Document Detail

Toxicity and blood concentrations of xylazine and its metabolite, 2,6-dimethylaniline, in rats after single or continuous oral administrations.
MedLine Citation:
PMID:  10845188     Owner:  NLM     Status:  MEDLINE    
To cast light on whether the carcinogenic risk of 2,6-dimethylaniline (DMA), a metabolite of xylazine, may increase by ingestion of edible tissues from domestic animals treated with xylazine, the following studies of xylazine and DMA were performed. In Experiment I, male F344 rats received a single oral administration of 150 mg/kg of xylazine hydrochloride. Rats showed symptoms suggesting loss of sensation and pain immediately after the treatment. These signs had disappeared after 3 hr, but the animals died of hydrothorax and pulmonary edema by 9 hr. The plasma concentration of xylazine was 2.88 +/- 0.95 micrograms/ml at 15 min, and then decreased to 0.10 +/- 0.01 microgram/ml at 6 hr. The plasma level of DMA remained at 0.03 to 0.04 microgram/ml during the measurement period. In Experiment II, male F344 rats were fed a diet containing 1000 ppm of xylazine hydrochloride, regarded as the maximum tolerated dose, for 4 weeks. No clear clinical signs were evident and the plasma levels of xylazine and DMA were at the detection limit (0.02 microgram/ml) or less, although follicular cell hypertrophy of the thyroid was observed in all the treated animals. In Experiment III, male F344 rats were fed a diet containing 3000 ppm or 300 ppm of DMA for 4 weeks. Histological changes, such as atrophy of Bowman's gland and irregular arrangement of olfactory epithelial cells, were only observed in the olfactory epithelium of the 3000 ppm group. The plasma levels of DMA were 0.20 to 0.36 microgram/ml in the 3000 ppm group, but under the detection limit in the 300 ppm group. These results suggest that the probability of nasal carcinogenic effects of DNA on consumers via ingestion of edible tissues from food-producing animals treated with xylazine is extremely low, since DMA levels in the blood of rats subjected to continuous administration of high doses of xylazine remained under the detection limit.
K Yasuhara; H Kobayashi; Y Shimamura; T Koujitani; H Onodera; H Takagi; M Hirose; K Mitsumori
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of toxicological sciences     Volume:  25     ISSN:  0388-1350     ISO Abbreviation:  J Toxicol Sci     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-09-19     Completed Date:  2000-09-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7805798     Medline TA:  J Toxicol Sci     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  105-13     Citation Subset:  IM    
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
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MeSH Terms
Administration, Oral
Aniline Compounds / administration & dosage,  blood*,  toxicity*
Drug Administration Schedule
Hypertrophy / chemically induced,  pathology
Maximum Tolerated Dose
Nasal Cavity / drug effects,  pathology
Olfactory Mucosa / drug effects,  pathology
Rats, Inbred F344
Thyroid Gland / drug effects,  pathology
Xylazine / administration & dosage,  blood*,  toxicity*
Reg. No./Substance:
0/Aniline Compounds; 7361-61-7/Xylazine; 87-62-7/2,6-xylidine

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