A toxicological evaluation of lithium orotate
Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events. Nonetheless, there have been some concerns in the scientific literature regarding orotic acid, and pharmaceutical lithium salts are known to have...
Uloženo v:
| Vydáno v: | Regulatory toxicology and pharmacology Ročník 124; s. 104973 |
|---|---|
| Hlavní autoři: | , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
Elsevier Inc
01.08.2021
|
| Témata: | |
| ISSN: | 0273-2300, 1096-0295, 1096-0295 |
| On-line přístup: | Získat plný text |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events. Nonetheless, there have been some concerns in the scientific literature regarding orotic acid, and pharmaceutical lithium salts are known to have a narrow therapeutic window, albeit, at lithium equivalent therapeutic doses 5.5–67 times greater than typically recommended for supplemental lithium orotate. To our knowledge, the potential toxicity of lithium orotate has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test in order to further explore its safety. Lithium orotate was not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 28-day, repeated-dose oral toxicity study, rats were administered 0, 100, 200, or 400 mg/kg body weight/day of lithium orotate by gavage. No toxicity or target organs were identified; therefore, a no observed adverse effect level was determined as 400 mg/kg body weight/day. These results are supportive of the lack of a postmarket safety signal from several decades of human consumption.
•This is the first preclinical toxicologic evaluation of lithium orotate.•No in vitro or in vivo genotoxic effects were observed in a standard test battery.•No treatment related adverse effects were observed in Wistar rats.•No target organs were identified in Wistar rats.•The NOAEL was 400 mg/kg bw/day, the highest dose tested. |
|---|---|
| AbstractList | Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events. Nonetheless, there have been some concerns in the scientific literature regarding orotic acid, and pharmaceutical lithium salts are known to have a narrow therapeutic window, albeit, at lithium equivalent therapeutic doses 5.5–67 times greater than typically recommended for supplemental lithium orotate. To our knowledge, the potential toxicity of lithium orotate has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test in order to further explore its safety. Lithium orotate was not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 28-day, repeated-dose oral toxicity study, rats were administered 0, 100, 200, or 400 mg/kg body weight/day of lithium orotate by gavage. No toxicity or target organs were identified; therefore, a no observed adverse effect level was determined as 400 mg/kg body weight/day. These results are supportive of the lack of a postmarket safety signal from several decades of human consumption.
•This is the first preclinical toxicologic evaluation of lithium orotate.•No in vitro or in vivo genotoxic effects were observed in a standard test battery.•No treatment related adverse effects were observed in Wistar rats.•No target organs were identified in Wistar rats.•The NOAEL was 400 mg/kg bw/day, the highest dose tested. Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events. Nonetheless, there have been some concerns in the scientific literature regarding orotic acid, and pharmaceutical lithium salts are known to have a narrow therapeutic window, albeit, at lithium equivalent therapeutic doses 5.5-67 times greater than typically recommended for supplemental lithium orotate. To our knowledge, the potential toxicity of lithium orotate has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test in order to further explore its safety. Lithium orotate was not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 28-day, repeated-dose oral toxicity study, rats were administered 0, 100, 200, or 400 mg/kg body weight/day of lithium orotate by gavage. No toxicity or target organs were identified; therefore, a no observed adverse effect level was determined as 400 mg/kg body weight/day. These results are supportive of the lack of a postmarket safety signal from several decades of human consumption.Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events. Nonetheless, there have been some concerns in the scientific literature regarding orotic acid, and pharmaceutical lithium salts are known to have a narrow therapeutic window, albeit, at lithium equivalent therapeutic doses 5.5-67 times greater than typically recommended for supplemental lithium orotate. To our knowledge, the potential toxicity of lithium orotate has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test in order to further explore its safety. Lithium orotate was not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 28-day, repeated-dose oral toxicity study, rats were administered 0, 100, 200, or 400 mg/kg body weight/day of lithium orotate by gavage. No toxicity or target organs were identified; therefore, a no observed adverse effect level was determined as 400 mg/kg body weight/day. These results are supportive of the lack of a postmarket safety signal from several decades of human consumption. |
| ArticleNumber | 104973 |
| Author | Hirka, Gábor Murbach, Timothy S. Endres, John R. Béres, Erzsébet Glávits, Róbert Szakonyiné, Ilona Pasics Vértesi, Adél |
| Author_xml | – sequence: 1 givenname: Timothy S. orcidid: 0000-0002-7658-858X surname: Murbach fullname: Murbach, Timothy S. email: tim@aibmr.com organization: AIBMR Life Sciences, Inc., 1425 Broadway, Suite 458, Seattle, WA, 98122, USA – sequence: 2 givenname: Róbert surname: Glávits fullname: Glávits, Róbert email: glavits.robert.dr@gmail.com organization: Toxi-Coop Zrt., Berlini utca 47–49, H-1045, Budapest, Hungary – sequence: 3 givenname: John R. surname: Endres fullname: Endres, John R. email: john@aibmr.com organization: AIBMR Life Sciences, Inc., 1425 Broadway, Suite 458, Seattle, WA, 98122, USA – sequence: 4 givenname: Gábor surname: Hirka fullname: Hirka, Gábor email: gabor.hirka@toxicoop.com organization: Toxi-Coop Zrt., Berlini utca 47–49, H-1045, Budapest, Hungary – sequence: 5 givenname: Adél surname: Vértesi fullname: Vértesi, Adél email: adel.vertesi@toxicoop.com organization: Toxi-Coop Zrt., Arácsi út 97, 8230, Balatonfüred, Hungary – sequence: 6 givenname: Erzsébet surname: Béres fullname: Béres, Erzsébet email: erzsebet.beres@toxicoop.com organization: Toxi-Coop Zrt., Arácsi út 97, 8230, Balatonfüred, Hungary – sequence: 7 givenname: Ilona Pasics surname: Szakonyiné fullname: Szakonyiné, Ilona Pasics email: ilona.pasics@toxicoop.com organization: Toxi-Coop Zrt., Berlini utca 47–49, H-1045, Budapest, Hungary |
| BookMark | eNqFkEtLAzEUhYMo2FZ_gZtZupma10wmCxel-IKCm-5DSG5sSjqpSVrsv7ftuHKhqwOX81043xhd9rEHhO4InhJM2of19JDKdjWlmJLjhUvBLtCIYNnWmMrmEo0wFaymDONrNM55jTGmXSdGqJ5VJX55E0P88EaHCvY67HTxsa-iq4IvK7_bVDHFogvcoCunQ4bbn5yg5fPTcv5aL95f3uazRW1YR0otCOWcua6lVndgG2jASsklFpZRLZzTlkveUtdY0QnHMcUGMDjJtJC8YxN0P7zdpvi5g1zUxmcDIege4i4r2nDGOW_oqcqGqkkx5wRObZPf6HRQBKuTG7VWZzfq5EYNbo6U_EUZX86jS9I-_MM-DiwcBew9JJWNh96A9QlMUTb6P_lvbk-CYQ |
| CitedBy_id | crossref_primary_10_1016_j_phanu_2022_100307 crossref_primary_10_1016_j_tox_2022_153298 crossref_primary_10_1016_j_tox_2022_153323 |
| Cites_doi | 10.1002/(SICI)1098-2744(199903)24:3<188::AID-MC5>3.0.CO;2-# 10.1111/j.2042-7158.1979.tb13461.x 10.1016/j.yrtph.2020.104581 10.1016/0165-1110(86)90002-3 10.1080/15257770.2016.1147580 10.1007/BF03160910 10.3181/00379727-96-23508 10.1016/S0890-6238(03)00107-2 10.1084/jem.105.4.279 10.1093/carcin/15.11.2497 10.4172/2168-9652.1000e157 10.1111/j.1476-5381.1976.tb07449.x 10.1093/carcin/14.9.1771 10.1080/07315724.2002.10719188 10.1042/bj3250711 10.1016/0304-3835(82)90060-X 10.1177/0192623312438736 10.2337/diab.28.7.680 10.1093/toxsci/kfv003 10.1093/jn/110.4.816 10.1194/jlr.M015263 10.1093/carcin/6.5.765 10.1177/0004867418810185 10.1007/s12011-018-1455-2 10.1016/j.nut.2010.03.005 10.1093/carcin/12.2.181 10.1016/0300-483X(90)90075-R 10.1111/j.2042-7158.1978.tb13258.x 10.1177/019262338401200210 10.1152/physiolgenomics.00158.2003 10.1093/jn/81.4.348 10.1016/0165-1110(81)90030-0 10.1016/0165-1161(75)90046-1 10.1016/0741-8329(86)90018-2 10.1016/0165-1161(83)90010-9 10.1016/S0027-5107(00)00064-6 10.1093/carcin/4.12.1541 10.1093/jn/110.4.822 10.5694/j.1326-5377.1981.tb132056.x 10.1007/BF00401402 10.5487/TR.2013.29.1.043 10.1016/0890-6238(94)00069-7 |
| ContentType | Journal Article |
| Copyright | 2021 The Authors Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. |
| Copyright_xml | – notice: 2021 The Authors – notice: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. |
| DBID | 6I. AAFTH AAYXX CITATION 7X8 |
| DOI | 10.1016/j.yrtph.2021.104973 |
| DatabaseName | ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access CrossRef MEDLINE - Academic |
| DatabaseTitle | CrossRef MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Public Health Pharmacy, Therapeutics, & Pharmacology |
| EISSN | 1096-0295 |
| ExternalDocumentID | 10_1016_j_yrtph_2021_104973 S0273230021001136 |
| GroupedDBID | --- --K --M .~1 0R~ 123 1B1 1RT 1~. 1~5 29P 4.4 457 4G. 53G 5VS 6I. 7-5 71M 8P~ 9JM AACTN AAEDT AAEDW AAFTH AAIAV AAIKJ AAKOC AALRI AAOAW AAQFI AAQXK AATCM AAXUO ABEFU ABFYP ABJNI ABLST ABMAC ABXDB ABYKQ ABZDS ACDAQ ACGFS ACRLP ADBBV ADEZE ADFGL ADMUD AEBSH AEKER AENEX AFKWA AFTJW AFXIZ AGHFR AGUBO AGYEJ AHEUO AHHHB AIEXJ AIKHN AITUG AJBFU AJOXV AKIFW ALCLG ALMA_UNASSIGNED_HOLDINGS AMFUW AMRAJ ASPBG AVWKF AXJTR AZFZN BKOJK BLECG BLXMC C45 CAG COF CS3 DM4 DU5 EBS EFBJH EFLBG EJD EO8 EO9 EP2 EP3 F3I F5P FDB FEDTE FGOYB FIRID FNPLU FYGXN G-2 G-Q GBLVA HMT HVGLF HZ~ IHE J1W KCYFY KOM LG5 M33 M41 MO0 N9A O-L O9- OAUVE OGGZJ OVD OZT P-8 P-9 P2P PC. Q38 R2- RIG ROL RPZ SCC SDF SDG SDP SES SEW SPCBC SPT SSJ SSP SSZ T5K TEORI UHS WUQ XPP ZGI ZMT ZU3 ZXP ~G- ~KM 9DU AAHBH AATTM AAXKI AAYWO AAYXX ABWVN ACLOT ACRPL ACVFH ADCNI ADNMO AEIPS AEUPX AFJKZ AFPUW AGQPQ AIGII AIIUN AKBMS AKRWK AKYEP ANKPU APXCP CITATION EFKBS ~HD 7X8 |
| ID | FETCH-LOGICAL-c381t-712443f862da8ed5e5ed994907d32a7ffad49462f5d787f4020ce0ef93a79483 |
| ISICitedReferencesCount | 5 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000679358600013&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0273-2300 1096-0295 |
| IngestDate | Sun Sep 28 06:40:58 EDT 2025 Sat Nov 29 07:16:38 EST 2025 Tue Nov 18 22:51:21 EST 2025 Fri Feb 23 02:43:32 EST 2024 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Keywords | Lithium orotate MPCE LO Repeated-dose toxicity Toxicity Genotoxicity SPF ALT GLP ICH 2AA NDI OA OECD TG SCE ANOVA TBIL NOAEL LC FOB Safety |
| Language | English |
| License | This is an open access article under the CC BY-NC-ND license. |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c381t-712443f862da8ed5e5ed994907d32a7ffad49462f5d787f4020ce0ef93a79483 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0002-7658-858X |
| OpenAccessLink | https://dx.doi.org/10.1016/j.yrtph.2021.104973 |
| PQID | 2543444528 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2543444528 crossref_primary_10_1016_j_yrtph_2021_104973 crossref_citationtrail_10_1016_j_yrtph_2021_104973 elsevier_sciencedirect_doi_10_1016_j_yrtph_2021_104973 |
| PublicationCentury | 2000 |
| PublicationDate | August 2021 2021-08-00 20210801 |
| PublicationDateYYYYMMDD | 2021-08-01 |
| PublicationDate_xml | – month: 08 year: 2021 text: August 2021 |
| PublicationDecade | 2020 |
| PublicationTitle | Regulatory toxicology and pharmacology |
| PublicationYear | 2021 |
| Publisher | Elsevier Inc |
| Publisher_xml | – name: Elsevier Inc |
| References | Johnson (bib18) 2013 Kokkinakis, Albores-Saavedra (bib23) 1994; 54 Laurier (bib26) 1984; 44 (bib62) 2008 Sarma (bib52) 1986; 5 Durschlag, Robinson (bib9) 1980; 110 Marshall (bib31) 2015; 20 Schrauzer (bib54) 2002; 21 (bib10) 2009; 1187 (bib40) 2016 Pauze, Brooks (bib42) 2007; 3 Salamone, Heddle (bib51) 1983 Sidransky, Verney (bib55) 1965; 46 West (bib67) 2017; 6 (bib39) 2016 Nieper (bib35) 1973; 14 Preston (bib44) 1981; 87 Rogers (bib50) 1957; 105 Rogers (bib49) 1957; 96 (bib11) 2012; 10 Kling (bib22) 1978; 30 Rao (bib47) 1984; 12 Moore (bib32) 1995; 9 Rao (bib48) 1985; 6 Hard (bib15) 1999 Dumler (bib7) 1979; 28 (bib36) 2014 (bib41) 2018 Perez-Granados, Vaquero (bib43) 2002; 6 Chu, Malmgren (bib4) 1964; 24 Sidransky (bib57) 1963; 81 Rao (bib46) 1983; 4 Venitt, Parry (bib64) 1984 Frazier (bib12) 2012; 40 Thakur (bib61) 2003; 17 Hebbachi (bib16) 1997; 325 Maron, Ames (bib30) 1983; 113 Mortelmans, Zeiger (bib33) 2000; 455 Jung (bib19) 2011; 52 Sartori (bib53) 1986; 3 Brusick (bib2) 1989 Columbano (bib5) 1982; 16 Durschlag, Robinson (bib8) 1980; 110 (bib37) 1997 Griffin (bib14) 2004; 17 Kokkinakis (bib24) 1991; 12 Manjeshwar (bib29) 1999; 24 Wang (bib65) 2011; 27 Kang (bib20) 2013; 29 Ames (bib1) 1975; 31 Choi (bib3) 2015; 144 Szklarska, Rzymski (bib60) 2019; 189 Ramoju (bib45) 2020; 111 Devadason (bib6) 2018; 52 Laconi (bib25) 1993; 14 Loffler (bib28) 2016; 35 Weiner (bib66) 1990; 65 Garson (bib13) 1981; 2 Vasudevan (bib63) 1994; 15 Kier (bib21) 1986; 168 Smith, Schou (bib59) 1979; 31 Smith (bib58) 1976; 56 Sidransky, Verney (bib56) 1970; 44 (bib34) 2011 Irwin (bib17) 1968; 13 Lin, Tung (bib27) 1965; 64 (bib38) 1998 Jung (10.1016/j.yrtph.2021.104973_bib19) 2011; 52 Rao (10.1016/j.yrtph.2021.104973_bib46) 1983; 4 Mortelmans (10.1016/j.yrtph.2021.104973_bib33) 2000; 455 (10.1016/j.yrtph.2021.104973_bib34) 2011 Pauze (10.1016/j.yrtph.2021.104973_bib42) 2007; 3 Sarma (10.1016/j.yrtph.2021.104973_bib52) 1986; 5 Sidransky (10.1016/j.yrtph.2021.104973_bib57) 1963; 81 Ramoju (10.1016/j.yrtph.2021.104973_bib45) 2020; 111 Columbano (10.1016/j.yrtph.2021.104973_bib5) 1982; 16 Smith (10.1016/j.yrtph.2021.104973_bib58) 1976; 56 Manjeshwar (10.1016/j.yrtph.2021.104973_bib29) 1999; 24 Kling (10.1016/j.yrtph.2021.104973_bib22) 1978; 30 Thakur (10.1016/j.yrtph.2021.104973_bib61) 2003; 17 Garson (10.1016/j.yrtph.2021.104973_bib13) 1981; 2 Dumler (10.1016/j.yrtph.2021.104973_bib7) 1979; 28 (10.1016/j.yrtph.2021.104973_bib41) 2018 Lin (10.1016/j.yrtph.2021.104973_bib27) 1965; 64 Venitt (10.1016/j.yrtph.2021.104973_bib64) 1984 (10.1016/j.yrtph.2021.104973_bib11) 2012; 10 Preston (10.1016/j.yrtph.2021.104973_bib44) 1981; 87 Smith (10.1016/j.yrtph.2021.104973_bib59) 1979; 31 Rao (10.1016/j.yrtph.2021.104973_bib48) 1985; 6 (10.1016/j.yrtph.2021.104973_bib37) 1997 Laconi (10.1016/j.yrtph.2021.104973_bib25) 1993; 14 Kang (10.1016/j.yrtph.2021.104973_bib20) 2013; 29 Durschlag (10.1016/j.yrtph.2021.104973_bib8) 1980; 110 Choi (10.1016/j.yrtph.2021.104973_bib3) 2015; 144 Devadason (10.1016/j.yrtph.2021.104973_bib6) 2018; 52 (10.1016/j.yrtph.2021.104973_bib38) 1998 Durschlag (10.1016/j.yrtph.2021.104973_bib9) 1980; 110 Salamone (10.1016/j.yrtph.2021.104973_bib51) 1983 Wang (10.1016/j.yrtph.2021.104973_bib65) 2011; 27 Szklarska (10.1016/j.yrtph.2021.104973_bib60) 2019; 189 Sidransky (10.1016/j.yrtph.2021.104973_bib55) 1965; 46 Vasudevan (10.1016/j.yrtph.2021.104973_bib63) 1994; 15 Hard (10.1016/j.yrtph.2021.104973_bib15) 1999 Kokkinakis (10.1016/j.yrtph.2021.104973_bib24) 1991; 12 Rogers (10.1016/j.yrtph.2021.104973_bib50) 1957; 105 Brusick (10.1016/j.yrtph.2021.104973_bib2) 1989 (10.1016/j.yrtph.2021.104973_bib39) 2016 Maron (10.1016/j.yrtph.2021.104973_bib30) 1983; 113 (10.1016/j.yrtph.2021.104973_bib36) 2014 Laurier (10.1016/j.yrtph.2021.104973_bib26) 1984; 44 Sidransky (10.1016/j.yrtph.2021.104973_bib56) 1970; 44 Weiner (10.1016/j.yrtph.2021.104973_bib66) 1990; 65 Irwin (10.1016/j.yrtph.2021.104973_bib17) 1968; 13 (10.1016/j.yrtph.2021.104973_bib62) 2008 Johnson (10.1016/j.yrtph.2021.104973_bib18) 2013 Marshall (10.1016/j.yrtph.2021.104973_bib31) 2015; 20 Hebbachi (10.1016/j.yrtph.2021.104973_bib16) 1997; 325 Kokkinakis (10.1016/j.yrtph.2021.104973_bib23) 1994; 54 Griffin (10.1016/j.yrtph.2021.104973_bib14) 2004; 17 Ames (10.1016/j.yrtph.2021.104973_bib1) 1975; 31 Schrauzer (10.1016/j.yrtph.2021.104973_bib54) 2002; 21 West (10.1016/j.yrtph.2021.104973_bib67) 2017; 6 Chu (10.1016/j.yrtph.2021.104973_bib4) 1964; 24 (10.1016/j.yrtph.2021.104973_bib40) 2016 Perez-Granados (10.1016/j.yrtph.2021.104973_bib43) 2002; 6 Loffler (10.1016/j.yrtph.2021.104973_bib28) 2016; 35 Sartori (10.1016/j.yrtph.2021.104973_bib53) 1986; 3 Rogers (10.1016/j.yrtph.2021.104973_bib49) 1957; 96 (10.1016/j.yrtph.2021.104973_bib10) 2009; 1187 Nieper (10.1016/j.yrtph.2021.104973_bib35) 1973; 14 Moore (10.1016/j.yrtph.2021.104973_bib32) 1995; 9 Frazier (10.1016/j.yrtph.2021.104973_bib12) 2012; 40 Kier (10.1016/j.yrtph.2021.104973_bib21) 1986; 168 Rao (10.1016/j.yrtph.2021.104973_bib47) 1984; 12 |
| References_xml | – volume: 15 start-page: 2497 year: 1994 end-page: 2500 ident: bib63 article-title: Perturbations of endogenous levels of orotic acid and carcinogenesis: effect of an arginine-deficient diet and carbamyl aspartate on hepatocarcinogenesis in the rat and the mouse publication-title: Carcinogenesis – start-page: 209 year: 2013 end-page: 254 ident: bib18 article-title: Chapter 8. Spontaneous lesions in control animals used in toxicity studies publication-title: Toxicologic Pathology. Nonclinical Safety Assessment – volume: 27 start-page: 571 year: 2011 end-page: 575 ident: bib65 article-title: Study on possible mechanism of orotic acid-induced fatty liver in rats publication-title: Nutrition – volume: 113 start-page: 173 year: 1983 end-page: 215 ident: bib30 article-title: Revised methods for the Salmonella mutagenicity test publication-title: Mutat. Res. – volume: 189 start-page: 18 year: 2019 end-page: 27 ident: bib60 article-title: Is lithium a micronutrient? From biological activity and epidemiological observation to food fortification publication-title: Biol. Trace Elem. Res. – volume: 24 start-page: 188 year: 1999 end-page: 196 ident: bib29 article-title: The regulation of ribonucleoside diphosphate reductase by the tumor promoter orotic acid in normal rat liver in vivo publication-title: Mol. Carcinog. – volume: 44 start-page: 1201 year: 1970 end-page: 1215 ident: bib56 article-title: Influence of orotic acid on liver tumorigenesis in rats ingesting ethionine, N-2-fluorenylacetamide, and 3'-methyl-dimethylaminoazobenzene publication-title: J. Natl. Cancer Inst. – year: 1998 ident: bib38 article-title: OECD Principles of Good Laboratory Practice – volume: 29 start-page: 43 year: 2013 end-page: 52 ident: bib20 article-title: Evaluation of oxidative DNA damage using an alkaline single cell gel electrophoresis (SCGE) comet assay, and the protective effects of N-acetylcysteine amide on zearalenone-induced cytotoxicity in chang liver cells publication-title: Toxicol. Res. – volume: 31 start-page: 161 year: 1979 end-page: 163 ident: bib59 article-title: Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate publication-title: J. Pharm. Pharmacol. – volume: 30 start-page: 368 year: 1978 end-page: 370 ident: bib22 article-title: Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate publication-title: J. Pharm. Pharmacol. – volume: 2 start-page: 37 year: 1981 end-page: 39 ident: bib13 article-title: Chromosome studies of patients on long-term lithium therapy for psychiatric disorders publication-title: Med. J. Aust. – start-page: 11 year: 1983 end-page: 149 ident: bib51 article-title: Chapter 4. The bone marrow micronucleus assay: rationale for a revised protocol publication-title: Chemical Mutagens – volume: 87 start-page: 143 year: 1981 end-page: 188 ident: bib44 article-title: Mammalian in vivo and in vitro cytogenetic assays: a report of the U.S. EPA's gene-tox program publication-title: Mutat. Res. – volume: 9 start-page: 175 year: 1995 end-page: 210 ident: bib32 article-title: An assessment of lithium using the IEHR evaluative process for assessing human developmental and reproductive toxicity of agents. IEHR Expert Scientific Committee publication-title: Reprod. Toxicol. – volume: 5 start-page: 781 year: 1986 end-page: 798 ident: bib52 article-title: Liver tumour promotion by chemicals: models and mechanisms publication-title: Canc. Surv. – year: 2014 ident: bib36 article-title: Nonneoplastic Lesion Atlas. Kidney, Pelvis - Dilation – volume: 65 start-page: 1 year: 1990 end-page: 22 ident: bib66 article-title: Genotoxicity evaluation of lithium hypochlorite publication-title: Toxicology – volume: 13 start-page: 222 year: 1968 end-page: 257 ident: bib17 article-title: Comprehensive observational assessment: ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse publication-title: Psychopharmacologia – volume: 20 start-page: 104 year: 2015 end-page: 109 ident: bib31 article-title: Lithium as a nutrient publication-title: J. Am. Phys. Surg. – volume: 21 start-page: 14 year: 2002 end-page: 21 ident: bib54 article-title: Lithium: occurrence, dietary intakes, nutritional essentiality publication-title: J. Am. Coll. Nutr. – volume: 31 start-page: 347 year: 1975 end-page: 364 ident: bib1 article-title: Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test publication-title: Mutat. Res. – volume: 17 start-page: 140 year: 2004 end-page: 149 ident: bib14 article-title: An integrated reverse functional genomic and metabolic approach to understanding orotic acid-induced fatty liver publication-title: Physiol. Genom. – start-page: 16 year: 2018 ident: bib41 article-title: Test No. 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents, OECD Guidelines for the Testing of Chemicals, Section 4 – volume: 3 start-page: 61 year: 2007 end-page: 62 ident: bib42 article-title: Lithium toxicity from an Internet dietary supplement publication-title: J. Med. Toxicol. – volume: 1187 start-page: 1 year: 2009 end-page: 25 ident: bib10 article-title: Orotic acid salts as sources of orotic acid and various minerals added for nutritional purposes to food supplements publication-title: EFSA J. – start-page: 407 year: 1989 end-page: 434 ident: bib2 article-title: Chapter 14. Genetic toxicology publication-title: Principles and Methods of Toxicology – volume: 144 start-page: 307 year: 2015 end-page: 317 ident: bib3 article-title: Orotic acid induces hypertension associated with impaired endothelial nitric oxide synthesis publication-title: Toxicol. Sci. – volume: 40 start-page: 14S year: 2012 end-page: 86S ident: bib12 article-title: Proliferative and nonproliferative lesions of the rat and mouse urinary system publication-title: Toxicol. Pathol. – start-page: 31 year: 2008 ident: bib62 article-title: Provisional Peer Reviewed Toxicity Values for Lithium – start-page: 21 year: 2016 ident: bib40 article-title: Test No. 474: Mammalian Erythrocyte Micronucleus Test, OECD Guidelines for the Testing of Chemicals – volume: 110 start-page: 822 year: 1980 end-page: 828 ident: bib9 article-title: Species specificity in the metabolic consequences of orotic acid consumption publication-title: J. Nutr. – start-page: 1 year: 2011 end-page: 220 ident: bib34 article-title: Guide for the Care and Use of Laboratory Animals. Committee for the Update of the Guide for the Care and Use of Laboratory Animals – volume: 44 start-page: 2186 year: 1984 end-page: 2191 ident: bib26 article-title: Promotion by orotic acid of liver carcinogenesis in rats initiated by 1,2-dimethylhydrazine publication-title: Canc. Res. – volume: 28 start-page: 680 year: 1979 end-page: 685 ident: bib7 article-title: Effects of orotate administration on the normal rat kidney: similarity to changes observed in diabetes mellitus publication-title: Diabetes – volume: 325 start-page: 711 year: 1997 end-page: 719 ident: bib16 article-title: Decreased secretion of very-low-density lipoprotein triacylglycerol and apolipoprotein B is associated with decreased intracellular triacylglycerol lipolysis in hepatocytes derived from rats fed orotic acid or n-3 fatty acids publication-title: Biochem. J. – year: 1997 ident: bib37 article-title: Test No. 471: Bacterial Reverse Mutation Test, OECD Guidelines for the Testing of Chemicals, Section 4 – volume: 10 start-page: 2579 year: 2012 ident: bib11 article-title: Guidance on selected default values to be used by the EFSA Scientific Committee, Scientific Panels and Units in the absence of actual measured data publication-title: EFSA J. – start-page: 22 year: 2016 ident: bib39 article-title: Test No. 473 publication-title: Vitro Mammalian Chromosomal Aberration Test, OECD Guidelines for the Testing of Chemicals – volume: 110 start-page: 816 year: 1980 end-page: 821 ident: bib8 article-title: Orotic acid-induced metabolic changes in the rat publication-title: J. Nutr. – volume: 14 start-page: 1171 year: 1993 end-page: 1775 ident: bib25 article-title: Studies on liver tumor promotion in the rat by orotic acid: dose and minimum exposure time required for dietary orotic acid to promote hepatocarcinogensis publication-title: Carcinogenesis – volume: 168 start-page: 69 year: 1986 end-page: 240 ident: bib21 article-title: The Salmonella typhimurium/mammalian microsomal assay. A report of the U.S. Environmental Protection Agency Gene-Tox Program publication-title: Mutat. Res. – volume: 6 year: 2017 ident: bib67 article-title: Orotic acid: why it is important to understand its role in metabolism publication-title: Biochem. Physiol. – volume: 35 start-page: 566 year: 2016 end-page: 577 ident: bib28 article-title: Orotate (orotic acid): an essential and versatile molecule publication-title: Nucleos Nucleot. Nucleic Acids – volume: 12 start-page: 173 year: 1984 end-page: 178 ident: bib47 article-title: Orotic acid, a new promoter for experimental liver carcinogenesis publication-title: Toxicol. Pathol. – volume: 6 start-page: 765 year: 1985 end-page: 768 ident: bib48 article-title: Orotic acid, a promoter of liver carcinogenesis induces DNA damage in rat liver publication-title: Carcinogenesis – volume: 17 start-page: 683 year: 2003 end-page: 690 ident: bib61 article-title: Subchronic supplementation of lithium carbonate induces reproductive system toxicity in male rat publication-title: Reprod. Toxicol. – volume: 24 start-page: 671 year: 1964 end-page: 673 ident: bib4 article-title: Effect of orotic acid on the metastasis of mammary tumors in mice publication-title: Canc. Res. – volume: 52 start-page: 1617 year: 2011 end-page: 1625 ident: bib19 article-title: Role of the AMPK/SREBP-1 pathway in the development of orotic acid-induced fatty liver publication-title: J. Lipid Res. – volume: 455 start-page: 29 year: 2000 end-page: 60 ident: bib33 article-title: The Ames Salmonella/microsome mutagenicity assay publication-title: Mutat. Res. – volume: 111 start-page: 104581 year: 2020 ident: bib45 article-title: Derivation of whole blood biomonitoring equivalents for lithium for the interpretation of biomonitoring data publication-title: Regul. Toxicol. Pharmacol. – volume: 64 start-page: 501 year: 1965 end-page: 511 ident: bib27 article-title: Effect of orotic acid on DAB-hepatocarcinogenesis in rats publication-title: Taiwan Yi Xue Hui Za Zhi – volume: 105 start-page: 279 year: 1957 end-page: 306 ident: bib50 article-title: Studies of the mechanism of action of urethane in initiating pulmonary adenomas in mice. II. Its relation to nucleic acid synthesis publication-title: J. Exp. Med. – volume: 81 start-page: 348 year: 1963 end-page: 356 ident: bib57 article-title: Factors influencing the induction of fatty liver by orotic acid publication-title: J. Nutr. – volume: 14 start-page: 407 year: 1973 end-page: 411 ident: bib35 article-title: The clinical applications of lithium orotate. A two years study publication-title: Agressologie – volume: 4 start-page: 1541 year: 1983 end-page: 1545 ident: bib46 article-title: Dietary orotic acid enhances the incidence of gamma-glutamyltransferase positive foci in rat liver induced by chemical carcinogens publication-title: Carcinogenesis – start-page: 1 year: 1999 end-page: 32 ident: bib15 article-title: Non-proliferative lesions of the kidney and lower urinary tract in rats publication-title: Guides Toxicol. Pathol. – volume: 52 start-page: 1107 year: 2018 end-page: 1108 ident: bib6 article-title: Is there a role for lithium orotate in psychiatry? publication-title: Aust. N. Z. J. Psychiatr. – volume: 16 start-page: 191 year: 1982 end-page: 196 ident: bib5 article-title: Dietary orotic acid, a new selective growth stimulus for carcinogen altered hepatocytes in rat publication-title: Canc. Lett. – volume: 56 start-page: 399 year: 1976 end-page: 402 ident: bib58 article-title: Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats publication-title: Br. J. Pharmacol. – year: 1984 ident: bib64 article-title: Mutagenicity Testing, a Practical Approach – volume: 54 start-page: 5324 year: 1994 end-page: 5332 ident: bib23 article-title: Orotic acid enhancement of preneoplastic and neoplastic lesions induced in the pancreas and liver of hamsters by N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine publication-title: Canc. Res. – volume: 12 start-page: 181 year: 1991 end-page: 186 ident: bib24 article-title: Enhancement of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine-induced tumorigenesis in Sprague-Dawley rats by orotic acid publication-title: Carcinogenesis – volume: 6 start-page: 154 year: 2002 end-page: 162 ident: bib43 article-title: Silicon, aluminium, arsenic and lithium: essentiality and human health implications publication-title: J. Nutr. Health Aging – volume: 96 start-page: 464 year: 1957 end-page: 465 ident: bib49 article-title: Inhibitory influence of a normally occurring pyrimidine precursor upon methylcholanthrene carcinogenesis publication-title: Proc. Soc. Exp. Biol. Med. – volume: 3 start-page: 97 year: 1986 end-page: 100 ident: bib53 article-title: Lithium orotate in the treatment of alcoholism and related conditions publication-title: Alcohol – volume: 46 start-page: 1007 year: 1965 end-page: 1014 ident: bib55 article-title: Chronic fatty liver without cirrhosis induced in the rat by dietary orotic acid publication-title: Am. J. Pathol. – volume: 24 start-page: 188 year: 1999 ident: 10.1016/j.yrtph.2021.104973_bib29 article-title: The regulation of ribonucleoside diphosphate reductase by the tumor promoter orotic acid in normal rat liver in vivo publication-title: Mol. Carcinog. doi: 10.1002/(SICI)1098-2744(199903)24:3<188::AID-MC5>3.0.CO;2-# – volume: 6 start-page: 154 year: 2002 ident: 10.1016/j.yrtph.2021.104973_bib43 article-title: Silicon, aluminium, arsenic and lithium: essentiality and human health implications publication-title: J. Nutr. Health Aging – volume: 31 start-page: 161 year: 1979 ident: 10.1016/j.yrtph.2021.104973_bib59 article-title: Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate publication-title: J. Pharm. Pharmacol. doi: 10.1111/j.2042-7158.1979.tb13461.x – volume: 111 start-page: 104581 year: 2020 ident: 10.1016/j.yrtph.2021.104973_bib45 article-title: Derivation of whole blood biomonitoring equivalents for lithium for the interpretation of biomonitoring data publication-title: Regul. Toxicol. Pharmacol. doi: 10.1016/j.yrtph.2020.104581 – volume: 168 start-page: 69 year: 1986 ident: 10.1016/j.yrtph.2021.104973_bib21 article-title: The Salmonella typhimurium/mammalian microsomal assay. A report of the U.S. Environmental Protection Agency Gene-Tox Program publication-title: Mutat. Res. doi: 10.1016/0165-1110(86)90002-3 – volume: 46 start-page: 1007 year: 1965 ident: 10.1016/j.yrtph.2021.104973_bib55 article-title: Chronic fatty liver without cirrhosis induced in the rat by dietary orotic acid publication-title: Am. J. Pathol. – volume: 10 start-page: 2579 year: 2012 ident: 10.1016/j.yrtph.2021.104973_bib11 article-title: Guidance on selected default values to be used by the EFSA Scientific Committee, Scientific Panels and Units in the absence of actual measured data publication-title: EFSA J. – volume: 35 start-page: 566 year: 2016 ident: 10.1016/j.yrtph.2021.104973_bib28 article-title: Orotate (orotic acid): an essential and versatile molecule publication-title: Nucleos Nucleot. Nucleic Acids doi: 10.1080/15257770.2016.1147580 – volume: 3 start-page: 61 year: 2007 ident: 10.1016/j.yrtph.2021.104973_bib42 article-title: Lithium toxicity from an Internet dietary supplement publication-title: J. Med. Toxicol. doi: 10.1007/BF03160910 – volume: 96 start-page: 464 year: 1957 ident: 10.1016/j.yrtph.2021.104973_bib49 article-title: Inhibitory influence of a normally occurring pyrimidine precursor upon methylcholanthrene carcinogenesis publication-title: Proc. Soc. Exp. Biol. Med. doi: 10.3181/00379727-96-23508 – start-page: 11 year: 1983 ident: 10.1016/j.yrtph.2021.104973_bib51 article-title: Chapter 4. The bone marrow micronucleus assay: rationale for a revised protocol – start-page: 1 year: 1999 ident: 10.1016/j.yrtph.2021.104973_bib15 article-title: Non-proliferative lesions of the kidney and lower urinary tract in rats publication-title: Guides Toxicol. Pathol. – start-page: 407 year: 1989 ident: 10.1016/j.yrtph.2021.104973_bib2 article-title: Chapter 14. Genetic toxicology – start-page: 209 year: 2013 ident: 10.1016/j.yrtph.2021.104973_bib18 article-title: Chapter 8. Spontaneous lesions in control animals used in toxicity studies – volume: 17 start-page: 683 year: 2003 ident: 10.1016/j.yrtph.2021.104973_bib61 article-title: Subchronic supplementation of lithium carbonate induces reproductive system toxicity in male rat publication-title: Reprod. Toxicol. doi: 10.1016/S0890-6238(03)00107-2 – volume: 105 start-page: 279 year: 1957 ident: 10.1016/j.yrtph.2021.104973_bib50 article-title: Studies of the mechanism of action of urethane in initiating pulmonary adenomas in mice. II. Its relation to nucleic acid synthesis publication-title: J. Exp. Med. doi: 10.1084/jem.105.4.279 – start-page: 16 year: 2018 ident: 10.1016/j.yrtph.2021.104973_bib41 – volume: 15 start-page: 2497 year: 1994 ident: 10.1016/j.yrtph.2021.104973_bib63 article-title: Perturbations of endogenous levels of orotic acid and carcinogenesis: effect of an arginine-deficient diet and carbamyl aspartate on hepatocarcinogenesis in the rat and the mouse publication-title: Carcinogenesis doi: 10.1093/carcin/15.11.2497 – volume: 6 year: 2017 ident: 10.1016/j.yrtph.2021.104973_bib67 article-title: Orotic acid: why it is important to understand its role in metabolism publication-title: Biochem. Physiol. doi: 10.4172/2168-9652.1000e157 – volume: 56 start-page: 399 year: 1976 ident: 10.1016/j.yrtph.2021.104973_bib58 article-title: Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats publication-title: Br. J. Pharmacol. doi: 10.1111/j.1476-5381.1976.tb07449.x – volume: 14 start-page: 1171 year: 1993 ident: 10.1016/j.yrtph.2021.104973_bib25 article-title: Studies on liver tumor promotion in the rat by orotic acid: dose and minimum exposure time required for dietary orotic acid to promote hepatocarcinogensis publication-title: Carcinogenesis doi: 10.1093/carcin/14.9.1771 – volume: 44 start-page: 1201 year: 1970 ident: 10.1016/j.yrtph.2021.104973_bib56 article-title: Influence of orotic acid on liver tumorigenesis in rats ingesting ethionine, N-2-fluorenylacetamide, and 3'-methyl-dimethylaminoazobenzene publication-title: J. Natl. Cancer Inst. – volume: 21 start-page: 14 year: 2002 ident: 10.1016/j.yrtph.2021.104973_bib54 article-title: Lithium: occurrence, dietary intakes, nutritional essentiality publication-title: J. Am. Coll. Nutr. doi: 10.1080/07315724.2002.10719188 – volume: 325 start-page: 711 issue: Pt 3 year: 1997 ident: 10.1016/j.yrtph.2021.104973_bib16 article-title: Decreased secretion of very-low-density lipoprotein triacylglycerol and apolipoprotein B is associated with decreased intracellular triacylglycerol lipolysis in hepatocytes derived from rats fed orotic acid or n-3 fatty acids publication-title: Biochem. J. doi: 10.1042/bj3250711 – volume: 16 start-page: 191 year: 1982 ident: 10.1016/j.yrtph.2021.104973_bib5 article-title: Dietary orotic acid, a new selective growth stimulus for carcinogen altered hepatocytes in rat publication-title: Canc. Lett. doi: 10.1016/0304-3835(82)90060-X – volume: 40 start-page: 14S year: 2012 ident: 10.1016/j.yrtph.2021.104973_bib12 article-title: Proliferative and nonproliferative lesions of the rat and mouse urinary system publication-title: Toxicol. Pathol. doi: 10.1177/0192623312438736 – volume: 28 start-page: 680 year: 1979 ident: 10.1016/j.yrtph.2021.104973_bib7 article-title: Effects of orotate administration on the normal rat kidney: similarity to changes observed in diabetes mellitus publication-title: Diabetes doi: 10.2337/diab.28.7.680 – volume: 54 start-page: 5324 year: 1994 ident: 10.1016/j.yrtph.2021.104973_bib23 article-title: Orotic acid enhancement of preneoplastic and neoplastic lesions induced in the pancreas and liver of hamsters by N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine publication-title: Canc. Res. – start-page: 21 year: 2016 ident: 10.1016/j.yrtph.2021.104973_bib40 – volume: 144 start-page: 307 year: 2015 ident: 10.1016/j.yrtph.2021.104973_bib3 article-title: Orotic acid induces hypertension associated with impaired endothelial nitric oxide synthesis publication-title: Toxicol. Sci. doi: 10.1093/toxsci/kfv003 – start-page: 22 year: 2016 ident: 10.1016/j.yrtph.2021.104973_bib39 article-title: Test No. 473 – volume: 110 start-page: 816 year: 1980 ident: 10.1016/j.yrtph.2021.104973_bib8 article-title: Orotic acid-induced metabolic changes in the rat publication-title: J. Nutr. doi: 10.1093/jn/110.4.816 – volume: 52 start-page: 1617 year: 2011 ident: 10.1016/j.yrtph.2021.104973_bib19 article-title: Role of the AMPK/SREBP-1 pathway in the development of orotic acid-induced fatty liver publication-title: J. Lipid Res. doi: 10.1194/jlr.M015263 – volume: 6 start-page: 765 year: 1985 ident: 10.1016/j.yrtph.2021.104973_bib48 article-title: Orotic acid, a promoter of liver carcinogenesis induces DNA damage in rat liver publication-title: Carcinogenesis doi: 10.1093/carcin/6.5.765 – volume: 52 start-page: 1107 year: 2018 ident: 10.1016/j.yrtph.2021.104973_bib6 article-title: Is there a role for lithium orotate in psychiatry? publication-title: Aust. N. Z. J. Psychiatr. doi: 10.1177/0004867418810185 – year: 2014 ident: 10.1016/j.yrtph.2021.104973_bib36 – start-page: 31 year: 2008 ident: 10.1016/j.yrtph.2021.104973_bib62 – volume: 189 start-page: 18 year: 2019 ident: 10.1016/j.yrtph.2021.104973_bib60 article-title: Is lithium a micronutrient? From biological activity and epidemiological observation to food fortification publication-title: Biol. Trace Elem. Res. doi: 10.1007/s12011-018-1455-2 – volume: 5 start-page: 781 year: 1986 ident: 10.1016/j.yrtph.2021.104973_bib52 article-title: Liver tumour promotion by chemicals: models and mechanisms publication-title: Canc. Surv. – volume: 20 start-page: 104 year: 2015 ident: 10.1016/j.yrtph.2021.104973_bib31 article-title: Lithium as a nutrient publication-title: J. Am. Phys. Surg. – volume: 27 start-page: 571 year: 2011 ident: 10.1016/j.yrtph.2021.104973_bib65 article-title: Study on possible mechanism of orotic acid-induced fatty liver in rats publication-title: Nutrition doi: 10.1016/j.nut.2010.03.005 – year: 1984 ident: 10.1016/j.yrtph.2021.104973_bib64 – volume: 1187 start-page: 1 year: 2009 ident: 10.1016/j.yrtph.2021.104973_bib10 article-title: Orotic acid salts as sources of orotic acid and various minerals added for nutritional purposes to food supplements publication-title: EFSA J. – volume: 12 start-page: 181 year: 1991 ident: 10.1016/j.yrtph.2021.104973_bib24 article-title: Enhancement of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine-induced tumorigenesis in Sprague-Dawley rats by orotic acid publication-title: Carcinogenesis doi: 10.1093/carcin/12.2.181 – volume: 65 start-page: 1 year: 1990 ident: 10.1016/j.yrtph.2021.104973_bib66 article-title: Genotoxicity evaluation of lithium hypochlorite publication-title: Toxicology doi: 10.1016/0300-483X(90)90075-R – volume: 30 start-page: 368 year: 1978 ident: 10.1016/j.yrtph.2021.104973_bib22 article-title: Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate publication-title: J. Pharm. Pharmacol. doi: 10.1111/j.2042-7158.1978.tb13258.x – volume: 12 start-page: 173 year: 1984 ident: 10.1016/j.yrtph.2021.104973_bib47 article-title: Orotic acid, a new promoter for experimental liver carcinogenesis publication-title: Toxicol. Pathol. doi: 10.1177/019262338401200210 – volume: 17 start-page: 140 year: 2004 ident: 10.1016/j.yrtph.2021.104973_bib14 article-title: An integrated reverse functional genomic and metabolic approach to understanding orotic acid-induced fatty liver publication-title: Physiol. Genom. doi: 10.1152/physiolgenomics.00158.2003 – year: 1998 ident: 10.1016/j.yrtph.2021.104973_bib38 – volume: 81 start-page: 348 year: 1963 ident: 10.1016/j.yrtph.2021.104973_bib57 article-title: Factors influencing the induction of fatty liver by orotic acid publication-title: J. Nutr. doi: 10.1093/jn/81.4.348 – volume: 87 start-page: 143 year: 1981 ident: 10.1016/j.yrtph.2021.104973_bib44 article-title: Mammalian in vivo and in vitro cytogenetic assays: a report of the U.S. EPA's gene-tox program publication-title: Mutat. Res. doi: 10.1016/0165-1110(81)90030-0 – volume: 31 start-page: 347 year: 1975 ident: 10.1016/j.yrtph.2021.104973_bib1 article-title: Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test publication-title: Mutat. Res. doi: 10.1016/0165-1161(75)90046-1 – start-page: 1 year: 2011 ident: 10.1016/j.yrtph.2021.104973_bib34 – year: 1997 ident: 10.1016/j.yrtph.2021.104973_bib37 – volume: 3 start-page: 97 year: 1986 ident: 10.1016/j.yrtph.2021.104973_bib53 article-title: Lithium orotate in the treatment of alcoholism and related conditions publication-title: Alcohol doi: 10.1016/0741-8329(86)90018-2 – volume: 113 start-page: 173 year: 1983 ident: 10.1016/j.yrtph.2021.104973_bib30 article-title: Revised methods for the Salmonella mutagenicity test publication-title: Mutat. Res. doi: 10.1016/0165-1161(83)90010-9 – volume: 455 start-page: 29 year: 2000 ident: 10.1016/j.yrtph.2021.104973_bib33 article-title: The Ames Salmonella/microsome mutagenicity assay publication-title: Mutat. Res. doi: 10.1016/S0027-5107(00)00064-6 – volume: 4 start-page: 1541 year: 1983 ident: 10.1016/j.yrtph.2021.104973_bib46 article-title: Dietary orotic acid enhances the incidence of gamma-glutamyltransferase positive foci in rat liver induced by chemical carcinogens publication-title: Carcinogenesis doi: 10.1093/carcin/4.12.1541 – volume: 110 start-page: 822 year: 1980 ident: 10.1016/j.yrtph.2021.104973_bib9 article-title: Species specificity in the metabolic consequences of orotic acid consumption publication-title: J. Nutr. doi: 10.1093/jn/110.4.822 – volume: 2 start-page: 37 year: 1981 ident: 10.1016/j.yrtph.2021.104973_bib13 article-title: Chromosome studies of patients on long-term lithium therapy for psychiatric disorders publication-title: Med. J. Aust. doi: 10.5694/j.1326-5377.1981.tb132056.x – volume: 13 start-page: 222 year: 1968 ident: 10.1016/j.yrtph.2021.104973_bib17 article-title: Comprehensive observational assessment: ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse publication-title: Psychopharmacologia doi: 10.1007/BF00401402 – volume: 44 start-page: 2186 year: 1984 ident: 10.1016/j.yrtph.2021.104973_bib26 article-title: Promotion by orotic acid of liver carcinogenesis in rats initiated by 1,2-dimethylhydrazine publication-title: Canc. Res. – volume: 24 start-page: 671 year: 1964 ident: 10.1016/j.yrtph.2021.104973_bib4 article-title: Effect of orotic acid on the metastasis of mammary tumors in mice publication-title: Canc. Res. – volume: 29 start-page: 43 year: 2013 ident: 10.1016/j.yrtph.2021.104973_bib20 article-title: Evaluation of oxidative DNA damage using an alkaline single cell gel electrophoresis (SCGE) comet assay, and the protective effects of N-acetylcysteine amide on zearalenone-induced cytotoxicity in chang liver cells publication-title: Toxicol. Res. doi: 10.5487/TR.2013.29.1.043 – volume: 64 start-page: 501 year: 1965 ident: 10.1016/j.yrtph.2021.104973_bib27 article-title: Effect of orotic acid on DAB-hepatocarcinogenesis in rats publication-title: Taiwan Yi Xue Hui Za Zhi – volume: 9 start-page: 175 year: 1995 ident: 10.1016/j.yrtph.2021.104973_bib32 article-title: An assessment of lithium using the IEHR evaluative process for assessing human developmental and reproductive toxicity of agents. IEHR Expert Scientific Committee publication-title: Reprod. Toxicol. doi: 10.1016/0890-6238(94)00069-7 – volume: 14 start-page: 407 year: 1973 ident: 10.1016/j.yrtph.2021.104973_bib35 article-title: The clinical applications of lithium orotate. A two years study publication-title: Agressologie |
| SSID | ssj0002887 |
| Score | 2.3378346 |
| Snippet | Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events.... |
| SourceID | proquest crossref elsevier |
| SourceType | Aggregation Database Enrichment Source Index Database Publisher |
| StartPage | 104973 |
| SubjectTerms | Genotoxicity Lithium orotate NOAEL Repeated-dose toxicity Safety Toxicity |
| Title | A toxicological evaluation of lithium orotate |
| URI | https://dx.doi.org/10.1016/j.yrtph.2021.104973 https://www.proquest.com/docview/2543444528 |
| Volume | 124 |
| WOSCitedRecordID | wos000679358600013&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVESC databaseName: Elsevier SD Freedom Collection Journals 2021 customDbUrl: eissn: 1096-0295 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0002887 issn: 0273-2300 databaseCode: AIEXJ dateStart: 19950201 isFulltext: true titleUrlDefault: https://www.sciencedirect.com providerName: Elsevier |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3db9MwELfYxgMSQjBAjMFkJLSXNlU-nCZ-LGgweJiq0Ye-Rak_RLaRVEk6tf_9zrHjpJuo2AMvVhvFJ6u_6_l35_MdQp9pKiSRqp62O2YwMNehfAGOK3FTLqKQh5FuNhFdXMTzOZ2aYE7VtBOI8jxer-nyv0INzwBsdXX2EXBbofAAPgPoMALsMP4T8BOgk-uMWaPW1fNWxBBY9-9s9WdQlIWimX1ueqnb0qtDdytBV2dadvWtNz2EFqnuI2XwHvwa2Wyem-YA3rvNah3JUV-_BCqJ21J4lUlZtdnAg0s79zwrrxtG-13LWBRlPzThezYxrrVgwI0c8HHcLXPrk57BBG-Q6l4mD2y5DitcjTZlvVTHRr436t7erpx9b0ezeYZtCttV0ghJlJBEC9lDB34UUjCEB5MfZ_Ofdvv246arol17W6qqSQp8sJa_0Zl7G3vDVmYv0QvjZuCJVo9X6InID9HpVOO4GeJZd-2uGuJTPO0hfIie62Au1nfUXiNngrd0Cnc6hQuJjU5ho1Nv0Ozb2ezruWP6bDgM-FrtRIrjBRJ8W57GgociFJxSQt2IB34aSZlyQsnYlyEH8y5VxIEJV0gapGDN4-At2s-LXLxD2AuZkgJeL4kJD4BuSlVgEKy-8GjI6BHy218rYaYGvWqFcpPsQOoIDe2kpS7Bsvv1cQtDYlikZocJKNbuiZ9a0BKwsergLM1FsaoSVTCCEBL68fvHreUYPev-Fx_Qfl2uxEf0lN3WWVWeoL1oHp8Y_bsDD06dgQ |
| linkProvider | Elsevier |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+toxicological+evaluation+of+lithium+orotate&rft.jtitle=Regulatory+toxicology+and+pharmacology&rft.au=Murbach%2C+Timothy+S.&rft.au=Gl%C3%A1vits%2C+R%C3%B3bert&rft.au=Endres%2C+John+R.&rft.au=Hirka%2C+G%C3%A1bor&rft.date=2021-08-01&rft.issn=0273-2300&rft.volume=124&rft.spage=104973&rft_id=info:doi/10.1016%2Fj.yrtph.2021.104973&rft.externalDBID=n%2Fa&rft.externalDocID=10_1016_j_yrtph_2021_104973 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0273-2300&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0273-2300&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0273-2300&client=summon |