Does the nature of the solvent affect the anti-inflammatory capacity of triclosan? An experimental study

Abstract The anti-inflammatory properties of triclosan have been revealed in several recent studies, including an effect on histamine-induced inflammation. In other studies, the nature of the solvent has been shown to be of importance for the plaque inhibiting as well as the antibacterial potential of triclosan. This study was aimed at examining whether the nature of the solvent also may influence the anti-inflammatory capacity of triclosan and further to study a possible dose/response relationship. The study was performed as 3 separate, double-blind experiments, comprising 10, 11 and 12 healthy females. In all 3 experiments, 5 sites on the lower part of the back of the volunteers were intradermally exposed to one drop of 1% histamine dihydrochloride for 15 min. The size of the resulting wheals was recorded before and after 40 min of triclosan treatment. In experiment I. 4 different concentrations of triclosan in 2-fold dilutions in absolute alcohol (0.125%-1%) were applied on the histamine-induced wheals. In experiments 2 and 3, 4 different solutions containing 0.5% triclosan and a saline solution as negative control were used. The solvents in experiment 2 were as follows: (1) absolute alcohol (positive control). (2) propylene glycol (PG), (3) polyethylene glycol (PEG). (4) olive oil, and in experiment 3: (1) absolute alcohol (positive control). (2) Tween 80. (3) sodium carbonate, (4) soy oil. The results showed a dose/ response effect of triclosan and further that the solvent may be of importance for its anti-inflammatory potential.     

Polychlorinated biphenyls and organochlorine pesticides in milk of Norwegian women during lactation

Milk samples of 14 women were analyzed for PCBs (polychlorinated biphenyls),p,p-DDE, and HCB (hexachlorobenzene) during 11 intervals of a 120 day-lactation period. A general downward trend in residue levels was evident, and a statistically significant decline was observed for residue levels of PCBs (P<0.01) and HCB (P=0.02) on the milk fat basis. Primipara (n=9) had from 1.5 to 2.1 times higher mean residue levels than mothers nursing their second or third child (n=9). Significant declines in residue levels during lactation of the first child were found, while no pronounced changes in residue levels were observed during lactation of the second or third child. Overall, residue levels in this study were lower than corresponding levels found earlier in Norway, and within the range of the corresponding levels found in another Norwegian human milk survey done at the same time.     

Relationships Between Persistent Organic Pollutants and Circulating Immunoglobulin-Y in Black-Legged Kittiwakes and Atlantic Puffins

Have Although persistent organic pollutants (POPs) may affect the immune system, few field studies actually examined this effect. There are indications that POP exert effects on the immune system; however, in the Arctic ecosystem data are scarce. The aim of this study was to examine immune functions in two medium trophic-positioned seabirds, the black-legged kittiwakes (Rissa tridactyla) and Atlantic puffins (Fratercula arctica). Overall POP concentrations were higher in kittiwakes than puffins and males had significantly higher concentrations than females. Mean concentrations of total polychlorinated biphenyls (ΣPCB₉) were 4700 ± 200 and 9600 ± 1400 ng/g lipid weight and 2800 ± 180 and 3900 ± 200 ng/g lipid weight in female and male kittiwake and puffin blood, respectively. Levels of immunoglobulin-Y (IgY) in blood of kittiwakes were not markedly affected by concentrations of POP. Similarly, the primary IgY response to tetanus toxoid was not affected by POP concentrations in a subsample of immunized kittiwakes. In puffins, there were significant correlations between the IgY-response and some of the POPs, but with low explanatory values. These results suggest that POPs concentrations were lower than, or just at the threshold level for effects of the proposed IgY biomarker. It is also conceivable that the IgY levels are not a suitable endpoint for evaluating perturbation of the immune system in free-living seabirds.     

Behavioural effects in female rats of postnatal exposure to sub-toxic doses of polychlorinated biphenyl congener 153.

Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that are also present in human tissues and breast milk. Behavioural disturbances have been reported in both children and animals exposed perinatally to PCBs. The present study assessed the behavioural consequences in female rats of postnatal exposure to the di-ortho-substituted 2,2',4,4',5,5'-hexachlorobiphenyl (IUPAC no. 153), which is one of the PCB congeners most frequently detected in human milk. The different groups of mothers were dosed via gavage with 5 mg/kg bodyweight of PCB 153 in corn oil or 5 ml/kg bodyweight corn oil vehicle every second day from day 3 to day 13 after delivery. The exposure did not affect the bodyweight of the dams nor the physical development of the pups. Operant behavioural testing of the female offspring by two different schedules of reinforcement was performed. First, the animals were tested by a multiple schedule with two components: fixed interval (FI) and extinction (EXT), which has proved sensitive in revealing changes in activity level. There were no statistically significant differences in frequency or interresponse times of lever pressing between the PCB-exposed female rats and the controls. These results were in contrast to a previous, analogous study where PCB 153 produced an increased frequency of lever presses during the FI in male rats, indicating a sex-specific behavioural effect of PCB 153. The female offspring was also tested by a conjunctive schedule with two components: variable interval (VI) and differential reinforcement of low rate (DRL). This schedule revealed slower acquisition of time discrimination in the PCB 153-exposed females as compared with the controls. The VI-DRL results showed that PCB 153 may also produce long-lasting behavioural effects in female rats following postnatal exposure through the mother's milk.     

Interseasonal variation in blood concentrations of organochlorines in great black-backed gulls (Larus marinus)

In two subsequent breeding seasons (2001 and 2002), we measured 12 organochlorines (OCs), including hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), p,p'-dichlorodiphenyldichloroethylene (DDE), oxychlordane, and eight polychlorinated biphenyl congeners (PCBs), in the blood of the same 25 great black-backed gulls (Larus marinus). The wet-weight concentrations of different OCs in the blood decreased between 45 and 60% from 2001 to 2002. The main reasons for this were lower blood-lipid concentrations and higher body condition in 2002 compared to 2001. The differences in blood lipids and body condition probably resulted from changes in the availability of different prey types between the years. Despite the variation in the blood concentrations of OCs, there was a high predictability of the relative relationship among individuals between the years, especially for the most-persistent compounds (persistent PCBs, oxychlordane, and DDE); that is, individuals with high levels in 2001 still had relatively high levels compared to other individuals in 2002. This suggests that a concentration obtained from a single blood sample is a relatively reliable measurement of OC burdens for individual great black-backed gulls compared to other individuals, independent of changes in mean OC levels within the population. However, by including information about the nutritional status of individuals, more precise interference from samples in different years and locations may be made. Moreover, the great seasonal variation in OC levels within individuals may have implications for how OC monitoring should be conducted in gull populations.     

Organochlorines affect the steroid hormone cortisol in free-ranging polar bears (Ursus maritimus) at Svalbard, Norway

Since the polar bear (Ursus maritimus) is among the most highly organochlorine-contaminated species of the Arctic mammals, there is growing concern that in addition to the natural stressors in the polar bear's environment, several organochlorines (OCs) may be able to change basic endocrine pathways. Alterations in the hypothalamic-pituitary-adrenal (HPA) axis may affect plasma cortisol concentrations and inhibit physiological processes involved in the maintenance of homeostasis in a way that may endanger the animal's health. Between 1995 and 1998, samples were collected from 121 male and 130 female free-ranging polar bears from the Svalbard area. The aim of the study was to investigate relationships between plasma cortisol concentrations, biological factors, and OCs. The variation in plasma cortisol concentrations was determined for the total sample. Axillary girth and body mass together with their interactions explained more than 50% of the variation in the plasma cortisol concentration. The sum of pesticides (Sigma pesticides) combined with the sum of polychlorinated biphenyls (Sigma PCBs) and their interactions explained over 25% of the variation in the cortisol concentration. Although Sigma pesticides contributed negatively and Sigma PCBs contributed positively to the variation in the plasma cortisol, the over-all contribution of the OCs to the plasma cortisol variation was negative. Despite the complexity on stress responses and the interactions with environmental factors, this study demonstrated that high concentrations of OCs in polar bears might alter plasma cortisol concentrations.     

Effects of perinatal exposure to low doses of PCB 153 and PCB 126 on lymphocyte proliferation and hematology in goat kids

Pregnant does (10 goats/group) were dosed orally with either PCB 153 or PCB 126 dissolved in corn oil or only corn oil (control group) from day 60 of gestation until delivery. Effects on in vitro mitogen-induced lymphocyte proliferation and blood cell counts in their goat kids exposed to low levels of PCB 153 and PCB 126 during gestation and lactation were assessed. The concentrations of PCB 153 and PCB 126 in adipose tissue in the goat kids 9 mo postpartum were 5800 ng/g (fat weight) and 0.49 ng/g (fat weight), respectively. Kids exposed to PCB 153 had a significantly higher number of white blood cells, neutrophils, and lymphocytes at 2 wk of age compared to controls. In the kids exposed to PCB 126 there was a significantly lower concentration of monocytes at 2, 4, and 8 wk of age. The mean lymphocyte response to phytohemagglutinin (PHA) and to concanavalin A (Con A) was significant lower in the PCB 153 compared to the control group at wk 2, 4, and 8 postnatally. The results of the present study support previous reports on immunotoxic effects of PCB exposure in animals. However, this is the first report to demonstrate immunotoxicity in animals by using low doses of PCB 153. The difference in results between PCB 126 and PCB 153 treatment groups may strengthen the hypothesis that PCBs mediate immunotoxic effects through both AhR-dependent and -independent mechanisms.     

Polychlorinated biphenyls and organochlorine pesticides in Baltic and Atlantic gray seal (Halichoerus grypus) pups

Organochlorine pollutants (OCs), such as polychlorinated biphenyls (PCBs), DDT, chlordanes (CHLs), hexachlorobenzene (HCB) and hexachlorocyclohexanes (HCHs) were determined in blubber biopsies from free-ranging Baltic and Atlantic gray seal (Halichoerus grypus) pups. Well-fed pups from the Baltic Sea had concentrations of DDT, PCBs, and HCHs that were 2 to 10 times higher than in corresponding pups from populations in the Atlantic Ocean. The OC pattern in the Baltic seals differed significantly from that of their Atlantic relatives, reflecting the predominance of regional point source inputs into the Baltic Sea and long-range atmospheric inputs into the Atlantic Ocean. The differences in the pattern of the compounds also indicated an enhanced metabolism of the more metabolizable compounds in the more contaminated Baltic seals. Surprisingly, the proportions of the high chlorinated and low-volatile PCB congeners (> 6 Cl atoms) were comparable or lower in the Baltic pups as compared to the Atlantic pups. This difference might be due to Baltic seals occupying a lower trophic level than Atlantic seals and/or to the eutrophication situation in the Baltic Sea, which causes sedimentation of these PCB congeners. Significantly higher OC concentrations were found in starved and/or abandoned Baltic pups as compared to well-fed pups. The most contaminated Baltic seal pups in the present study had PCB concentrations that are comparable or higher than those reported to impair the immune systems and vitamin A dynamics in phocids.     

Polychlorinated biphenyls and reproductive hormones in female polar bears at Svalbard

High concentrations of polychlorinated biphenyls (PCBs) in polar bears from Svalbard have increased concern for that population's reproductive health. We examined whether there were associations between the plasma concentrations of PCBs and reproductive hormones [progesterone (P4)] and 17 beta-estradiol (E2)] in free-living female polar bears from Svalbard. Concentrations of P4 depended on reproductive status, and concentrations were lowest in females with offspring--females with cubs and females with yearlings. In these females, the P4 concentrations were positively correlated with plasma sigma PCBs (sum of all analyzed polychlorinated biphenyl congeners) concentrations. The sigma PCBs concentrations explained 27% of the variation in the P4 concentrations. There were no correlations between sigma PCBs and E2 and cortisol in any of the groups of polar bears, or between sigma PCBs and P4 in single polar bears. Although the sigma PCBs-P4 relationship in female polar bears with offspring is not evidence per se of a direct cause-effect association, the results indicate that PCBs may affect levels of P4 in polar bear females. There is a clear need to further assess the hormone balance and population health of polar bears at Svalbard.