No abstract

This study analyzed 9,086 human exposures involving N,N-diethyl-m-toluamide--containing insect repellents that were reported to Poison Control Centers from 1985-1989. Nearly two-thirds of those exposed had no adverse effects or only experienced minor symptoms that resolved rapidly. Symptoms were more likely to occur after ocular or inhalation exposures and least likely to occur if the product was ingested. The only reported death occurred in a patient who suicidally ingested 8 oz of an insect repellent containing N,N-diethyl-m-toluamide. Five patients may have experienced a serious or potentially life-threatening effect but the poison center record did not provide unequivocal substantiation of the effect or clearly establish N,N-diethyl-m-toluamide as the causative agent. From the analysis of those patients calling Poison Control Centers, it appears the risk of serious medical effects with the labeled use of N,N-diethyl-m-toluamide-containing insect repellents is low in comparison with its reported annual use by about 30% of Americans. For patients contacting Poison Control Centers, the occurrence of adverse effects appears to be related to the route of exposure rather than age or gender of the patient or the concentration of N,N-diethyl-m-toluamide in the product.

No abstract

Current methods of estimating absorbed dosage ( AD ) of chemicals were evaluated to determine residue transfer from a carpet treated with chlorpyrifos (CP) to humans who performed a structured exercise routine. To determine the dislodgeability of residue, a California Department of Food and Agriculture ( CDFA ) roller was applied to a flat cotton cloth upon a treated carpet. Levels ranged from 0.06 to 0.99 g CP/cm 2 . Cotton whole body dosimeters ( WBD ) were also used to assess residue transfer. The dosimeters retained 1.5 to 38 mg CP / person. Urine biomonitoring ( 3 days ) for 3,5,6 -trichloro -2 -pyridinol ( TCP ) of persons who wore only swimsuits revealed a mean AD of 176 g CP equivalents / person. The results show that the AD depends on the extent of contact transfer and dermal absorption of the residue. Default exposure assessments based upon environmental levels of chemicals and hypothetical transport pathways predict excessive exposure. The cotton WBD retains chemical residues and may be effectively used to predict dermal dose under experimental conditions.

Chronic toxicity and/or oncogenicity studies were conducted in rats, mice, and dogs with the insect repellent DEET. DEET was mixed in the diet and administered to CD rats for two years at concentrations that corresponded to dosage levels of 10, 30 or 100 mg/kg/day for males and 30, 100, or 400 mg/kg/day for females; to CD-1 mice for 18 months at dosage levels of 250, 500, or 1000 mg/kg/day; and to dogs for one year, via gelatin capsules, at dosage levels of 30, 100, or 400 mg/kg/day. In the rodent studies, each group consisted of 60 animals of each sex, and two concurrent independent control groups, each containing 60 animals/sex were included in each study. Each group in the dog study consisted of four male and four female dogs and one control group was included in the study. Treatment-related effects were observed at the highest dose level in all three studies. For rats, the effects included decreases in body weight and food consumption and an increase in serum cholesterol in females only. In mice, the effects observed were decreases in body weight and food consumption in both sexes. The effects observed in dogs included increased incidences of emesis and ptyalism, and levels of transient reduction in hemoglobin and hematocrit, increased alkaline phosphatase (males only), decreased cholesterol, and increased potassium. One male dog in the high-dose group also exhibited ataxia, tremors, abnormal head movements, and/or convulsions on several occasions during the study. The highest no-observed-effect levels (NO-ELs) for rats, mice and dogs were determined to be 100, 500, and 100 mg/kg/day, respectively. No specific target organ toxicity or oncogenicity was observed in any of the studies.

Based on (1) the animal toxicology database on N,N-diethyl-m-toluamide, (2) the reports of adverse events in humans, and (3) the possible alternate etiologies for the symptoms reported in most patients, the risk of adversity from label-directed use of N,N-diethyl-m-toluamide appears low. Future efforts should focus on the prospective collection of adversity data with special attention paid to the documentation of clinical effects.

No abstract

High doses of pyrethrins have been shown to produce liver tumors in female rats. Pyrethrins are not genotoxic agents. Pyrethrins produce liver tumors in rats by a mode of action (MOA) involving induction of hepatic xenobiotic metabolising enzymes, hypertrophy, increased cell proliferation, and the development of altered hepatic foci. The relevance of pyrethrins-induced rat liver tumors to human health was assessed by using the 2006 International Programme on Chemical Safety Human Relevance Framework. The postulated rodent tumor MOA was tested against the Bradford Hill criteria and was found to satisfy the conditions of dose and temporal concordance, biological plausibility, coherence, strength, consistency, and specificity that fit with an established mode of action for rodent liver tumor formation by phenobarbital and related compounds, which are activators of the constitutive androstane receptor. Other possible MOAs including mutagenicity, cytotoxicity, hepatic peroxisome proliferation, porphyria, and hormonal pertubation were excluded. The proposed MOA is considered not to be plausible in humans because pyrethrins, like phenobarbital, do not induce cell proliferation in human hepatocytes. Moreover, epidemiological studies with phenobarbital demonstrate that such compounds do not increase the risk of liver tumors in humans. It is concluded that pyrethrins do not pose a hepatocarcinogenic hazard for humans.