Browsing by Subject "Organophosphates"

Now showing 1 - 6 of 6
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    Developmental exposure to an organophosphate flame retardant alters later behavioral responses to dopamine antagonism in zebrafish larvae.
    (Neurotoxicology and teratology, 2018-05) Oliveri, Anthony N; Ortiz, Erica; Levin, Edward D
    Human exposure to organophosphate flame retardants (OPFRs) is widespread, including pregnant women and young children with whom developmental neurotoxic risk is a concern. Given similarities of OPFRs to organophosphate (OP) pesticides, research into the possible neurotoxic impacts of developmental OPFR exposure has been growing. Building upon research implicating exposure to OP pesticides in dopaminergic (DA) dysfunction, we exposed developing zebrafish to the OPFR tris(1,3-dichloroisopropyl) phosphate (TDCIPP), during the first 5 days following fertilization. On day 6, larvae were challenged with acute administration of dopamine D1 and D2 receptor antagonists and then tested in a light-dark locomotor assay. We found that both developmental TDCIPP exposure and acute dopamine D1 and D2 antagonism decreased locomotor activity separately. The OPFR and DA effects were not additive; rather, TDCIPP blunted further D1 and D2 antagonist-induced decreases in activity. Our results suggest that TDCIPP exposure may be disrupting dopamine signaling. These findings support further research on the effects of OPFR exposure on the normal neurodevelopment of DA systems, whether these results might persist into adulthood, and whether they interact with OPFR effects on other neurotransmitter systems in producing the developmental neurobehavioral toxicity.
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    Developmental Exposure to Low Concentrations of Organophosphate Flame Retardants Causes Life-Long Behavioral Alterations in Zebrafish.
    (Toxicological sciences : an official journal of the Society of Toxicology, 2018-10) Glazer, Lilah; Hawkey, Andrew B; Wells, Corinne N; Drastal, Meghan; Odamah, Kathryn-Ann; Behl, Mamta; Levin, Edward D
    As the older class of brominated flame retardants (BFRs) are phased out of commercial use because of findings of neurotoxicity with developmental exposure, a newer class of flame retardants have been introduced, the organophosphate flame retardants (OPFRs). Presently, little is known about the potential for developmental neurotoxicity or the behavioral consequences of OPFR exposure. Our aim was to characterize the life-long neurobehavioral effects of 4 widely used OPFRs using the zebrafish model. Zebrafish embryos were exposed to 0.1% DMSO (vehicle control); or one of the following treatments; isopropylated phenyl phosphate (IPP) (0.01, 0.03, 0.1, 0.3 µM); butylphenyl diphenyl phosphate (BPDP) (0.003, 0.03, 0.3, 3 µM); 2-ethylhexyl diphenyl phosphate (EHDP) (0.03, 0.3, 1 µM); isodecyl diphenyl phosphate (IDDP) (0.1, 0.3, 1, 10 µM) from 0- to 5-days postfertilization. On Day 6, the larvae were tested for motility under alternating dark and light conditions. Finally, at 5-7 months of age the exposed fish and controls were tested on a battery of behavioral tests to assess emotional function, sensorimotor response, social interaction and predator evasion. These tests showed chemical-specific short-term effects of altered motility in larvae in all of the tested compounds, and long-term impairment of anxiety-related behavior in adults following IPP, BPDP, or EHDP exposures. Our results show that OPFRs may not be a safe alternative to the phased-out BFRs and may cause behavioral impacts throughout the lifespan. Further research should evaluate the risk to mammalian experimental models and humans.
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    Developmental exposure to the flame retardant, triphenyl phosphate, causes long-lasting neurobehavioral and neurochemical dysfunction.
    (Birth defects research, 2023-02) Hawkey, Andrew B; Evans, Janequia; Holloway, Zade R; Pippen, Erica; Jarrett, Olivia; Kenou, Bruny; Slotkin, Theodore A; Seidler, Frederic J; Levin, Edward D

    Background

    Human exposures to organophosphate flame retardants result from their use as additives in numerous consumer products. These agents are replacements for brominated flame retardants but have not yet faced similar scrutiny for developmental neurotoxicity. We examined a representative organophosphate flame retardant, triphenyl phosphate (TPP) and its potential effects on behavioral development and dopaminergic function.

    Methods

    Female Sprague-Dawley rats were given low doses of TPP (16 or 32 mg kg-1  day-1 ) via subcutaneous osmotic minipumps, begun preconception and continued into the early postnatal period. Offspring were administered a battery of behavioral tests from adolescence into adulthood, and littermates were used to evaluate dopaminergic synaptic function.

    Results

    Offspring with TPP exposures showed increased latency to begin eating in the novelty-suppressed feeding test, impaired object recognition memory, impaired choice accuracy in the visual signal detection test, and sex-selective effects on locomotor activity in adolescence (males) but not adulthood. Male, but not female, offspring showed marked increases in dopamine utilization in the striatum, evidenced by an increase in the ratio of the primary dopamine metabolite (3,4-dihydroxyphenylacetic acid) relative to dopamine levels.

    Conclusions

    These results indicate that TPP has adverse effects that are similar in some respects to those of organophosphate pesticides, which were restricted because of their developmental neurotoxicity.
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    Levels of Urinary Metabolites of Organophosphate Flame Retardants, TDCIPP, and TPHP, in Pregnant Women in Shanghai.
    (J Environ Public Health, 2016) Feng, Liping; Ouyang, Fengxiu; Liu, Liangpo; Wang, Xu; Wang, Xia; Li, Yi-Ju; Murtha, Amy; Shen, Heqing; Zhang, Junfeng; Zhang, Jun Jim
    Flame retardants are widely used in consumer products to reduce their flammability. Previously used flame retardants have been sequentially banned due to their environmental and human toxicity. Currently, tris(1,3-dichloropropyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) are among the most commonly used flame retardants. TDCIPP and TPHP are reproductive toxins and have carcinogenic, neurotoxic, and endocrine-disrupting properties. Although high levels of TDCIPP and TPHP have been found in drinking water, seawater, and office air in China, data regarding human exposure are lacking. In this study, we assessed the level of urinary TPHP and TDCIPP metabolites (DPHP and BDCIPP, resp.) in a cohort of pregnant women (N = 23) from Shanghai, China, using liquid chromatography-tandem mass spectrometry. DPHP were detected in 100% urine samples, while only four urine samples had detectable level of BDCIPP in this cohort (17% detected). Geometric means of DPHP and BDCIPP concentrations were 1.1 ng/mL (interquartile range [IQR]: 0.6, 1.5 ng/mL) and 1.2 ng/mL (IQR: 0.6, 2.2 ng/mL), respectively. In this small cohort, urinary DPHP and BDCIPP levels were not significantly correlated with miscarriages, neonatal birthweight, gestational diabetes, or maternal age. These data suggest that exposure to TPHP is widespread, and they demonstrate the feasibility of using urinary biomarkers to measure exposures to modern flame-retardant chemicals.
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    Persistent neurobehavioral and neurochemical anomalies in middle-aged rats after maternal diazinon exposure.
    (Toxicology, 2022-04) Hawkey, Andrew B; Pippen, Erica; Kenou, Bruny; Holloway, Zade; Slotkin, Theodore A; Seidler, Frederic J; Levin, Edward D
    Diazinon is an organophosphate pesticide that has a history of wide use. Developmental exposures to organophosphates lead to neurobehavioral changes that emerge early in life and can persist into adulthood. However, preclinical studies have generally evaluated changes through young adulthood, whereas the persistence or progression of deficits into middle age remain poorly understood. The current study evaluated the effects of maternal diazinon exposure on behavior and neurochemistry in middle age, at 1 year postpartum, comparing the results to our previous studies of outcomes at adolescence and in young adulthood (4 months of age) (Hawkey 2020). Female rats received 0, 0.5 or 1.0 mg/kg/day of diazinon via osmotic minipump throughout gestation and into the postpartum period. The offspring were tested on a battery of locomotor, affective, and cognitive tests at young adulthood and during middle age. Some of the neurobehavioral consequences of developmental DZN seen during adolescence and young adulthood faded with continued aging, whereas other neurobehavioral effects emerged with aging. At middle age, the rats showed few locomotor effects, in contrast to the locomotor hyperactivity that had been observed in adolescence. Notably, though, DZN exposure during development impaired reference memory performance in middle-aged males, an effect that had not been seen in the younger animals. Likewise, middle-aged females exposed to DZN showed deficient attentional accuracy, an effect not seen in young adults. Across adulthood, the continued potential for behavioral defects was associated with altered dopaminergic function, characterized by enhanced dopamine utilization that was regionally-selective (striatum but not frontal/parietal cortex). This study shows that the neurobehavioral impairments from maternal low dose exposure to diazinon not only persist, but may continue to evolve as animals enter middle age.
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    The organophosphate insecticide diazinon and aging: Neurobehavioral and mitochondrial effects in zebrafish exposed as embryos or during aging.
    (Neurotoxicology and teratology, 2021-09) Boyda, Jonna; Hawkey, Andrew B; Holloway, Zade R; Trevisan, Rafael; Di Giulio, Richard T; Levin, Edward D
    Organophosphate (OP) compounds comprise one of the most widely used classes of insecticides worldwide. OPs have been shown to have negative human health impacts, particularly developmental neurotoxicity. However, neurotoxic impacts in later adulthood and during the aging process are relatively uncharacterized. The present study examined diazinon (DZN), an OP, to determine the neurobehavioral consequences, in addition to mitochondrial dysfunction on a macroscale (whole organism basal respiration) and on a microscale (whole organ mitochondrial respiration), using zebrafish (ZF) as a model. One group of 14-month-old adult ZF were exposed acutely as adults (0.4, 1.25, and 4.0 μM) for five days and tested as adults, and another group was exposed developmentally 5-120 h post-fertilization (70, 210, and 700 nM) and tested at larval, adolescent, adult, and aging life stages. ZF exposed acutely as adults did not display many significant neurobehavioral impacts or mitochondrial dysfunction. Conversely, the embryonically exposed ZF showed altered behavioral functions at each stage of life which emerged and attenuated as fish transitioned from each developmental stage to the next. Mitochondrial oxygen consumptions measurement results for developmentally DZN exposed ZF showed significant increases in the low and middle dose groups in organs such as the brain and testes. Overall, there is an indication that early developmental exposure to DZN had continuing adverse neurobehavioral and cellular consequences throughout their lives well into adulthood and aging periods.