Toxicity can depend on sex, circadian rhythms, and age. Such dependence is well documented in both laboratory animals and humans. The variation is mostly related to eating and sleeping habits. Nocturnal animals usually have more food in their stomach in the morning than in the late afternoon. Agents that affect activity and are ingested by animals that normally eat at night exhibit a different effect compared with agents ingested by animals that sleep throughout the night.
Gender differences have been found for organophosphate insecticides. Overall, female rats are more susceptible to the toxic effects of parathion than are male rats. In addition to the toxicity differences that can occur between genders, several other hormone-dependent effects influence the toxicity of compounds. Pregnancy markedly increases the susceptibility of animals to pesticides, and lactating animals are more susceptible to heavy metals. Hyperthyroidism and hyperinsulinism may alter the susceptibility of animals and humans to toxicants.
With age, our ability to metabolize foreign compounds reduces. Xenobiotic metabolism is low or absent in the fetus and neonates, develops rapidly after birth, and is highest in early adulthood. Before birth, the capacity for handling metabolism of foreign compounds is through the mother’s metabolism. Clusters of different enzymes seem to develop rapidly during development periods, birth, weaning, and puberty. Many of the age-related differences, particularly between the young and old, can be explained by quantitative differences in detoxification processes. There is also a difference in hepatic and renal clearances of toxicants between newborn and adult animals. The necessity for dose adjustment is well recognized in pediatrics and in certain situations wherein patients have impaired kidneys. Many phase II enzymes are expressed soon after birth like Enzymes for metabolism of steroids and bilirubin develop after birth, which explains the development of neonatal jaundice. Phase I and II enzymes can be expressed at higher levels during lactation and decline following weaning.