Harry Emmen

Effects of perinatal exposure to PCBs on neuropsychological functions in the Rotterdam cohort at 9 years of age.

PCBs are known for their neurotoxic properties, especially on the developing brain. To increase insight into the neurotoxic effects of PCB exposure, the authors studied the effects of perinatal exposure to environmental levels of these compounds on different neuropsychological domains. In 9-year-old children of the Rotterdam PCB--dioxin cohort, higher prenatal PCB levels were associated with longer response times (RTs), more variation in RTs, and lower scores on the Tower of London (TOL; Shallice, 1982). A longer breast-feeding duration was associated with lower TOL scores and with better spatial organizational skills. There was some evidence of negative effects of lactational exposure to PCBs on scores on the TOL.

Behavioral effects of exposure to organic solvents in Dutch painters

The report describes the results of a cross-sectional study of solvent-exposed young and older Dutch painters and two age-matched control groups. Both traditional and computerized neurobehavioral tests were applied. The study did not detect any major differences between the two groups of painters and their two age-matched control groups. It is argued that this absence of differences is probably not due to a lack of sensitivity of the tests applied or the size of the groups studied. The level of exposure was estimated to be within a range at which previous authors have reported solvent-induced CNS effects.

An analysis of human response to the irritancy of acetone vapors

Studies on the irritative effects of acetone vapor in humans and experimental animals have revealed large differences in the lowest acetone concentration found to be irritative to the respiratory tract and eyes. This has brought on much confusion in the process of setting occupational exposure limits for acetone. A literature survey was carried out focusing on the differences in results between studies using subjective (neuro)behavioral methods (questionnaires) and studies using objective measurements to detect odor and irritation thresholds. A critical review of published studies revealed that the odor detection threshold of acetone ranges from about 20 to about 400 ppm. Loss of sensitivity due to adaptation and/or habituation to acetone odor may occur, as was shown in studies comparing workers previously exposed to acetone with previously unexposed subjects. It further appeared that the sensory irritation threshold of acetone lies between 10,000 and 40,000 ppm. Thus, the threshold for sensory irritation is much higher than the odor detection limit, a conclusion that is supported by observations in anosmics, showing a ten times higher irritation threshold level than the odor threshold found in normosmics. The two-times higher sensory irritation threshold observed in acetone-exposed workers compared with previously nonexposed controls can apart from adaptation be ascribed to habituation. An evaluation of studies on subjectively reported irritation at acetone concentrations <1000 ppm shows that perception of odor intensity, information bias, and exposure history (i.e., habituation) are confounding factors in the reporting of irritation thresholds and health symptoms. In conclusion, subjective measures alone are inappropriate for establishing sensory irritation effects and sensory irritation threshold levels of odorants such as acetone. Clearly, the sensory irritation threshold of acetone should be based on objective measurements.

Symptoms indicative of the effects of organic solvent exposure in Dutch painters.

The report describes the results of a cross-sectional study among two groups of young and older painters and two age-matched control groups. The study was intended to gather information on the occurrence of solvent-exposure symptoms among Dutch workers using a mailed questionnaire. Results indicated that among young painters and to a lesser extent among older painters what is commonly accepted as specific symptoms and additional solvent-related symptoms showed a higher frequency than among the controls. The most interesting observation was a significant relationship between the frequency of periods of heavy exposure and the severity of most symptom categories, whereas there was a lack of consistent relationships with other exposure parameters.

From cutting edge to guideline: A first step in harmonization of the zebrafish embryotoxicity test (ZET) by describing the most optimal test conditions and morphology scoring system

In the last couple of years, the interest in the zebrafish embryotoxicity test (ZET) for use in developmental toxicity assessment has been growing exponentially. This is also evident from the recent proposal for updating the ICHS5 guideline. The methodology of the ZET used by the different groups varies greatly. To further evaluate its successfulness and to take the ZET to the next level, harmonization of procedures is crucial. In the present study, based on literature and empirical data, the most optimal study design regarding temperature, test chamber, exposure period, presence of chorion, solvent use, exposure method, choice of concentrations, and teratogenic classification is proposed. Furthermore, our morphology scoring system is reported in detail as protocol to further enhance study design harmonization.

Behavioral effects of exposure to organic solvents in carpet layers

Carpet layers and age-matched controls were investigated both at the beginning of a working day and at the end with four subtests of a neuropsychological test battery (NES2). Exposure to toluene, cyclohexane, ethyl acetate, and heptane was measured with personal air sampling methods. One group of carpet layers used water-based adhesives (WBA) on the day the investigation took place and the other group used contact adhesives (CA) on that day. The WBA group was exposed primarily to toluene, and the CA group was exposed to other solvents as well. Initial (before work) differences in neuropsychological scores between all exposed workers and controls could be attributed to differences in education, the carpet layers being somewhat higher educated. No differences were found between the solvent-exposed and control groups that would suggest persistent effects of chronic solvent exposures. The improvement in test scores over the day was the same in both groups. However, evidence for exposure-related changes in test scores over the day were found within the exposed group.

Visualizing Compound Distribution during Zebrafish Embryo Development: The Effects of Lipophilicity and DMSO

The predictability of the zebrafish embryo model is highly influenced by internal exposure of the embryo/larva. As compound uptake is likely to be influenced by factors such as lipophilicity, solvent use, and chorion presence, this article focuses on investigating their effects on compound distribution within the zebrafish embryo. To visualize compound uptake and distribution, zebrafish embryos were exposed for 96 hr, starting at 4 hr postfertilization, to water-soluble dyes: Schiffs reagent (logP -4.63), Giemsa stain (logP -0.77), Van Gierson stain (logP 1.64), Cresyl fast violet (logP 3.5), Eosine Y (logP 4.8), Sudan III (logP 7.5), and Oil red O (logP 9.81), with and without 1% dimethyl-sulfoxide (DMSO). Three additional compounds were used to analytically determine the uptake and distribution: Acyclovir (logP -1.56), Zidovudine (logP 0.05), and Metoprolol Tartrate Salt (logP 1.8). Examinations were performed every 24 hr. Both methods (visualization and specific analysis) showed that exposure to higher logP values results in higher compound uptake. Specific analysis showed that for lipophilic compounds >90% of compound is taken up by the embryo. For hydrophilic compounds, >90% of compound within the complete egg could not be associated to embryo or chorion and is probably distributed into the perivitelline space. Overall, internal exposure analyses on at least two occasions (i.e., before and after hatching) is crucial for interpretation of zebrafish embryotoxicity data, especially for compounds with extreme logP values. DMSO did not affect exposure when examined with the visualization method, however, this method might be not sensitive enough to draw hard conclusions.

Neurobehavioral Effects of Cyclohexane in Rat and Human

The neurobehavioral effects of inhaled cyclohexane in rats and humans are investigated to define relationships between internal doses and acute central nervous system effects. Rats are exposed for 3 consecutive days at target concentrations of 0, 1.4, 8, and 28 g/m3, 8 h/d. Measurements include standardized observational measures, spontaneous motor activity assessments, and learned visual discrimination performance. Cyclohexane concentrations in blood and brain are measured to assess internal exposure. Human volunteers are exposed for 4 hours to 86 or 860 mg/m3 in 2 test sessions. Neurobehavioral effects are measured using a computerized neurobehavioral test battery. In rats, there are slight reductions in psychomotor speed in the high-exposure group but minimal central nervous system effects. In humans, there are no significant treatment-related effects at the levels tested.

Subchronic toxicity evaluation of potato protein isolates.

The protein content of potatoes has a high nutritional value on par with eggs and soybeans. As a result, processed potato protein isolates may have commercial value for addition to other food products to increase protein content. A manufacturing process has been developed to produce total potato (TP), as well as low (LMW) and high molecular (HMW) weight, protein isolates as food ingredients. To assess the safety of these isolates, groups of 10 Wistar rats/sex were administered dietary admixtures containing 15% HMW, 7.5% LMW or 15% TP protein isolates for a period of 90days. There was no effect of treatment on clinical signs, mortality, body weight and body weight gain. No biologically significant changes occurred in hematological and clinical chemistry parameters. No statistically significant changes in organ weights were recorded. Histopathological analyses revealed no clear, treatment-related changes. A slight increase in the incidence, but not severity, of vacuolation of the zona fasciculate of the adrenal gland was noted in males of the 15% HMW and 7.5% LMW groups. The finding was not considered adverse or ascribed any toxicological significance. Overall, HMW, LMW, and TP protein isolates were well-tolerated and without adverse effect. These data support the safety of potato protein isolates.

Update of OECD DART guidelines with endocrine disruptor relevant endpoints: Practical considerations.

In 1998, the OECD initiated a high-priority project aimed at revising existing test guidelines and developing new test guidelines for screening of potential endocrine disruptors. In 2011, OECD 443 was adopted, and in 2015 OECD 421 and OECD 422 were updated with endocrine disruptor relevant endpoints. A feasibility study for the enhancement of OECD 414 with endocrine disruptor relevant endpoints is currently ongoing. The addition of these endpoints is considered crucial for gaining more information on endocrine disruptor potency of tested chemicals, however it should be noted that these additions have a major impact on the study designs and give rise to several practical challenges. The aim of this review is to discuss important aspects of these challenging study designs and to share our knowledge on their implementation in our laboratory. Together, this review can be used as guidance for other laboratories, study monitors and registration officers.