Jos Mes

Polychlorinated biphenyls and organochlorine pesticides in milk and blood of Canadian women during lactation.

Blood and breast milk samples of 16 women were analyzed for PCBs (polychlorinated biphenyls) and some organochlorine pesticides during eight intervals of a 98 day lactation period. Although a general downward trend in residue levels of blood and breast milk was evident, this trend was interrupted by sporadic increases. Most residues in breast milk showed an apparent increase during the first 30 days of lactation, which was not statistically significant. However, during lactation a statistically significant decrease was observed for the following residues, expressed on a milkfat basis: HCB (hexachlorobenzene), oxychlordane, transnonachlor (1-exo, 2-endo, 3-exo-4,5,6,7,8,8-nonachloro-3a,4,7,7a-tetrahydro-4,7-methanoindene), βHCH (hexachlorocyclohexane),p,p′-DDE andp,p′-DDT. Average milk/blood ratios for PCBs, HCB, oxychlordane(1-exo,2-endo-4,5,6,7,8,8-oc-tachloro-2,3-exo-epoxy 2,3,3a,4,7,7a-hexa-hydro-4,7-methanoindene),p,p′-DDE (2,2-bis-(p-chlorophenyl)- 1, 1-dichloroethylene), dieldrin (1,2,3,4, 10,10-hexachloro-exo-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro- 1,4-endo- exo- 5,8-dimethanonaphthalene) and p,p′-DDT (1,l-bis-(p-chlorophenyl)-2,2,2-trichloroethane) levels were 23, 20, 9, 19, 5 and 30 respectively. Milk/blood ratios for PCB andp,p′-DDE levels remained relatively constant during lactation (coefficient of variation ∼20). Accumulation of residues in infant body fat were theoretically estimated

Di-n-butyl-and Di-2-ethylhexyl phthalate in human adipose tissue

phthalate in humans warranted a limited survey of these esters in human adipose tissue. Analytical data presented in this paper were obtained from the fatty tissue of the abdominal region only. Sampling Human adipose tissue was collected during autopsies on accident victims. The fat samples were deposited in glass jars, previously acid washed and rinsed with residue free aletone and hexane. The caps were supplied with aluminum foil liners. Samples were immediately frozen and kept frozen until analysed. Except for 2 samples from Vancouver and one from Montreal, all samples came from the Toronto area.

Polychlorinated biphenyl and other chlorinated hydrocarbon residues in adipose tissue of Canadians.

The data reported in this paper are part of a continuing monitoring program of chlorinated hydrocarbons in adipose tissue of Canadians in order to determine a possible trend in both the disappearance of restricted OC pesticides, such as p,p,-DDT, as well as the appearance of new environmental contaminants, such as hexachloro-1,3-butadiene (HCBD).

A PILOT STUDY ON THE EFFECTS OF AROCLOR 1254 INGESTION BY RHESUS AND CYNOMOLGUS MONKEYS AS A MODEL FOR HUMAN INGESTION OF PCBS

A pilot study using female cynomolgus (Macaca fascicularis) and female rhesus (Macaca mulatta) monkeys was conducted to study the effects of chronic ingestion of polychlorinated biphenyls (PCBs). Four control and four treated monkeys of each species received an apple juice-gelatin mixture containing 0 and 280 micrograms Aroclor 1254/kg body weight/day, respectively, 5 days/wk. The cynomolgus monkeys, which were mature monkeys with a poor breeding history, were treated for approximately 55 wk, while the rhesus monkeys, which were just attaining sexual maturity, were treated for approximately 120 wk. After 38 wk on test, the treated and control rhesus monkeys were mated with untreated males. The clinical signs resulting from the Aroclor 1254 ingestion were similar for both species, and the time of onset after initiation of treatment was not appreciably different between the two species. Several treatment and interspecies differences were found with regard to the haematological and serum biochemistry parameters monitored, but age differences between the two species may have contributed to these findings. Periodic analysis of adipose tissue, blood and faecal specimens for PCBs suggested that the rhesus monkey retained more of the ingested PCB than did the cynomolgus monkey. Following mating, all of the treated rhesus monkeys aborted within 30-60 days after becoming pregnant, while all of the control monkeys had viable offspring.

Toxicological consequences of aroclor 1254 ingestion by female rhesus (macaca mulatta) monkeys. Part 1B. Prebreeding phase: Clinical and analytical laboratory findings

A group of 80 menstruating rhesus (Macaca mulatta) monkeys, with an average estimated age of 11.1 +/- 4.1 yr SD were first randomly allocated to four similar test rooms (20 monkeys/room), and then randomly allocated to one of five dose groups (four females/dose group/room). Each day, the monkeys self-ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body weight. After 25 months of daily dosing, approximately 90% of the treated females attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl (PCB) in their adipose tissue. Subsequently, oestrogen and progesterone concentrations in serum were determined for one complete oestrous cycle and various immunological tests were conducted, while the monkeys continued to receive their daily dose of PCB. During the prebreeding phase of the study, blood for clinical and analytical monitoring including haematology, serum biochemistry, serum hydrocortisone, serum proteins (alpha 1, alpha 2, beta and gamma-globulins), serum immunoglobulins (A, G and M) and thyroid variables (thyroxine/triiodothyronine (T3) uptake ratio, percentage T3 uptake and free thyroxine index), were obtained monthly, as were specimens to ascertain the concentration of PCB in the blood, adipose tissue and faeces. Major findings among treated monkeys included the following: changes in haematology (decreased erythrocyte count, haematocrit, reticulocyte count, and mean platelet volume), serum biochemistry (decreased cholesterol and total bilirubin), immunotoxicity (decreased antibody production to sheep red blood cells and alterations in the percentage of T helper and T suppressor cells) and pathology (the number of regions of sebaceous gland lobules per unit of histological length was significantly reduced). These effects were observed at PCB doses lower than those previously reported for non-human primates.

Assessment of human exposure to chemical contaminants in foods

One of the most important factors in assessing risk to human health from potentially harmful chemicals in foods is the availability of good data on the exposure of the public to such substances. The means of acquiring these data generally involves monitoring programmes using appropriate sampling procedures and reliable analytical methods for measuring the compounds of concern in a variety of substrates. Two approaches are generally employed: a biological monitoring programme which measures substances in human fluids and tissues, and a food analysis monitoring programme, preferably a total diet study, wherein food is prepared for consumption prior to analysis. The choice of approach to use and chemicals to monitor depend on the situation within a particular country. The analysis of food has the advantage of short term impact since problems can be identified relatively quickly and control measures established. Biological monitoring on the other hand tends to indicate both accumulated and current exposure from all sources, including air, water and food. In Canada both approaches have been used for a number of years with major surveys of human milk and adipose tissue, and the total diet study, being conducted approximately every five years. Details of these programmes together with some of the pertinent findings are presented.

Polychlorinated biphenyl toxicity in the pregnant cynomolgus monkey: A pilot study

Three pregnant cynomolgus monkeys (Macaca fascicularis) were dosed with 100 or 400 μg/kg/day of Aroclor® 1254 from approximately 60 days of gestation. One additional pregnant monkey was given dose vehicle only. The two monkeys dosed with 100 μg/kg/day delivered stillborn infants and the 400 μg/kg/day dosed monkey delivered a term infant that had impaired immunologic function compared with the control infant, and died at 139 days post partum. The three dams also had impaired immunologic capacity assessed at approximately 50 days post partum (148 days treatment). With the exception of loss of fingernails in two monkeys, no overt clinical signs of toxicity were observed in the adults. Polychlorinated biphenyl (PCB) concentrations and peak ratios in breast milk and tissues are reported.

Polychlorinated biphenyl (PCB) Toxicity in Adult Cynomolgus Monkeys (M. fascicularis): A Pilot Study

Aroclor 1254 and Aroclor 1248, at doses of 11.7 and 4.7 mg/kg body weight (equivalent to 5 and 2 mg/kg/day), were given 3 days per week to groups of cynomolgus monkeys, and caused weight loss, fingernail loss, facial edema, epiphora, and death. Blood and adipose tissue PCB concentrations rose with the length of treatment. Tissue concentrations in blood, adipose tissue, liver and kidneys were highest in monkeys treated with Aroclor 1254, reflecting dose differences. There was considerable variation, both within and between groups, in hematologic responses to PCB treatment. Aroclor 1254-treated monkeys had depressed and weakly responsive erythropoiesis. Aroclor 1248-treated monkeys had active but ineffective or depressed erythropoiesis with severe macrocytic or moderate normocytic anemia. Biochemical determination of blood serum constituents revealed treatment and time-related trends towards hypoalbuminemia and increased alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactic dehydrogenase, cholesterol, triglycerides, total bilirubin and direct bilirubin values. Pathologic lesions common in both Aroclor groups were dilatation of meibomian glands duct; mucinous hyperplasia of the gastric mucosa; atrophy and loss of germinal centers in the splenic and other lymphoid follicles; enlargement, fatty degeneration, and necrosis of hepatocytes; bile duct and gall bladder epithelial cell hypertrophy and hyperplasia; and thyroid aberrations in follicular cell size and number of intracytoplasmic lysosomes. Lesions seen exclusively in an Aroclor 1254-treated monkey were widespread mucinous metaplasia and hyperplasia of the fundic mucosa. The results suggest that in general, cynomolgus monkeys may be more refractory or less susceptible to PCB toxicity than rhesus monkeys and, that Aroclor 1248 may be more toxic than Aroclor 1254.

A pilot study in adult rhesus monkeys (M. mulatta) treated with Aroclor 1254 for two years.

Aroclor 1254, at a dose level of 280 μg/kg body weight equivalent to 200 μg/kg/day, was given 5 days per week to rhesus monkeys over a 27 to 28 month period. Terminal clinical signs of varying severity included fingernail detachment, exuberant nail beds, weight loss, stomatitis and normocytic anemia. At necropsy the bone marrow was hypocellular with increased M:E ratio and cytoplasmic vacuoles in crythroid precursor cells. Histopathologic lesions included dilatation of the tarsal gland ducts, atrophy or absence of splenic and lymphonodal germinal centers, bone marrow depletion, gingival erosion and ulceration, moderate mucinous hypertrophic gastropathy with cystic dilatation of occasional gastric glands, hepatocellular enlargement and necrosis, hypertrophy of biliary duct epithelium, hyperplasia of biliary ducts, hypertrophy of the gall bladder epithelium, and an equivocal increase in the number of lysosomes in thyroid follicular epithelial cells. PCB tissue concentrations were lowest in brain and highest in blood. The results suggest that severe potentially fatal PCB toxicity can develop in rhesus monkeys following ingestion of Aroclor 1254 at 200 μg/kg/day for a period of 27 months or longer.

Comparative aspects of Aroclor® 1254 toxicity in adult cynomolgus and rhesus monkeys: A pilot study

Aroclor® 1254 (PCB), at a dose of 280 μg/kg body weight (equivalent to 200 μg/kg/day) was given 5 days per week to groups of cynomolgus and rhesus monkeys. Cynomolgus monkeys were treated for 12 to 13 months and rhesus monkeys for 27 to 28 months. The study compares selected clinical, hematologic, immunologic, and analytical findings in the two species up to the time the cynomolgus were killed (12–13 months) and includes the pathologic findings in the latter (terminal findings in the rhesus are the subject of a separate report). Treated rhesus had enlarged tarsal glands, conjunctivitis, loss of eyelashes, progressive detachment of finger nails, exuberant nail beds, and somewhat depressed hematologie values of the erythron. In contrast, treated cynomolgus had temporary enlargement of the tarsal glands, distortion and temporary loss or lifting of nails with limited exposure of the nail beds, and moderate erythroid depression and vacuolization of early erythroid precursors. Histopathologic findings in the cynomolgus monkeys included mild dilatation of tarsal gland ducts, moderately keratinized finger nail beds, and hepatocellular and biliary duct epithelial cell hypertrophy. Immunologie testing was inconclusive due to large interspecies variability. PCB analysis revealed that during the first 18 weeks of treatment rhesus monkeys accumulated PCB faster than did the cynomolgus. It appears that rhesus monkeys are more susceptible to PCB toxicity than cynomolgus monkeys.