Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2,3,3,3,2',3',3',3'-Octachlorodipropyl ether (Abbreviation; S-421) is originally developed as synergist of a pyrethroid insecticide. In recent years, S-421 is used widely at home, for a mosquito-repellent incense, electric mosquito-repellent, an insect-killing spray, a vacuum cleaner paper pack, etc. as well. On the other hand, S-421 has been detected in vacuum cleaner dust samples as well as human milk samples in Japan indicating that our living environment is already contaminated by this compound. Long term toxicity studies including a carcinogenesis study have been performed and NOEL of chronic toxicity has been settled. However, it is clear that S-421 is used in close proximity so that acute or subacute exposure at relatively higher dose levels than chronic NOEL values are easily assumed, such as use of a spray in an ill-ventilated room, etc. This study, 28 day repeated oral dose toxicity study of S-421 was performed to monitor the outcome of acute and subacute exposure assuming possible exposure accidents mentioned above. The protocol is as follows; Groups of 10 rats of each sex(5 week-old), were treated with intragastric administration of S-421 with a dose of 0 (olive oil, control), 10, 40, 160 or 640 mg/kg body weight. For recovery test, 14 day after the last treatment, the control and 640 mg/kg groups were examined, respectively. All animals of all groups in both sexes survived. In the 640 mg/kg groups of the both sexes, all animals were set to drowsiness from about 5 hours after administration, however, they recovered by the next morning. In the hematology examination, Hb, MCH, MCHC, WBC values were significantly decreased and MCV value was significant increased in the 640 mg/kg group of both sexes. In the serum biochemistry, items increased in the 640 mg/kg groups of both sexes returned to normal level after 14 days recovery period. Absolute and relative liver weight increase seen in the 160 mg/kg and above also returned to control level after recovery. Histopathologically, slight hepatocellular swelling was observed in the 160 mg/kg groups and severe hepatocellular swelling with vacuolization and slight necrosis was seen in the 640 mg/kg group. In conclusion, the no-observed-effect levels (NOEL) of S-421 under these conditions was judged to be 40 mg/kg/day.
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PMID:[Twenty-eight day repeated dose oral toxicity test of synergist of a pyrethroid insecticide, 2,3,3,3,2',3',3',3'-Octachlorodipropyl ether (S-421) in rats]. 1474 Apr 4

Nitrotoluenes are important intermediates in the chemical industry. 2,6-Dinitrotoluene (26DNT), 2,4-dinitrotoluene (24DNT) and 2-nitrotoluene are carcinogenic in animals and possibly carcinogenic in humans. It is therefore important to develop methods to biomonitor workers exposed to such chemicals. Hemoglobin (Hb) adducts of nitroarenes are established markers of the biological effective dose. We developed a method to measure Hb adducts in biological samples. Hb adducts were measured in rats after a single exposure (0.5 mmol/kg) of 24DNT, 26DNT, 2,4-toluenediamine (24TDA) and 26TDA. Hydrolysis of Hb from rats dosed with 24DNT yields, 4-amino-2-nitrotoluene (4A2NT) (16.3 nmol/g Hb), 24TDA (4.3 nmol/g Hb) and 4-acetylamino-2-aminotoluene (4AA2AT) (0.51 nmol/g Hb). Hydrolysis of Hb from rats dosed with 26DNT yields three amines, 2-amino-6-nitrotoluene (2A6NT) (2.5 nmol/g Hb), 26TDA (1.2 nmol/g Hb) and 2-acetylamino-6-aminotoluene (2AA6AT) (0.17 nmol/g Hb). A similar Hb adduct pattern was found in Chinese workers exposed to nitrotoluenes. With respect to 24DNT, 4A2NT was the predominant adduct, and the amount was approximately 24-fold higher than 24TDA. With respect to 26DNT, 2A6NT was the predominant adduct, and the amount was approximately 20-fold higher than 26TDA. With respect to the mononitrotoluenes, the Hb adduct of 2NT was present in the highest concentrations. Each worker was examined for adverse health effects linked to exposure to DNT. The health effects were compared with the Hb adduct levels using logistic regression analysis. The odds of suffering from inertia were 3.2 times higher [95% confidence interval (CI) = 1.8-5.8] when the level of 4A2NT Hb adducts increased by one log-unit. Similar odds ratios were observed with somnolence (3.1, CI = 1.4-6.9), nausea (2.4, CI = 1.3-4.3) and dizziness (5.5, CI = 1.3-24.2). These results inferred that quantification of DNT-Hb adducts provided an effective biomarker of toxicity and could be used to estimate the risk associated with a particular exposure to DNT.
Carcinogenesis 2005 Jan
PMID:Hemoglobin adducts in workers exposed to nitrotoluenes. 1547 93