As has been noted in previous posts, toxicological effects of various chemicals are often first analyzed using tests on cells, followed by tests on various animals (particularly rats and mice). Pyrethroid pesticides are widely used worldwide. [See http://en.wikipedia.org/wiki/Pyrethroid for a brief overview of the pesticide.] They appear to work by delaying the closure of cellular sodium channels. [See http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~KhDuE9:10:actn.] They are considerably less toxic to mammals than are other classes of insecticides, such as organochlorines, organophosphates, and carbamates, and thus represent one-quarter of worldwide market for insecticides. [An overview of various types of insecticides can be found at http://en.wikipedia.org/wiki/Insecticide.] Their popularity appears to be growing. Because of their low toxicity, they are frequently used around homes and daycare facilities. Their low toxicity to mammals may result from their rapid biodegradation by liver enzymes, followed by rapid excretion through the kidneys of the metabolites. [See http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~KhDuE9:10:ade.] Pyrethroids have been detected in baby food, urine, and breast milk. The most likely route of exposure is through the consumption of food. [See, for example, http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~KhDuE9:10:rtex.] In http://www.ehponline.org/members/2008/11119/11119.html, the researchers investigated whether the pyrethroid insecticide Esfenvalerate (Esf) had estrogenic effects. They exposed immature female Sprague-Dawley rats. The rats were bred and allowed to deliver their pups normally. On postnatal day (PND) 2, the pups were culled from individual litters, if necessary, so that the litter size for each dam was 10–12 pups total, with at least 5–6 females per litter. Female pups from 50 separate litters were used for the experiments. For all experiments, littermates were randomly assigned to treatment groups. Esf was mixed with corn oil and administered into the stomach beginning on PND22 and continuing until vaginal opening (VO) occurred. The results showed that Esf did not effect weight gain. However, Esf did delay VO and the onset of puberty. In those rats exposed to the higher doses of Esf, an effect was observed on certain puberty related hormones. In commenting on the results, the authors note: "Although the exact mechanism of action is unknown at this time, we observed the effects at dosage levels below the NOEL established through chronic dietary exposure studies in rats. The U.S. EPA (1998) stated that ''There is no evidence of additional sensitivity to young rats or rabbits following pre- or postnatal exposure to esfenvalerate.'' The present study shows that immature female rats exposed to 1.0 mg/kg/day are sensitive to this pesticide, as evidenced by their delay in the onset of puberty. Delayed pubertal onset in humans has been associated with low bone mass density (Ho and Kung 2005), and estrogen is necessary for bone mineral acquisition in both girls and boys (Yilmaz et al. 2005). Importantly, a lowered endogenous estrogen level in females is one factor associated with bone fragility (Hoffman and Bradshaw 2003). This could potentially affect current established exposure levels for humans, because the reference dose for ESF of 0.02 mg/kg/day is based directly on the rodent NOEL of 2.0 mg/kg/day. Obviously, more basic research is needed in this area; because of the worldwide use of this class of pesticide, further studies are warranted."