Two-year oral chronic toxicity and carcinogenicity study in rats of diets fumigated with methyl bromide

Mitsumori, Kunitoshi; Maita, Keizo; Kosaka, Toshio; Miyaoka, Teiji; Shirasu, Yasuhiko

doi:10.1016/0278-6915(90)90018-i

Cited by 17 publications

(7 citation statements)

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“…Older studies reported that methyl bromide induces squamous cell papillomas and carcinomas in the forestomach of the rat [4,46]. No carcinogenic effect was observed in further studies applying methyl bromide orally with gavages [51]. A technical report from the US National Toxicology Program showed no evidence of carcinogenic activity in mice exposed to methyl bromide by inhalation [52].…”

Section: Resultsmentioning

confidence: 99%

Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

Budnik¹,

Kloth²,

Velasco-Garrido

et al. 2012

Environ Health

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BackgroundAlthough ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage). The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity.MethodsWe performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis.ResultsOut of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49), P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage.ConclusionsBoth the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious health problems, including prostate cancer risk from occupational and community exposure. The environmental risks of methyl bromide are not in doubt, but also its health risks, especially for genetically predisposed subjects, should not be underestimated.

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Section: Resultsmentioning

confidence: 99%

Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

Budnik¹,

Kloth²,

Velasco-Garrido

et al. 2012

Environ Health

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“…However, regression of the lesions following cessation of exposure raised uncertainty about the malignant nature of the lesions [20], and the relevance of rodent forestomach carcinogenesis to human cancer risk has also been questioned [21]. In addition, other studies in rats, using different routes of exposure, observed no evidence of methyl bromide carcinogenicity [22, 23]. …”

Section: Discussionmentioning

confidence: 99%

Methyl bromide exposure and cancer risk in the Agricultural Health Study

Barry

Koutros

Lubin

et al. 2012

Cancer Causes Control

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Purpose Methyl bromide is a genotoxic soil fumigant with high acute toxicity, but unknown human carcinogenicity. Although many countries have reduced methyl bromide use because of its ozone depleting properties, some uses remain in the United States and other countries, warranting further investigation of human health effects. Methods We used Poisson regression to calculate rate ratios (RR) and 95% confidence intervals (CI) for associations between methyl bromide use and all cancers combined and 12 specific sites among 53,588 Agricultural Health Study (AHS) pesticide applicators with follow-up from 1993–2007. We also evaluated interactions with a family history for four common cancers (prostate, lung, colon, and lymphohematopoietic). We categorized methyl bromide exposure based on lifetime days applied weighted by an intensity score. Results A total of 7,814 applicators (14.6%) used methyl bromide, predominantly before enrollment. Based on 15 exposed cases, stomach cancer risk increased monotonically with increasing methyl bromide use (RR=1.42; 95% CI: 0.51–3.95 and RR=3.13; 95% CI: 1.25–7.80 for low and high use compared with no use; ptrend=0.02). No other sites displayed a significant monotonic pattern. Although we previously observed an association with prostate cancer (follow-up through 1999), the association did not persist with longer follow-up. We observed a non-significant elevated risk of prostate cancer with methyl bromide use among those with a family history of prostate cancer, but the interaction with a family history did not achieve statistical significance. Conclusions Our results provide little evidence of methyl bromide associations with cancer risk for most sites examined; however, we observed a significant exposure-dependent increase in stomach cancer risk. Small numbers of exposed cases and declining methyl bromide use might have influenced our findings. Further study is needed in more recently exposed populations to expand on these results.

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“…Activation of the thyroid, characterized by an increase in relative weight of the organ and a reduction in follicle size, was observed. Mitsumori et al (1990) carried out a 2year, oral, long-term toxicity and carcinogenicity study on rats fed diets fumigated with methyl bromide, containing 80, 200, or 500 mg kg À1 total bromide, and a diet containing 500 mg kg À1 potassium bromide. As a consequence of the effects on the gonads, Van Leeuwen et al (1983) examined the influence of bromide on the reproductive performance of rats in a three-generation reproduction study.…”

Section: Effects Of Organic and Inorganic Bromides On Animalsmentioning

confidence: 99%

Bromine

Pavelka¹

2004

Elements and Their Compounds in the Environment

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Two-year oral chronic toxicity and carcinogenicity study in rats of diets fumigated with methyl bromide

Cited by 17 publications

References 13 publications

Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

Methyl bromide exposure and cancer risk in the Agricultural Health Study

Bromine

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