A study on the acute inhalation toxicity of phosphine to albino rats

Muthu, M.; Krishnakumari, M. K.; Muralidhara, .; Majumder, S. K.

doi:10.1007/bf01608130

Cited by 15 publications

(6 citation statements)

References 3 publications

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“…This value is 4 times that previously reported for the LC 50 of a 24 hour fumigation at 25°C, ∼185 ppm (0.26 mg/L) [6]. This is consistent with previous observations of a positive correlation between temperature and toxicity of phosphine in several insect species [21]–[28] and also in rats [29]. This result is explained as an increase in the uptake and metabolism of phosphine by the animals due to higher metabolic rates at higher temperatures [27].…”

Section: Resultssupporting

confidence: 93%

Comparative Toxicity of Fumigants and a Phosphine Synergist Using a Novel Containment Chamber for the Safe Generation of Concentrated Phosphine Gas

Valmas

Ebert

2006

PLoS ONE

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BackgroundWith the phasing out of ozone-depleting substances in accordance with the United Nations Montreal Protocol, phosphine remains as the only economically viable fumigant for widespread use. However the development of high-level resistance in several pest insects threatens the future usage of phosphine; yet research into phosphine resistance mechanisms has been limited due to the potential for human poisoning in enclosed laboratory environments.Principal FindingsHere we describe a custom-designed chamber for safely containing phosphine gas generated from aluminium phosphide tablets. In an improvement on previous generation systems, this chamber can be completely sealed to control the escape of phosphine. The device has been utilised in a screening program with C. elegans that has identified a phosphine synergist, and quantified the efficacy of a new fumigant against that of phosphine. The phosphine-induced mortality at 20°C has been determined with an LC50 of 732 ppm. This result was contrasted with the efficacy of a potential new botanical pesticide dimethyl disulphide, which for a 24 hour exposure at 20°C is 600 times more potent than phosphine (LC50 1.24 ppm). We also found that co-administration of the glutathione depletor diethyl maleate (DEM) with a sublethal dose of phosphine (70 ppm,

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Section: Resultssupporting

confidence: 93%

Comparative Toxicity of Fumigants and a Phosphine Synergist Using a Novel Containment Chamber for the Safe Generation of Concentrated Phosphine Gas

Valmas

Ebert

2006

PLoS ONE

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“…Waritz and Brown [1975] reported a slight decrease in weight gain in rats following 10 exposures for 4 hr at 4 ppm, normalising after the first week of recovery. Muthu et al [1980] also found a general body weight decrease 1 week after a single acute exposure for 6 hr at an approximate concentration of 20 ppm, but weight gain subsequently returned to normal. Recently, Newton et al…”

Section: Short Term Repeated-dose Studymentioning

confidence: 89%

Determination of genotoxic and other effects in mice following short term repeated‐dose and subchronic inhalation exposure to phosphine

Barbosa¹,

Rosinova²,

Dempsey

et al. 1994

Environ and Mol Mutagen

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Phosphine is an important fumigant in the grain industry and has been reported to be genotoxic in occupationally exposed fumigators. This study reports on the effects of phosphine inhalation exposure at up to, and exceeding, occupational relevant levels in a subchronic (0.3, 1.0 and 4.5 ppm, 13 weeks) and a short term repeated-dose (5.5 ppm, 2 weeks) study in both sexes of Balb-c mice. The following end-points were examined: micronucleus induction in bone marrow, peripheral blood, spleen lymphocytes and skin keratinocytes, mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in lymphocytes, and weight gain and relative organ weights (kidneys, lungs, liver, heart, brain and spleen). After subchronic exposure, there was a highly significant negative linear correlation between proportional weight gain and exposure in both sexes (multiple linear regression, r = -0.56, P < 0.0001), with female mice showing a greater effect. Females also showed an increase in relative organ weights at the highest test dose, in contrast to males where there was a slight decrease. A statistically significant increase in micronucleus frequency was seen in the bone marrow and spleen lymphocytes of both sexes, but only at the highest concentration. The short term repeated-dose study revealed a slight decrease in weight gain in both sexes, with a greater effect in females. It is concluded that phosphine is weakly genotoxic in both sexes of mice, and has an effect on weight gain. However, the weak genotoxic effect may not be biologically significant as it was seen only in the subchronic study and only at the highest test concentration of 4.5 +/- 0.8 ppm (approaching the LD50). Although such exposure conditions are unlikely to be encountered in an occupational environment, caution should continue to be exercised in the use of phosphine until more data become available.

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“… Klimmer, ( 27 ) Morgan et al , ( 28 ) Newton et al , ( 29 ) Omae et al , ( 32 ) and Muthu et al ( 60 ) …”

Section: Phosphine Toxicologymentioning

confidence: 99%

“…The effects of inhaled phosphine have been studied in a variety of animal species (1,2,(23)(24)(25)(26)(27)(28)(29)(30) and a couple of interesting observations relevant to estimation of safe occupational exposure levels have been reported. First, regardless of duration of exposure (acute, subchronic, chronic), lethality is the primary Klimmer, (27) Morgan et al, (28) Newton et al, (29) Omae et al, (32) and Muthu et al (60) outcome associated with phosphine inhalation. The dose response reported in these studies is characterized by a steep nonlinear threshold relationship consistent with Haber's Law (the product of inhaled concentration and time (C × T) is a constant).…”

Section: Animal Inhalation Studiesmentioning

confidence: 99%

Worker Exposure Standard for Phosphine Gas

Pepelko¹,

Seckar²,

Harp³

et al. 2004

Risk Analysis

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The 1998 U.S. Environmental Protection Agency Office of Pesticide Programs (OPP) re-registration eligibility decision (RED) for phosphine fumigants has generated much interest in defining safe levels of exposure for workers and worker bystanders. This report summarizes the pertinent literature on phosphine toxicity, including animal inhalation studies and human epidemiology studies, and also describes a margin-of-exposure (MOE) analysis based on available worker exposure data. In addition, a safe occupational exposure limit is estimated using typical OPP assumptions, after determination of appropriate uncertainty factors, based on quality of data in the principal study and pharmacokinetic considerations. While a conservative 8-hour time-weighted average (TWA) of 0.1 ppm was calculated, the overall weight of evidence, from a risk-management perspective, supports a conclusion that an occupational TWA of 0.3 ppm provides adequate health protection. In addition, a 15-minute short-term exposure limit (STEL) of 3 ppm was estimated. Finally, in contrast to the MOE analysis described in the OPP's phosphine RED, the MOE analysis described herein does not indicate that fumigation workers are currently being exposed to unacceptable levels of phosphine. Collectively, these findings support the occupational exposure limits of 0.3 ppm (8-hour TWA) and 1 ppm (STEL) established in the updated applicator's manuals for phosphine-generating products, which recently received approval from OPP.

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A study on the acute inhalation toxicity of phosphine to albino rats

Cited by 15 publications

References 3 publications

Comparative Toxicity of Fumigants and a Phosphine Synergist Using a Novel Containment Chamber for the Safe Generation of Concentrated Phosphine Gas

Comparative Toxicity of Fumigants and a Phosphine Synergist Using a Novel Containment Chamber for the Safe Generation of Concentrated Phosphine Gas

Determination of genotoxic and other effects in mice following short term repeated‐dose and subchronic inhalation exposure to phosphine

Worker Exposure Standard for Phosphine Gas

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