Malathion dermal permeability in relation to dermal load: Assessment by physiologically based pharmacokinetic modeling of in vivo human data

Estimates of dermal permeability (K_p), obtained by fitting an updated human PBPK model for malathion to previously reported data on excreted urinary metabolites after 29 volunteers were dermally exposed to measured values of [¹⁴C]malathion dermal load (L), were used to examine the empirical relationship between K_p and L. The PBPK model was adapted from previously reported human biokinetic and PBPK models for malathion, fit to previously reported urinary excretion data after oral [¹⁴C]malathion intake by volunteers, and then augmented to incorporate a standard K_p approach to modeling dermal-uptake kinetics. Good to excellent PBPK-model fits were obtained to all of 29 sets of cumulative urinary metabolite-excretion data (ave. [±1 SD] R² = 0.953 [±0.064]). Contrary to the assumption that K_p and L are independent typically applied for dermally administered liquids or solutions, the 29 PBPK-based estimates of K_p obtained for malathion exhibit a strong positive association with the 2/3rds power of L (log-log Pearson correlation = 0.925, p = ～0). Possible explanations of this observation involving physico-chemical characteristics and/or in vivo cutaneous effects of malathion are discussed. The PBPK model presented, and our observation that K_p estimates obtained by fitting this model to human experimental urinary-excretion data correlate well with L^2/3, allow more realistic assessments of absorbed and metabolized dose during or after a variety of scenarios involving actual or potential dermal or multi-route malathion exposures, including for pesticide workers or farmers who apply malathion to crops.     

The role of percutaneous umbilical blood sampling in the management of immune thrombocytopenic purpura

On consultation, percutaneous umbilical blood sampling (PUBS) was offered to women with immune thrombocytopenic purpura (ITP) to determine the mode and site of delivery prior to labour. Between January 1989 and December 1993, 41 pregnant women underwent PUBS. All women had a history of ITP, a platelet count less than 90 K, (+) antiplatelet antibody, and/or thrombocytopenia diagnosed early in pregnancy. PUBS was performed at term except in one patient with preterm labour, who underwent PUBS at 31 weeks' gestation. Patients with fetal platelet counts greater than 50 K returned to their referring physician for delivery. Records were complete in 39 pregnancies. Fetal blood was successfully obtained in 37 of 39 cases (95 per cent). Fetal platelet counts correlated with neonatal platelet counts in 36 of 37 cases (97 per cent). The interval between PUBS and delivery ranged from 0 to 31 days. Six of 37 fetuses (16 per cent) had significant fetal thrombocytopenia (<50 K). These six patients underwent Caesarean section. Vaginal delivery was recommended in all others. There were two procedure-related complications. There were no cases of intraventricular haemorrhage in any of the neonates. In conclusion, there is a high incidence of fetal thrombocytopenia in women with ITP. PUBS reliably detects fetal thrombocytopenia and is therefore useful in the perinatal planning of the mode and site of delivery.     

Tumour-associated antigens in maternal and fetal blood

Normal levels of cancer-associated antigen (CA) 19-9, neurone-specific enolase (NSE), cancer-associated antigen (CA) 125, and mucin-like carcinoma-associated antigen (MCA) during pregnancy were determined in 87 mothers and fetuses, using a solid-phase sandwich enzyme immunoassay. CA 19-9 concentrations were higher in the fetuses, whereas the other three tumour-associated antigen levels were higher in the mothers. Only fetal NSE and MCA levels were positively correlated with those in maternal serum. Contrary to adult samples, no difference was demonstrated between male and female fetal levels of CA 125. MCA was the only maternal marker that increased significantly with gestational age between 20 and 34 weeks' pregnancy.