Felice Giordano

Maternal exposures to endocrine disrupting chemicals and hypospadias in offspring

BACKGROUND Prenatal exposures to endocrine-disrupting chemicals (EDCs) are suspected risk factors in the etiology of hypospadias. The aim of this case-control study was to test the hypothesis of an association between maternal environmental exposures to EDCs and hypospadias in the offspring. METHODS Detailed questionnaire data on occupational and dietary exposures to EDCs in the perinatal period were collected from 80 mothers with hypospadiac infants and from 80 mothers with healthy controls within 24 months of childbirth. Maternal exposure to selected EDCs was also ascertained by measuring the concentration of dichlorodiphenyldichloroethylene, hexachlorobenzene, and several polychlorinated biphenyl congeners in the serum of primiparous mothers of 37 cases and 21 controls. RESULTS The risk to bear an hypospadiac infant was associated with perinatal maternal occupational exposures to EDCs evaluated by a job-exposure matrix: jobs with exposure to one class of EDCs (odds ratios [OR](crude), 2.83; 95% confidence intervals [CI], 1.32-6.07; OR(adjusted), 2.44; 95% CI, 1.06-5.61) and jobs with exposure to more than one group of EDCs (OR(crude), 4.27; 95% CI, 1.43-12.78; OR(adjusted), 4.11; 95%CI, 1.34-12.59). Increase in risk was also found among mothers consuming a diet rich in fish or shellfish (OR(crude), 3.41; 95% CI, 1.42-8.23; OR(adjusted), 2.73; 95%CI, 1.09-6.82). Serum hexachlorobenzene concentration above the median of all subjects was significantly associated with the risk of hypospadias (OR(adjusted), 5.50; 95% CI, 1.24-24.31). CONCLUSIONS This study, although based on a limited number of cases, for the first time provides evidence of an association between maternal exposure to EDCs, in particular elevated plasma hexachlorobenzene concentration, and the development of hypospadias in the offspring.

Maternal diet and the risk of hypospadias and cryptorchidism in the offspring.

Male genital tract birth defects have been associated in previous studies with several prenatal exposures to environmental and dietary risk factors. The purpose of this study was to explore the association between hypospadias and cryptorchidism, and the dietary habits of an agricultural population in Italy. A population-based case-control study was conducted in the Sicilian Province of Ragusa. Cases (n = 90) and controls (n = 202) included births for the period 1998-2002. Data on dietary habits of the mothers, as well as health-related social, occupational and environmental exposures prior to and during the index birth, were collected through interviews. Adjusted odds ratios (OR) were calculated by logistic regression after adjustment for confounding variables. Increased ORs were observed for mothers of children with hypospadias who, during pregnancy, frequently consumed fish (OR = 2.33 [95% confidence interval (CI) 1.03, 5.31]) and market-purchased fruit (OR = 5.10 [95% CI 1.31, 19.82]). For cryptorchidism, increased risk was observed in mothers consuming liver (OR = 5.21 [95% CI 1.26, 21.50]), and smoked products (OR = 2.46 [95% CI 1.15, 5.29]). For the two malformations pooled together, increased risk was associated with maternal consumption of liver (OR = 4.38 [95% CI 1.34, 14.26]) and with frequent consumption of wine (OR = 1.98 [95% CI 1.01, 3.86]). This study suggests that some maternal dietary factors may play a role in the development of congenital defects of the male reproductive tract. In particular, our data indicate that further research may be warranted on the endocrine-disrupting effects resulting from the bioaccumulation of contaminants (fish, liver), pesticides (marketed fruit, wine) and/or potentially toxic food components (smoked products, wine, liver).

Surveillance of paediatric exposures to liquid laundry detergent pods in Italy

Objective To analyse paediatric exposures to pod and traditional laundry detergents in Italy and changes in exposure trends. Methods Analyses of a series of patients aged <5 years and exposed to laundry detergents between September 2010 and June 2015, identified by the National Poison Control in Milan. Results In comparison with patients exposed to traditional laundry detergents (n=1150), a higher proportion of those exposed to pods (n=1649) were managed in hospital (68% vs 42%), had clinical effects (75% vs 22%) and moderate/high severity outcomes (13% vs <1%). Exposure rates were stable over time for traditional detergents (average 0.65 cases/day), but an abrupt decline in major company pods was seen in December 2012, 4 months after the introduction of opaque outer packaging (from 1.03 to 0.36 cases/day and from 1.88 to 0.86 cases/million units sold). The odds of clinical effects was higher for exposure to pods than for traditional detergents (OR=10.8; 95% CI 9.0 to 12.9). Among patients exposed to pods, the odds of moderate/high severity outcomes was four times higher for children aged <1 years than for the other age groups (OR=3.9; 95% CI 2.2 to 7.0). Ten children exposed to laundry detergent pods had high severity outcomes while no children exposed to traditional laundry detergents developed high severity effects. Conclusions The study confirms that exposure to laundry detergent pods is more dangerous than exposure to traditional detergents. In Italy, 4 months after the introduction of opaque outer packaging by a major company, product-specific exposure rates decreased sharply, suggesting that reducing visibility of laundry detergent pods may be an effective preventive measure. Further efforts are needed to improve safety.

375 Surveillance of Plant Protection Pesticides-related poisonings and injuries

Background Regulation 2009/1185/EU on sustainable use of pesticides requires reporting from European Member States on plant protection pesticide (PPP) poisonous exposures. These data can provide information to identify emerging problems and populations at risk, support the development of preventive and regulatory measures and evaluate their effectiveness. In Italy, a surveillance of acute PPP-related poisonings (SAPReP), based on Poison Control Centres data, has been implemented since 2001. In this contribution are presented the main characteristics of cases exposed in Italy in 2007–2012. Methods series of cases identified by the National Poison Control Centre in Milan, reviewed and classified by the Italian National Institute of Health according to standard procedures. Results In 2007–2012, SAPReP identified 2,108 cases of accidental PPP-related poisonings and injuries. Male patients were 1,442 (68%) while females were 442 (20%). Gender was unknown in 12% of cases (No. 224) Severity of poisoning was low in 84% of cases (No. 1,774), moderate in 14% (n. 305), high in 1% (n. 28). One case of death was identified. About 50% of poisonings occurred at work, in agricultural settings, and 36% at home. Some 70% of exposures occurred between May and September. Insecticides/acaricides were responsible in 42% of poisonings, fungicides/bactericides in 16%, herbicides in 15%, and soil sterilants in 13%. Five mass exposures were identified: two incidents were caused by off-site drift of metam sodium, a soil sterilant, and involved 86 and 103 by-standers, respectively; two incidents were caused by chlorpyrifos methyl, an organophosphate insecticide/acaricide (one occurred in a hospital, 10 cases; one occurred in agricultural setting, 20 agricultural workers); one incident was caused by phenthoate and involved 40 agricultural workers Conclusions Surveillance based on data collected by Poison Control Centres provides an important tool to identify emerging problems and associated risk factors. The observations available in Italy on PPP-related poisonings and injuries suggest that greater efforts are needed to prevent these types of incidents.

239 Surveillance of toxic exposures to liquid laundry detergents in pods in Italy

Background Previous investigations have shown that liquid laundry detergents in pods have the potential to cause corrosive eye damages, pulmonary toxicity and serious laryngopharyngeal injuries. In Italy, different actions had been undertaken to prevent hazardous exposures in young children. The present study is mainly aimed at providing a preliminary evaluation of impact of these preventive measures. Methods Exposures to laundry detergents involving children aged <5 years occurred during 2010–2014 were extracted from the National Poison Control Centre in Milan (NPCCM). The main characteristics of cases exposed to the two main categories of laundry detergents, i.e., liquid laundry detergents in pods (LDPs) and traditional laundry detergents (TLDs) were compared by means of Pearson’s X2 test or Fisher’s exact test. The mean daily number of exposure to main category of laundry detergents by month and year, and quantity of LDPs sold by month and company, i.e., MC and OCs, as provided by industry, were used to calculate exposure rates, i.e., number of cases exposed to LDPs/millions of units sold/month by year and company. Change-point analysis was used to determine significant changes in exposure occurrence during the study period. A change was considered significant when the level of confidence that the change actually occurred was 95% or higher, as estimated by bootstrapping technics. Significant change points were used to define pre- and post-change point periods. Results In comparison to cases exposed to TDLs (n = 1,203) those exposed to LDPs (n = 1,551) were more frequently treated at an hospital (68% vs 41%, p < 0.001), and suffered moderate/high severity clinical effects (13% vs <1%, p < 0.0001). During the study period, the number of cases exposed to pods changed from an average of 1.3 cases/day, observed in September 2010–November 2012, to an average of 0.6 cases/day, observed in December 2012–December 2014. The observed change was specifically driven by products from a major company whose average rates were 2.10 cases/million units sold before December 2012, and 0.97 cases/million units sold in the following period. The rate change occurred four months after this company started selling its brands in obscure outer-packaging. Conclusions The present study indicates that reducing visibility of LDPs could be associated with about a 50% decrease of incidents among young children. However, considering that these products are strongly associated with severity of poisoning, further efforts should be devoted to prevent hazardous exposure and reduce the intrinsic toxicity of mixtures in pods.

Inadvertent oral administration of methylergometrine maleate to children in the first months of life: from surveillance to prevention.

Methylergometrine maleate is an ergot alkaloid frequently used in obstetrics for prevention and treatment of post partum haemorrhage. Accidental administration of this medicine to newborns can cause severe effects and should be carefully prevented. The present paper is aimed at describing the main characteristics of cases accidentally exposed to this medicine in Italy before and after Novartis, the manufacturer of Methergin®, a widely used methylergometrine maleate‐containing gynecological medication, decided to withdraw the drop preparation from the European market.