BackgroundA study in frog and chicken embryos, and reports of a high incidence of birth defects in regions of intensive GM-soy planting have raised concerns on the teratogenic potential of glyphosate-based herbicides. These public concerns prompted us to conduct a systematic review of the epidemiological studies testing hypotheses of associations between glyphosate exposure and adverse pregnancy outcomes including birth defects.MethodsA systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Bireme-BVS and SCOPUS databases using different combinations of exposure and outcome terms. A case–control study on the association between pesticides and congenital malformations in areas of extensive GM soy crops in South America, and reports on the occurrence of birth defects in these regions were reviewed as well.ResultsThe search found ten studies testing associations between glyphosate and birth defects, abortions, pre-term deliveries, small for gestational date births, childhood diseases or altered sex ratios. Two additional studies examined changes of time-to-pregnancy in glyphosate-exposed populations. Except for an excess of Attention Deficit Hyperactivity Disorder - ADHD (OR = 3.6, 1.3-9.6) among children born to glyphosate appliers, no significant associations between this herbicide and adverse pregnancy outcomes were described. Evidence that in South American regions of intensive GM-soy planting incidence of birth defects is high remains elusive.ConclusionsCurrent epidemiological evidence, albeit limited to a few studies using non-quantitative and indirect estimates and dichotomous analysis of exposures, does not lend support to public concerns that glyphosate-based pesticides might pose developmental risks to the unborn child. Nonetheless, owing to methodological limitations of existing analytical observational studies, and particularly to a lack of a direct measurement (urine and/or blood levels), or an indirect estimation of exposure that has proven valid, these negative findings cannot be taken as definitive evidence that GLY, at current levels of occupational and environmental exposures, brings no risk for human development and reproduction.

This survey is part of a more comprehensive study on the health consequences of pesticide exposure. In the county (municipality) of Paty do Alferes, Rio de Janeiro State, Brazil, 55 agricultural workers were interviewed on the use of pesticides, use of personal protective equipment, data on health status, and symptoms related to pesticide exposure, disposal of agrochemical containers, and technical assistance. The most widely used pesticides were insecticides such as abamectin, organophosphate compounds, and pyrethroids, and fungicides such as mancozeb, chlorothalonil, and copper products. As a rule, pesticides are handled carelessly, and 92% of workers involved in the mixing, loading, and spraying of insecticides and fungicides used no protective clothing or equipment whatsoever. Some 62% of workers reported at least one illness associated with mixing or spraying pesticides. The most frequently reported symptoms were headache, nausea, vomiting, dizziness, skin irritation, and blurred vision, and 21% of affected workers required medical care. In more than half (51%) of the cases, workers reported using organophosphate insecticides from toxicological class I when they felt sick.

Skin sensitization test data are required or considered by chemical regulation authorities around the world. These data are used to develop product hazard labeling for the protection of consumers or workers and to assess risks from exposure to skin-sensitizing chemicals. To identify opportunities for regulatory uses of non-animal replacements for skin sensitization tests, the needs and uses for skin sensitization test data must first be clarified. Thus, we reviewed skin sensitization testing requirements for seven countries or regions that are represented in the International Cooperation on Alternative Test Methods (ICATM). We noted the type of skin sensitization data required for each chemical sector and whether these data were used in a hazard classification, potency classification, or risk assessment context; the preferred tests; and whether alternative non-animal tests were acceptable. An understanding of national and regional regulatory requirements for skin sensitization testing will inform the development of ICATM's international strategy for the acceptance and implementation of non-animal alternatives to assess the health hazards and risks associated with potential skin sensitizers.

Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of the skin sensitisation adverse outcome pathway. Nevertheless, the currently adopted methods, when used in isolation, are not sufficient to fulfil regulatory requirements on the skin sensitisation potential and potency of chemicals comparable to that provided by the regulatory animal tests. For this reason, a number of defined approaches integrating data from these methods with other relevant information have been proposed and documented by the OECD. With the aim to further enhance regulatory consideration and adoption of defined approaches, the European Union Reference Laboratory for Alternatives to Animal testing in collaboration with the International Cooperation on Alternative Test Methods hosted, on 4–5 October 2016, a workshop on the international regulatory applicability and acceptance of alternative non-animal approaches, i.e., defined approaches, to skin sensitisation assessment of chemicals used in a variety of sectors. The workshop convened representatives from more than 20 regulatory authorities from the European Union, United States, Canada, Japan, South Korea, Brazil and China. There was a general consensus among the workshop participants that to maximise global regulatory acceptance of data generated with defined approaches, international harmonisation and standardisation are needed. Potential assessment criteria were defined for a systematic evaluation of existing defined approaches that would facilitate their translation into international standards, e.g., into a performance-based Test Guideline. Informed by the discussions at the workshop, the ICATM members propose practical ways to further promote the regulatory use and facilitate adoption of defined approaches for skin sensitisation assessments.

Following spontaneous delivery (n = 12) a pronounced increase in the maternal total white blood cell count was found (to [X ± SD]: 20 ± 6 × 10⁹ total leukocytes/1), which would be considered highly ‘pathological’ in nonpregnant women. The alteration was predominantly due to an increase in polymorph-nuclear cells and band forms. Simultaneously, a drastic decrease in the percentage and the absolute number of lymphocytes was noticed in venous blood (from 32 to 5%, or [X ± SD]: from 2.7 ± 0.7 to 1.1 ± 0.3 × 10⁹ total lymphocytes/1). In this decrease nearly all lymphocyte subtypes were involved, although to differing extents. Following elective caesarean delivery (n = 6), no leukocytosis was found, however the percentage and absolute number of lymphocytes was also decreased, although not as pronounced as after spontaneous delivery. Again not all the lymphocyte subpopulations were affected to the same degree, and the effect was especially obvious for the suppressor T cells and B cells. Following emergency caesarean delivery (n = 5), no obvious effect on the absolute number of lymphocytes or on the pattern of lymphocyte sub-populations was observed. However, the total number of white blood cells was clearly increased, as after spontaneous deliveries. The possible significance of these findings, also for therapeutic consequences during the perinatal period, is discussed.

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