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Biomedical subjects

A N Worden

Publications and source records attributed to A N Worden.

At least 19 recordsLinked to original sources
PubMed1978

Clioquinol toxicity in the dog.

A number of instances have been reported in the scientific literature in which acute intoxication with halogenated oxyquinolines has led in some species to convlusions, often followed by death. The toxicity of repeated doses of clioquinol has been investigated extensively in the dog. The clinical syndrome induced in this species is characterized by anorexia, weight loss, extremem muscle weakness and emaciation. In some animals surviving this impairment of condition for several weeks, neuropathy of the central nervous system, but not of the peripheral nerves ensued. It is suggested that these toxicological manifestations are less dependent on the dose-level than on the degree of absorption. Some suggestions regarding the aetiology of the lesions are made.

Animals↗
PubMed1978

Effect of lindane on pregnancy in the rabbit and rat.

There was no evidence of any teratogenic effect of lindane when administered during pregnancy at levels equivalent to 5, and 15 mg/kg body weight to New Zealand White rabbits from days 6 to 18 inclusive, or to CFY rats from days 6 to 16 inclusive. These findings are consistent with the negative teratogenicity results in mice mutagenicity studies and 3-generation rat reproduction studies already reported.

Animals↗
PubMed1978

Effects of feeding lindane to dogs for periods of up to 2 years.

Lindane was administered to male and female Beagle dogs at dietary levels of 25, 50 and 100 ppm for 104 weeks, and of 200 ppm for 32 weeks. One death at 25 ppm and one at 200 ppm were not considered to be related to the test compound. At 100 and 200 ppm, SAP levels were raised and the livers were dark, friable and slightly enlarged but without any detected histopathological change. HVSA changes, possibly indicative of non-specific neuronal irritation, were recorded in the EEG tracings at 200 but not at 100 ppm. There were no other indications of an adverse effect of lindane. The negative findings at 50 ppm are consistent with a 'no-effect level' for this species of 1.25 mg/kg body weight, comparable with for the rat, and with proposed human ADI of 0.0125 mg/kg body weight.

Adipose Tissue↗
PubMed1978

Effects of lindane upon reproductive function in a 3-generation study in rats.

A 3-generation study, involving the feeding of lindane at dietary concentrations of 25, 50 or 100 ppm to CD strain rats, did not reveal any adverse effects upon reproductive function as compared with that of control animals. There were no major malformations, while the distribution of minor variants was not compound or dose-related. An examination at 21 days of age of 10 males and 10 females F3B animals in each group revealed a dosage related tendency for increased liver weight and enlarged hepatocytes were seen in some control and treated animals. The relevance of these latter findings was considered of doubtful importance compared with the lack of effects on the growth and reproductive performance of the preceding generations.

Abnormalities, Drug-Induced↗
PubMed1976

The oral toxicity of clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) in beagle dogs.

When clioquinol was administered to Beagle dogs, disturbances in gait which were associated with abnormal reflexes and reactions, were seen in animals receiving 250 and 400 mg/kg body weight per day. Histopathological examination of the central nervous system (CNS) showed pathological change in the posterior columns of the spinal cord.

Animals↗
PubMed1975

The effect of disodium 5-ribonucleotide on reproductive function over three generations in the rat.

Deitary levels of 0.1, 1.0 and 2.0% disodium 5-ribonucleotide were administered to rats of the CD strain over 3 generations, and the growth and reproductive performance were compared with those of a control group. Treatment did not appear to affect parent animals, as assessed by the incidence of mortality, bodyweight change, food consumption, mating performance, Pregnancy rate, Gestation Peroid, and post-mortem findings. Total litter loss, Litter size, Litter and mean pup weights, pup mortality and the incidence of skeletal or other variants in the offspring were unaffected by treatment at any dosage level. Additional organ weight analysis and skeletal staining of 10 males and 10 females from all groups, and the histological examination of 10 male and 10 females of the control and 2.0% level groups of the third generation did not provide any evidence of effects that could be related to treatment.

Abnormalities, Drug-Induced↗
PubMed1975

Long-term feeding study on disodium 5-ribonucleotide in dogs.

Groups of 4 male and 4 female Beagle dogs were fed for 2 years on diets containing 0 (control), 0.1, 1.0 and 2.0%, respectively, of disodium 5'-ribonucleotide (a 50 : 50 mixture of disodium 5'-inosinate and disodium 5'-guanylate). The mean daily intakes of the 3 test groups ranged during the experiment from 0.04-0.03, 0.48-0.26 and 0.93-0.51 g/kg, respectively. No effects attributable to treatment were found in mortality, food consumption, water consumption, bodyweight gain, ophthalmoscopy, clinical signs, haematology, serum chemistry (other than allantoin levels), organ weights, macroscopic pathology or histology, Small differences were observed between mean values in treatment and control dogs for serum allantoin but there was no indication of any persistent significant difference throughout the 2-year study. In a 6-week preliminary test, dietary levels of up to 10% disodium 5'-ribonucleotide were without detectable adverse effect upon beagle dogs of either sex.

Allantoin↗
PubMed1975

The toxicity of dimethyl sulphoxide (DMSO) for the dog, pig, rat and rabbit.

Dimethyl sulphoxide (DMSO) was tested for oral toxicity in rats and dogs, and dermal toxicity in rabbits and pigs. Oral administration was by gastric intubation as a 50% equeous solution, 5 days/week at levels equivalent to 9.0, 3.0 or 1.0 ml undiluted DMSO/hg/day. For dermal application 50% and 90% equeous solutions were used to give levels equivalent to 8.1, 4.5, 2.7 or 1.5 ml DMSO/hg/day, as one daily application for rabbits, and divided into two applications/day for pigs. Dogs were dosed for approximately 2 years and pigs for 1 year, although half the animals of both species were dosed for only 18 weeks. Rats were dosed for 18 months, but some were used for interim sacrifice after a year. Rabbits received applications to normal and abraded skin for 6 months. Minor changes in bodyweight and haematological values were observed, together with a physiological diuretic response to DMSO, but the target organ was the eye, principally the lenticular nucleus. Ocular effects in dogs started after 5-10 weeks dosing at 9 ml/kg and consisted of central (nuclear) lens changes with alteration of the refractive index (myopia); transitory equatorial opacities during the 5th month; central (nuclear) opalescence; and changes in the vitreous humour. Similar changes occurred more slowly at 3 ml/kg, the alterations to the vitreous being first observed after 9-10 months at this level. Progressive nuclear refractive changes occurred after dosing for considerably longer than 6 months at 1ml/kg, but none of the animals in this group manifested the opalescence. Biochemical investigation of the lenses revealed reduction of soluble protein (mainly alpha-crystallin), glutathione and water levels, and an increase of insoluble protein. Evidence of recovery was limited mainly to a reduction in the number of dioptres needed to correct nuclear refractive change. Cessation of dosing led to regression of refractive nuclear changes but did not prevent the appearance of opalescence at 3 ml/kg and above. Dogs were the most severely affected of the 4 species, with nuclear effects at 1ml/kg, extensive changes in the lens, and involvement of the vitreous. Pigs and rabbits were affected by dose levels of 2.7 ml/kg and 1.5 ml/kg respectively. Rats occasionally showed minimal changes at 9 ml/kg. The importance of the findings in dogs is discussed in relation to general toxicological protocols. It is emphasised that reversibility of signs, and adequate duration of administration, must both be considered when ascertaining whether changes occur at levels approximating to those of human intake.

Administration, Oral↗