Robert F. Herrick

Phthalate exposure and human semen parameters

Background. There is scientific and public concern about commonly used chemicals, including phthalates, that are associated with reproductive toxicity in laboratory animals and are hormonally active. People are exposed to phthalates through diet, consumer products and medical devices. The present study explored whether environmental levels of phthalates are associated with altered semen quality in humans. Methods. We recruited 168 men who were part of subfertile couples and who presented to the Massachusetts General Hospital andrology laboratory for semen analysis between January 2000 and April 2001. Semen parameters were dichotomized based on 1999 World Health Organization reference values for sperm concentration (<20 million/ml) and motility (<50% motile), as well as Tygerberg Strict criteria for morphology (<4% normal). The comparison group was men for whom these semen parameters were all above the reference values. In urine, eight phthalate metabolites were measured with high-performance liquid chromatography and tandem mass spectrometry. Specific gravity-adjusted phthalate metabolite levels were categorized into tertiles. Results. There was a dose-response relation between tertiles of mono-butyl phthalate and sperm motility (odds ratio per tertile = 1.0, 1.8, 3.0;P-value for trend = 0.02) and sperm concentration (1.0, 1.4, 3.3;P-value for trend = 0.07). In addition, there was a dose-response relation between tertiles of monobenzyl phthalate and sperm concentration (1.0, 1.4, 5.5;P-value for trend = 0.02). Conclusions. There were dose-response relations for mono-butyl phthalate and monobenzyl phthalate with one or more semen parameters, and suggestive evidence for monomethyl phthalate with sperm morphology. The lack of a relation for other phthalates may indicate a difference in spermatotoxicity among phthalates.

Characterization of Phthalate Exposure among Pregnant Women Assessed by Repeat Air and Urine Samples

Background Although urinary concentrations of phthalate metabolites are frequently used as biomarkers in epidemiologic studies, variability during pregnancy has not been characterized. Methods We measured phthalate metabolite concentrations in spot urine samples collected from 246 pregnant Dominican and African-American women. Twenty-eight women had repeat urine samples collected over a 6-week period. We also analyzed 48-hr personal air samples (n = 96 women) and repeated indoor air samples (n = 32 homes) for five phthalate diesters. Mixed-effects models were fit to evaluate reproducibility via intraclass correlation coefficients (ICC). We evaluated the sensitivity and specificity of using a single specimen versus repeat samples to classify a woman’s exposure in the low or high category. Results Phthalates were detected in 85–100% of air and urine samples. ICCs for the unadjusted urinary metabolite concentrations ranged from 0.30 for mono-ethyl phthalate to 0.66 for monobenzyl phthalate. For indoor air, ICCs ranged from 0.48 [di-2-ethylhexyl phthalate (DEHP)] to 0.83 [butylbenzyl phthalate (BBzP)]. Air levels of phthalate diesters correlated with their respective urinary metabolite concentrations for BBzP (r = 0.71), di-isobutyl phthalate (r = 0.44), and diethyl phthalate (DEP; r = 0.39). In women sampled late in pregnancy, specific gravity appeared to be more effective than creatinine in adjusting for urine dilution. Conclusions Urinary concentrations of DEP and DEHP metabolites in pregnant women showed lower reproducibility than metabolites for di-n-butyl phthalate and BBzP. A single indoor air sample may be sufficient to characterize phthalate exposure in the home, whereas urinary phthalate biomarkers should be sampled longitudinally during pregnancy to minimize exposure misclassification.

An Unrecognized Source of PCB Contamination in Schools and Other Buildings

An investigation of 24 buildings in the Greater Boston Area revealed that one-third (8 of 24) contained caulking materials with polychlorinated biphenyl (PCB) content exceeding 50 ppm by weight, which is the U.S. Environmental Protection Agency (U.S. EPA) specified limit above which this material is considered to be PCB bulk product waste. These buildings included schools and other public buildings. In a university building where similar levels of PCB were found in caulking material, PCB levels in indoor air ranged from 111 to 393 ng/m3; and in dust taken from the building ventilation system, < 1 ppm to 81 ppm. In this building, the U.S. EPA mandated requirements for the removal and disposal of the PCB bulk product waste as well as for confirmatory sampling to ensure that the interior and exterior of the building were decontaminated. Although U.S. EPA regulations under the Toxic Substances Control Act stipulate procedures by which PCB-contaminated materials must be handled and disposed, the regulations apparently do not require that materials such as caulking be tested to determine its PCB content. This limited investigation strongly suggests that were this testing done, many buildings would be found to contain high levels of PCBs in the building materials and potentially in the building environment. The presence of PCBs in schools is of particular concern given evidence suggesting that PCBs are developmental toxins.

Mortality From Lymphohematopoietic Malignancies and Brain Cancer Among Embalmers Exposed to Formaldehyde

BACKGROUND Excess mortality from lymphohematopoietic malignancies, in particular myeloid leukemia, and brain cancer has been found in surveys of anatomists, pathologists, and funeral industry workers, all of whom may have worked with formaldehyde. We investigated the relation of mortality to work practices and formaldehyde exposure levels among these professionals to address cancer risk in the funeral industry. METHODS Professionals employed in the funeral industry who died between January 1, 1960, and January 1, 1986, from lymphohematopoietic malignancies (n = 168) or brain tumors (n = 48) (ie, case subjects) were compared with deceased matched control subjects (n = 265) with regard to lifetime work practices and exposures in the funeral industry, which were obtained by interviews with next of kin and coworkers, and to estimated levels of formaldehyde exposure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by use of logistic regression. All statistical tests were two-sided. RESULTS Mortality from myeloid leukemia increased statistically significantly with increasing number of years of embalming (P for trend = .020) and with increasing peak formaldehyde exposure (P for trend = .036). Compared with subjects who performed fewer than 500 lifetime embalmings, mortality from myeloid leukemia was elevated among those who performed embalmings for more than 34 years (OR = 3.9, 95% CI = 1.2 to 12.5, P = .024), who performed more than 3068 embalmings (OR = 3.0, 95% CI = 1.0 to 9.2, P = .057), and those whose estimated cumulative formaldehyde exposure exceeded 9253 parts per million-hours (OR = 3.1; 95% CI = 1.0 to 9.6, P = .047). These exposures were not related to other lymphohematopoietic malignancies or to brain cancer. CONCLUSION Duration of embalming practice and related formaldehyde exposures in the funeral industry were associated with statistically significantly increased risk for mortality from myeloid leukemia.

The Relationship of Urinary Metabolites of Carbaryl/Naphthalene and Chlorpyrifos with Human Semen Quality

Most of the general population is exposed to carbaryl and other contemporary-use insecticides at low levels. Studies of laboratory animals, in addition to limited human data, show an association between carbaryl exposure and decreased semen quality. In the present study we explored whether environmental exposures to 1-naphthol (1N), a metabolite of carbaryl and naphthalene, and 3,5,6-trichloro-2-pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, are associated with decreased semen quality in humans. Subjects (n = 272) were recruited through a Massachusetts infertility clinic. Individual exposures were measured as spot urinary concentrations of 1N and TCPY adjusted using specific gravity. Semen quality was assessed as sperm concentration, percent motile sperm, and percent sperm with normal morphology, along with sperm motion parameters (straight-line velocity, curvilinear velocity, and linearity). Median TCPY and 1N concentrations were 3.22 and 3.19 μg/L, respectively. For increasing 1N tertiles, adjusted odds ratios (ORs) were significantly elevated for below-reference sperm concentration (OR for low, medium, and high tertiles = 1.0, 4.2, 4.2, respectively; p-value for trend = 0.01) and percent motile sperm (1.0, 2.5, 2.4; p-value for trend = 0.01). The sperm motion parameter most strongly associated with 1N was straight-line velocity. There were suggestive, borderline-significant associations for TCPY with sperm concentration and motility, whereas sperm morphology was weakly and nonsignificantly associated with both TCPY and 1N. The observed associations between altered semen quality and 1N are consistent with previous studies of carbaryl exposure, although suggestive associations with TCPY are difficult to interpret because human and animal data are currently limited.

Maternal Urinary Metabolites of Di-(2-Ethylhexyl) Phthalate in Relation to the Timing of Labor in a US Multicenter Pregnancy Cohort Study

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in consumer and medical products that can cross the placenta, disrupt steroid hormone synthesis, and activate peroxisome proliferator-activated receptor gamma. The authors examined DEHP exposure in relation to the timing of labor in a pregnancy cohort study of 283 women recruited in 4 US states (California, Iowa, Minnesota, and Missouri) between 2000 and 2004. The authors estimated associations between concentrations of DEHP metabolites and gestational age at delivery using linear regression models and associations between DEHP metabolites and clinical outcomes using logistic regression models. After covariate adjustment, women at the 75th percentile of DEHP metabolite concentrations had a 2-day-longer mean length of gestation than women at the 25th percentile (95% confidence interval: 1.4, 3.3). Log-unit increases in mono-2-ethylhexyl phthalate and mono-2-ethyl-5-oxohexyl phthalate concentrations were associated with increased odds of cesarean section delivery (30% and 50% increased odds, respectively), increased odds of delivering at 41 weeks or later (100% and 120% increased odds), and reduced odds of preterm delivery (50% and 60% decreased odds). These data suggest that DEHP may interfere with signaling related to the timing of parturition.

Temporal variability of urinary levels of nonpersistent insecticides in adult men

Widespread application of contemporary-use insecticides results in low-level exposure for a majority of the population through a variety of pathways. Urinary insecticide biomarkers account for all exposure pathways, but failure to account for temporal within-subject variability of urinary levels can lead to exposure misclassification. To examine temporal variability in urinary markers of contemporary-use insecticides, nine repeated urine samples were collected over 3 months from 10 men participating in an ongoing study of male reproductive health. These 90 samples were analyzed for urinary metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPY)) and carbaryl (1-naphthol (1N)). Volume- based (unadjusted), as well as creatinine (CRE)- and specific gravity (SG)-adjusted concentrations were measured. TCPY had low reliability with an intraclass correlation coefficient between 0.15 and 0.21, while 1N was moderately reliable with an intraclass correlation coefficient between 0.55 and 0.61. When the 10 men were divided into tertiles based on 3-month geometric mean TCPY and 1N levels, a single urine sample performed adequately in classifying a subject into the highest or lowest exposure tertiles. Sensitivity and specificity ranged from 0.44 to 0.84 for TCPY and from 0.56 to 0.89 for 1N. Some differences in the results between unadjusted metabolite concentrations and concentrations adjusted for CRE and SG were observed. Questionnaires were used to assess diet in the 24 h preceding the collection of each urine sample. In mixed-effects models, TCPY was significantly associated with season as well as with consuming grapes and cheese, while 1N levels were associated with consuming strawberries. In conclusion, although a single sample adequately predicted longer-term average exposure, a second sample collected at least 1 month following the first sample would reduce exposure measurement error.

PM2.5 metal exposures and nocturnal heart rate variability: a panel study of boilermaker construction workers.

BackgroundTo better understand the mechanism(s) of particulate matter (PM) associated cardiovascular effects, research priorities include identifying the responsible PM characteristics. Evidence suggests that metals play a role in the cardiotoxicity of fine PM (PM2.5) and in exposure-related decreases in heart rate variability (HRV). We examined the association between daytime exposure to the metal content of PM2.5 and night HRV in a panel study of boilermaker construction workers exposed to metal-rich welding fumes.MethodsTwenty-six male workers were monitored by ambulatory electrocardiogram (ECG) on a workday while exposed to welding fume and a non-workday (baseline). From the ECG, rMSSD (square root of the mean squared differences of successive intervals) was summarized over the night (0:00–7:00). Workday, gravimetric PM2.5 samples were analyzed by x-ray fluorescence to determine metal content. We used linear mixed effects models to assess the associations between night rMSSD and PM2.5 metal exposures both with and without adjustment for total PM2.5. Matched ECG measurements from the non-workday were used to control for individual cardiac risk factors and models were also adjusted for smoking status. To address collinearity between PM2.5 and metal content, we used a two-step approach that treated the residuals from linear regression models of each metal on PM2.5 as surrogates for the differential effects of metal exposures in models for night rMSSD.ResultsThe median PM2.5 exposure was 650 μg/m3; median metal exposures for iron, manganese, aluminum, copper, zinc, chromium, lead, and nickel ranged from 226 μg/m3 to non-detectable. We found inverse linear associations in exposure-response models with increased metal exposures associated with decreased night rMSSD. A statistically significant association for manganese was observed, with a decline of 0.130 msec (95% CI: -0.162, -0.098) in night rMSSD for every 1 μg/m3 increase in manganese. However, even after adjusting for individual metals, increases in total PM2.5 exposures were associated with declines in night rMSSD.ConclusionThese results support the cardiotoxicity of PM2.5 metal exposures, specifically manganese. However the metal component alone did not account for the observed declines in night HRV. Therefore, results suggest the importance of other PM elemental components.

A case-crossover study of transient risk factors for occupational acute hand injury

Background: Workers with acute hand injuries account for over 1 000 000 emergency department visits annually in the United States. Aims: To determine potential transient risk factors for occupational acute hand injury. Methods: Subjects were recruited from 23 occupational health clinics in five northeastern states in the USA. In a telephone interview, subjects were asked to report the occurrence of seven potential risk factors within a 90-minute time period before an acute hand injury. Each case also provided control information on exposures during the month before the injury. The self-matched feature of the study design controlled for stable between-person confounders. Results: A total of 1166 subjects were interviewed (891 men, 275 women), with a mean age (SD) of 37.2 years (11.4). The median time interval between injury and interview was 1.3 days. Sixty three per cent of subjects had a laceration. The relative risk of a hand injury was increased when working with equipment, tools, or work pieces not performing as expected (11.0, 95% CI 9.4 to 12.8), or when using a different work method to do a task (10.5, 95% CI 8.7 to 12.7). Other transient factors in decreasing order of relative risk were doing an unusual task, being distracted, and being rushed. Wearing gloves reduced the relative risk by 60% (0.4, 95% CI 0.3 to 0.5). Occupational category, job experience, and safety training were found to alter several of these effects. Conclusion: The results suggest the importance of these transient, potentially modifiable factors in the aetiology of acute hand injury at work. Attempts to modify these exposures by various strategies may reduce the incidence of acute hand injury at work.

Acute traumatic occupational hand injuries: type, location, and severity.

The National Electronic Injury Surveillance System reports that the fingers and hand are the most frequent body parts injured at work and treated in hospital emergency departments. In this study, we describe the type, location, and severity of occupational hand injuries among 1166 patients recruited from 23 occupational health clinics in five New England states. Subjects ranged in age from 18 to 77 years, with a mean of 37.2 years (SD, 11.4), and approximately 75% were men. In decreasing order of frequency, subjects were employed in machine trades, service work, structural work, and less frequently, in benchwork, professional, technical managerial and clerical, and sales work. The majority of subjects (83.4%) had a single type of injury: 62.6% were lacerations, 13.1% were crush injuries, 8.0% were avulsions, and 6.1% were punctures. Metal items, such as nails, metal stock, and burrs accounted for 38.4% of the injuries, followed by hand tools with blades and powered machinery (24.4% and 12.3%, respectively). Hand tools with blades were least likely to result in multiple types of injuries, whereas powered machines or nonpowered hand tools were more likely to result in multiple types of injuries than other injury sources. The generalizability of these results should be limited to clinic-based patients employed in similar occupations. The results of this study may suggest possible prevention strategies for acute traumatic hand injuries.