Oestrogen receptor evaluation in Pomeranian dogs with hair cycle arrest (alopecia X) on melatonin supplementation

The role of oestrogen receptors in dogs with hair cycle arrest (alopecia X) was investigated by immunohistochemistry. The purpose of this study was to determine if hair regrowth in dogs with hair cycle arrest treated with melatonin was associated with a decrease in follicular oestrogen receptors. Fifteen Pomeranians (excluding intact females) with hair cycle arrest were enrolled. Two biopsies were obtained from alopecic areas of the trunk before and after 3 months on melatonin. Haematoxylin and eosin-stained tissues were examined and oestrogen receptor-alpha was demonstrated immunohistochemically. Common histopathological findings included hyperkeratosis, follicular keratosis, excessive tricholemmal keratinization (flame follicles), thin epidermis, few small anagen bulbs, epidermal pigmentation and melanin aggregates within follicular keratin. Melanin aggregates within basal cells and hair were an occasional finding. After 3 months, 40% (six) dogs had mild to moderate hair regrowth. Biopsies from six dogs showed histological evidence of an increase in anagen hairs and eight dogs had a decrease in epidermal pigmentation. Moderate to marked staining intensity of oestrogen receptor-alpha was noted in all sebaceous gland basal cells, all small hair bulbs and follicular epithelium of telogen hairs. There was no oestrogen receptor-alpha staining of nuclei within the epidermis, apocrine glands or dermal fibroblasts. Large anagen hair bulbs had minimal to no oestrogen receptor staining. Hair regrowth was not associated with a change in oestrogen receptor-alpha staining.     

Adrenal steroid hormone concentrations in dogs with hair cycle arrest (Alopecia X) before and during treatment with melatonin and mitotane

The purpose of the study was to evaluate intermediate adrenal steroid hormones (ISH) in neutered dogs with hair cycle arrest (Alopecia X) during treatment with melatonin, and to see if hair re-growth is associated with sex hormone concentrations within the normal ranges. Twenty-nine neutered, euthyroid, and normo-cortisolemic dogs were enrolled in the study (23 Pomeranians, three keeshonds, two miniature poodles, and one Siberian husky). Coat assessment and an ACTH stimulation test were performed pre-treatment and approximately every 4 months for a year post treatment. Melatonin was administered initially at 3-6 mg, every 12 h. Based on clinical progression, each dog was continued on the current dose of melatonin, given an increased dose of melatonin or changed to mitotane. Partial to complete hair re-growth occurred in 14/23 Pomeranians, and partial re-growth in 3/3 keeshond and 1/2 poodle dogs. A Siberian husky dog failed to re-grow hair. Fifteen dogs had partial hair re-growth at the first re-evaluation. Melatonin dosage was increased in eight dogs but only one had improved hair re-growth. On mitotane treatment, partial to complete hair re-growth was seen in 4/6 dogs and no re-growth in 2/6 dogs. No significant decrease in sex hormone concentrations were seen during melatonin or mitotane treatment. Concentrations of ISH in dogs with hair re-growth did not differ significantly from pre-treatment values. At the completion of the study, androstenedione, progesterone and 17-hydroxyprogesterone were still above reference ranges in 21, 64 and 36%, respectively, of dogs with partial to complete hair re-growth. In conclusion, 62% of dogs had partial to complete hair re-growth. However, not all dogs with hair re-growth had concentrations of ISH within the normal range.     

The effects of thyroid hormones on the skin of beagle dogs

The effects of hypothyroidism on canine skin were determined by comparing morphologic, morphometric, and hair cycle differences in skin biopsy samples from 3 groups of age- and gender-matched Beagle dogs: (1) euthyroid dogs; (2) dogs made hypothyroid by administration of 131I; and (3) dogs made hypothyroid and maintained in a euthyroid state by treatment with synthetic thyroxine. After 10 months of observation, there was slower regrowth of hair 2 months after clipping in the untreated-hypothyroid dogs. Untreated-hypothyroid dogs had a greater number of follicles in telogen and fewer hair shafts (ie, a greater number of hairless telogen follicles) than did the control group. The control dogs had a greater number of telogen follicles but the same number of hair shafts as the treated-hypothyroid group. Treated-hypothyroid dogs had the greatest number of follicles in the growing stage of the hair cycle (anagen). This study suggests that, at least in Beagles, induced hypothyroidism does not affect the pelage as dramatically as has been described in naturally occurring disease. This is because normal Beagles retain hair shafts in follicles for long periods, and the alopecia of hypothyroidism appears to evolve slowly because of the prolongation of this haired telogen stage. The evaluation of thyroxine-treated hypothyroid dogs demonstrates that thyroid hormone supplementation of Beagle dogs with induced hypothyroidism stimulates hair growth.     

Treatment of canine Alopecia X with trilostane

Sixteen Pomeranians and eight miniature poodles presenting with clinical signs of alopecia X, elevated blood concentrations of 17-hydroxyprogesterone post stimulation with adrenocorticotropic hormone and increased urinary cortisol/creatinine ratios were treated with trilostane, a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase. Trilostane was given once or twice daily at a mean dose of 10.85 mg kg(-1) day(-1). Adrenal function was evaluated with a follow-up of 28 months in the Pomeranians and 33 months in the miniature poodles. Treatment with trilostane led to complete hair re-growth in 85% of the Pomeranians and in all of the miniature poodles within 4 to 8 weeks. No adverse events attributed to treatment with trilostane were recognized. The hair re-growth might have been the result of a down-regulation of adrenal steroids and/or of the noncompetitive inhibition of the oestrogen receptors at the hair follicle level.     

The canine hair cycle - a guide for the assessment of morphological and immunohistochemical criteria

The hair follicle has a lifelong capacity to cycle through recurrent phases of controlled growth (anagen), regression (catagen) and quiescence (telogen), each associated with specific morphological changes. A comprehensive classification scheme is available for mice to distinguish the cycle stages anagen I-VI, catagen I-VIII and telogen. For dogs, such a classification system does not exist, although alopecia associated with hair cycle arrest is common. We applied analogous morphological criteria and various staining techniques to subdivide the canine hair cycle stages to the same extent as has been done in mice. Of all the staining techniques applied, haematoxylin and eosin stain, Sacpic, Masson Fontana and immunohistochemistry for vimentin and laminin proved to be most useful. To evaluate the applicability of our criteria, we investigated skin biopsies from healthy beagle dogs (n=20; biopsies from shoulder and thigh) kept in controlled conditions. From each biopsy, at least 50 hair follicles were assessed. Statistical analysis revealed that 30% of the follicles were in anagen (12% early and 18% late), 8% in catagen (2% early, 5% late and 1% not determinable) and 27% in telogen. Thirty-five per cent of hair follicles could not be assigned to a specific cycle stage because not all follicles within one biopsy were oriented perfectly. In conclusion, this guide will not only be helpful for the investigation of alopecic disorders and possibly their pathogenesis, but may also serve as a basis for research projects in which the comparison of hair cycle stages is essential, e.g. comparative analysis of gene expression patterns.     

Skin distribution of imidacloprid by microautoradiography after topical administration to beagle dogs

To investigate the cutaneous distribution, localization, and persistence of imidacloprid in dogs, Advantage Topical Solution labeled with carbon 14 (14C) was topically applied as a single treatment at label rates and application pattern based on body weight to two adult beagles. One dog (8.5 kg) received 1.0 mL of the test solution at a single spot in the interscapular area (14 mg active ingredient/kg body weight); the second dog (12.3 kg) was treated with 2.5 mL of the test solution at four sites, each site receiving approximately 0.625 mL, along the dorsal thoracic and lumbar spine area (21 mg active ingredient/kg body weight). Samples of hair, skin surface residue, and skin taken from the application sites and/or distal body regions of the dogs at four intervals between 7 and 56 days after treatment demonstrated the migration of 14C radioactivity from the application sites to distal areas of the canine haircoat and skin. The 14C radioactivity concentrations in the skin biopsy and stratum corneum samples diminished steadily over 56 days after treatment. Microautoradiography of the skin showed focal concentrations of radioactivity in the superficial epidermis, hair follicles, and sebaceous glands. The presence of imidacloprid-derived radioactivity within hair follicles and sebaceous glands and on the skin surface is in good agreement with the reported efficacy of imidacloprid against fleas on dogs and cats for up to 1 month despite posttreatment bathing, shampooing, and/or swimming.     

Evaluation of lung pathology in Dirofilaria immitis-experimentally infected dogs treated with doxycycline or a combination of doxycycline and ivermectin before administration of melarsomine dihydrochloride

Adulticide therapy in heartworm (Dirofilaria immitis)-infected dogs can lead to thromboembolism, which can seriously compromise post-treatment health status. Lung pathology following adulticide therapy was evaluated in three groups of experimentally infected dogs. Group 1 was treated with doxycycline at 20 mg/kg per os once daily for 30 days post infection followed by an intramuscular injection of melarsomine dihydrochloride (2.5 mg/kg) at Week 12, followed 1 month later by two injections 24 h apart. Group 2 was treated as described for Group 1, with the addition of ivermectin at 6 mcg/kg given monthly per os for 24 weeks post-infection. Group 3 received melarsomine alone, as described above. All dogs were necropsied at Week 24 and lung pathology was evaluated. Lesion criteria included perivascular inflammation and endothelial proliferation. Lesions were scored by two independent pathologists who were blinded as to treatment. Results indicate that doxycycline treatment alone or combined with ivermectin had lower lesion scores than lungs from dogs who had received melarsomine alone. Dogs that received the combined doxycycline/ivermectin protocol and treated with adulticide showed less severe arterial lesions and the virtual absence of thrombi.     

Primary hair growth in dogs depends on dietary selenium concentrations

Selenium (Se) plays an important role in hair growth. The objective of this study was to investigate the effect of dietary selenium concentration on hair growth in dogs. Thirty-six beagles were stratified into six groups based on age, gender and body condition score. The dogs were fed a torula yeast-based canned food for 3 weeks. Then the dogs were fed varying amounts of selenium supplied as selenomethionine for an additional 24 weeks. Analysed selenium concentrations in the experimental foods for the six groups were 0.04, 0.09, 0.12, 0.54, 1.03 and 5.04 mg/kg dry matter respectively. Body weight and food intake were not affected by the selenium treatments. Serum selenium concentration was similar initially but was significantly different at the end of the study among groups. Dietary selenium concentration below 0.12 mg/kg diet may be marginal for an adult dog. Dietary treatment had no effect on serum total thyroxine (TT(4)), free thyroxine (FT(4)), and free 3,3',5-triiodothyronine (FT(3)). There was a significant diet and time interaction (p = 0.038) for total 3,3',5 triiodothyronine (TT(3)). Hair growth was similar among groups initially but significantly reduced in dogs fed diets containing 0.04, 0.09 or 5.04 mg Se/kg when compared with 0.12, 0.54 and 1.03 mg Se/kg at week 11 (p < 0.05) and week 22 (p = 0.061). These results demonstrated that both low and high selenium diets reduce hair growth in adult dogs.     

Wolbachia and its influence on the pathology and immunology of Dirofilaria immitis infection

Since the definitive identification in 1995 of the bacterial endosymbiont Wolbachia that resides in different tissues of the filarial worm Dirofilaria immitis, there has been increasing interest to understand whether and what role it plays in the pathogenesis of and immune response to heartworm infection. The present study evaluated the effects of treatments on lung pathology in 20 beagle dogs experimentally infected with D. immitis. Dogs in Group 1 were treated with doxycycline (10 mg/kg/day) orally from weeks 0-6, 10-12, 16-18, 22-26, and 28-34. Dogs in Group 2 served as infected, non-treated controls. Dogs in Group 3 were given doxycycline as described for Group 1 combined with weekly oral doses of ivermectin (6 mcg/kg) for 34 weeks and intramuscular (IM) melarsomine (2.5 mg/kg) at week 24, followed by two additional melarsomine injections 24h apart 1 month later. Group 4 received only melarsomine as described for Group 3. Lung lesion criteria, scored by two independent blinded pathologists, included perivascular inflammation and endothelial proliferation. Doxycycline treatment alone had no effect on lesion scores, whereas the combination of doxycycline and ivermectin resulted in less severe perivascular inflammation. All lungs were evaluated for positive immunostaining for the Wolbachia surface protein (WSP). Control dogs showed numerous thrombi, intense perivascular and interstitial inflammation and, occasionally, positive staining for WSP. Interestingly, dogs receiving doxycycline/ivermectin/melarsomine showed significantly less severe arterial lesions and the virtual absence of thrombi.     

Pharmacokinetics of metaflumizone and amitraz in the plasma and hair of dogs following topical application

Controlled laboratory studies have shown that a metaflumizone plus amitraz combination (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) applied topically is effective for the treatment and control of fleas and ticks on dogs. Two studies were conducted to determine the distribution of both metaflumizone and amitraz in the plasma and hair of dogs following treatment at the minimum recommended dose of approximately 20mg/kg of each active ingredient. Six purpose-bred, adult Beagle dogs were used in each study. Plasma or hair samples were collected from each dog just prior to dosing and periodically through 56 days after treatment. Samples were analyzed by HPLC methods validated for the simultaneous determination of metaflumizone and amitraz. Amitraz was detectable (>3.2ng/ml) but not quantifiable (<50ng/ml) in only two plasma samples, collected 1 and 2 days post-treatment from different dogs. Metaflumizone concentrations in plasma were generally detectable (>1.0ng/ml) but not quantifiable (<50ng/ml). Measurable levels were found in one dog 7 days post-treatment, increasing to a maximum of four dogs at 42 days after dosing, with a metaflumizone range of 59-138ng/ml. Analysis of hair samples indicated that both metaflumizone and amitraz were widely distributed at basically similar levels in the hair within 1-day after administration, reaching maximum concentrations between 2 and 7 days post-treatment. Low but quantifiable levels of both compounds were still present on hair at the end of the 56-day study. These studies indicate that the ectoparasitic activity is due to exposure of the parasites to metaflumizone and amitraz on the surface of the host (hair and/or skin), not to exposure via the circulatory system of the host.     

The impact of body site, topical melatonin and brushing on hair regrowth after clipping normal Siberian Husky dogs

The aims of this study were to determine the impact of body site, vigorous brushing and topical melatonin treatment on hair regrowth after clipping normal dogs. Siberian Husky dogs were randomly assigned to three groups of eight dogs each. All dogs had the lumbosacral region and both lateral thighs clipped. The left thigh and lumbosacral area received no treatment and were compared in all 24 dogs. Eight dogs had the right thigh treated with 0.1% melatonin twice daily for 2 months, and hair regrowth was compared with the left thigh. Eight dogs had the right thigh brushed twice daily for 2 months, and hair regrowth was compared with the left thigh. Eight dogs had neither thigh treated. Hairs were plucked before and 2 months postclipping, and the proportion of hair growth from the original length was calculated and compared as described above. Biopsy samples were collected before and after treatment to determine if brushing induced dermal inflammation and melatonin increased the proportion of anagen follicles. Proportionally, left thigh hairs were significantly longer compared to lumbosacral hairs 2 months postclipping. No significant differences in hair regrowth were noted between the nontreated thigh and the thigh treated with melatonin or brushed. No significant difference in dermal inflammation was noted before and after brushing. No significant differences were observed in the proportion of anagen follicles before and after topical melatonin treatment. Our results showed that the hairs in the lumbosacral region were proportionally shorter than lateral thigh hairs 2 months postclipping. Moreover, topical melatonin and brushing had no impact on hair regrowth after clipping normal dogs.     

Effect of insulin dosage on glycemic response in dogs with diabetes mellitus: 221 cases (1993-1998)

OBJECTIVE: To evaluate glycemic response to insulin treatment in dogs with diabetes mellitus. DESIGN: Retrospective study. ANIMALS: 221 dogs with diabetes mellitus. PROCEDURE: Type and dosage of insulin used, minimum and maximum blood glucose concentrations, time of blood glucose concentration nadir, and optimal duration of action of insulin were determined on the basis of data obtained prior to initial examination at the teaching hospital (127 dogs), at the time of initial examination (212 dogs), at the time a second follow-up blood glucose curve was performed (59 dogs), and at the time of clinical control of diabetes mellitus (83 dogs). RESULTS: Prior to examination, 69 of 127 dogs (54%) received 1 s.c. insulin injection daily. Thirty-one dogs (24%) received a high dose of insulin (i.e., > 1.5 U/kg [0.7 U/lb] of body weight); 27 of these dogs (87%) received 1 injection/d. Eleven of 16 dogs (69%) that were hypoglycemic (blood glucose concentration < 80 mg/dl) also received 1 injection/d. However, optimal duration of action of insulin was > 12 hours in only 5 of 83 dogs (6%) evaluated at the time diabetes mellitus was clinically controlled. At that time, only 1 dog (1%) received a high dose of insulin, and the dog received 2 injections/d. Moreover, 8 of 10 dogs (80%) with hypoglycemia received 1 injection/d. CONCLUSIONS AND CLINICAL RELEVANCE: Most dogs with diabetes mellitus are clinically regulated with 2 daily insulin injections. Administration of a high dose of insulin or development of hypoglycemia may be more common in diabetic dogs that receive insulin once daily, compared with dogs that receive insulin twice daily.     

Endocrine alopecia in a miniature poodle

Hypothyroidism and concurrent sex hormone imbalance associated with alopecia was diagnosed in a 5 year-old entire male Miniature Poodle. The dog had a 3-year history of alopecia, seborrhoea and recurrent superficial pyoderma. Abnormal thyrotropin releasing hormone stimulation test results supported a diagnosis of hypothyroidism. Partial hair regrowth occurred after interstitial cell tumours, which were present in both testicles, were removed by castration. Complete hair regrowth, however, occurred only after thyroid hormone supplementation. This case highlighted difficulties which may be encountered when interpreting serum hormone concentrations and endocrine function tests.     

Use of a low-dose ACTH stimulation test for diagnosis of hypoadrenocorticism in dogs

BACKGROUND: Although definitive diagnosis of hypoadrenocorticism usually is made by an adrenocorticotrophic hormone (ACTH) stimulation test using 250 microg/dog of synthetic ACTH (cosyntropin/tetracosactrin), increased costs have prompted a search for less-expensive diagnostic methods. HYPOTHESIS: A low-dose ACTH stimulation test (5 microg/kg) will distinguish between dogs with nonadrenal illness and hypoadrenocorticism. Additionally, administration of cosyntropin will not affect the results of another ACTH stimulation test performed 24 hours later. ANIMALS: Eight healthy adult dogs and 29 hospitalized dogs with suspected hypoadrenocorticism. METHODS: In this prospective study, each healthy dog received 4 ACTH stimulation tests. Dogs received either 5 microg/kg or 250 microg/dog of cosyntropin on day 1 and the alternate dose on day 2. The opposite dosing sequence was used after a 2-week washout period (days 15 and 16). Dogs with suspected Addison's disease received 2 ACTH stimulation tests, 24 hours apart, using either a dose of 5 microg/kg cosyntropin or 250 microg/dog on the 1st day and the alternate dose on the 2nd day. RESULTS: In healthy dogs, poststimulation cortisol concentrations on days 2 and 16 and days 1 and 15 were equivalent (90% confidence interval [CI]: 86.7-101.2%). In dogs with suspected Addison's disease, mean (+/-SD) cortisol responses to ACTH in the 5 microg/kg dose (16.2+/-7.7 microg/dL) and 250 microg/dog dose (15.9+/-6.3 microg/dL) were statistically equivalent (90% CI: 91.2-105.4%). CONCLUSIONS AND CLINICAL IMPORTANCE: Low-dose ACTH stimulation testing distinguishes between dogs with nonadrenal illness and hypoadrenocorticism. Additionally, the administration of 2 ACTH stimulation tests on consecutive days does not affect results of the second test.     

Alopecia in a black Labrador retriever associated with focal sub‐follicular panniculitis and sebaceous adenitis

A 6‐year‐old entire male black Labrador retriever was presented with nonpruritic multicentric, well‐demarcated alopecia of 12‐weeks duration. Skin biopsies from the margins of alopecic regions showed sebaceous adenitis and sub‐follicular panniculitis. Biopsies from alopecic areas showed severe follicular atrophy with residual fibrous tracts, loss of sebaceous glands and lymphohistiocytic panniculitis beneath individual atrophic hair follicle groups. These features differed from previous reports of pilosebaceous diseases of dogs and appeared to extend the spectrum of inflammatory patterns in presumed immune‐mediated adnexal diseases of this species. During the 12‐month follow‐up, there was partial hair regrowth without treatment but alopecia was permanent in the centre of larger lesions.     

Inherited alopecia X in Pomeranians

Four male Pomeranians that showed alopecia with an age of onset between five months and eight years were investigated.The aim of the investigation was to clarify whether the affected dogs had alopecia X and whether their symptoms might be due to a hereditary defect.The four affected dogs showed hairless patches at the root of the tail, at the back, at the limbs from the thigh to the tarsus and at the abdomen. Within the hairless patches some islets with sparse hair were present. In hairless patches the skin was dark pigmented. Besides the alopecia and hyperpigmentation no other symptoms were found according to anamnestic and clinical examination. History, clinical examinations, laboratory diagnostics, and histopathology of skin biopsies allowed the diagnosis of alopecia X in three affected male dogs.The last one of the affected dogs additionally had slightly reduced thyroid hormone levels. Based on identical symptoms and the close relatedness of all four animals, it was assumed that the fourth affected dog also had alopecia X.The available data possibly indicate a monogenic autosomal dominant inheritance, however a recessive inheritance can not be excluded at this time.     

The effect of body region on the canine hair cycle as defined by unit area trichogram

The impact of anatomic location on trichogram analysis of the hair cycle phases was evaluated in 15 clinically normal dogs. The purposes of this study were to determine if the number of hairs in anagen and telogen vary among anatomic sites within a dog and to see whether there is an optimal region to sample hairs for canine trichogram evaluation of the hair cycle phases. In each dog eight sites were sampled. Four (26.7%) of the 15 dogs had no significant differences in the number of hairs in anagen and telogen among the eight body sites examined. Nine (81.8%) of the remaining 11 dogs had only one site that revealed significant differences in the number of hairs in anagen or telogen. In seven (77.8%) of these dogs only the anagen differed significantly, and in two (22.2%) dogs both phases differed significantly. Two (18.2%) dogs revealed two sites with significant differences in the number of hairs in anagen. The number of hairs in anagen and telogen in the shoulder area did not vary significantly in any of the dogs. This observation, coupled with the ease of sampling at this site, indicates that the shoulder is the site of choice when studying variations in ratios of hair cycle phases using unit area trichogram. Our results also suggest that numbers of telogen and anagen hairs from body regions with different hair shaft lengths do not vary significantly, and the occasional inconsistent results noted at some body sites might be due to sample collection technique.     

Comparison of aqueous porcine ACTH with synthetic ACTH in adrenal stimulation tests of the female dog

The adrenocortical (plasma corticosteroid) responses in female dogs given porcine ACTH in gelatin (1-39 amino acid sequence) and synthetic ACTH (1-24 amino acid sequence) were compared. Sixteen dogs were used. Each dog underwent 4 different ACTH stimulation studies, these being done with a 4- to 8-week interval. The studies in each dog included injections of 2 doses of porcine ACTH--2.2 IU and 4.4 IU/kg of body weight--and of 2 doses of synthetic ACTH--0.25 mg/dog and 0.50 mg/dog. The dogs were arbitrarily allotted to 4 groups, each group being subjected to a given sequence of stimulation studies. The purpose in this project was to determine whether the established methods for synthetic and porcine ACTH stimulation tests had similar results. Statistical analysis of the 4 stimulation methods revealed no significance (P greater than 0.05) in the resting or poststimulation plasma corticosteroid concentrations. Thus, it was concluded that either recommended method using ACTH (porcine ACTH at 2.2 IU/kg or synthetic ACTH at 0.25 mg/dog) causes maximal secretion of adrenocortical reserve. Either ACTH preparation, using the established method, can be used interchangeably.     

Toxicokinetics of mercury in blood compartments and hair of fish-fed sled dogs

Background

Understanding mercury (Hg) distribution in blood and the importance of hair as an excretory pathway is critical for evaluating risk from long term dietary Hg exposure. The major objective of this study was to characterize changes in total Hg concentrations in specific blood compartments and hair over time due to long term piscivory.

Methods

Eight sled dogs (Canis lupus familiaris) were fed either a fish and kibble diet (n = 4), or a fish-free control diet (n = 4) for 12 weeks. Concentrations of Hg were monitored throughout the exposure period, and for 10 weeks post exposure, until Hg concentrations in all blood compartments of one of the exposed dogs dropped below detection limit. Additionally, foreleg hair was sampled during acclimation and weeks 0 and 12.

Results

Hg was detected primarily in whole blood and packed cells, although it was sporadically detected at low concentrations in plasma and serum in two of the fish fed dogs. Dogs ingested an estimated average of 13.4 ± 0.58 μg Hg per kg body weight per day. Hg was detectable in whole blood and packed cells within a week of exposure. Detected concentrations continued to rise until plateauing at approximately 3-6 weeks of exposure at a mean of 9.2 ± 1.97 ng/g (ppb) in whole blood. Hg concentration decreased post exposure following 1st order elimination. The mean half-life (t_1/2) in whole blood for Hg was 7 weeks. Mean Hg in hair for the fish-fed dogs at week 12 was 540 ± 111 ppb and was significantly greater (about 7-fold) than the Hg hair concentration for the control dogs. The hair to blood ratio for Hg in fish-fed dogs was 59.0 ± 7.6:1.

Conclusions

This study found the sled dog model to be an effective method for investigating and characterizing blood Hg distribution (whole blood, serum, plasma, packed cells) and toxicokinetics associated with a piscivorous diet, especially for Hg-exposed fur bearing mammals (such as polar bears). Although hair excretion and hair to blood Hg ratios were not similar to human concentrations and ratios, the sled dog toxicokinetics of Hg in blood, was more similar to that of humans than traditional laboratory animals (such as the rat).