Biomarker assays that provide measures of the toxic effects of chemicals on key organisms are of particular interest in ecotoxicology and environmental risk assessment. Typically, such assays provide measures of the molecular mechanisms that underlie toxicity (e.g., inhibition of brain acetylcholinesterase activity by organophosphorus insecticides and retardation of the vitamin K cycle by anticoagulant rodenticides). They are particularly valuable for detecting and quantifying toxicity where organisms are exposed to mixtures of compounds and for identifying cases of potentiation. In birds, inhibition of brain acetylcholinesterase activity can provide an index of potentiation of organophosphorus and carbamate insecticides by other pesticides. Inhibition of serum butyrylcholinesterase also is very useful as a nondestructive assay but is not simply related to inhibition of brain acetylcholinesterase. Assays for DNA damage can indicate where there is an increase in the rate of activation of carcinogens and mutagens due to induction of the cytochrome P450 system. Assays for blood levels of retinol (vitamin A) and thyroxine can establish thyroxine antagonism by metabolites of 3,3,4,4-tetrachlorobiphenyl. Assays for changes in levels of clotting protein in serum can give an indication of the effect of mixtures of anticoagulant rodenticides on the vitamin K cycle. The interactive effects of mixtures of pesticides in the field are starting to be investigated by this approach (e.g., a recent study of the combined action of malathion and prochloraz in the red-legged partridge).

Animals↗

PubMedDate not supplied

Comparative aspects of congener specific PCB metabolism.

Despite the large number of PCB congeners identified (in some environmental samples more than 70 isomers and congeners) only some 12 of them account for 80% of the total PCB adipose tissue burden. These compounds are a selective group of PCBs which are highly chlorinated or alternatively lack meta-para-vicinal protons. Comparison of the persistent and non-persistent PCB congeners between human adipose tissue, human breast milk and fish-eating sea birds revealed similarities in the bioaccumulation pattern. These findings suggest a certain inability of cytochrome P-450 mono-oxygenases to metabolise a specific group of PCBs.

Animals↗

PubMedDate not supplied

Administration of chlordiazepoxide affects [3H][3-MeHis2]thyrotropin-releasing hormone binding in rat brain.

The effects of acute and subchronic administration of chlordiazepoxide (CDZ) on [3H][3-methyl-histidyl2]thyrotropin-releasing hormone binding to thyrotropin-releasing hormone (TRH) receptors in membrane preparations from various regions of rat brain were examined. Acute administration of CDZ (50 mg/kg x 3 within 24 h) did not alter either the equilibrium dissociation constant (Kd) or the maximum number of binding sites (Bmax) in cerebellum (CB), olfactory bulbs (OB), frontal cortex (Cx), hypothalamus (HT) or corpus striatum (ST). However, the Kds of the pyriform cortex/amygdala (PC/A) (Kd = 3.6 +/- 0.1 nM compared to 1.9 +/- 0.1 nM in the control group; p less than 0.01) and the hippocampus (HP) (Kd = 7.8 +/- 0.7 nM compared to 2.1 +/- 0.1 nM in the control group; p less than 0.01) were increased. There were no changes in Bmax. Subchronic administration of CDZ (50 mg/kg/day for 7 days) increased the Kd of the PC/A complex (p less than 0.05), the OB (p less than 0.05) and the HP (p less than 0.01) without altering in Bmax. These results, showing regional differences in the response of TRH receptors to acute and subchronic CDZ administration, suggest that reduced affinity of TRH receptors in the PC/A complex, OB and HP may be related to some of the neurobiological actions of CDZ and/or its metabolites.

Animals↗

PubMedDate not supplied

A dose-response study of chronic cocaine on maternal behavior in rats.

To determine if there was a dose-response relationship with regard to cocaine treatment and maternal behavior exhibited by lactating rats at doses that had not been previously investigated, we examined the effects of three doses of chronic cocaine administration throughout gestation on both onset and established maternal behavior. Dams were injected (SC) with 6.3, 13, or 25 mg/kg cocaine HCl or an equivalent volume of saline throughout gestation; maternal behavior was tested on postpartum days 1 and 3. At the doses employed, cocaine disrupted the onset of only one pup-directed component of maternal behavior significantly in a dose-response manner, although there were several statistically nonsignificant dose-dependent trends of behavioral disruptions. No pup-directed behaviors were disrupted during testing for established maternal behavior. These results indicate that gestational cocaine treatment at doses of 25 mg/kg and less have only minimal effects on the onset and no effect on the maintenance of maternal behavior using our paradigm. The relationship of the present findings to previous work is discussed.

Animals↗

PubMedDate not supplied

Neurotoxic pesticides and behavioural effects upon birds.

Organochlorine, organophosphorus, carbamate, pyrethroid and neonicotinoid insecticides and organomercury fungicides are all neurotoxic and therefore have the potential to cause behavioural disturbances in birds. A number of studies have described behavioural effects caused to captive birds by neurotoxic pesticides, but it is very difficult to measure such effects in the field, which is a serous limitation given their potential to cause adverse effects at the population level. The mode of action, and the neurotoxic and behavioural effects of these compounds are briefly reviewed before considering evidence for their effects in the laboratory and field. Behavioural effects may cause adverse changes at the population level either directly or indirectly. Direct effects upon avian populations may be due to disturbances of reproduction, feeding, or avoidance of predation. Indirect effects on predators may be the consequence of direct action upon the prey population leading to either (1) reduction of numbers of the prey population, or (2) selective predation by the predator upon the most contaminated individuals within the prey population. Attention is given to the historic evidence for neurotoxic and behavioural effects of persistent organochlorine insecticides, raising the question of retrospective analysis of existing data for this once important and intensively studied class of compounds. Less persistent pesticides currently in use may also have neurotoxic effects upon birds in the field. Sometimes, as with some OPs, their effects may outlast the persistence of their residues, and the ecotoxicity and persistence of some may be affected by interactions with other environmental chemicals. The development of new mechanistic biomarker assays could improve understanding of behavioural effects and possible associated effects at the population level caused by such compounds in the field.

Animals↗