Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 212-634-7 | CAS number: 834-12-8
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
The low molecular weight (227.3 g/mol) and log P value (2.63) of Ametryn favour its absorption following oral exposure. The absorption and excretion of Ametryn following oral exposure was demonstrated by the results of 4 toxicokinetic studies, in which radiolabeled Ametryn (administered in doses of 0.5 or 200 mg/kg body weight) was observed to be excreted via urine and feces in rats [3, 4, 5, 6]. Radioactivity levels detected in urine and feces up to 7 days following exposure ranged from 42.1 to 64.51%, and 29.99 to 42.06%, of the administered dose, respectively. As no radioactivity was detected in exhaled carbon dioxide, it was determined that Ametryn is not excreted via expired air. One toxicokinetic study, in which radiolabeled Ametryn was administered intravenously to rats, demonstrated that the radioactivity detected in the feces of animals orally exposed to Ametryn was due to biliary excretion of Ametryn metabolites rather than the presence of unabsorbed compound [6]. The results of the 4 available toxicokinetic studies indicated that Ametryn was rapidly absorbed following oral exposure, and that Ametryn reaching the systemic circulation was extensively metabolized to mostly polar compounds. These metabolites were excreted primarily via the urine, with large amounts detected also in the feces, regardless of oral or intravenous exposure. The low levels of radioactivity detected in test animal carcasses 7 days after exposure (1.325 to 5.06% of the administered dose) suggests that bioaccumulation of Ametryn is unlikely.
No studies were available in which the toxicokinetics/toxicity of Ametryn following dermal or inhalation exposure were assessed. Although the low molecular weight (227.3 g/mol), log P value (2.63), and moderate water solubility (200 mg/L) of Ametryn favour its absorption following dermal exposure, its physical state (i.e., powder) does not. Furthermore, quaternary ammonium ions, heterocyclic ammonium ions, and di-/tri- nitrobenzenes tend to bind to skin components, slowing dermal absorption. Therefore, absorption of Ametryn following dermal exposure is expected to be minimal. The low molecular weight, log P value, and moderate solubility of Ametryn favour absorption following inhalation exposure. However, since no inhalation studies or information regarding average particle size were available, the extent of absorption of Ametryn following inhalation exposure cannot be estimated.
Twenty-three oral toxicity studies (including 3 acute, five 90-day, five 12- to 24-month, 4 carcinogenicity, 2 reproductive, and 4 developmental studies) investigating the effects of Ametryn on rats, dogs, rabbits, and mice were available [3, 4, 5, 7–22]. Clinical effects observed in these studies, including changes in organ weight, clinical chemistry, and death, were likely caused by treatment-related reductions in feed intake and body weight [as reported by all studies except one [15], in which no clinical signs were reported]. Considering the observed reductions in body weight and feed consumption, Ametryn is likely unpalatable in high concentrations. These studies did not report effects indicative of systemic absorption, nor did they provide any pertinent toxicokinetic information (i.e., distribution to target organs). No fetal effects, other than those attributed to reduced maternal feed intake and weight loss, were observed in the 2 reproductive and 4 developmental toxicity studies available; thus, whether Ametryn crosses the placenta following oral exposure cannot be deduced from the results of these studies.
The excretion half-life of Ametryn is expected to be short based on its log P value (2.63). This expectation is supported by the 4 available toxicokinetic studies, in which the rapid and extensive excretion of Ametryn and its metabolites following oral or intravenous exposure was demonstrated. Following oral or intravenous exposure to rats, Ametryn metabolites detected in urine and feces were primarily polar, low levels of residual radioactivity were detected in carcasses (up to 7 days following exposure), and up to 98.6% of the administered dose was excreted within 48 hours; thus, Ametryn and its metabolites are not expected to bioaccumulate.
References
[1] Glanzel, A., 1999, Volatilization of 14C-Labeled G 34162 from Soil Surface under Controlled Laboratory Conditions, Novartis Crop Protection AG Environmental Safety, Ecochemistry, 4002 Basel, Switzerland, Study number 98AG06.
[2] Smeykal, H., 2006, VAPOUR PRESSURE A.4. (OECD 104), Siemens AG Prozess-Sicherheit Industriepark Höchst, C 487 D-65926 Frankfurt am,, Report number 20060260.01.
[3] Purshottam, 1998, Absorption, distribution, and excretion of radiolabelled 14C Ametryn technical in Wistar rats, Toxicology department Rallis Research Centre Rallis India Limited Post Box No. 5813, Plot Nos. 21 and 22 Peenya II Phase, Bangalore-560 058, India, Report number TOXI-2114-96.
[4] Reynolds, 1990, Metabolism of 14C-Ametryn in rats – Phase I preliminary study, Xenobiotic Laboratories, Inc., Report number RPT0007.
[5] Braun, 1990, Absorption, distribution, and excretion studies of 14C-AMetryn in the rat, Biological Test Center 2525 McGaw Avenue Irvine, CA 92713 (714) 660-3184, Report number P01744.
[6] Wu, 1990, Analysis, quantitation, and structure elucidation of metabolites in urine and feces from the rat dosed with 14C-Ametryn, XenoBiotic Laboratories, Inc. P.O. Box 3205, Princeton, NJ 08543, Report number RPT0022.
[7] Bachmann M, 1998, 3-MONTH ORAL TOXICITY STUDY IN RATS (ADMINISTRATION IN FOOD), Novartis Crop Protection AG (Successor in business of Sandoz Ltd. and Ciba-Geigy Ltd), Toxicology/Experimental Toxicology, 4332 Stein/Switzerland, Report number 961100.
[8] Prakash, 1999, SUBCHRONIC (90 DAY) ORAL TOXICITY STUDY WITH AMETHYN TECHNICAL IN BEAGLE DOGS, Toxicology Department Rallis Research Centre. Rallis India Limited. Post Box No. 5813, Plot Nos. 21 & 22. Peenya II Phase,560 058,, Report number 2100/96
[9] Kumar, 1999, SUBCHRONIC (90 DAY) ORAL TOXICITY STUDY WITH AMETRYN TECHNICAL IN SWISS ALBINO MICE, RALLIS RESEARCH CENTRE, Toxicology Department, RALLIS INDIA LIMITED, Plot Nos. 21 & 22, Post Box No. 5813, Peenya II Phase, Bangalore - 560 058, India, Report number 2102/96.
[10] Krishnappa, 1998, SUBCHRONIC (90 DAY) ORAL TOXICITY STUDY WITH AMETRYN TECHNICAL IN WISTAR RATS, RALLIS RESEARCH CENTRE, Toxicology Department, RALLIS INDIA LIMITED, Post Box No. 5813, Plot Nos. 21 & 22, Peenya II Phase, Bangalore - 560 058, India, Report number 2097/96.90-OR.
[11] Dickhaus, 1984, THREE MONTHS SUBACUTE TOXICITY "AMETRYNE TECHN." AS FEEDING STUDY IN THE SPECIES RAT, Pharmatox Forschung and Beratung GmbH. Vogtei-Ruthe-Str 26. 3163 Sehnde 13 (Wirringen) Landkreis Hannover, Report number HANS DE 2H.
[12] Krishnappa H, 2002, Combined Chronic Toxicity and Carcinogenicity Study with Ametryn Technical in Wistar Rats, Toxicology Department, Rallis Research Centre, Rallis India Limited, Post Box No. 5813, PLOT Nos. 21 &22, Peenya II Phase, Bangalore - 560 058, India, Report number 2098/96.
[13] Hazelette and Green, 1987, Combined chronic toxicity/oncogenicity study in rats, Pharmaceuticals Division Ciba-Geigy Corporation 556 Morris Ave. Summit, NJ 07901, Report number 87043.
[14] O'Connor D, McCormick GC & Green JD, 1987, CHRONIC TOXICITY STUDY IN DOGS, RESEARCH DEPARTMENT, PHARMACEUTICALS DIVISION, CIBA-GEIGY CORPORATION, NEW JERSEY 07901, Report number 842118.
[15] Burdock, 1981, 102-WEEK CARCINOGENICITY STUDY IN MICE, HAZLETON LABORATORIES AMERICA, INC, 3200 Leesburg Turnpike Vienna, Virginia 22180 U.S.A., Report number 483-128.
[16] Kumar, 2002, CARCINOGENICITY STUDY WITH AMETRYN TECHNICAL IN SWISS ALBINO MICE, TOXICOLOGY DEPARTMENT RALLIS RESEARCH CENTRE RALLIS INDIA LIMITED, POST BOX NO. 5813, PLOT Nos. 21 & 22, PEENYA II PHASE,- 560 058,, Report number 2103/96.
[17] Ganiger, 1999, Two Generation Reproduction Toxicity Study with Ametryn Technical in Wistar Rats, Toxicology Department, Rallis Research Centre, Rallis India Limited, Post Box No. 5813, Plot Nos. 21 & 22, Peenya II Phase, Bangalore 560 058, India, Report number 2105/96.
[18] Hummel H, Youreneff M & Yau ET, 1987, TWO-GENERATION REPRODUCTION STUDY IN RATS, CIBA-GEIGY CORPORATION (Research Department, Pharmaceuticals Division), 556 Morris Avenue, Summit, New Jersey 07901, Report number 852048.
[19] Ponnana, 1999, Teratogenicity Study in Rabbits with Ametryn Technical, Rallis Research Centre, Rallis India Limited, Post Box No. 5813, Plot nos. 21 & 22, Peenya, Bangalore - 560058, India, Report number 2107/96.
[20] Infurna 1985a, A Teratology Study in Rabbits, Pharmaceuticals Division CIBA-GEIGY Corporation,, Report number 85063.
[21] Infurna RN, Wimbert KV & Arthur AT, 1985b, AMETRYN TECHNICAL A TERATOLOGY STUDY IN RATS, CIBA-GEIGY Corporation (Pharmaceuticals Division), Report number 85140.
[22] Veena, 1998, Tertogenicity Study in Wistar Rats, Toxicology Department Rallis Research Centre Rallis India Limited5813, Plot Nos. 21 & 22 Peenya II Phase, Bangalore 560058 India, Report number TOXI: 2106/96 TER.R.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
