Dose and Time Determining, and Other Factors Influencing, Toxicity

Rozman, Karl K.; Doull, John; Hayes, Wayland J.

doi:10.1016/b978-0-12-374367-1.00001-x

Cited by 21 publications

(11 citation statements)

References 308 publications

(346 reference statements)

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“…Although the knowledge gained has been put to good practical use in certain situations, it is curious that the concept of ‘chronicity’ is not more prominent in toxicology and hazard assessment. The term is not widely used and has slightly different meanings where it arises ( Hayes, 1967 ; Rozman et al, 2010 ) but in general it describes the relationship between PoDs derived from acute and chronic studies, expressed quantitatively as a ratio or an index. Lower values indicate a low cumulative rate of effect with increasing exposure time, and vice versa .…”

Section: Discussionmentioning

confidence: 99%

“…Lower values indicate a low cumulative rate of effect with increasing exposure time, and vice versa . For example, comparing LD50 values derived from acute and 90-day rodent studies shows the significant cumulative effects of warfarin and some chemical biocides, whereas very little cumulative behaviour is observed for caffeine, potassium cyanide and some organic phosphorus compounds ( Rozman et al, 2010 ). Since chronicity can be very high for some substances and vary significantly between substances, it is clearly an important factor to take into consideration when extrapolating to long exposure times ( e.g.…”

Section: Discussionmentioning

confidence: 99%

“…This is the case for some essential nutrients and vitamins ( e.g. A and D) which are clearly necessary for maintaining health but which can cause adverse effects at high doses and prolonged chronic exposure ( Rozman et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

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Extrapolating from acute to chronic toxicity in vitro

Macko

Palosaari

Whelan

2021

Toxicology in Vitro

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Chemical safety assessment requires information on both chronic and acute effects of toxicants. Traditionally, such information has been provided by a set of animal studies conducted over different durations, ranging from a single dose with observation of effects over a few days, to repeat daily dosing and observations made over many months. With the advent of modern mechanistic approaches to toxicology, the role of in vitro studies within alternative approaches has never been more prominent. Typical in vitro experiments are conducted over short durations with measurements of response at a single time point, with a focus on providing effect and concentration-response information as input to hazard and risk assessment. This limits the usefulness of such data since potential chronic effects that cumulate over time are not usually considered. To address this, an experimental design is presented to characterise the toxicodynamics of a response not only in terms of concentration, but also as a function of time. Generation of concentration-time-effect responses allows both the extrapolation of points of departure from an acute to chronic exposure, and the determination of a chronicity index that provides a quantitative measure of a chemical's potential to cause cumulative effects over time. In addition, the approach provides a means to characterise the dynamics of key event relationships for the development of quantitative adverse outcome pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Extrapolating from acute to chronic toxicity in vitro

Macko

Palosaari

Whelan

2021

Toxicology in Vitro

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“…There was an increasing number of aphids which included nymphs weeks later. Toxicity is a function of time after application, and time after application is a function of dose and length of the time (Rozman et al, 2009). The positive control (dimethoate 40% EC) in the current study which caused a high mortality to aphids agrees with study of Bezerra-Silva et al (2012) who assessed the contact effect of synthetic pesticide, and found that it is equally highly deleterious to Bucephalogonia xanthophis.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of lantana (Lantana camara) extract application against aphids (Brevicoryne brassicae) in rape (Brassica napus) over varied periods of time

Mvumi¹,

Maunga²

2018

Afr. J. Biotechnol.

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Contact bioefficacy of lantana (Lantana camara L.) leaf extract (LLE) against rape aphids (Brevicoryne) and distilled water were the positive and negative controls, respectively. Treatments were arranged in a randomized complete block design (RCBD); 3 x 5 factorial arrangement, replicated 5 times. Adult aphids (10) were introduced to each plant. Aphid mortality at 6, 12, 18 and 24 h after application of treatments was evaluated. There was no significant interaction between seed brand and treatment at all times. Lantana treatments showed significant mortality effect (p < 0.001) on aphids at all times. The highest LLC (3 kg l -1 ) showed the highest aphid mortality at each period of time after application, and of all the periods, the longest time after application (24 h), showed the highest mortality (9.67). It is recommended that smallholder farmers use 3 kg l -1 LLC to control aphids on rape, and allow 24 h after application to get the greatest kill.

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“…or acute. While chronic involves repeated or continuous exposures over long periods, acute generally refer to single and higher dose of toxin exposure [12]. Despite the significant biological association of carcinogenic risks attributable to acute exposures, there exists many missing links and mechanistic details that have not been adequately addressed.…”

Section: Introductionmentioning

confidence: 99%

Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy

Mishra¹,

Raghuram²,

Bunkar³

et al. 2015

Int J Occup Med Environ Health

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International Journal of Occupational Medicine and Environmental AbstractDecember 2014 marked the 30th year anniversary of Bhopal gas tragedy. This sudden and accidental leakage of deadly poisonous methyl isocyanate (MIC) gas instigated research efforts to understand the nature, severity of health damage and sufferings of 570 000 ailing survivors of this tragedy. In a decade-long period, our systematic laboratory investigations coupled with long-term molecular surveillance studies have comprehensively demonstrated that the risk of developing an environmental associated aberrant disease phenotype, including cancer, involves complex interplay of genomic and epigenetic reprogramming. These findings poised us to translate this knowledge into an investigative framework of "molecu lar biodosimetry" in a strictly selected cohort of MIC exposed individuals. A pragmatic cancer risk-assessment strategy pursued in concert with a large-scale epidemiological study might unfold molecular underpinnings of host-susceptibility and exposureresponse relationship. The challenges are enormous, but we postulate that the study will be necessary to establish a direct initiation-promotion paradigm of environmental carcinogenesis. Given that mitochondrial retrograde signaling-induced epigenetic reprogramming is apparently linked to neoplasticity, a cutting-edge tailored approach by an expert pool of biomedical researchers will be fundamental to drive these strategies from planning to execution. Validating the epigenomic signatures will hopefully result in the development of biomarkers to better protect human lives in an overburdened ecosystem, such as India, which is continuously challenged to meet population demands. Besides, delineating the mechanistic links between MIC exposure and cancer morbidity, our investigative strategy might help to formulate suitable regulatory policies and measures to reduce the overall burden of occupational and environmental carcinogenesis.

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Dose and Time Determining, and Other Factors Influencing, Toxicity

Cited by 21 publications

References 308 publications

Extrapolating from acute to chronic toxicity in vitro

Extrapolating from acute to chronic toxicity in vitro

Efficacy of lantana (Lantana camara) extract application against aphids (Brevicoryne brassicae) in rape (Brassica napus) over varied periods of time

Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy

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