Pesticide use modifies the association between genetic variants on chromosome 8q24 and prostate cancer.

Genome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In the Agricultural Health Study, a prospective study of licensed pesticide applicators, we observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, we evaluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors estimated odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, 49 pesticides, and prostate cancer risk in 776 cases and 1,444 controls. The ORs for a previously identified variant, rs4242382, and prostate cancer increased significantly (P<0.05) with exposure to the organophosphate insecticide fonofos, after correction for multiple testing, with per allele ORnonexposed of 1.17 (95% CI, 0.93-1.48), per allele OR(low) of 1.30 (95% CI, 0.75-2.27), and per allele ORhigh of 4.46 (95% CI, 2.17-9.17; P-interaction=0.002, adjusted P-interaction=0.02). A similar effect modification was observed for three other organophosphate insecticides (coumaphos, terbufos, and phorate) and one pyrethroid insecticide (permethrin). Among ever users of fonofos, subjects with three or four risk alleles at rs7837328 and rs4242382 had approximately three times the risk of prostate cancer (OR, 3.14; 95% CI, 1.41-7.00) compared with subjects who had zero risk alleles and never used fonofos. We observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk.

Fonofos poisons raptors and waterfowl several months after granular application.

From 1994 to 1999 in the Lower Fraser Valley region of southwest Canada, fonofos (Dyfonate G) was recommended for control of introduced wireworm (Agriotes spp.) pests on potato and other root crops. As part of a wildlife-monitoring program, we collected 15 raptors, including 12 bald eagles (Haliaeetus leucocephalus), found dead or debilitated on or near agricultural lands with severely inhibited brain and/or plasma cholinesterase activity and fonofos residues in ingesta. Bird remains, in nine cases waterfowl, were identified in the ingesta samples. Another seven bald eagles had severe cholinesterase inhibition, but without evidence of fonofos residues. During two winters from 1996 to 1998, 420 ha of potato fields, half of which had been treated the previous spring with fonofos and the remainder untreated, were searched weekly for evidence of wildlife mortality. Search efficiency was assessed with placed duck carcasses. Waterfowl outnumbered other species in field-use counts and comprised the greatest proportion of birds found dead. We found 211 wildlife remains, most scavenged; 35 intact carcasses were suitable for postmortem examination and/or toxicology analyses. Cholinesterase activity was assayed in brains of 18 waterfowl, five of which had severely depressed activity (average inhibition 74%; range, 69-78%). The gastrointestinal tract of a mallard found in a field treated with granular product contained 49 microg/g fonofos residues, linking waterfowl mortality with labelled use of the product. These findings demonstrate the risk of both primary and secondary poisoning by anticholinesterase insecticides where wildlife make intensive use of farmed fields.

Fonofos exposure and cancer incidence in the agricultural health study.

BACKGROUND: The Agricultural Health Study (AHS) is a prospective cohort study of licensed pesticide applicators from Iowa and North Carolina enrolled 1993-1997 and followed for incident cancer through 2002. A previous investigation in this cohort linked exposure to the organophosphate fonofos with incident prostate cancer in subjects with family history of prostate cancer. OBJECTIVES: This finding along with findings of associations between organophosphate pesticides and cancer more broadly led to this study of fonofos and risk of any cancers among 45,372 pesticide applicators enrolled in the AHS. METHODS: Pesticide exposure and other data were collected using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RRs) and 95% confidence intervals (CIs) while controlling for potential confounders. RESULTS: Relative to the unexposed, leukemia risk was elevated in the highest category of lifetime (RR = 2.24; 95% CI, 0.94-5.34, Ptrend = 0.07) and intensity-weighted exposure-days (RR = 2.67; 95% CI, 1.06-6.70, Ptrend = 0.04), a measure that takes into account factors that modify pesticide exposure. Although prostate cancer risk was unrelated to fonofos use overall, among applicators with a family history of prostate cancer, we observed a significant dose-response trend for lifetime exposure-days (Ptrend = 0.02, RR highest tertile vs. unexposed = 1.77, 95% CI, 1.03-3.05; RRinteraction = 1.28, 95% CI, 1.07-1.54). Intensity-weighted results were similar. No associations were observed with other examined cancer sites. CONCLUSIONS: Further study is warranted to confirm findings with respect to leukemia and determine whether genetic susceptibility modifies prostate cancer risk from pesticide exposure.

[Epidemic outbreak of acute food poisoning caused by pesticides]. / Brote epidémico de intoxicación aguda alimentaria por plaguicidas.

OBJECTIVES: 1) To identify the causes of the outbreak. 2) To adopt the appropriate measures to control it. DESIGN: Observational crossover study. SETTING: San Benito Health District in Jerez de la Frontera (Cádiz). PATIENTS AND OTHER PARTICIPANTS: Diners who attended a family celebration. MEASUREMENTS AND MAIN RESULTS: On Friday 11th March 1994 there was an outbreak of acute food poisoning. The clinical notes of 9 ill diners were checked; they and 7 unaffected diners answered epidemiological questionnaires. A proportional comparison was then made between those not exposed and those exposed to each one of the foods consumed at this celebration. The clinical picture showed: high level of the Creatine phosphokinase enzyme, general myalgias, vomiting or nausea and visual problems. The average incubation period was 7 hours. The odds ratios of the foods involved was calculated. Although this reached 4 in some cases, the significance tests were not significant in any case because of the study's low statistical power. In the investigation of the trophic chain of the game-birds eaten, the presence of nitrogen or phosphorus atoms, compatible with the pattern of fonofos in the pesticide used on the hunting estate where the birds came from, was isolated. CONCLUSIONS: Epidemiological, clinical and biological evidence was found, which places us before acute organophosphorus poisoning. Coordination between the different institutions involved was decisive in finding the cause of the outbreak.

[Poisoning with cholinesterase inhibitors]. / Intoxikation mit Cholinesterasehemmern.

A 32-year-old woman who had ingested 300 ml of a potent cholinesterase inhibitor insecticide (Fonofos) with suicidal intent became progressively comatose and finally suffered respiratory arrest. Tracheal intubation, mechanical ventilation, vigorous gastric lavage and intravenous administration of atropine and obidoxime brought about complete clinical recovery within 24 hours of ingestion of this potentially fatal dose of Fonofos.

Fonofos toxicosis and milk residues in dairy cattle.

An organophosphate toxicosis due to fonofos was diagnosed in an Iowa Dairy herd. Fonofos was detected in the feed source and in the rumen contents, liver, and kidney tissue of one cow that died acutely. Bulk tank milk contained detectable levels of fonofos.

Fonofos toxicosis in dairy cows: an accidental poisoning (1977).

An accidental poisoning (in 1977) of 28 Holstein cows occurred when approximately 0.9 kg of 25% active ingredient fonofos, O-ethyl S-phenyl ethylphosphonothiolothionate, was spilled onto bulk feed in a delivery truck. Eight cows died within 2 days; the remaining 20 were necropsied 29 days later. Of the 8 fatally poisoned, 7 were being fed a high-grain diet and 1 was fed a medium-grain diet. Fonofos concentrations in feed cart and storage bin samples were 100 micrograms/g and 61 micrograms/g, respectively. Tissues from 6 animals were analyzed extensively for fonofos concentrations: 2 had died immediately; the other 4 were in the recovery state when they were necropsied. Rumen contents and liver, kidney, brain, heart, and milk samples were analyzed. Fonofos concentrations in these samples were significantly higher in the cows fatally affected than in the cows necropsied 3 weeks later. The oral acute LD50 and LD1 of fonofos in Holstein cows were calculated by the Litchfield and Wilcoxon method to be 1.30 and 0.84 mg/kg, respectively, with a 95% confidence range of +/- 0.20 mg/kg.