variation in the sequence of PON1 and its promoter region that may influence the effectiveness of PON1 at detoxifying chlorpyrifos oxon and the amount of PON1 available to do so. Some evidence indicates that children born to women with low PON1 may be particularly susceptible to chlorpyrifos exposure. Further, infants produce low levels of PON1 until six months to several years after birth, likely increasing the risk from chlorpyrifos exposure early in life. Combined exposures Several studies have examined the effects of combined exposure to chlorpyrifos and other chemical agents, and these combined exposures can result in different effects during development. Female rats exposed first to dexamethasone, a treatment for premature labor, for three days in utero and then to low levels of chlorpyrifos for four days after birth experienced additional damage to the acetylcholine system upstream of the synapse that was not observed with either exposure alone. In both male and female rats, combined exposures to dexamethasone and chlorpyrifos decreased serotonin turnover in the synapse, for female rats with a greater-than-additive result. Rats that were co-exposed to dexamethasone and chlorpyrifos also exhibited complex behavioral differences from exposure to either chemical alone, including lessening or reversing normal sex differences in behavior. In the lab, in rats and neural cells co-exposed to both nicotine and chlorpyrifos, nicotine appears to protect against chlorpyrifos acetylcholinesterase inhibition and reduce its effects on neurodevelopment. In at least one study, nicotine appeared to enhance chlorpyrifos detoxification. Human exposure In 2011, EPA estimated that, in the general US population, people consume 0.009 micrograms of chlorpyrifos per kilogram of their body weight per day directly from food residue. Children are estimated to consume a greater quantity of chlorpyrifos per unit of body weight from food residue, with toddlers the highest at 0.025 micrograms of chlorpyrifos per kilogram of their body weight per day. People may also ingest chlorpyrifos from drinking water or from residue in food handling establishments. The EPA's acceptable daily dose is 0.3 micrograms/kg/day. However, as of 2016, EPA scientists had not been able to find any level of exposure to the pesticide that was safe. The EPA 2016 report states in part "... this assessment indicates that dietary risks from food alone are of concern ..." The report also states that previous published risk assessments for "chlorpyrifos may not provide a sufficiently health protective human health risk assessment given the potential for neurodevelopmental outcomes." Humans