Health effects of mycotoxins in indoor air: a critical review.

Industrial hygienists (IHs) are called upon to investigate exposures to mold in indoor environments, both residential and commercial. Because exposure standards for molds or mycotoxins do not exist, it is important for the industrial hygienist to have a broad knowledge of the potential for exposure and health effects associated with mold in the indoor environment. This review focuses on the toxic effects of molds associated with the production of mycotoxins, and the putative association between health effects due to mycotoxin exposure in the indoor environment. This article contains background information on molds and mycotoxins, and a brief summary and review of animal exposure studies, case reports, and epidemiological studies from the primary literature concerning inhalation of mycotoxins or potentially toxin-producing molds. The relevance of the findings in the reviewed articles to exposures to mold in indoor, non-agricultural environments is discussed. Although evidence was found of a relationship between high levels of inhalation exposure or direct contact to mycotoxin-containing molds or mycotoxins, and demonstrable effects in animals and health effects in humans, the current literature does not provide compelling evidence that exposure at levels expected in most mold-contaminated indoor environments is likely to result in measurable health effects. Even though there is general agreement that active mold growth in indoor environments is unsanitary and must be corrected, the point at which mold contamination becomes a threat to health is unknown. Research and systematic field investigation are needed to provide an understanding of the health implications of mycotoxin exposures in indoor environments.

Chemical components of shredded paper insulation: a preliminary study.

We conducted an evaluation of shredded paper insulation to identify potentially toxic components. The study was to provide a preliminary characterization of a few samples of insulation currently in use. The following samples were analyzed: previously produced insulation (PPI) containing fire retardants, shredded recycled paper (PPI feedstock), freshly produced insulation (FPI), and insulation which had been installed in a residence (II). Volatile constituents were analyzed by GC-MS from headspace air of samples held at room temperature or heated to 90 degrees C. Extractable constituents were sampled by extracting with methylene chloride, and analyzing by GC-MS. Formaldehyde analysis was done according to EPA Method TO11. Headspace air at room temperature contained no detectable quantities of volatile constituents for any sample measured. In headspace air at 90 degrees C, only PPI contained traces of aliphatic and aromatic hydrocarbons and higher aldehydes, and FPI traces of toluene. Extracts of PPI contained traces of octadecadienoic acid methyl ester and aliphatic and aromatic hydrocarbons and higher aldehydes. Extracts of PPI feedstock contained traces of a substituted cyclohexenecarboxylic acid. FPI contained extractable diethyl phthalate (30-50 micrograms/g). Extracts of II contained traces of methyl palmitate, an octadecenoic acid methyl ester, and a phthalate plasticizer. No formaldehyde was detected. PPI was composed of approximately 98 percent paper fiber and 2 percent pre-gelatinized starch. PPI samples agglomerated together with less than 0.01 percent separating from clumps as fine dust. Boron and sodium were expected and confirmed because they were added to PPI and FPI as fire retardants. Chromium, copper, iron, potassium, magnesium, manganese, phosphorus, and silicon were present at detectable concentrations. Study calculations indicate that an occupant would have to completely consume all the fine particles produced from 3.3 kg of insulation per day to have an intake of boron equivalent to the EPA RfD. No other constituent appeared to be present even close to toxicologically relevant amounts.

Factors affecting the placental transfer of actinides.

The primary goal of this paper is to consider factors that affect the availability and transport of actinides from maternal blood, through the placenta, to the conceptus. These factors, of particular importance in scaling results from animals to man, include the route and temporal pattern of administration, the mass and physicochemical state of material administered, metabolism of the pregnant animal and fetal organs or tissue, and species-specific changes in placental structure relative to stage of gestation at exposure. Preliminary concepts for descriptive and kinetic models are proposed to integrate these results, to identify additional information required for developing more comprehensive models, and to provide a basis for scaling to human pregnancies for purposes of radiation dosimetry.

The influence of maternal cadmium exposure or fetal cadmium injection on hepatic metallothionein concentrations in the fetal rat.

The ability of Cd to induce the synthesis of fetal hepatic metallothionein (MT) was investigated in rat fetuses exposed to Cd throughout gestation via the mother's drinking water or injected directly with Cd through the uterine wall on Day 18 of gestation. On Day 21 all dams were killed and fetal and maternal tissues were removed. Tissue MT, Zn, Cu, and Cd concentrations were measured. Fetal hepatic Cd concentration was increased only at the high maternal Cd exposure, whereas Zn concentration was significantly reduced by Cd exposure. Both fetal liver and kidney MT were reduced following maternal Cd exposure. Unlike maternal hepatic MT, fetal hepatic MT was not increased after maternal Cd exposure nor did the direct injection of Cd into the 18 days of gestation fetus induce fetal MT synthesis. These data suggest that fetal rat liver is incapable of synthesizing MT in response to Cd, possibly because Cd is not transported to the site of MT synthesis in the fetal system. Furthermore, neither the route of exposure, the duration of prenatal Cd exposure, nor the stage of gestation appear to account for the differences observed between fetal and adult hepatic MT induction by Cd.

Availability of toxic trace metals to the conceptus.

Energy production releases numerous toxic metals into the environment. Among those metals which have been shown to be toxic to the conceptus are cadmium, lead, mercury, plutonium and vanadium. This paper reviews the results from the authors' studies of pregnant rats exposed to these metals by parenteral administration, inhalation or gastric intubation. In addition, direct measurements were made of maternal blood flow and clearance of metals across the guinea pig placenta to serve as conceptual examples of factors which regulate the effects of the metals on the fetus. Discussion includes the influence of route of maternal exposure and subsequent absorption, gestational age at exposure, metal behavior in the maternal bloodstream, movement of metals across the placenta, and distribution of metals in the products of conception.

Fetal distribution of mercury following introduction of methylmercury into porcine maternal circulation.

Tissue samples were obtained from 115 swine fetuses from 10 litters and analyzed for tissue-bound Hg 24 h after mothers were exposed to low levels of methylmercury by iv injection. Absorption of Hg by the fetus and placenta increased throughout gestation in concert with increasing fetal weight, as did fetal hepatic Hg. Fetal renal Hg increased throughout gestation, but the increase appeared to be much greater than would be expected on the basis of weight increase alone. Blood Hg concentrations did not change significantly. Fetal brain Hg content and concentration increased dramatically toward the end of pregnancy, the gestational period during which the rate of brain growth is greatest in swine. The finding that a period of increased Hg concentration in brain corresponded with the period of maximal brain growth velocity is particularly interesting because of the hypothesis that the brain is especially sensitive to nutritional and, presumably, toxicological perturbation while it is growing most rapidly.

The influence of zinc on the ontogeny of hepatic metallothionein in the fetal rat.

The ontogeny of hepatic metallothioneins (Mt) in fetal tissue as related to dietary and hepatic Zn was investigated. Sixty 6-month-old female rats were divided into two groups and given either double-distilled water or water containing 700 mug of Zn per milliliter. Dams from each group were killed on 16, 19, or 21 days of gestation, and maternal and fetal livers were removed. Mt content of the tissue was estimated by Piotrowski's Hg-saturation method. Results established the presence of an endogenous hepatic Mt in the fetal rat as early as 16 days of gestation. We further demonstrated a marked progressive increase in fetal Mt from Day 16 through gestation accompanied by a decrease in maternal hepatic Mt. It is suggested that Zn increased fetal Mt by inducing fetal synthesis, redistributing fetal Mt, or increasing Mt transport to the fetus, because both fetal and maternal hepatic Mt were increased. Fetal hepatic Mt concentration was several times greater than maternal Mt at corresponding stages of gestation. Mt may serve to either ensure adequate storage of Zn or Cu for fetal development or protect the fetus against metal toxicity, but the significance of these high endogenous levels of fetal Mt are not clear at this time.

Plutonium movements across the haemochorial placenta of the guinea pig.

In order to measure transplacental movements of plutonium without the complications of fetal accumulation, the fetal circulation of the guinea pig placenta (at 59 to 61 days of gestation) was perfused in situ. Dams were administered trace quantities of tritiated water (to indicate changes in maternal blood flow to the placenta) and 30 mu Ci/kg (i.e., approximately 500 micrograms/kg) of citrated 239Pu by intravenous injection. Plutonium-239 doses were large, approaching the LD50/30 (20 to 80 mu Ci/kg) for other species. Perfusion pressure, maternal cardiac rate, electrocardiogram, blood pressure, and respiratory rate were monitored continuously during each perfusion. Our measurements show that the clearance of plutonium from mother to fetus is small--2.5 +/- 0.5 microliter/min--an amount that is less than 20 per cent of the clearance of inorganic mercury. The indirect measurements of maternal blood flow to the placenta indicate that placental blood flow is greatly diminished in dams dosed with plutonium, which may partially account for the low clearance of plutonium.

Absorption of methylmercury by the fetal guinea pig during mid to late gestation.

Pregnant guinea pigs were injected with approximately 1 microgram/kg of CH3 203HgCl at 22,40,47,59,and 66 days of gestation, and fetal tissues were obtained 24 hours later. Autologous fetal erythrocytes were labeled with 51Cr and used to label the fetal blood pool at each gestational age except 22 days so that tissue-bound Hg could be calculated. In general, Hg absorbed by the whole fetus increased during gestation, in parallel with increasing tissue mass, while Hg found in whole placentas remained the same. Hg concentrations in the whole fetus and placenta were closely correlated, as were Hg concentrations in brain, liver, and kidney. Liver, kidney, blood, and brain contained the highest Hg concentration early in gestation. While it is difficult to interpret the potential effects of the increased Hg concentrations, particular attention should be paid to the brain, since it is considered a target tissue in MeHg toxicity.

A proposed mechanism(s) of transitory ischemic injury to myocardium.

The main objective of this study was to produce primary acute ischemic injury to myocardium in a live animal. In vitro, guinea pig platelets were sensitive to perturbation and aggregation by a suspension of ultrafine fibrillary collagen material isolated from the aorta of an aged burro (Equus asinus). The platelets responded to the stimulatory action of this material down to 100 to 200 ng (dry weight) added to 0.45 ml of platelet-rich plasma, as determined by aggregometric technique. Aortic fibrillary collagen material injected IV into guinea pigs (350 to 1900 microgram protein/kg of weight) produced a transitory disappearance of virtually all circulating platelets within 5 minutes. In animals in which blood samples were taken 2.5 hours after injection, 50 to 75% of the average base-line platelets in the circulation of controls returned to the circulation. In other experiments, 3 anesthetized animals were injected by jugular vein with an amount of active fibrillary collagen material (300 microgram as protein/kg of animal weight) estimated to produce reversible platelet aggregation in vivo. Two control animals were injected with the same dose of the material that had been inactivated (15 minutes at 100 C) to abolish platelet aggregation. Treated and control animals were maintained under general anesthesia for 2.5 hours. Intraventricular pressures and electrocardiographs (ECG) were monitored continuously for the first 30 minutes. The injection of the active fibrillary collagen material caused a large ventricular pressure elevation (170/10, 180/10, and 150/10 mm of Hg) in approximately 40 s. Preinfusion ventricular pressures in the 3 animals were 65/0, 85/5, and 88/0 mm of Hg, respectively. Within 60 s, there was a reduction in the absolute platelet number in the peripheral circulation. The elevation of ventricular pressure persisted for approximately 5 minutes and was followed within 30 minutes by a set of ECG events suggestive of acute myocardial ischemic injury, which included premature ventricular contractions, transient S-T segment depression concurrent with ventricular hypertension, and S-T segment elevation with reversed tall upright T-waves in association with a decrease to the preinfusion ventricular base line. Other ECG changes included prolongation of the P-R segment, missed ventricular contractions, and arrhythmia. The ECG changes seemed to be subsequent to platelet microthrombus formation in the pulmonary arterial microcirculation. By 2.5 hours after the treatment, platelets "rebounded" into the circulation in 2 surviving guinea pigs, and left ventricular pressures and ECG profiles returned to the preinfusion base lines. Guinea pigs IV infused with similar amounts of inactivated (15 minutes at 100 C) fibrillary collagen material did not show changes.