Survey of the Asp f 1 allergen in office environments.

Sick Building Syndrome remains a prevalent problem with patient complaints similar to typical allergy symptoms. Unlike household allergens typically found in domestic reservoirs, the allergen from a common fungus like Aspergillus fumigatus (i.e., Asp f 1) is conceivably widespread in the work environment. This project surveyed airborne levels of the Asp f 1 allergen in office and non-industrial occupational environments, as well as the dust reservoirs of A. fumigatus believed to be responsible for those levels. Airborne and bulk dust samples were collected, extracted, and assayed for Asp f 1. Concurrently, bulk dusts collected from the same locations were selectively cultured for A. fumigatus, and mesophilic fungi and bacteria. Samples were collected during both wet and dry climatological conditions from paired wet and dry building locations to examine the possibility of Asp f 1 increases due to fungal growth blooms. Very low levels of Asp f 1 were detected but only in the airborne samples (2/120 positive samples, with 3.6 ng/m3 and 1.8 ng/m3; LOD < 1.2 ng/m3). No dust samples showed even detectable traces of the allergen (LOD = 5 ng/g dust). Although A. fumigatus counts from dusts fluctuated significantly with exterior moisture events, analysis of wet versus dry period samples showed no differences in Asp f 1 levels. These results indicate that even in the presence of measurable fungal concentrations, background levels of Asp f 1 are low. Nonindustrial office buildings devoid of indoor air quality issues were not observed to have significant levels of the Asp f 1 allergen in the geographical region studied.

Frequency of minisatellite repeat number changes at the MS205 locus in human sperm before and after cancer chemotherapy.

To determine whether the measurement of repeat number mutations at a minisatellite locus could detect human germline mutations induced by chemotherapy, we performed a longitudinal study of the mutation frequencies in sperm from 10 patients treated for Hodgkin's disease. Polymerase chain reaction on small pools of DNA equivalent to 100 sperm and Southern blotting were used to screen at least 7900 sperm in each sample to quantify the mutation frequency at the minisatellite MS205 locus. Pretreatment and posttreatment semen samples were obtained at least 2 months after completion of therapy from 4 patients treated with a regimen (Novantrone, Oncovin, vinblastine and prednisone [NOVP]) that lacks alkylating agents and from three patients treated with regimens (Cytoxan, vinblastine, procarbazine and prednisone/Adriamycin, bleomycin, dacarbazine, lomustine, and prednisone [CVPP/ABDIC] or mechlorethamine, Oncovin, procarbazine and prednisone [MOPP]) containing alkylating agents. There were no effects of NOVP or CVPP/ABDIC on the mutation frequencies. In the 1 patient treated with MOPP, the treatment with the highest dose of gonadotoxic alkylating agents, there was a statistically significant increase in mutation frequency from 0.79% pretreatment to 1.14% posttreatment, indicating induction of mutations in stem spermatogonia. During-treatment semen samples obtained from 2 patients treated with ABVD, which does not contain gonadotoxic alkylating agents, and 1 with NOVP also did not show any increases above the baseline mutation frequencies, indicating no increase in the minisatellite mutation frequency in spermatocytes. Thus, measurement of repeat number changes at minisatellite MS205 appears to be able to detect induced germline mutations in human sperm. However, most chemotherapy regimens do not significantly increase this class of mutations.

A comparison of methods for determining lead content in drinking water: a portable anodic stripping voltammetry instrument method versus the standard EPA 239.2 method.

Lead levels in drinking water were measured by the standard U.S. Environmental Protection Agency (EPA)-approved atomic absorption spectroscopy-graphite furnace Method 239.2 and compared with determinations made with a newly available portable anodic stripping voltammetry (PASV) instrument. A standard curve was prepared at 2, 5, 10, 15, 20, 25, and 30 microg/L of lead. PASV instrument readings were lower than standard EPA method values, with a mean difference and standard error (SE) of the mean between the two of 1.538+/-0.588 microg/L (n = 7, p = 0.040, significant at the 95% confidence interval [CI]). First-flush drinking water samples collected from 144 water fountains/coolers were preserved with nitric acid. Total lead content was tested twice for 29 EPA method samples and 54 PASV instrument samples to determine the variation within each method; results were not significant at the 95% CI. Total lead content was determined for 144 samples by both methods. PASV instrument readings were lower than standard EPA method values (mean difference and SE of the mean 0.630+/-0.206 microg/L; n = 144, p = 0.0027, significant at the 95% CI). Mean and standard deviation of the 144 samples for the EPA method and the PASV instrument were 6.5+/-11.8 microg/L and 5.9+/-11.6 microg/L, respectively. Means were below the action level for lead of 15 ppb (microg/L), but some values were above the action level (18 [13%] using the EPA method; 20 [14%] using the PASV instrument). Retesting by EPA method showed two false positive PASV values. Results indicate that in some field situations the PASV instrument may prove useful due to its relatively low price, small size, ease of use, and quick readings.

Determination of the vaporization of solutions of mutagenic antineoplastic agents at 23 and 37 degrees C using a desiccator technique.

This study evaluated the ability of mutagenic antineoplastic agents to vaporize at room temperature (23 degrees C) and 37 degrees C. A bacterial mutagenicity assay was used to determine the mutagenicity of these agents in the vapor phase. Open plates of bacteria were exposed to varying amounts of drug solutions in sealed glass containers for 24h. The drug solutions were prepared as they would be for patient treatment and were tested at 0.25, 0.5 and 1.0 ml of each drug solution per 10 l of air. Following exposure, the plates exposed at 23 degrees C were incubated an additional 48 h at 37 degrees C to allow for expression of mutations. Those exposed at 37 degrees C were incubated for an additional 24h at 37 degrees C. Carmustine, cyclophosphamide, ifosfamide, thiotepa, and mustargen demonstrated vaporization at 37 degrees C. Carmustine and mustargen also demonstrated significant vaporization at 23 degrees C, while cyclophosphamide demonstrated a 50% increase in revertants at this temperature. In addition, sodium azide, a known mutagen used as a control was also mutagenic as a vapor at both temperatures. Doxorubicin, cisplatin, etoposide, 5-fluorouracil and mitomycin were not detected as vaporizing in this assay. The study found that vaporization of standard solutions of some antineoplastic agents is possible at room temperature and increases as the temperature increases. Therefore, vaporization of spilled antineoplastic agents may present an additional route of exposure to healthcare workers through inhalation.

Permeability of nitrile rubber, latex, polyurethane, and neoprene gloves to 18 antineoplastic drugs.

The permeability of four glove materials to various antineoplastic drugs was studied. Eighteen antineoplastic drugs posing potential health hazards to handlers were prepared at the highest concentrations normally encountered by hospital personnel. Four glove materials-nitrile rubber, latex, polyurethane, and neoprene-were exposed to the drugs for 30, 60, 90, and 120 minutes. Glove thickness was measured with an electronic digital caliper. Random samples of material were selected from the glove fingertips, and triplicate samples were tested for each drug at each interval. For a majority of the drugs, a bacterial mutagenicity assay was used to measure the amount of drug (if any) that permeated the material. High-performance liquid chromatography was used for drugs not tested with the bacterial assay. The nitrile gloves were the thinnest (0.12 mm), and the latex gloves were the thickest (0.18 mm). The four materials were generally impermeable to each drug. One sample of the nitrile gloves appeared to have a defect, allowing >5% of the drug solution to pass through at 30 minutes. One sample each of the latex, polyurethane, and neoprene gloves demonstrated minimal permeability (< or =1%): One latex glove sample was permeated by carmustine, and paclitaxel permeated one sample each of the polyurethane and neoprene materials. Nitrile rubber, latex, polyurethane, and neoprene gloves were impermeable to 18 antineoplastic drugs in most, but not all, cases.

Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States.

The level of contamination by antineoplastic agents in drug preparation and administration areas in cancer treatment centers in Canada and the United States was determined. Sampling locations at three cancer treatment centers in Canada and three centers in the United States were selected (biological safety cabinets, countertops, and floors in and adjacent to preparation areas; tabletops, chairs, and floors in administration areas). A solution of sodium hydroxide (0.03 M) was spread over the surface of each area. The surface was wiped with one or two absorbent tissues, which were then stored in plastic screw-top containers. Samples were stored at -40 degrees C before analysis of ifosfamide content (U.S. centers only) and cyclophosphamide content by gas chromatography in tandem with mass spectroscopy-mass spectroscopy and fluorouracil content by reverse-phase high-performance liquid chromatography with ultraviolet-light detection. Measurable amounts of the antineoplastic agents were detected in 75% of the pharmacy samples and 65% of the administration samples. In general, the levels of contamination were higher in the pharmacy areas than in the drug administration areas. The pharmacy area at the site with the highest number of drug preparations had considerably more drug contamination than the other sites. The results were similar for Canadian and U.S. centers. Substantial levels of contamination from three antineoplastic agents were detected on a variety of surfaces in pharmacy drug preparation areas and drug administration areas in six cancer treatment centers in Canada and the United States.

Detection of ozone-induced DNA single strand breaks in murine bronchoalveolar lavage cells acutely exposed in vivo.

Single-strand breaks (SSBs) in DNA have been used a biomarker of oxidative damage. The comet assay, also known as single-cell gel electrophoresis, was used to investigate the ability of ozone (O(3)) to induce DNA SSBs in murine bronchoalveolar lavage (BAL) cells. The comet assay is more sensitive than other techniques currently utilized for detecting SSBs and requires fewer cells. In the present study, 3 mice were exposed for 3 h to 0.25 ppm of O(3), and 3 to 0.5 ppm of O(3) for 3 h. Two air-exposed mice served as negative controls. All mice were euthanized 3 h after exposure, at which time BAL cells were recovered from the lungs and stained with ethidium bromide. BAL cells recovered from an air-exposed mouse were exposed to various concentrations of H(2)O(2) in vitro for 1 h at 4 degrees C. Excluding cells from the H(2)O(2) group (n = 25), 50 randomly selected BAL cells were graded by comet tail length into 1 of 4 categories: no damage (0 mm), low damage (1-10 mm), medium damage (11-30 mm), and high damage (31 + mm). The nonparametric Wilcoxon rank-sum test was used for statistical analysis, and p values lower than .05 were considered significant. The H(2)O(2) and the 0.25 and 0.5 ppm O3 groups showed statistically significant increases in DNA SSBs as compared to air-exposed controls. The results of this study indicate that (1) O(3) induces DNA strand breaks in murine BAL cells at 0.25 and 0.5 ppm, as evidenced by statistically significant increases in the length of comet tails for O(3)-exposed groups, and (2) the comet assay can be used to assess O(3)-induced SSBs for in vivo exposures. Therefore, it has the potential as a biomarker for in vivo oxidant exposures.

An evaluation of the permeability of chemotherapy gloves to three cancer chemotherapy drugs.

PURPOSE/OBJECTIVES: To evaluate the permeability of chemotherapy gloves when using carmustine (BCNU), etoposide, and paclitaxel, which were selected based on their reported toxicity and unique solvent systems. SAMPLE: Thirteen brands of chemotherapy gloves and one brand of examination glove. Of the 14 glove types tested, 11 were made of latex, and 3 were made of nitrile. METHODS: Ten samples of each type of glove were evaluated using rigorous laboratory test conditions usually not encountered in normal usage. The thickness of the gloves was measured using a digital caliper. The glove material was secured over glass vials containing the drug solution and inverted in plastic cell wells containing a filter paper disc. After a two-hour exposure time, the filter paper discs were removed and analyzed for the presence of the drug. MAIN RESEARCH VARIABLES: Permeability (i.e., greater than or equal to 1% of the total amount of drug passing through the glove material.) FINDINGS: All 14 types of gloves tested were impermeable to BCNU at two hours of exposure. Only two gloves, the Ansell Perry EP glove and the U.S. Clinical Chemo Bloc T glove, were impermeable to all three drugs. The remaining 12 gloves all demonstrated some level of permeation with etoposide at two hours, although 9 of the gloves had only 1 of 10 samples that were permeable. In all cases, percent of permeation was less than 2% of the amount of the drug in the test solution. Thirteen gloves tested for paclitaxel permeability were impermeable at the two-hour time period. CONCLUSIONS: The results of this study indicate that most of the chemotherapy gloves on the market are either impermeable or minimally permeable to these three chemotherapy drugs. IMPLICATIONS FOR NURSING PRACTICE: Because gloves are universally recognized as a means of personal protection when handling cancer chemotherapy drugs, selection of a glove that is impermeable would be an obvious choice for healthcare workers. Although the present study was a static, laboratory-based study that did not duplicate actual work practice conditions. It should offer some guidance in the selection of glove types when handling chemotherapy drugs.

Monitoring occupational exposure to cancer chemotherapy drugs.

Reports of the health effects of handling cytotoxic drugs and compliance with guidelines for handling these agents are briefly reviewed, and studies using analytical and biological methods of detecting exposure are evaluated. There is little conclusive evidence of detrimental health effects from occupational exposure to cytotoxic drugs. Work practices have improved since the issuance of guidelines for handling these drugs, but compliance with the recommended practices is still inadequate. Of 64 reports published since 1979 on studies of workers' exposure to these drugs, 53 involved studies of changes in cellular or molecular endpoints (biological markers) and 12 described chemical analyses of drugs or their metabolites in urine (2 involved both, and 2 reported the same study). The primary biological markers used were urine mutagenicity, sister chromatid exchange, and chromosomal aberrations; other studies involved formation of micronuclei and measurements of urinary thioethers. The studies had small sample sizes, and the methods were qualitative, nonspecific, subject to many confounders, and possibly not sensitive enough to detect most occupational exposures. Since none of the currently available biological and analytical methods is sufficiently reliable or reproducible for routine monitoring of exposure in the workplace, further studies using these methods are not recommended; efforts should focus instead on wide-spread implementation of improved practices for handling cytotoxic drugs.

Survival of cells with bleomycin-induced chromosomal lesions in the cultured lymphocytes of lung cancer patients.

In a previous study of lung cancer, we showed that bleomycin, a radiomimetic agent, induced breaks preferentially on chromosomes 4 and 5. The molecular cytogenetic study reported here, using chromosome painting and G banding, was designed to assess whether the chromatid breaks induced by bleomycin could survive as chromosome-type aberrations after treated lymphocyte populations were allowed to recover in a drug-free medium for one or two cell generations and whether the survival rates of lesions on chromosomes 4 and 5 differed in cases with lung cancer and controls. The findings from 16 cases and 14 controls showed that in samples allowed to recover for 48 h, most aberrations were of the chromosome type. The proportion of chromosome 5 abnormalities surviving as chromosome-type aberrations was significantly higher in the cells of lung cancer cases (13.4%) than in controls (4.6%; P < 0.0001). However, no significant differences in survival of chromosome 4 abnormalities were detected between cases and controls. The proportions of chromosome 5q13-q22 abnormalities were 5.3% in the cases and 0.6% in the controls (P < 0.0001). 5q13-q22 regions encompassed 38.4% of all abnormalities on chromosome 5 in the cases but only 14.5% in the controls. Therefore, the survival rate of chromosome 5 lesions (especially those at 5q13-q22) in lymphocytes might be used as a biomarker to identify populations at high risk for lung cancer.

Mutagenicity of cosmetic products containing Kathon.

A variety of shampoos, conditioners, skin-care lotions, and other cosmetic products contain the biocide Kathon CG, which is a mixture of two heterocyclic isothiazolinones: methylisothiazolinone and methylchloroisothiazolinone. This mixture and the related biocide, Kathon 886, have been shown to be potent sensitizers and bacterial mutagens. Five cosmetic products that list the components of Kathon on their labels and two that do not were screened for mutagenicity with Salmonella typhimurium TA100 without S-9. Five of these products and Kathon 886 were further evaluated in TA100 without and with S-9. Kathon 886, a cosmetic product that contained Kathon, and thin layer chromatography-separated components of Kathon 886 were identified by GC/MS analysis. Three of the five products that listed Kathon were direct acting mutagens with TA100. The remaining two products were considerably more toxic than the other products and could not be evaluated for mutagenicity. The addition of S-9 reduced toxicity but did not eliminate mutagenicity. The mutagenic evaluation of Kathon 886 resulted in a dose response similar to that seen with some cosmetic products but at a 1,000-fold lower concentration, and activity was also reduced by the addition of S-9 mix. S-9 reduced activity both with and without cofactors present. Thin layer chromatography separation of the components and subsequent identification by GC/MS indicated that methylisothiazolinone was nonmutagenic while methylchloroisothiazolinone was mutagenic. Additionally, a dichlorinated compound was identified which was also mutagenic. In light of these findings and the reported skin sensitization by Kathon CG in various cosmetics, we recommend that additional testing be done to assure the safety of products containing Kathon CG.

Permeability testing of glove materials for use with cancer chemotherapy drugs.

The present study evaluated the effectiveness of several types of hospital gloves that are recommended by the manufacturers for handling chemotherapy drugs. Gloves were examined for permeability against five cancer chemotherapy drugs (doxorubicin, cyclophosphamide, 5-fluorouracil, carmustine, and cisplatin) at several time points up to 2 h using a bacterial mutation assay as the measure of permeation. Of the 5 types of gloves tested at a single thickness, 4 were completely impermeable to all drugs and the remaining 1 demonstrated only limited permeability. A latex examination glove used for comparison was permeable to carmustine. One glove material that was tested as a double thickness was impermeable to the 5 drugs. Results indicate that various types of gloves may offer protection against exposure to chemotherapy drugs for healthcare workers.

Degradation and inactivation of antitumor drugs.

Chemical methods for the degradation of 11 antineoplastic drugs [etoposide, teniposide, bleomycin, mitomycin C, cisplatin, cis-dichloro-trans-dihydroxy-bis(isopropylamine) platinum IV (CHIP), cyclophosphamide, ifosfamide, carmustine, lomustine, and methotrexate] were investigated. The success of the degradation procedures was assessed by HPLC and degree of biological inactivation by mutagenicity assays. The most widely applicable procedure was oxidation with potassium permanganate or 5.25% sodium hypochlorite solution (bleach). Oxidation completely degraded and inactivated etoposide, teniposide, bleomycin, mitomycin C, and methotrexate. In addition, oxidation followed by nucleophilic substitution resulted in the complete degradation and inactivation of cyclophosphamide and ifosfamide. Although carmustine and lomustine were chemically degraded by treatment with acidic potassium permanganate, the resulting reaction mixtures remained mutagenic. Therefore, this procedure cannot be recommended. The platinum-containing compounds, cisplatin and CHIP, were rendered nonmutagenic by reaction with sodium diethyldithiocarbamate. These easily performed, relatively safe procedures can be used to prevent exposure to mutagenic wastes and spills in the hospital setting.

Pentamidine isethionate is negative in tests for microbial mutagenicity and chromosomal breakage in vitro.

Pentamidine isethionate, a drug used for the treatment of Pneumocystis carinii pneumonia in AIDS patients, was assayed for mutagenicity in five strains of Salmonella typhimurium and for clastogenicity and mutagen-induced chromosomal breakage in five human lymphoblastoid cell lines. The mutagenicity assay employed both repair-deficient and repair-positive strains without and with the addition of rat liver S-9. There was no indication of a mutagenic response in any of the strains of Salmonella. Chromosomal breakage was measured in lymphoblastoid cell lines, both in the absence and presence of bleomycin. Following 2, 5 and 24 h of treatment, pentamidine alone did not induce clastogenicity, nor was there an increase in chromosomal breakage when the cell lines were treated with bleomycin simultaneously with, or 22 h prior to, the addition of pentamidine. From these data it can be concluded that pentamidine is not mutagenic or clastogenic in the two assays employed in this study.

Reduction of the mutagenicity of lead chromate-based pigments by encapsulation with silica.

13 lead chromate-based pigments were assayed for mutagenicity and toxicity using Salmonella typhimurium TA100. The compounds were assayed with and without S9, both in the presence and absence of the chelating agent, nitrilotriacetic acid (NTA). In general, the use of NTA to solubilize the compounds resulted in mutagenicity and/or toxicity being observed where it had not in the absence of NTA, or being observed at lower concentrations than when water alone was used. Encapsulation of pigments with amorphous silica rendered these pigments non-mutagenic and non-toxic, indicating that the active moieties were biologically unavailable to the bacteria. Varying the percentage of silica encapsulation on one pigment, medium chrome yellow, indicated that 5% encapsulation did not alter the mutagenicity while 10% encapsulation inhibited the mutagenicity without or with NTA.

Genotoxic effects of fly ash in bacteria, mammalian cells and animals.

The increasing use of fossil fuels has raised concerns about possible deleterious health effects of the final combustion product, fly ash. Seven ash samples from coal sources obtained from Battelle Columbus Laboratories were evaluated in the Salmonella/mammalian microsome mutagenicity assay to determine their mutagenic potential. While dimethyl sulfoxide extracts of five samples showed no mutagenicity, sample 102 caused an increase in the number of revertants per plate over controls in TA100 and TA98 with activation by liver homogenate (2-fold and 2.4-fold, respectively), and without (2-fold and 6-fold). This ash was thus evaluated in whole animal studies. Animals treated by inhalation or oral gavage were assayed for the presence of mutagens in the urine, micronuclei in polychromatic erythrocytes, and chromosomal aberrations in metaphase bone marrow cells. Those animals treated by inhalation were also examined for local damage in the lung. The assay for mutagens in the urine was negative as shown by the Ames assay with TA100 and TA98 and there was no increase in micronuclei or in metaphase aberrations. Histological sections from the animals treated by inhalation did not show the presence of particles, macrophage infiltrations and generalized lung damage. We tested the same fly ash with an in vitro cell transformation assay with the cell line Balb/c 3T3 subclone A31-1-13. Although there was not an increase in Type III foci, there was a dose-dependent increase of Type II foci in the treated cells over the controls. In one assay, there was approximately a 14-fold increase in Type II foci in the highest dose (2 mg/ml) compared to the solvent control. One other ash sample induced cell transformation without being markedly cytotoxic, while a third sample was highly toxic but did not induce transformation.

Aromatic amines and acetamides in Salmonella typhimurium TA98 and TA100: a quantitative structure-activity relation study.

The mutagenicity of a series of 19 aromatic amines had been previously measured in Salmonella typhimurium strains TA98 (frame-shift) and TA100 (base-pair) with the addition of S9 from Aroclor 1254-induced rat liver. A quantitative structure-activity relation (QSAR) study using multiple regression analysis points out the influence of three factors on mutagenicity: lipophilic character, position of the amine group, and whether it is free or acetylated, as expressed by log P and two indicator variables I1 and I2, respectively. The multiple regression equations explain 78 and 88% of the variance in log mutagenicity in TA98 and TA100, respectively. First of all, mutagenicity was shown to increase with lipophilicity. On the other hand, mutagenicity is reduced when the amine or acetamido position is ortho to the juncture because of steric hindrance in its biotransformation compared with a non-ortho isomer. It is decreased also by the acetylation of the amine group, probably because the acetyl group needs to be first split off prior to oxidation of the amine group to -NHOH.

Dinitrochlorobenzene is inherently mutagenic in the presence of trace mutagenic contaminants.

2,4-Dinitrochlorobenzene (DNCB) is used for immunotherapy of alopecia areata and verruca vulgaris. We initially postulated that the presence of mutagenic contaminants in commercially available DNCB might account for part of its mutagenicity. We have now characterized changes in the dose-mutagenic response curve of 99% DNCB modified by adding 1% concentrations of known contaminants: 1-chloro-2-nitrobenzene; 1,3-dinitrobenzene; and 2,4-dichloronitrobenzene. Dose-response curves were generated using Salmonella typhimurium tester strains TA-98 and TA-100 at concentrations of 0, 1, 5, 10, 25, 50, and 100 micrograms per plate in a modified Ames assay. We observed a linear dose-response relationship with a slight, but nonsignificant, shift to the right when contaminants were added. We conclude that DNCB is itself mutagenic, and that contaminants play a minor role in its observed mutagenicity.

The mutagenicity of urine fractions from patients administered antineoplastic therapy.

A concern among hospital personnel is their exposure to mutagenic drugs and in the incidental exposures that could occur in caring for the patients. In a recent published study the mutagenicity of urine from patients administered antineoplastic drugs was determined and techniques were developed to chemically inactivate the mutagenicity. A question still remained as to what components of the excreted urine were mutagenic. Urine samples from patients receiving mutagenic drugs were fractionated by high pressure liquid chromatography (HPLC) to then assay by the Ames test the collected and concentrated fractions to determine what were the mutagenic compounds in the urine. Urine samples from patients on single agent cancer treatment with cisplatin, cyclophosphamide, doxorubicin and mitomycin C were assayed. In general, all urine samples containing the cytotoxic agents studied were mutagenic because of the presence of the parent compound, except cyclophosphamide which requires activation and therefore an active metabolite was the major mutagenic constituent in the urine sample. This data indicates that the mutagenicity of urine from patients receiving these antineoplastic agents is the result of the parent compound or a single major metabolite.

Chromosomal aberrations in the cotton rat, Sigmodon hispidus, exposed to hazardous waste.

The study of chromosome damage in rodents living on hazardous-waste sites may provide evidence of important biological consequences of chronic exposure to toxic chemical wastes. This study compared bone-marrow cells of animals (Sigmodon hispidus) taken from two superfund waste-disposal sites with those from an uncontaminated site and demonstrated that both populations exposed to hazardous wastes had significantly more structural and numerical aberrations than the control population.