Development of the chemical exposure monitor with indoor positioning (CEMWIP) for workplace VOC surveys.

The purpose of this article was to research and develop a direct-reading exposure assessment method that combined a real-time location system with a wireless direct-reading personal chemical sensor. The personal chemical sensor was a photoionization device for detecting volatile organic compounds. The combined system was calibrated and tested against the same four standard gas concentrations and calibrated at one standard location and tested at four locations that included the standard locations. Data were wirelessly collected from the chemical sensor every 1.4 sec, for volatile organic compounds concentration, location, temperature, humidity, and time. Regression analysis of the photo-ionization device voltage response against calibration gases showed the chemical sensor had a limit of detection of 0.2 ppm. The real-time location system was accurate to 13 cm ± 6 cm (standard deviation) in an open area and to 57 cm ± 31 cm in a closed room where the radio frequency has to penetrate drywall-finished walls. The streaming data were collected and graphically displayed as a three-dimensional hazard map for assessment of peak exposure with location. A real-time personal exposure assessment device with indoor positioning was practical and provided new knowledge on direct reading exposure assessment methods.

Developmental toxicity interactions of methanol and radiofrequency radiation or 2-methoxyethanol in rats.

This research was undertaken to determine potential interactions among chemical and physical agents. Radiofrequency (RF) radiation is used in numerous workplaces, and many workers are concurrently exposed to RF radiation and various chemicals. The developmental toxicity of RF radiation is associated with the degree and duration of hyperthermia induced by the exposure. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), enhanced teratogenicity in rats. Interactions were noted at even the lowest levels of 2ME tested, but only at hyperthermic levels of RF radiation. The purpose of the present research is to investigate if the interactive effects noted for RF radiation and 2ME are unique to these agents, or if similar interactions might be seen with other chemicals. Because methanol is widely used as a solvent as well as fuel additive, and, at high levels, is teratogenic in animals, we selected methanol as a chemical to address generalizability. Based on the literature and our pilot studies, 0, 2, or 3 g/kg methanol (twice, at 6-hour intervals) were administered on gestation day 9 or 13 to groups of 10 Sprague-Dawley rats. Dams treated on day 9 were given methanol and exposed to RF radiation sufficient to maintain colonic temperature at 41 degrees C for 60 minutes (or sham). Those treated on day 13 were given methanol plus either 0 or 100 mg/kg 2ME. Because we observed that methanol produced hypothermia, some groups were given the initial dose of methanol concurrently with the RF or 2ME, and others were given the first dose of methanol 1.5 hours prior to RF or 2ME. Dams were sacrificed on gestation day 20, and the fetuses were examined for external malformations. The results indicate that RF radiation or methanol on day 9 increased the incidence of resorbed fetuses, but no interactive effects were observed. The resorptions were highest in groups given the experimental treatments 1.5 hours apart. The higher dose of methanol also reduced fetal weights. Administration of 2ME or methanol on day 13 increased the rate of malformations, and there was evidence of a positive interaction between 2ME and methanol. Fetal weights were reduced by 2ME and methanol alone, but no interaction was observed. Also, separation of the dosing with the teratogens did not affect the results. These results point out that interactions in developmental toxicology, such as those of RF radiation, 2ME, and methanol that we have studied, are complex, and such interactions cannot be fully understood or predicted without more research. It is important that combined exposure effects be considered when developing both physical agent and chemical agent exposure guidelines and intervention strategies.

Developmental toxicity interactions of salicylic acid and radiofrequency radiation or 2-methoxyethanol in rats.

Radiofrequency (RF) radiation is used in a variety of workplaces where workers are concurrently exposed to chemicals. Combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), produces enhanced teratogenicity in rats. The purpose of the present research was to determine if the synergistic effects noted for RF radiation and 2ME are generalizable to other chemicals. Since salicylic acid (SA) is widely used as an analgesic and is teratogenic in animals, SA was selected to address generalizability. Based on the literature and our pilot studies, 0, 250, or 350 mg/kg SA were administered by gavage on gestation Day 9 or 13 to rats. Concurrently rats given SA on Day 9 were exposed to RF radiation sufficient to maintain colonic temperature at 41 degrees C for 60 min (or sham). Those given SA on Day 13 were also given 0 or 100 mg/kg 2ME (gavage). Dams were sacrificed on gestation Day 20, and the fetuses were examined for external malformations. The data provide no evidence of synergistic interactions between RF radiation and salicylic acid (resorptions and malformations). Limited evidence of antagonism was observed between 2ME and salicylic acid (fetal weights). This investigation highlights the importance of additional research on interactions in developmental toxicology, and emphasizes the need to consider combined exposure effects when developing both physical agent and chemical agent exposure guidelines and intervention strategies.

Paternal exposure of rabbits to lead: behavioral deficits in offspring.

Paternal exposures to exogenous agents have been reported to produce a variety of developmental defects in the offspring. In experimental animals, these effects include decreased litter size and weight, increased stillbirth and neonatal death, birth defects, tumors, and functional/behavioral abnormalities-some of these effects being transmitted to the second and third generations. The majority of experimental studies assessing nervous system function of offspring following paternal exposures have utilized rats as the experimental animal, but other species can be used. The National Toxicology Program (NTP) has initiated studies to validate the rabbit as an animal model for human reproductive toxicity, because rabbits are the smallest laboratory animal from which ejaculates can be collected repeatedly. An important part of reproductive toxicology is assessment of the reproductive ability of males following exposure, as well as developmental and functional assessment of their offspring. This article describes a pilot study and a main study to investigate the feasibility of using rabbits to assess the functional effects of paternal exposure to lead. The pilot study included seven male rabbits per group exposed for 15 weeks to lead acetate sufficient to produce 0, 50, or 110 micrograms/dl blood lead. The main study included 15 male rabbits per group exposed for 15 weeks to lead acetate to produce 0, 20, 40, and 80 micrograms/dl blood lead. At the conclusion of the exposure, male rabbits were mated with unexposed females. These females carried their litters to term, delivered, and reared their own offspring. The offspring were weighed at 5, 10, 15, 20, 25, 30, and some at 35 days of age. They were also tested for exploratory activity in a standard figure-eight "maze" for 30 min/day on days 15, 20, 25, and 30. A second assessment of exploratory behavior, along with a simple test of aversive conditioning, was attempted in the pilot study, but was judged not to be suitable for the main study. Of the 21 male rabbits that were mated in the pilot study, 16 produced viable litters (6/7, 6/7, and 4/7 in control, low- and high-lead groups, respectively), with a mean number of 6 live births/litter in each treatment group (range 2-8). Of the 60 rabbits mated in the main study, 57 produced litters, and two rabbits died giving birth. Significant postnatal deaths were observed in all groups, with about one half of the offspring dying before testing was initiated at day 15. There were no treatment-related effects on offspring weight gain through wearing. The data suggest that paternal lead exposure of rabbits may reduce figure-eight activity on day 25, the time of peak activity in the offspring.

Interactions of radiofrequency radiation on 2-methoxyethanol teratogenicity in rats.

Concurrent exposures to chemical and physical agents occur in the workplace; exposed workers include those involved with microelectronics industry, plastic sealers and electrosurgical units. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to radiofrequency (r.f.; 10 MHz) radiation, which also induces hyperthermia and is teratogenic to exposed animals, and the industrial solvent 2-methoxyethanol (2ME) produces enhanced teratogenicity in rats. A subsequent study replicated and extended that research by investigating the interactive dose-related teratogenicity of r.f. radiation (sham exposure or maintaining colonic temperatures at 42.0 degrees C for 0, 10, 20 or 30 min by r.f. radiation absorption) and 2ME (0, 75, 100, 125 or 150 mg/kg) on gestation days 9 or 13 of rats. The purpose of the present research is to determine the effects of r.f. radiation (sufficient to maintain colonic temperatures at 42.0 degrees C for 10 min) on a range of doses of 2ME (0, 20, 40, 60, 80, 100, 120 and 140 mg kg-1) administered on gestation day 13 of rats. Focusing on characterizing the dose-response pattern of interactions, this research seeks to determine the lowest interactive effect level. Day 20 fetuses were examined for external and skeletal malformations. The results are consistent with previous observations. Dose-related developmental toxicity was observed for 2ME both in the presence and absence of r.f. radiation. However, concurrent RF radiation exposure changed the shape of the dose-effect curve of 2ME. These data indicate that combined exposure effects should be considered when developing exposure guidelines and intervention strategies.

Interactive developmental toxicity of radiofrequency radiation and 2-methoxyethanol in rats.

Concurrent exposures to chemical and physical agents occur in the workplace; exposed workers include those involved with the microelectronics industry, plastic sealers, and electrosurgical units. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to radiofrequency (RF; 10 MHz) radiation, which also induces hyperthermia and is teratogenic to exposed animals, and the industrial solvent, 2-methoxyethanol (2ME), produces enhanced teratogenicity in rats. The present study replicates and extends the previous research investigating the enhanced teratogenicity of combined RF radiation and 2ME exposures. The interactive dose-related teratogenicity of RF radiation (sham exposure or maintaining colonic temperatures at 42.0 degrees C for 0, 10, 20, or 30 min) and 2ME (0, 75, 100, 125, or 150 mg/kg) was investigated by administering various combinations of RF radiation and 2ME to groups of rats on gestation days 9 or 13; gestation-day 20 fetuses were examined for external, skeletal, and visceral malformations. The results are consistent with and extend our previous research findings. Synergism was observed between RF radiation and 2ME for some treatment combinations, but not for others. The study also clarified which gestational periods, RF radiation exposure durations, and 2ME doses would be most informative in future interaction studies to determine the lowest interactive effect level. Day 9 exposures generally evidenced little effect by 2ME, either by itself or in combination with RF radiation. In contrast, day 13 exposures resulted in highly significant effects from 2ME and RF radiation. The structures showing strong evidence of effects from both 2ME and RF radiation after exposure on gestation day 13 were the forepaw digits, forepaw phalanges, hindpaw digits, hindpaw phalanges, hind limbs, metacarpals, and metatarsals. Statistical analyses did not show a global synergistic effect, but did show evidence for a synergistic effect at intermediate levels of the dose ranges. Future research will address potential interactions at lower doses.

Marked increase in the teratogenicity of the combined administration of the industrial solvent 2-methoxyethanol and radiofrequency radiation in rats.

Limited published animal research reports synergistic teratogenic effects following combined hyperthermia (induced by elevated ambient temperature) and administration of chemical teratogens. Radiofrequency (RF) radiation is widely used in occupational environments. Since RF radiation also elevates the body temperature of, and is teratogenic to, exposed animals, concurrent RF radiation and chemical agent administration may enhance teratogenicity. The present exploratory study, consisting of preliminary dose-finding studies and the primary study, was designed to investigate whether concurrent exposure of rats to RF radiation and the industrial solvent 2-methoxyethanol (2ME) can enhance the developmental toxicity of either agent acting alone. Preliminary dose-finding studies using small numbers of rats investigated the ability of various RF radiation conditions and doses of 2ME to produce external malformations (primarily of the paws) when administered on gestation day 13. Based on these preliminary studies, RF radiation exposure [sufficient to elevate rectal temperature to 42.0 degrees C (4 degrees C above normal for rats) for 30 min] and 2ME administration (150 mg/kg) were selected for the primary study. In the primary study, groups of 18 to 27 pregnant rats were administered RF radiation exposure and distilled water gavage, 2ME gavage and sham RF exposure, RF radiation exposure and 2ME gavage concurrently, or sham RF exposure and distilled water gavage. Pregnant rats were sacrificed on gestation day 20, and the offspring were examined for external malformations. Combined exposures enhanced the adverse effects produced by either experimental agent alone (no malformations were detected in the double sham group). Mean fetal malformations/litter increased from 14% after 2ME and sham RF (15/26 litters affected, with an average of 2 fetuses/litter malformed) and 30% after RF radiation and water gavage (10/18 litters affected, with an average of 4 fetuses/litter malformed), to 76% after the combined treatment (18/18 litters affected, with an average of 12 fetuses/litter malformed). In addition to a significant increase in the frequency of malformations, the severity of malformations also was enhanced by the combination treatment (on a relative severity ranking scale, the 2ME severity score was less than 1, the RF score was 3, and the combination score was 6). This study provided evidence of synergism between RF radiation and 2ME administration, but additional research will be required to characterize the extent of synergism between these two agents. Potential interactive effects between chemical and physical agents need to be investigated to determine the extent to which such interactions should impact occupational exposure standards.

Automated surface area measurement of cultured cardiac myocytes.

An automated method for rapidly measuring surface area of individual cardiac myocytes was used as an index of myocyte growth. Hearts from 2- to 4-day-old rats were digested by overnight incubation in cold trypsin solution. Enriched suspensions of myocytes were plated at 2 x 10(5) cells/well in 12-well-culture plates. Cells were grown in M199 supplemented with 1%, 10% serum or 10% serum plus 10(-7) M norepinephrine. On days 1-4 after plating, cells were fixed in Bouin's Solution and stained with Weigert's Iron Hematoxylin and Biebrich Scarlet-Acid Fuchsin. An inverted microscope, video camera and monitor were coupled to a video image processor (Image Technology Corp.). The enhanced image of stained heart cells was digitized, and perimeter, length, width and area of each selected cell were calculated. One hundred randomly selected cells were measured in each of eight wells from each treatment-day group. Areas of individual myocytes varied widely in culture dishes and the distribution was skewed toward larger cells. The standard deviation increased in proportion to an increase in mean cell area. A logarithmic transformation of the data normalized the data and yielded a more homogeneous variance. The geometric mean area of heart cells supplemented with 1% serum increased only slightly, but significantly, during four days in culture. Geometric mean area of cells supplemented with 10% serum increased nearly four-fold. Supplementing cells with norepinephrine (10(-7) M) in addition to 10% serum did not induce a further increase in cell size. This technique has the potential to rapidly and objectively monitor heart cell growth following pharmacological or toxicological treatments.