Chronic toxicity and carcinogenicity testing in the Sprague–Dawley rat of a prospective insect repellant (KBR 3023) using the dermal route of exposure

Wahle, B.S.; Sangha, G.K.; Lake, Stephen G.; Sheets, Larry P.; Croutch, Claire R.; Christenson, W. R.

doi:10.1016/s0300-483x(99)00129-8

Cited by 11 publications

(11 citation statements)

References 10 publications

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“…Picaridin was administered at dosages of 0, 50, 100, and 200 mg/kg BW/day in a 2-year dermal toxicity study in rats (Wahle et al, 1999). Body-weight gain, food consumption, clinical observations, and survival were unaffected at all ages for both sexes.…”

Section: Chronic Toxicitymentioning

confidence: 99%

“…The authors also noted several possible treatment-related effects which were attributed to methodology and inherent difficulties associated with lifetime bioassay tests via dermal route. Therefore, the changes at the dosage sites associated with picaridin were non-dose responsive, and could be described as adaptive, non-adverse, predictable responses to chronic exposure (Wahle et al, 1999).…”

Section: Chronic Toxicitymentioning

confidence: 99%

“…For subchronic and chronic exposures, we used a NOEL of 200 mg/kg BW/day as the endpoint (Table 2), based on the lack of adverse and non-skin compound-related effects (Wahle et al, 1999) and no signs of behavioral or pathological anatomical neurotoxicity (WHO, 2000).…”

Section: Endpoint Selectionmentioning

confidence: 99%

“…Picaridin [2-(2-hydroxyethyl)-1-piperidinecarboxylic acid 1-methylpropyl ester] is a new insect repellent for human use (Wahle et al, 1999;WHO, 2000;Scheinfeld, 2004;Carpenter et al, 2005), with initial registration in the U.S. in 2001 (USEPA, 2005). It has been shown to be effective against mosquitoes and a wide range of hematophagous arthropods (Frances et al, 2004;Scheinfeld, 2004;Carpenter et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…These special situations point to the need for human health risk assessments for population subgroups. Although there have been some toxicity studies and safety reviews for DEET (Robbins and Cherniack, 1986;Osimitz and Grothaus, 1995;Qiu et al, 1997Qiu et al, , 1998Fradin, 1998;Goodyer and Behrens, 1998;USEPA, 1998;Young and Evans, 1998;McGready et al, 2001;Health Canada, 2002;Koren et al, 2003;Sudakin and Trevathan, 2003;Blanset et al, 2007) and picaridin (Wahle et al, 1999;WHO, 2000), quantitative dermal risk assessments are lacking in the scientific literature. Peterson et al (2006), Davis et al (2007), Macedo et al (2007), and Schleier et al (2008) have estimated human health and environmental risks from other mosquito management and personal protective tactics.…”

Section: Introductionmentioning

confidence: 99%

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Risk assessments for the insect repellents DEET and picaridin

Antwi

Shama²,

Peterson

2008

Regulatory Toxicology and Pharmacology

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a b s t r a c tFor the use of topical insect repellents, DEET and picaridin, human health risk assessments were conducted for various population subgroups. Acute, subchronic, and chronic dermal exposures were examined. No-observed-effect-levels (NOELs) of 200, 300, and 100 mg/kg body weight (BW) were used as endpoints for DEET for acute, subchronic, and chronic exposures, respectively. For picaridin, a NOEL of 2000 mg/kg BW/day for acute exposure and a NOEL of 200 mg/kg BW/day for subchronic and chronic exposures were used. Daily exposures to several population subgroups were estimated. Risks were characterized using the Margin of Exposure (MOE) method (NOEL divided by the estimated exposure), whereby estimated MOEs were compared to an MOE of 100. Estimates of daily exposures ranged from 2 to 59 mg/kg BW/day for DEET and 2 to 22 mg/kg BW/day for picaridin. Children had the lowest MOEs. However, none of the estimated exposures exceeded NOELs for either repellent. At 40% DEET for acute exposure, children 612 years had MOEs below 100. For subchronic and chronic exposures children at P25% DEET and at 15% picaridin had MOEs below 100. Therefore, we found no significant toxicological risks from typical usage of these topical insect repellents.

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Section: Chronic Toxicitymentioning

confidence: 99%

Section: Chronic Toxicitymentioning

confidence: 99%

Section: Endpoint Selectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Risk assessments for the insect repellents DEET and picaridin

Antwi

Shama²,

Peterson

2008

Regulatory Toxicology and Pharmacology

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The role of urinary pH in o‐phenylphenol‐induced cytotoxicity and chromosomal damage in the bladders of F344 rats

Balakrishnan

Hasegawa

Eastmond

2016

Environ and Mol Mutagen

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o-Phenylphenol (OPP) is a widely used fungicide and antibacterial agent that at high doses has been shown to cause bladder cancer in male F344 rats. The mechanisms underlying OPP-induced bladder carcinogenicity remain unclear but it has been proposed that a non-enzymatic pH-dependent autoxidation of phenylhydroquinone (PHQ), a primary metabolite of OPP, may be a key step in OPP-induced rat bladder carcinogenesis. To investigate this mechanism and to provide insights into the potential human health relevance of OPP-induced cancer, a series of in vitro and in vivo experiments were conducted. In human lymphoblastoid TK-6 cells and rat bladder epithelial NBT-II cells, strong increases in cytotoxicity were seen at a constant concentration of PHQ by increasing the buffer pH as well as by increasing concentrations of PHQ at a constant pH. In in vivo studies, male rats were administered OPP (4,000 and 8,000 ppm) in a diet supplemented with either 1% ammonium chloride or 3% sodium bicarbonate to produce acidic and alkaline urinary pH, respectively. Significant increases in cell proliferation as detected by 5-bromo-2'-deoxyuridine incorporation and micronucleus formation were seen in the bladder cells of OPP-treated rats with neutral or alkaline urinary pH but not in animals with the acidified urine. The results from these in vitro and in vivo studies provide support for the autoxidation hypothesis of bioactivation, and provide additional evidence that urinary pH can significantly influence the genotoxicity and carcinogenicity of this important agent.

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Toxicology and Safety Evaluation of the New Insect Repellent Picaridin (Saltidin)

Sangha

2010

Hayes' Handbook of Pesticide Toxicology

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Chronic toxicity and carcinogenicity testing in the Sprague–Dawley rat of a prospective insect repellant (KBR 3023) using the dermal route of exposure

Cited by 11 publications

References 10 publications

Risk assessments for the insect repellents DEET and picaridin

Risk assessments for the insect repellents DEET and picaridin

The role of urinary pH in o‐phenylphenol‐induced cytotoxicity and chromosomal damage in the bladders of F344 rats

Toxicology and Safety Evaluation of the New Insect Repellent Picaridin (Saltidin)

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