' compensation data for children are hard to obtain., Methods: Workers' compensation data were used to evaluate occupational injuries among children in Washington State from 1986 through 1989. The frequency and severity of injuries among minors doing farm work were compared with the distributions of injuries among minors working in food service and all other occupations by year of injury, age of injury, and month and hour of injury., Results: A total of 16,481 claims filed by children under age 18 were evaluated. Although farm workers accounted for only 7% of all claims, they made up 36% of claims filed by children under age 14, and 17% of claims filed by children aged 14 or 15. Injuries classified as serious accounted for 26% of farm worker claims compared with only 16% of all claims filed by children., Conclusions: Although injury rates could not be developed owing to the lack of denominator data, this study demonstrates that farm work is dangerous for young children.

Although firefighters have been shown in some studies to suffer chronic respiratory morbidity from their occupational exposures, an increased risk for dying from non-malignant respiratory diseases has not been documented in any previous retrospective cohort mortality study. In order to assess the possibility that an unusually strong "healthy worker effect" among firefighters might mask this increased risk, a mortality analysis of firefighters was carried out in three cities in relation to the United States population and also to a comparison cohort of police officers. The firefighters were employed between 1945 and 1980 and experienced 886 deaths by 1 January 1984; compared with the United States population they had a significantly reduced risk of dying from all causes (SMR = 82, 95% confidence interval, 77-87), and from non-malignant circulatory diseases (SMR = 81, 95% confidence interval 73-89), but no significant difference in risk of non-malignant respiratory diseases (SMR = 88, 95% confidence interval 66-117). Compared with police, the firefighters experienced a trend toward improved mortality outcomes for all causes investigated (SMR = 82), but they had an excess of deaths from non-malignant respiratory diseases (SMR = 141). The results indicate that firefighters are probably at increased risk for dying from non-malignant respiratory diseases; this increased risk may have been missed in previous studies because of the limitations of using a general reference population.

Although the diagnosis of work-related illness relies heavily on the occupational history, there is no validated or widely used questionnaire available to obtain this information. We designed an occupational health history questionnaire (OHHQ) in order to assess (1) its usefulness in obtaining exposure and work histories and (2) its ability to discriminate among workers with different degrees of hazardous exposure. A self-administered OHHQ was completed by 100 consecutive patients known to have a high probability of work-related disease (group 1) and by 55 consecutive workers at low risk for occupational toxic exposures (group 2). Group 1 was found to have a significantly higher number of self-assessed overall exposures (SAESs) than group 2 (p less than .001). Within group 1, scores of SAESs were highly correlated with an assessment by an industrial hygienist of the degree of hazardous exposure (p less than .001). The OHHQ can be feasibly self-administered; it has discriminant validity (correctly identifying groups of workers with high and low hazardous exposures) and convergent validity (correlating with an independent assessment of hazardous exposures).

To evaluate the etiologic role of asbestos exposure in B cell neoplasms, we compared the estimated level of occupational exposure to asbestos of cases with chronic lymphocytic leukemia (CLL; N = 429) and multiple myeloma (MM; N = 698) with that of controls (N = 1,683). Cases were identified through four population-based cancer registries in the U.S. and controls were randomly selected from the same geographic areas. Exposure to asbestos was assessed by classifying each job held by a subject into one of four categories, based on the estimated intensity of exposure to asbestos. Evidence was found for a modest increasing risk of CLL with increasing asbestos exposure. Relative to persons with no known occupational exposure to asbestos, the risk for CLL was 1.1 (95% confidence interval (CI) = 0.8-1.6) for low, 1.2 (CI = 0.8-1.8) for medium, and 1.4 (CI = 0.8-2.3) for high peak asbestos exposure (p value for trend = 0.13). The association was strongest in white study subjects and in those individuals exposed 10 to 19 years prior to the interview. No association was observed between MM and occupational exposure to asbestos in the entire study population or within specific subgroups. Given the pattern of immunologic abnormalities that occur with increased frequency in asbestos-exposed persons, our observation of an association between occupational asbestos exposure and CLL deserves attention in subsequent studies.

To clarify the clinical value of the International Labor Office (ILO) roentgenographic classification of pneumoconiosis in assessing asbestos-exposed persons, we determined the relationships among spirometric values, radiographic evidence of parenchymal pulmonary fibrosis and/or pleural thickening, and cigarette smoking history in 684 consecutively enrolled male plumbers and pipefitters participating in a larger cross-sectional prevalence study. The subjects were mainly marine pipefitters (35%), plumbers (24%), and steamfitters/welders (23%); 28% had never smoked, 39% were ex-smokers, and 33% currently smoked cigarettes. Mean values for FVC and FEV1 were 95.0 and 91.9% of predicted, respectively, with mean FEV1/FVC ratio 77.7%; by standard criteria, 7.8% had restrictive impairment, and 21.7%, obstructive defects. Chest radiographs were normal in 63% and showed pleural abnormalities only in 17%, parenchymal abnormalities only in 7%, and both pleural and parenchymal abnormalities in 12%. Both FVC and FEV1 correlated with the degree of small opacity profusion, as assessed by ILO grade. Pleural abnormalities were associated with lower FVC values, independently of ILO profusion grade for Grades less than or equal to 1/0, and were unexplained by smoking status. In addition, there was a positive association between smoking history and degree of ILO parenchymal abnormality, particularly in those with the heaviest cumulative smoking history. Our results suggest that the ILO classification of pneumoconiosis, although a useful epidemiologic tool, should be applied with caution in persons with asbestos exposure, and that pleural abnormalities may be associated with physiologic impairment in such persons.

We studied three patients with a progressive neurologic disorder, all of whom had worked for over 12 years in the same potroom of an aluminum smelting plant. All had incoordination and an intention tremor. Two of the three patients had cognitive deficits, and the most severely affected patient also had spastic paraparesis. None had involvement of the peripheral nervous system. Despite extensive evaluations, the cause of these patients' problems remains obscure. It is tempting to implicate one of the numerous substances to which the patients were exposed in the potroom, but none is known to cause the neurologic problems seen in these patients. Neurotoxic effects of aluminum in animals are directed at the central nervous system, and theoretically long-term low-level exposure to aluminum in the potroom could explain the findings in our patients.