Effects of prednisolone and complex of vitamin B1, B2, B6 and B12 on organophosphorus compound-induced delayed neurotoxicity

Protective effects of prednisolone as a synthetic adrenal cortical hormone and complex of vitamin B(1), B(2), B(6) and B (12) on organophosphorus compound-induced delayed neurotoxicity (OPIDN) caused by leptophos and tri-o-cresyl phosphate (TOCP) as organophosphates (OPs) were examined. Nine groups of hens (six for each) were used. Eight groups received intravenous injection of 30 mg/kg of leptophos or 40 mg/kg of TOCP (four groups in each). Among them, three groups which received leptophos were given (p.o.) predonisolone (2 mg/body), vitamin B complex (25 mg/body) or both 3 h after OPs injection and then every day for 15 d (one group for each); the same treatment was performed on three groups which received TOCP. The remaining one group served as controls. It was observed that delayed neuropathy induced by OPs could not be resisted completely by the treatment with prednisolone or vitamin B complex, but clinical signs of OPIDN and pathological changes in hens that received these two protective agents after OPs were less severe than those in hens that received only OPs. Of these groups, the improvement in clinical signs was best shown in hens that received the both two protective agents. In addition, improvement in clinical signs among the hens that did not deteriorate to paralysis was observed. In particular, those which developed mild ataxia recovered well. It is indicated that combining administration of prednisolone and vitamin B complex early before clinical signs are manifest is effective in alleviating neuropathy. It is also suggested that recovery or good prognosis will be expected, as long as progression of the clinical signs is prevented before paralysis develops in delayed neuropathy.     

Assessment of the delayed neurotoxicity of tributyl phosphate, tributoxyethyl phosphate, and dibutylphenyl phosphate

There industrial organophosphorus compounds were tested for their ability to cause organophosphorus compound-induced delayed neurotoxicity (OPIDN) in the adult hen. The compounds tested were tributyl phosphate (TBP), tributoxyethyl phosphate (TBEP), and dibutylphenyl phosphate (DBPP). The acute oral LD50 of TBP and DBPP were estimated to be 1,863 and 1,500 mg/kg, respectively, and the dose equal to the LD50 was used as a test dose. The acute oral LD50 of TBEP was greater than 5,000 mg/kg and 5,000 mg/kg was used as a test dose. An oral dose of 750 mg tri-o-cresyl phosphate (TOCP) was used as a positive control. For the acute delayed neurotoxicity test, hens were given two test doses of the test materials 21 days apart and killed 21 days after the second dose. None of the hens given TBP, TBEP, or DBPP exhibited nerve damage or clinical signs which distinguished them from untreated control animals. A single dose of TOCP resulted in paralysis and a histopathological profile typical of a distal neuropathy. For the assay of the inhibition of esterases, hens were killed 24 hours after a single dose equal to the greater of either the LD50 or 5000 mg/kg. TOCP administration resulted in over 90% inhibition of brain neurotoxic esterase (NTE), but none of the other three compounds inhibited NTE to an extent (greater than 70%) which would be expected to result in OPIDN. Administration of TOCP, TBEP, or DBPP resulted in approximately a 70% decrease in plasma butyrylcholinesterase (BuChE) activity. TBP caused a 2-3 fold increase in BuChE activity. TBEP administration resulted in about 45% inhibition of acetycholinesterase (AChE) in brain. These results indicate that TBP, TBEP, and DBPP are all unlikely to cause OPIDN with any single sublethal dose.     

Effect of phenylmethylsulfonyl fluoride administration prior to and following leptophos administration on electrolyte concentration and enzyme activity in hen serum

We observed acute toxicity, delayed neurotoxicity, disappearance of leptophos from tisuues and biochemical changes in four groups of hens: a group given only 30 mg/kg leptophos (iv) as the 'leptophos group', two groups given a treatment of 30 mg/kg phenylmethylsulfonyl fluoride (PMSF) (sc) 24 hr prior to (as the 'pretreated group') and following (as the 'posttreated group') administration of the same dose of leptophos as the leptophos group, and a group given a vehicle only as the 'control group'. All groups other than the control group showed acute toxicity. The scores for organophosphate-induced delayed neurotoxicity (OPIDN) in the posttreated group reached the maximal level on the 16th day after leptophos administration and those in the leptophos group reached the maximal level on the 25th day. Serum acid phosphatase (AcP) activities in the leptophos group and the posttreated group were significantly lower than that in the control group (p<0.05) on the 6th day after leptophos administration and then recovered to the normal level on the 15th day. In these two groups, serum creatine phosphokinase (CPK) activity was significantly higher (p<0.01) and the concentration of serum Ca(2+) was significantly lower (p<0.05) than in the control group on the 15th day after leptophos administration. Serum leucine aminopeptidase (LAP) activity in the posttreated group was significantly lower than that in the control group (p<0.01). As for the significant changes by time interval between the 6th and the 15th days after leptophos administration, CPK activity was elevated and serum Ca(2+) reduced in both the leptophos group and the posttreated group, and LAP activity was also reduced in the posttreated group. The courses of leptophos disappearance in several tissues of these hens were similar in the 3 groups. These results suggest that the treatment by PMSF prior to or following the administration of leptophos can significantly modify not only clinical signs of OPIDN but also changes of several biochemical indices accompanied by OPIDN. Furthermore, it is possible to expect that these biochemical indices can provide some valuable clues for exploring the modification of OPIDN by PMSF treatment.     

Organophosphorus Ester-Induced Chronic Neurotoxicity

Organophosphorus compounds are potent neurotoxic chemicals that are widely used in medicine, industry, and agriculture. The neurotoxicity of these chemicals has been documented in accidental human poisoning, epidemiological studies, and animal models. Organophosphorus compounds have 3 distinct neurotoxic actions. The primary action is the irreversible inhibition of acetylcholinesterase, resulting in the accumulation of acetylcholine and subsequent overstimulation of the nicotinic and muscarinic acetylcholine receptors, resulting in cholinergic effects. Another action of some of these compounds, arising from single or repeated exposure, is a delayed onset of ataxia, accompanied by a Wallerian-type degeneration of the axon and myelin in the most distal portion of the longest tracts in both the central and peripheral nervous systems, and is known as organophosphorus ester-induced delayed neurotoxicity (OPIDN). In addition, since the introduction and extensive use of synthetic organophosphorus compounds in agriculture and industry half a century ago, many studies have reported long-term, persistent, chronic neurotoxicity symptoms in individuals as a result of acute exposure to high doses that cause acute cholinergic toxicity, or from long-term, low-level, subclinical doses of these chemicals. The author attempts to define the neuronal disorder that results from organophosphorus ester-induced chronic neurotoxicity (OPICN), which leads to long-term neurological and neurobehavioral deficits. Although the mechanisms of this neurodegenerative disorder have yet to be established, the sparse available data suggest that large toxic doses of organophosphorus compounds cause acute necrotic neuronal cell death in the brain, whereas sublethal or subclinical doses produce apoptotic neuronal cell death and involve oxidative stress.     

Organophosphorus ester-induced chronic neurotoxicity

Organophosphorus compounds are potent neurotoxic chemicals that are widely used in medicine, industry, and agriculture. The neurotoxicity of these chemicals has been documented in accidental human poisoning, epidemiological studies, and animal models. Organophosphorus compounds have 3 distinct neurotoxic actions. The primary action is the irreversible inhibition of acetylcholinesterase, resulting in the accumulation of acetylcholine and subsequent overstimulation of the nicotinic and muscarinic acetylcholine receptors, resulting in cholinergic effects. Another action of some of these compounds, arising from single or repeated exposure, is a delayed onset of ataxia, accompanied by a Wallerian-type degeneration of the axon and myelin in the most distal portion of the longest tracts in both the central and peripheral nervous systems, and is known as organophosphorus ester-induced delayed neurotoxicity (OPIDN). In addition, since the introduction and extensive use of synthetic organophosphorus compounds in agriculture and industry half a century ago, many studies have reported long-term, persistent, chronic neurotoxicity symptoms in individuals as a result of acute exposure to high doses that cause acute cholinergic toxicity, or from long-term, low-level, subclinical doses of these chemicals. The author attempts to define the neuronal disorder that results from organophosphorus ester-induced chronic neurotoxicity (OPICN), which leads to long-term neurological and neurobehavioral deficits. Although the mechanisms of this neurodegenerative disorder have yet to be established, the sparse available data suggest that large toxic doses of organophosphorus compounds cause acute necrotic neuronal cell death in the brain, whereas sublethal or subclinical doses produce apoptotic neuronal cell death and involve oxidative stress.     

两种有机磷酸酯对人成神经细胞瘤细胞生长与钙摄取的影响

目的　探讨具有迟发性神经毒性的有机磷酸酯 (organophosphates,OPs)对人成神经细胞瘤细胞SH SY5Y的毒性作用。方法　采用四甲基偶氮唑蓝 (MTT)比色法测定SH SY5Y细胞活力 ;用培养的SH SY5Y细胞与45CaCl2 和磷酸三邻甲苯酯 (tri o cresylphosphate ,TOCP)或甲胺磷共育后 ,洗脱 ,裂解 ,经液闪仪计数测定细胞对钙的摄取情况。结果　甲胺磷在较低浓度 (7× 10 -7～ 7× 10 -6mol/L)时可刺激SH SY5Y细胞的生长 ,在 7× 10 -7mol/L浓度时细胞的增长比对照增加了 2 8% ,而在高浓度 (7× 10 -4～ 7× 10 -3mol/L)时抑制细胞生长 ,在 7× 10 -3 mol/L时的抑制率为 6 2 % ;但TOCP只在高浓度 (7× 10 -3 mol/L)时才对细胞的生长有抑制作用 (抑制率为 34% )。TOCP在几乎所有的测试浓度下都对SH SY5Y细胞的钙摄取量有影响 :在低浓度 (1× 10 -9～ 1× 10 -7mol/L)时刺激细胞的钙摄取 ,细胞的钙摄取量最高增加 2 4 1% ,但在高浓度 (1× 10 -6～ 1× 10 -4mol/L)时抑制细胞的钙摄取 ,最高的抑制率达 5 5 %。结论　OPs的神经毒性可能涉及阻遏神经细胞生长和干扰细胞钙平衡。     

Mechanisms of organophosphate toxicity and detoxication with emphasis on studies in Croatia

This review comprises studies on the mechanisms of toxicity and detoxication of organophosphorus (OP) compounds done in Croatia in different research areas. One area is the synthesis of antidotes against OP poisoning and their in vivo testing in experimental animals. In vitro studies included in this review focus on the mechanisms of reversible inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), protection of cholinesterases from inhibition by OPs, and reactivation of phosphylated cholinesterases. The third area comprises distribution profiles of BChE and paraoxonase (PON) phenotypes in selected population groups and the detection of OPs and metabolites in humans. Finally, methods are described for the detection of OP compounds in human blood and other media by means of cholinesterase inhibition.     

Effect of phenobarbital on the delayed neurotoxicity of leptophos in hens

Intravenous administration of leptophos [O-(4-bromo-2,5-dichlorophenyl)O-methyl phenylphosphonothioate] caused a delayed neurotoxic effect in hens similar to that produced by oral and dermal administration. The intravenous (IV) ED50 for producing ataxia was estimated to be 21.6 mg/kg, less than one-tenth of the oral ED50 value. Pretreatment of the hens with the drug metabolizing enzyme inducer, phenobarbital (PB), caused a marked change in the biological half-life of leptophos in plasma. Plasma leptophos concentrations decreased in a first-order manner in control hens with a half-life of 36.0 min. In hens pretreated with PB, the elimination of leptophos from plasma consisted of at least two exponential phases, and the half-lives of the first and second phases were approximately 20 min and 140 min, respectively. When the birds received 40 mg/kg of leptophos IV, the incidence of ataxia was 8/18 (affected/tested) in the hens pretreated with PB and 19/19 in the hens without pretreatment. Phenobarbital significantly decreased the incidence of delayed neurotoxic signs (p < 0.01). The pretreatment of hens with PB resulted in a 59 to 69% decrease in the leptophos level in tissues including the brain and spinal cord after IV administration of 40 mg/kg. The results suggest that the protective effect of PB on delayed neurotoxicity is associated with a decreased concentration of leptophos in the target tissue(s).Presented at the 12th Annual Meeting of the Japanese Society of Toxicological Sciences, Tokyo, Japan, July 2, 1985.     

The interrelation between organophosphate toxicity and the epidemiology of depression and suicide

The literature on an association between organophosphate (OP) toxicity and depression or suicide is scarce. An interrelation exists among populations exposed to OPs, acute OP toxicity, neurobehavioral effects, depression, suicide, and fatality. Acute OP toxicity is characterized by the cholinergic syndrome with systemic and central nervous system effects. Organophosphate-induced neurobehavioral effects result in depression. A potential risk of depression and suicide exists in farm workers exposed to OPs. The sociodemographics of depression include age, gender, race, geographic region, social factors, economics, psychiatric disorders, medical conditions, and hereditary factors. Suicide is a major consequence of depression, with multiple sociodemographic risk factors. Developing countries have a higher incidence of OP toxicity, with limited information on the prevalence of depression. In these countries, the incidence of suicide is high, affecting more females. Suicide is more prevalent in rural areas, and in farming communities, commonly with ingestion of OPs. In industrialized countries, the incidence of OP toxicity is lower, but the prevalence of depression is higher. Suicide rates are lower in industrialized countries, affecting more males, the urban population, and farming communities. Other lethal methods of suicide, such as hanging, firearms, electrocution, and drug overdose are more common in industrialized countries. A potential risk of depression or suicide certainly exists from OP toxicity, largely depending on the epidemiology or sociodemographics of these disorders. Scientific evidence shows that the association between environmental toxicology and psychiatry has important public health implications.     

Muscular strength and vibration thresholds during two years after acute poisoning with organophosphate insecticides

Methods: This study concerns the third of a series of three examinations of hand strength and vibration thresholds in a two year period after acute OP poisoning among 48 Nicaraguan men. The first two examinations were performed at hospital discharge and seven weeks after poisoning, and the present examination two years later. Twenty eight cattle ranchers and fishermen who had never experienced pesticide poisoning were examined as controls, also three times over the two year period. The poisonings were categorised as caused by "non-neuropathic" OPs and "neuropathic" OPs, each subdivided in moderate and severe poisonings.

Results: Men poisoned with OP insecticides had persistent reduced hand strength. We previously reported weakness at hospital discharge for OP poisoned in all categories that worsened seven weeks later for those severely poisoned with neuropathic OPs. Strength improved over time, but the poisoned were still weaker than controls two years after the poisoning, most noticeably among the subjects most severely poisoned with neuropathic OPs. Also, index finger and toe vibration thresholds were slightly increased at the end of the two year period, among men with OP poisonings in all categories, but patterns of onset and evolvement of impairment of vibration sensitivity were less clear than with grip and pinch strength.

Conclusions: Persistent, mainly motor, impairment of the peripheral nervous system was found in men two years after OP poisoning, in particular in severe occupational and intentional poisonings with neuropathic OPs. This finding is possibly due to remaining organophosphate induced delayed polyneuropathy.

     

三邻甲苯磷酸酯暴露鸡脊髓神经中Stathmin的差异表达

目的 从三邻甲苯磷酸酯(TOCP)暴露鸡的脊髓组织中筛选可能与调控微管解聚作用相关的差异表达蛋白,为探讨有机磷化合物诱发的迟发性神经毒性( OPIDN)作用机制提供靶蛋白依据.方法 42只罗曼鹤母鸡随机分成1000 mg/kg TOCP组、给予40 mg/kg苯甲基磺酰氟(PMSF)后再给予1000 mg/kg TOCP的干预组和生理盐水对照组,每组14只.染毒第5和20天,每组分别处死4只动物,低温环境下分离腰髓,提取总蛋白.用双向电泳和质谱分析技术,筛选和鉴定可能与调控微管解聚作用相关的差异表达蛋白.结果 染毒第5天,TOCP暴露组部分鸡出现OPIDN症状,并随时间的推移其症状逐渐加重.双向电泳和质谱分析结果表明,在染毒早.期与对照组和PMSF前干预组比较,TOCP组鸡腰髓组织中微管解聚蛋白Stathmin表达分别下调3.4和2.8倍,而PMSF前干预组与对照组之间,Stathmin的表达无明显差异.结论 TOCP暴露诱导鸡脊髓神经组织Stathmin表达明显下调,而且该蛋白表达下调与微管的大量聚集及其OPIDN发生的机制可能有关.     

Suicide and exposure to organophosphate insecticides: Cause or effect?

BACKGROUND: Suicide using pesticides as agent is recognized as a major cause of pesticide poisoning. METHODS: A literature review of mortality and morbidity studies related to suicide among pesticide-exposed populations, and of human and animal studies of central nervous system toxicity related to organophosphate (OP) pesticides was performed. RESULTS: Suicide rates are high in farming populations. Animal studies link OP exposure to serotonin disturbances in the central nervous system, which are implicated in depression and suicide in humans. Epidemiological studies conclude that acute and chronic OP exposure is associated with affective disorders. Case series and ecological studies also support a causal association between OP use and suicide. CONCLUSIONS: OPs are not only agents for suicide. They may be part of the causal pathway. Emphasizing OPs solely as agents for suicide shifts responsibility for prevention to the individual, reducing corporate responsibility and limiting policy options available for control.     

Increased toxicity to invertebrates associated with a mixture of atrazine and organophosphate insecticides

This study examined the joint toxicity of atrazine and three organophosphate (OP) insecticides (chlorpyrifos, methyl parathion, and diazinon) exposed to Hyalella azteca and Musca domestica. A factorial design was used to evaluate the toxicity of binary mixtures in which the lethal concentration/lethal dose (LC1/LD1, LC5/LD5, LC15/LD15, and LC50/LD50) of each OP was combined with atrazine concentrations of 0, 10, 40, 80, and 200 microg/L for H. azteca and 0, 200, and 2,000 ng/mg for M. domestica. Atrazine concentrations (> or = 40 microg/L) in combination with each OP caused a significant increase in toxicity to H. azteca compared with the OPs dosed individually. Acetylcholinesterase (AChE) activity also was examined for the individual OPs with and without atrazine treatment. Atrazine in combination with each of the OPs resulted in a significant decrease in AChE activity compared with the OPs dosed individually. In addition, H. azteca that were pretreated with atrazine (> or = 40 microg/L) were much more sensitive to the OP insecticides compared with H. azteca that were not pretreated with atrazine before being tested. Topical exposure to atrazine concentrations did not significantly increase OP toxicity to M. domestica. The results of this study indicate the potential for increased toxicity in organisms exposed to environmental mixtures.     

Amplified esterases B1 and A2-B2 in field populations of Culex pipiens from China

The main organophosphate (OP) resistance mechanism in the Culex pipiens complex is increased activity of esterases A and B. Fourth-stage larvae from 2 field populations of C. pipiens from Gaomi and Kunming, China, were compared for tolerance to parathion, dichlorovos (OP), and bassa (carbamate) insecticides. Both populations were resistant to OPs but not to bassa. Starch gel electrophoresis indicated that elevated esterase activity was correlated with OP resistance. High frequencies of amplified esterase genes B1 and A2-B2 (0.85 and 0.50) were discovered in Gaomi and Kunming, respectively. However, only low levels of gene amplification were detected.     

Development of toxicity identification evaluation procedures for pyrethroid detection using esterase activity

Recent agrochemical usage patterns suggest that the use of organophosphate (OP) pesticides will decrease, resulting in a concomitant increase in pyrethroid usage. Pyrethroids are known for their potential toxicity to aquatic invertebrates and many fish species. Current toxicity identification evaluation (TIE) techniques are able to detect OPs, but have not been optimized for pyrethroids. Organophosphate identification methods depend upon the use of piperonyl butoxide (PBO) to identify OP-induced toxicity. However, the use of PBO in TIE assays will be confounded by the co-occurrence of OPs and pyrethroids in receiving waters. It is necessary, therefore, to develop new TIE procedures for pyrethroids. This study evaluated the use of a pyrethroid-specific antibody, PBO, and carboxylesterase activity to identify pyrethroid toxicity in aquatic toxicity testing with Ceriodaphnia dubia. The antibody caused significant mortality to the C. dubia. Piperonyl butoxide synergized pyrethroid-associated toxicity, but this effect may be difficult to interpret in the presence of OPs and pyrethroids. Carboxylesterase activity removed pyrethroid-associated toxicity in a dose-dependent manner and did not compromise OP toxicity, suggesting that carboxylesterase treatment will not interfere with TIE OP detection methods. These results indicate that the addition of carboxylesterase to TIE procedures can be used to detect pyrethroids in aquatic samples.     

Onset of grip- and pinch-strength impairment after acute poisonings with organophosphate insecticides

The course of organophosphate-induced delayed polyneuropathy (OPIDP) in humans has not been quantitatively measured in epidemiologic studies. This study evaluated the association of acute OP poisonings with motor neurologic impairment. Hand grip and pinch strength were evaluated among 62 Nicaraguan men hospitalized for acute OP poisoning between 1992 and 1996; 39 cattle ranchers and fishermen who had never experienced pesticide poisoning were controls. Exposure categories were moderate and severe poisonings with neuropathic and non-neuropathic OPs. Strength was measured at hospital discharge and seven weeks after poisoning. Grip and pinch strength were impaired among all OP-poisoned subjects at both examinations, more noticeably among those poisoned with OPs with suspected neuropathic effects, methamidophos and chlorpyrifos. In those with severe poisonings with neuropathic OPs, impairments were more marked among intentional than among occupational poisonings. The performances of suicidal subjects worsened at the second examination, consistent with OPIDP. Early motor impairment at the time of hospital discharge is consistent with cholinergic depolarization blockade after acute poisoning. The persistence of deficits in motor strength in all severely poisoned patients regardless of pesticide type was unexpected, and may reflect persistent cholinergic blockade or intermediate syndrome, neuropathy, or a combination of these.     

Effects of azinphos-methyl on cholinergic responses and general health in zebra finches (Taeniopygia guttata) after previous treatment with p,p'-DDE

Although organochlorine (OC) pesticides were replaced with organophosphates (OPs) in the early 1970s, they continue to persist in orchard environments today. Extensive research has been conducted to determine the effects of currently used OPs on cholinesterase (ChE) activity; however, although OCs continue to be prevalent in areas of previous use, few studies have looked at the toxicity of a combination of residual OC compounds with currently used OP pesticides. The focus of our study was to determine the effects of azinphos-methyl (a common OP used in apple orchards today) on ChE activity and general health in zebra finches (Taeniopygia guttata) previously exposed to p,p'-DDE (a commonly detected metabolite of DDT). The main results of our study were as follows: (1) azinphos-methyl alone caused a dose-dependent inhibition of plasma and brain ChE activity; (2) p,p'-DDE in combination with azinphos-methyl did not change azinphos-methyl inhibition of ChE activity; and (3) there were suggestions of immunostimulation in birds dosed 1 year previously to p,p'-DDE and of anemia when p,p'-DDE was combined with azinphos-methyl; however, there was no dose-response for these parameters in birds subsequently dosed with p,p'-DDE.     

Pharmacokinetics of the organophosphorous insecticide leptophos in the hen

In an attempt to carry out a pharmacokinetic study of the organophosphorous insecticide leptophos, which is known to produce delayed neurotoxicity (DNT), a practical method for the analysis of leptophos in tissue samples has been developed by utilizing high-performance liquid chromatography. Using this method, the pharmacokinetics of intravenously administered leptophos in hens were investigated. The following results were obtained: 1. The proposed method was suitable for the analysis of leptophos in biological tissues. The detection limit was 0.5 ng and the recovery rate was over 90%. 2. The disappearance rate of leptophos in hens after administration was 70% at 6 hours and 93% at 96 hours. The half-lives calculated bi-exponentially were 1.37 hours for the early phase and 45.53 hours for the late phase. Since the leptophos detected in excreta was only 0.1% of the administered dose, its disappearance from the hen's body was due to its metabolization in the hen's tissue. 3. The half-lives of leptophos in blood calculated bi-exponentially were 0.50 and 7.57 hours. 4. The decline patterns of leptophos in tissue were considerably different from each other. While leptophos concentrations in adipose tissue and sciatic nerves decreased mono-exponentially, leptophos in other tissues (liver, kidney, heart muscle, leg muscle, brain and spinal cord) decreased bi-exponentially. The distribution of leptophos from blood to tissue seemed to be very rapid; however, redistribution from tissue to blood was extremely limited. 5. The long half-life of leptophos in sciatic nerves was especially noteworthy considering the manifestation of DNT. 6. The short half-life of leptophos in liver indicated the predominant role of liver in leptophos metabolism. 7. The results of this study do not coincide with the hypothesis that the metabolism of leptophos in species susceptible to DNT such as hens is slower than in non-susceptible species such as rats and mice. That is, in spite of the fact that this study was carried out under experimental conditions in which nerve damage would normally be manifested, leptophos was metabolized rapidly.     

Effects of Temperature on the Toxicity of M-Parathion, Chlorpyrifos, and Pentachlorobenzene to Chironomus tentans

This study examined the influence of temperature (10, 20, and 30°C) on the acute toxicity and accumulation of two organophosphate (OP) insecticides and a narcotic chemical to the midge (Chironomus tentans). OP insecticides used in this study included chlorpyrifos and m-parathion, and pentachlorobenzene was the chosen narcotic. Chlorpyrifos was the most toxic chemical tested, followed by m-parathion and then pentachlorobenzene. A positive correlation was found between temperature and toxicity for each of the chemicals tested. A reverse trend was noted for total OP insecticide body residues with decreased concentrations found at the higher temperatures. Pentachlorobenzene body residues remained constant at all temperatures. All three chemicals showed increased uptake rates at 20 and 30°C in comparison to 10°C. The noted decrease in midge body residues at the higher temperatures for the OP insecticides was contributed to increased biotransformation and elimination rates at the higher temperatures. Overall, temperature had a greater influence on OP toxicity than for pentachlorobenzene, and this may be due to accelerated biotransformation of the OPs to more toxic o-analog metabolites at the higher temperatures. Accepted: 22 May 1999     

How to Engage Occupational Physicians in Recruitment of Research Participants: A Mixed-Methods Study of Challenges and Opportunities

Purpose To investigate barriers and facilitators for research participant recruitment by occupational physicians (OPs). Methods A mixed-methods approach was used. Focus groups and interviews were conducted with OPs to explore perceived barriers and facilitators for recruitment. Based on data of a cluster-randomised controlled trial (cluster-RCT), univariate and multivariate analyses were conducted to investigate associations between OPs’ personal and work characteristics and the number of recruited participants for the cluster-RCT per OP. Results Perceived barriers and facilitators for recruitment were categorised into: study characteristics (e.g. concise inclusion criteria); study population characteristics; OP’s attention; OP’s workload; context (e.g. working at different locations); and OP’s characteristics (e.g. motivated to help). Important facilitators were encouragement by colleagues and reminders by information technology tools. Multivariate analyses showed that the number of OPs within the clinical unit who recruited participants was positively associated with the number of recruited participants per OP [rate ratio of 1.43, 95 % confidence interval 1.24–1.64]. Conclusions When mobilising OPs for participant recruitment, researchers need to engage entire clinical units rather than approach OPs on an individual basis. OPs consider regular communication, especially face-to-face contact and information technology tools serving as reminders, as helpful.