Francesca Metruccio

Exposure to PFOA and PFOS and fetal growth: a critical merging of toxicological and epidemiological data

Abstract Toxicological and epidemiological evidence on the association between perfluorooctanoic acid (PFOA) or perfluorooctane sulfonic acid (PFOS) and birth/fetal weight was assessed. An extensive search for toxicological information in rats and mice, and a systematic search for epidemiological evidence were conducted. The linear regression coefficient (LRC) of birth weight (BrthW) on PFOA/PFOS was considered, and separate random effects meta-analyses for untransformed (i.e. not mathematically transformed) and log-transformed values were performed. Toxicological evidence: PFOA: 12 studies (21 datasets) in mice showed statistically significant lower birth/fetal weights from 5 mg/kg body weight per day. PFOS: most of the 13 studies (19 datasets) showed lower birth/fetal weights following in utero exposure. Epidemiological evidence: Sixteen articles were considered. The pooled LRC for a 1 ng/mL increase in untransformed PFOA (12 studies) in maternal plasma/serum was −12.8 g (95% CI −23.2; 2.4), and −27.1 g (95% CI −50.6; −3.6) for an increase of 1 loge ng/mL PFOA (nine studies). The pooled LRC for untransformed PFOS (eight studies) was −0.92 g (95%CI −3.4; 1.6), and for an increase of 1 loge ng/mL was −46.1(95% CI −80.3; −11.9). No consistent pattern emerged for study location or timing of blood sampling. Conclusions: Epidemiological and toxicological evidence suggests that PFOA and PFOS elicit a decrease in BrthW both in humans and rodents. However, the effective animal extrapolated serum concentrations are 102–103 times higher than those in humans. Thus, there is no quantitative toxicological evidence to support the epidemiological association, thus reducing the biological plausibility of a causal relationship.

The use of in vitro testing to refine cumulative assessment groups of pesticides: The example of teratogenic conazoles

The most relevant issues in cumulative risk assessment (CRA) are the identification of cumulative assessment groups and the hypothesis of dose-additivity, at relevant human exposures. In vitro methods can provide meaningful data to help solving those issues. Integration of in vitro studies, selected in vivo studies, and PBPK modeling for teratogenic conazoles confirmed that in vitro studies may give results in a cheaper and faster fashion. In particular, in vitro studies with explanted rat embryos provided support for dose-additivity for conazoles causing cranio-facial malformations. Although this could not be immediately quantitatively transferred to the in vivo situation, they provided indication on how to conduct targeted in vivo studies. In addition, by means of PBPK modeling, it was possible to estimate the dose in humans associated with a defined teratogenic risk and also to conclude that for cumulative risk assessment only exposures occurring within a short period of time (a day or less) need to be cumulated. Although PBPK modeling cannot be widely applied, at least in the short term, it should be considered if available. It is recommended to incorporate in vitro testing and PBPK modeling, whenever available and feasible in the process of risk assessment, particularly of CRA.

The Ascidian Embryo Teratogenicity assay in Ciona intestinalis as a new teratological screening to test the mixture effect of the co-exposure to ethanol and fluconazole

The aim of this work was to evaluate the Ascidian Embryo Teratogenicity assay (AET) as new alternative invertebrate model to test the developmental effects of the co-exposure to ethanol and fluconazole. Ciona intestinalis embryos were exposed to the azolic fungicide fluconazole, (FLUCO, 7.8-250μM), to ethanol (Eth, 0.01-0.5%) and to their mixture (0.01% Eth+FLUCO 7.8-250μM) from neurula to larval stage. At the end of the exposure period, larvae were morphologically evaluated and benchmark analysis performed by using the PROAST modelling software. Both compounds were teratogenic in a concentration-related manner, particularly affecting the pigmented organs. The co-exposure to Eth enhanced the effects of FLUCO, the additive hypothesis was not rejected by the modelling. The results demonstrated that AET could be considered a good vertebrate-free alternative model for toxicological investigation in embryos.

The Italian system of data reporting in agriculture occupational health: a critical appraisal

BackgroundAgriculture is one of the most hazardous sectors in both developing and industrialized countries. Agricultural workers suffer markedly higher rates of accidents and fatal injuries than other workers, with very few resources available for compensation. One of the difficulties in dealing with agriculture is that it is a very complex and heterogeneous sector. Due to inadequate and non-standardized recording and notification systems, official data on the incidence of agricultural occupational accidents and diseases are imprecise, notoriously underestimated, unsatisfactory and inadequate as an indicator for measuring the effect of interventions.AimTo explore the peculiarities of data reporting systems among agricultural sector focusing on the Italian situation.Results and conclusionIn recent decades far-reaching national efforts in the sector of occupational safety and health have led to redefinitions and shifts in national policies and priorities, with wide-scale involvement of public and social bodies, field experts, companies, trade unions, public and private insurance agencies. Even so, compared to workers in other sectors, agricultural workers are still under-protected. Occupational safety and health in agriculture need to be addressed with a well-defined strategy and must be integrated into a rural development policy. Integration into the primary health care structure is strongly recommended.