Initial Observation of Factors Interfering with the Treatment of Alveolar Osteitis Using Hyaluronic Acid with Octenidine-A Series of Case Reports.

Alveolar osteitis (AO) is a common complication following the extraction of the teeth, particularly the lower third molars. It starts within a few days after the extraction and manifests mainly as pain in the extraction site. Several strategies of treatment are available in order to relieve pain and heal the extraction wound. Recently, a novel medical device combining hyaluronic acid (HA) and octenidine (OCT) was introduced for the treatment of AO. This series of case reports aims to summarize the initial clinical experiences with this new device and to highlight factors possibly interfering with this treatment. The medical documentation of five patients with similar initial situations treated for AO with HA + OCT device was analyzed in detail. Smoking and previous treatment with Alveogyl (Septodont, Saint-Maur-des-Fossés, France) were identified as factors interfering with the AO treatment with the HA + OCT device. In three patients without these risk factors, the treatment led to recovery within two or three days. The patient pretreated with Alveogyl and the smoker required six and seven applications of the HA + OCT device, respectively. According to these initial observations, it seems smoking and previous treatment with Alveogyl prolong the treatment of AO using the HA + OCT device that, in turn, shows a rapid effect if these risk factors are not present.

Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer.

OBJECTIVES: Exposure to high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) may cause cancer in chimney sweeps and creosote-exposed workers, however, knowledge about exposure to low-molecular-weight PAHs in relation to cancer risk is limited. In this study, we aimed to investigate occupational exposure to the low-molecular-weight PAHs phenanthrene and fluorene in relation to different cancer biomarkers. METHODS: We recruited 151 chimney sweeps, 19 creosote-exposed workers and 152 unexposed workers (controls), all men. We measured monohydroxylated metabolites of phenanthrene and fluorene in urine using liquid chromatography coupled to tandem mass spectrometry. We measured, in peripheral blood, the cancer biomarkers telomere length and mitochondrial DNA copy number using quantitative PCR; and DNA methylation of F2RL3 and AHRR using pyrosequencing. RESULTS: Median PAH metabolite concentrations were higher among chimney sweeps (up to 3 times) and creosote-exposed workers (up to 353 times), compared with controls (p<0.001; adjusted for age and smoking). ∑OH-fluorene (sum of 2-hydroxyfluorene and 3-hydroxyfluorene) showed inverse associations with percentage DNA methylation of F2RL3 and AHRR in chimney sweeps (B (95% CI)=-2.7 (-3.9 to -1.5) for F2RL3_cg03636183, and -7.1 (-9.6 to -4.7) for AHRR_cg05575921: adjusted for age and smoking), but not in creosote-exposed workers. In addition, ∑OH-fluorene showed a 42% mediation effect on the inverse association between being a chimney sweep and DNA methylation of AHRR CpG2. CONCLUSIONS: Chimney sweeps and creosote-exposed workers were occupationally exposed to low-molecular-weight PAHs. Increasing fluorene exposure, among chimney sweeps, was associated with lower DNA methylation of F2RL3 and AHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.

Suitability of several naphthalene metabolites for their application in biomonitoring studies.

Naphthalene occurs together with polycyclic aromatic hydrocarbons (PAHs) at industrial workplaces and is ubiquitous in the environment. For biological monitoring of naphthalene exposures, up to now mainly 1- and 2-naphthol in urine have been used. Recently, we proposed 1,2-dihydroxynaphthalene (1,2-DHN) and the 1- and 2-naphthylmercapturic acid (1- and 2-NMA) as new urinary biomarkers to characterise a naphthalene exposure. In this study, in a collective of nine occupationally exposed workers handling with creosote the naphthalene metabolites 1,2-DHN, 1- and 2-NMA as well as 1- and 2-naphthol were analysed in order to evaluate the suitability of the different parameters for their application in biomonitoring studies. Additionally, air sampling was conducted to characterise the exposure in task related exposure situations at different workplaces. In the analysed 51 urine samples, 1,2-DHN was the main metabolite with concentrations ranging from 2.3 to 886 µg/g creatinine (crea) (median 34 µg/g crea). For the sum of 1- and 2-naphthol, concentrations in the range of 2.6-174 µg/g crea (median 15 µg/g crea) were observed. 1-NMA concentrations were in the range of < LOD-2.4 µg/g crea (61% > LOD), while 2-NMA was not detected in the analysed urine samples. The biomarkers 1,2-DHN, 1- and 2-naphthol as well as 1-NMA showed significant correlations, which pointed out to naphthalene as the common exposure source. The poor correlations between naphthalene in the air and the biomarkers in urine may be a result of the varying exposure situations and may indicate not solely inhalative, but additional dermal uptake. 1,2-DHN was the most sensitive and, together with 1-NMA, the most specific parameter of the biological monitoring of naphthalene exposure at workplaces. Further studies with this parameter are needed for individuals at different workplaces as well as for persons of the general population without occupational PAH exposure to characterise 1,2-DHN levels as well as to establish their relationship with the naphthalene exposure.

DNA methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons.

Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing. The median 1-hydroxypyrene (PAH metabolite) concentrations were highest in creosote-exposed workers (8.0 µg/g creatinine) followed by chimney sweeps (0.34 µg/g creatinine) and controls (0.05 µg/g creatinine). TL and mtDNAcn did not differ between study groups. Chimney sweeps and creosote-exposed workers had significantly lower methylation of AHRR CpG site cg05575921 (88.1 and 84.9%, respectively) than controls (90%). Creosote-exposed workers (73.3%), but not chimney sweeps (76.6%) had lower methylation of F2RL3 cg03636183 than controls (76.7%). Linear regression analyses showed that chimney sweeps had lower AHRR cg05575921 methylation (B = -2.04; P < 0.057, adjusted for smoking and age) and lower average AHRR methylation (B = -2.05; P < 0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B = -0.81; P < 0.042, adjusted for age) compared with controls. These cancer-related markers were not associated with urinary concentrations of PAH metabolites. In conclusion, although we found no associations with PAH metabolites in urine (short-term exposure), our results suggest dose-response relationship between PAH exposure and DNA hypomethylation of lung cancer-related loci. These findings indicate that further protective measures should be taken to reduce PAH exposure.

Comparison of the Potential Discoloration Effect of Bioaggregate, Biodentine, and White Mineral Trioxide Aggregate on Bovine Teeth: In Vitro Research.

INTRODUCTION: Tricalcium silicate cements can be used for pulp capping, pulpotomies, apical barrier formation in teeth with open apices, repair of root perforations, regenerative endodontics, and root canal filling. The aim of this study was to evaluate and compare the discoloration potential of 3 different tricalcium cements using a bovine tooth model. METHODS: Forty bovine anterior teeth have been used for the study. Crowns separated from the roots were randomly divided into 4 groups: the BioAggregate (IBC, Vancouver, Canada) group, the Biodentine (Septodont, Saint Maur des Fosses, France) group, the mineral trioxide aggregate Angelus (Angelus, Londrina, PR, Brazil) group, and the only blood group. Materials have been placed to the standardized cavities on the lingual surfaces of the crowns, and their contact with blood has been provided. The color values of the samples were measured with a digital tooth shade determinator (VITA Easyshade; VITA Zahnfabrik, Bad Sackingen, Germany) before the placement of the materials, after the placement of the materials, in the 24th hour, in the first week, in the first month, in the third month, and in the first year. The mean value of all groups was compared using the Tukey multiple comparison test (α = 0.05). RESULTS: All groups displayed increasing discoloration during a period of the first year. The "only blood group" showed the highest color change values, and it was followed as BioAggregate, mineral trioxide aggregate Angelus, and Biodentine, respectively. Statistically significant differences were found for Biodentine when compared with the only blood and BioAggregate groups (P < .05). CONCLUSIONS: Considering the results of the study, Biodentine is found to have the least discoloration potential among the tested materials.

[Specific features of materials for initial pulpitis treatment].

The aim of the current study was to assess antibacterial and cytotoxic properties of Biodentine (Septodont), Rootdent (TehnoDent) and adhesive Futurabond НР (Voco). Two lines of experiments were carried out using cements water solutions and firm tablet-like samples (made by means of special pattern). Citotoxic activity was tested on NCTC L929 mice line fibroblasts culture. All the examined materials showed antibacterial activity against E. coli, S. aureus, C. albiсans, St. faecalis, mostly evident in Futurabond and the poorest in Biodentine samples. As for cytotoxic properties, Biodentine proved not to suppress metabolic activity stimulating odontotropic impact. The results confirm the analyzed materials to be a useful tool for deep caries lesions and initial pulpitis treatment.

Superficial skin necrosis and neurological complications following administration of local anaesthetic: a case report.

Local anaesthesia is used routinely throughout dentistry. Complications are, however, relatively uncommon. A unique case of superficial skin necrosis and neurological symptoms following administration of local anaesthesia for dental treatment is reported and the possible mechanisms behind this unusual presentation are discussed. Awareness of this possible complication and its mechanism helps clinicians diagnose and manage patients with similar problems appropriately.

Bioindicators of immune function in creosote-adapted estuarine killifish, Fundulus heteroclitus.

Several populations of the estuarine killifish, Fundulus heteroclitus, also known as the mummichog, exhibit characteristics of adaptation to priority pollutants. One such population of mummichog inhabits the Elizabeth River in Virginia at the Atlantic Wood site (AW), a U.S. Environmental Protection Agency (EPA) Superfund site heavily contaminated with creosote containing a mixture of polyaromatic hydrocarbons (PAHs). Although PAHs are known to be immunotoxic in experimental animals, resident AW mummichogs seem to thrive. Mummichogs from the AW site and a reference site were subsequently examined over a 2-yr period for total immunoglobin (IgM), as well as circulating antibody levels against 5 ubiquitous marine bacteria. Expression profiles of circulating and lymphoid lysozyme and lymphoid cyclooxygenase-2 (COX-2) were also examined. Compared to relatively high total IgM and specific antibody responses in reference fish, AW mummichogs had lower circulating IgM and lower specific antibody levels against all bacteria examined, however they had higher levels of circulating lysozyme. Lymphoid cells in the AW mummichogs also expressed higher levels of lysozyme, as well as COX-2, which may indicate a state of macrophage activation. Elevated COX-2 levels may be associated with enhanced metabolism of PAHs through cooxidation-peroxidase pathways. Additional studies attempted to immunize AW mummichogs reared in uncontaminated water to compare their antibody responses to that of reference fish. AW mummichogs did not survive 40 d post culture, while reference fish thrived. Our findings suggest that the chemical environment at the AW site may be vicariously enhancing components of innate immunity, probably through oxidative stress pathways, in resident mummichogs, while actively suppressing humoral immune responses.

Retrospective cohort mortality study and nested case-control study of workers exposed to creosote at 11 wood-treating plants in the United States.

OBJECTIVE: The objective of this study was to assess both malignant and nonmalignant mortality risks of workers exposed to creosote. For background, a literature review is also presented. MATERIALS AND METHODS: The retrospective cohort study consisted of 2179 employees at 11 plants in the United States where wood (primarily railroad ties and utility poles) is treated with creosote-based preservatives. The observation period covered 1979-2001. Mortality data in the cohort study were analyzed in terms of cause-specific standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs), with expected deaths based on U.S. national cause-, gender-, race-, year-, age-specific mortality rates. In addition to the cohort investigation, a nested case-control study of lung cancer and multiple myeloma was conducted. Information on tobacco consumption and detailed employment (job titles) was obtained for cases and matched controls. Jobs were classified into 5 categories according to potential for exposure to creosote. Odds ratios (ORs) and 95% CIs were calculated for job categories and length of exposure. RESULTS: Overall mortality for the entire cohort was lower than expected (293 observed deaths vs. 325.37 expected, SMR = 90.1, 95% CI = 80.0-101.0). Close to 90% employees were hourly, whose potential for exposure was generally much higher than that of salaried employees. Among hourly employees, except for multiple myeloma, none of the specific cancer sites showed any significant increase. Furthermore, detailed analysis by length of employment did not reveal any significant mortality excess or upward trend. Six deaths were from multiple myeloma, whereas 1.50 deaths were expected (SMR = 401.1, 95% CI = 147.2-873.1). However, analysis by length of employment did not show any upward trend for multiple myeloma. No significant mortality increase was reported for any nonmalignant disease, and analysis by length of employment did not reveal any upward trend. In the case-control study, an increased risk of lung cancer was associated with tobacco consumption (OR = 4.92) but not with any job/exposure category. For example, the lung cancer odds ratio for routine exposure to creosote-based wood preservatives was 0.58 (95% CI = 0.11-3.03). Similarly, case-control analyses of multiple myeloma did not reveal any association with employment at the plants or with exposure to creosote-based wood preservatives or to creosote-treated products. CONCLUSION: Based on the present investigation and other studies, there was no evidence that employment at the 11 wood-treating plants or exposure to creosote-based wood preservatives was associated with any significant mortality increase from site-specific cancers or nonmalignant diseases. Some results should be interpreted with caution because they were based on small numbers.

Wood creosote, the principal active ingredient of seirogan, an herbal antidiarrheal medicine: a single-dose, dose-escalation safety and pharmacokinetic study.

STUDY OBJECTIVE: To assess the safety, tolerability and pharmacokinetics of escalating single doses of wood creosote, an herbal antidiarrheal and antispasmodic agent. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Clinical research center. SUBJECTS: Forty (32 men, 8 women) healthy volunteers aged 19-42 years. INTERVENTION: By random assignment, 22 men and 8 women received escalating single doses of wood creosote (45, 90, 135, 180, and 225 mg) and 10 men received placebo (for each of the five dose levels, 6 subjects received active substance and 2 subjects received placebo). MEASUREMENTS AND MAIN RESULTS: Vital signs, laboratory tests, and electrocardiograms were assessed; no dose-related or clinically significant changes were noted. Serial blood samples were obtained to determine the pharmacokinetics of four major active components of wood creosote: total (conjugated plus free) guaiacol, creosol, o-cresol, and 4-ethylguaiacol. The most common adverse events were mild headache and dizziness, with no dose-related trends being apparent. Area under the concentration-time curve from time zero to infinity increased in a dose-proportional manner for total guaiacol, creosol, and o-cresol and was not assessed for total 4-ethylguaiacol owing to lack of data at the low dose level. No apparent differences by sex were noted for any of the four active components. All four components were rapidly eliminated. CONCLUSION: Single oral doses of wood creosote up to 225 mg were safe and well tolerated in healthy men and women. Also, the doses of wood creosote were rapidly absorbed, conjugated, and eliminated. Such a rapid onset and short duration of action would appear desirable in the treatment of acute nonspecific diarrhea.

Health risks of residential exposure to polycyclic aromatic hydrocarbons.

A disease prevalence study and follow-up health surveillance were conducted among residents of an African-American community situated at the site of a former creosote wood-treatment facility contaminated with polycyclic aromatic hydrocarbons. Household interviews were conducted among 214 residents living around the hazardous waste site (target population) and 212 comparison residents in a neighborhood 2.4 km away from the site. Target area residents reported a higher prevalence of skin rashes than comparison residents (relative risk [RR] = 5.7; 95% confidence interval [CI] = 3.0, 10.9). The prevalence of reported rashes increased with increasing levels of anthracene detected in yards (test for linear trend, p = 0.02). With adjustment for environmental worry, reports of chronic bronchitis and difficulties becoming pregnant did not differ significantly between target and comparison residents (p > 0.05).

Health effects on nearby residents of a wood treatment plant.

OBJECTIVES: The aim of the study was to evaluate the health status of nearby residents of a wood treatment plant who had sustained prolonged low-level environmental exposure to wood processing waste chemicals. METHODS: A population of 1269 exposed residents who were plaintiffs or potential plaintiffs in a lawsuit against the wood treatment plant were evaluated by questionnaire for a health history and symptoms. A representative sample of 214 exposed subjects was included in the analysis. One hundred thirty-nine controls were selected from 479 unexposed volunteers and matched to the exposed subjects as closely as possible by gender and age. Subjects and controls completed additional questionnaires and were evaluated by a physician for medical history and physical examination, blood and urine testing, neurophysiological and neuropsychological studies, and respiratory testing. Environmental sampling for wood processing waste chemicals was carried out on soil and drainage ditch sediment in the exposed neighborhood. RESULTS: The exposed subjects had significantly more cancer, respiratory, skin, and neurological health problems than the controls. The subjective responses on questionnaires and by physician histories revealed that the residents had a significantly greater prevalence of mucous membrane irritation, and skin and neurological symptoms, as well as cancer. (Exposed versus unexposed, cancer 10.0% versus 2.08%, bronchitis 17.8% versus 5.8%, and asthma by history 40.5% versus 11.0%) There were significantly more neurophysiologic abnormalities in adults of reaction time, trails A and B, and visual field defects. CONCLUSIONS: Adverse health effects were significantly more prevalent in long-term residents near a wood treatment plant than in controls. The results of this study suggest that plant emissions from wood treatment facilities should be reduced.

Multiple-dose escalation, safety, and tolerability study of wood creosote, the principal active ingredient of seirogan, an herbal antidiarrheal medication, in healthy subjects.

Seirogan, an herbal medicine containing wood creosote (CAS 8021-39-4), a mixture of simple phenolic compounds, has been marketed for the past century in Asia for the treatment of acute diarrhea and associated symptoms, such as abdominal discomfort and cramping. The present study was designed to assess the safety and tolerability of an anticipated acute antidiarrheal dosing regimen. Sixty healthy males were randomized into five groups of 12 subjects each (9 wood creosote; 3 placebo) to receive 45-, 90-, 135-, 180-, and 225-mg tablets every 2 hours for five doses. Serial sitting and standing vital signs, ECG rhythm strips, and continuous telemetry monitoring were obtained predose and for 24 hours after the first dose. Clinical laboratory tests and 12-lead resting ECGs were obtained predose and 24 hours postdose. Of the subjects, 27% (12/45) receiving wood creosote and 27% (4/15) receiving placebo reported adverse events. The most common adverse events were altered taste and somnolence, reported more often with 180- and 225-mg doses. Wood creosote had no clinically significant effects on vital signs, ECG intervals or interpretations, or clinical laboratory tests. No clinically significant or serious dysrhythmias were reported on continuous telemetry monitoring. It was concluded that oral doses of wood creosote 45 to 225 mg every 2 hours for up to five doses were safe and well tolerated in 45 healthy subjects. Wood creosote doses ranging from 45 to 135 mg per dose, which are commonly administered antidiarrheal doses in Asia, were associated with minimal side effects.

Fish (Fundulus heteroclitus) populations with different exposure histories differ in tolerance of creosote-contaminated sediments.

Prior studies suggest that field-collected fish (Fundulus heteroclitus) from a creosote-contaminated Superfund site (Atlantic Wood Industries site, Elizabeth River, VA, USA) have enhanced tolerance to local, contaminated sediments. This study was designed to test whether other populations in the Elizabeth River at less contaminated sites also show similar tolerance and whether this tolerance is heritable. To test this, F. heteroclitus populations were sampled from four sites within the Elizabeth River with varying sediment polycyclic aromatic hydrocarbon (PAH) concentrations (3.9-264 ng PAH/g dry wt 10(3)) and one reference site in a nearby, uncontaminated estuary (York River, VA, USA; 0.27 ng PAH/g dry wt x 10(3)). Embryo assays were performed to quantify population differences in teratogenic effects during contaminated sediment exposure. Atlantic Wood sediment was mixed with reference sediment to achieve a range of sediment concentrations. Minimal differences were observed in teratogenic effects among fish taken from sites within the Elizabeth River; however, embryos of fish collected from a nearby, uncontaminated York River site and exposed to contaminated sediments had a significantly higher proportion of embryos with cardiac abnormalities than those from the Elizabeth River sites. Embryos from wild-caught and laboratory-reared Elizabeth River F. heteroclitus were simultaneously exposed to contaminated sediments, and no significant tolerance differences were found between embryos from fish taken directly from the field and those reared for a generation in the lab. Differences between fish populations from the two estuaries were larger than differences within the Elizabeth River, and these differences in tolerance were heritable.

Response of phytoplankton communities to liquid creosote in freshwater microcosms.

We assessed the response of phytoplankton communities in aquatic microcosms to single applications of liquid creosote. The creosote was applied to 14 microcosms at concentrations ranging from 0.06 to 109 mg/L. Two microcosms served as controls. Phytoplankton samples were collected from each microcosm one week and 1 d before treatment and at 7 and 21 d after treatment. Temporal changes (response-recovery) in phytoplankton community composition were assessed with principal response curves. Creosote had no direct toxic effect on the phytoplankton community based on total abundance and number of taxa. Population levels declined in all treatments between day -1 and day 7, but this trend mirrored a similar decline in the control microcosms. At both 7 and 21 d after treatment, population densities and number of taxa in most treatments exceeded those in the controls and exhibited a parabolic relationship relative to creosote concentration. This relationship was most pronounced at 21 d, at which time population densities and number of taxa at intermediate concentrations were up to twice those at low and high concentrations. This response pattern seems to represent an indirect response to impacts on zooplankton and a corresponding reduction in grazing pressure. In contrast, total algal biomass declined 52 to 97% relative to the controls at all but the lowest creosote concentration at 7 d. This apparent decline was due to a significant proliferation of the alga Closterium moniliforme in the controls and low creosote concentration. At 21 d, no difference was found in total biomass between treated and control microcosms. The results of this study suggest that creosote does not pose a significant direct risk to phytoplankton at concentrations likely to be encountered in most contaminated aquatic environments; however, stimulation of algal populations could occur in situations of long-term chronic exposure or spill events that remove predatory zooplankton populations.

Assessment of the bioactivity of creosote-contaminated sediment by liver biotransformation system of rainbow trout.

A sediment site in the Lake Jämsänvesi (municipality of Petäjävesi, Finland) contaminated by creosote was investigated to assess the possible ecotoxicological risks it may cause to benthic animals, including ones which may arise due to physical measures in remediating the site. It is suggested that polycyclic aromatic hydrocarbons (PAHs) are bioavailable to fish and other aquatic animals during exposure to contaminated water, sediment, and food. In order to assess toxicological risks of sediment contents to fish, juvenile rainbow trout (Onchorhynchus mykiss) were intraperitoneally dosed with extracts of the creosote-contaminated sediments and their elutriates. This was compared to pristine lake sediment spiked with creosote. Activity of CYP1A1 in trout liver was measured as ethoxyresorufin O-deethylase (EROD). When compared to vehicle controls and the pristine reference sediment (0.9-1.3 pmol/min/mg PMS protein), the extract of creosote-contaminated sediment of Lake Jämsänvesi induced EROD activity up 20-30 times with a dose of 100 mg/kg [total PAHs (mg)/(kg) in fish]. The rise of EROD was associated with increasing levels of PAH metabolites in bile, analyzed as 1-OH pyrene equivalents.

[Possible carcinogenic risk associated with production and use of creosote-treated wood]. / Mulig kreftrisiko ved tilvirkning og bruk av kreosotimpregnert trevirke.

Creosote is a coal tar product which contains varying amounts of mutagenic and carcinogenic substances such as polycyclic aromatic hydrocarbons (PAHs) and benzene. Marketing and use of creosote and preparations containing creosote, as well as creosote-treated wood, are regulated by a EU Directive. According to the EU classification of such mixtures, inclusion of a warning against creosote as a carcinogen is not necessary if the contents of benzo[a]pyrene (BaP) and benzene are lower than 50 ppm (parts per million) and 1000 ppm, respectively. A recent well designed skin painting study in mice clearly indicates that the creosote preparations had a five-fold higher potency to induce skin cancer than the potency based on BaP content. Furthermore, it was estimated that creosote containing 50 ppm BaP would induce a significant incidence of skin cancer. Preliminary results from determination of concentrations of various carcinogens (BaP and benzene) in the air close to creosote impregnation plants as well as the crudely estimated exposure of children to dermal contact with creosote-treated wood, indicate that the life-time cancer risk from such exposures is in the order of one per 10,000. Despite the uncertainty related to such estimates, these risk levels give reasons for some concern. A further reduction in the content of PAH and benzene in creosote preparations should be considered.

Pesticides and cancer.

Epidemiologic evidence on the relationship between chemical pesticides and cancer is reviewed. In animal studies, many pesticides are carcinogenic, (e.g., organochlorines, creosote, and sulfallate) while others (notably, the organochlorines DDT, chlordane, and lindane) are tumor promoters. Some contaminants in commercial pesticide formulations also may pose a carcinogenic risk. In humans, arsenic compounds and insecticides used occupationally have been classified as carcinogens by the International Agency for Research on Cancer. Human data, however, are limited by the small number of studies that evaluate individual pesticides. Epidemiologic studies, although sometimes contradictory, have linked phenoxy acid herbicides or contaminants in them with soft tissue sarcoma (STS) and malignant lymphoma; organochlorine insecticides are linked with STS, non-Hodgkin's lymphoma (NHL), leukemia, and, less consistently, with cancers of the lung and breast; organophosphorous compounds are linked with NHL and leukemia; and triazine herbicides with ovarian cancer. Few, if any, of these associations can be considered established and causal. Hence, further epidemiologic studies are needed with detailed exposure assessment for individual pesticides, taking into consideration work practices, use of protective equipment, and other measures to reduce risk.