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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/11/01 18:43:26」(JST)

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無有害作用量（むゆうがいさようりょう）または無毒性量（むどくせいりょう）(英: No observable adverse effect level, 略: NOAEL)とは暴露群と適切な対照と比較したとき、量的あるいは質的な悪影響（例えば形態学的、機能的能力、成長、寿命の変化）が生物学的あるいは統計学的に有意差を持たないと認められる実験や観察により得られた生体の暴露量を意味する^[1]^[2]。類似の概念で無影響量（英: No observable effect level, 略: NOEL）というものもあり、「影響がないわけでないが悪影響ではない」という意味で区別する場合もある。

毒性学では特に悪影響が認められない物質（化学物質など）や因子（放射線など）の最大の濃度や量であり、それを越えると悪影響が生じる濃度や量を意味する.^[3]。

無有害作用量はリスクアセスメントの手順の基本である用量反応関係の確立過程で用いられることがある。

「ヒト等価用量（HED）」も参照

例

アメリカ食品医薬品局 (FDA) によるミノサイクリンの2年間発癌性試験（ラット）では、「200mg/kg/日」群で甲状腺癌が有意に発現したが、「50mg/kg/日」群では非有意であった^[4]。

従って、NOAELは「50mg/kg/日」となる。HED換算値^{[注 1]}は「約8mg/kg/日」となり、臨床用量（200mg/日≒3.3mg/kg/日）の約2.5倍であることが分かる。

参考文献

脚注

[ヘルプ]

注釈

^ ラット用量を6.2で除算するとヒト相当用量となる。

出典

^ Seton Resource Center
^ [1]
^ Food Safety and Risk Assessment website at Glasgow Caledonian University
^ FDA 2006 - CENTER FOR DRUG EVALUATION AND RESEARCH PHARMACOLOGY REVIEW

この項目は、医学に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています（プロジェクト:医学／Portal:医学と医療）。

wiki en

[Wiki en表示]

In non-clinical assessment NOAEL (no-observed adverse effect level) plays a pivotal role. It is determined or proposed by qualified personnel (pharmacologist, toxicologist) depending on the study, drug indications and its pharmacological therapeutics side/adverse effects. NOAEL could be defined as "the highest experimental point that is without adverse effect,". It either does not provide the effects of drug with respect to duration and dose, or it does not address the interpretation of risk based on toxicologically relevant effects.^[1] The no observed adverse effect level (NOAEL) denotes the level of exposure of an organism, found by experiment or observation, at which there is no biologically or statistically significant (e.g. alteration of morphology, functional capacity, growth, development or life span) increase in the frequency or severity of any adverse effects in the exposed population when compared to its appropriate control.^[2]^[3]

In toxicology it is specifically the highest tested dose or concentration of a substance (i.e. a drug or chemical) or agent (e.g. radiation), at which no such adverse effect is found in exposed test organisms where higher doses or concentrations resulted in an adverse effect.^[4]^[5]

This level may be used in the process of establishing a dose-response relationship, a fundamental step in most risk assessment methodologies.

In drug development, NOAEL of a new drug is assessed in laboratory animals drugs prior to initiation of clinical trials to establish a safe clinical starting dose in human trials.

The United States Environmental Protection Agency defines NOAEL as 'an exposure level at which there are no statistically or biologically significant increases in the frequency or severity of adverse effects between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered as adverse, or as precursors to adverse effects. In an experiment with several NOAELs, the regulatory focus is primarily on the highest one, leading to the common usage of the term NOAEL as the highest exposure without adverse effects.'.^[6]

References

^ Engelhardt JA, Dorato MA (August 2005). "The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s).". Regul Toxicol Pharmacol. 42 (3): 265–274. doi:10.1016/j.yrtph.2005.05.004. PMID 15979222. Retrieved 15 July 2016.
^ Seton Resource Center
^ "IUPAC glossary of terms used in toxicology - terms starting with N". Environmental Health and Toxicology Specialized Information Services. U.S. Department of Health & Human Services. Retrieved February 18, 2013. based upon Duffus, J. H.; Nordberg, M.; Templeton, D. M. (2007). "Glossary of terms used in toxicology, 2nd edition (IUPAC Recommendations 2007)". Pure and Applied Chemistry. 79 (7): 1153. doi:10.1351/pac200779071153.
^ Faustman, E.M., Omenn, G.S. Risk assessment. (2001) In: C. D. Klaassen (ed.): Casarett & Doull's Toxicology, 6. ed., McGraw-Hill, New York, pp. 92-94. ISBN 0-07-134721-6.
^ Food Safety and Risk Assessment website at Glasgow Caledonian University
^ http://www.epa.gov/OCEPAterms/nterms.html

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English Journal

Oral toxicity and pharmacokinetic studies of SHetA2, a new chemopreventive agent, in rats and dogs.

Kabirov KK, Kapetanovic IM, Benbrook DM, Dinger N, Mankovskaya I, Zakharov A, Detrisac C, Pereira M, Martín-Jiménez T, Onua E, Banerjee A, van Breemen RB, Nikolić D, Chen L, Lyubimov AV.SourceToxicology Research Laboratory, Department of Pharmacology, University of Illinois at Chicago , Chicago, Illinois , USA.
Drug and chemical toxicology.Drug Chem Toxicol.2013 Jul;36(3):284-95. doi: 10.3109/01480545.2012.710632. Epub 2012 Sep 5.
SHetA2 is a heteroarotinoid that has shown selective inhibition of cancer cell growth and an induction of apoptosis without activation of nuclear retinoic acid receptors. In the rat study, SHetA2 was administered in 1% aqueous methylcellulose/0.2% Tween 80 by oral gavage at 0, 100, 500, and 2,000
PMID 22947079

Preclinical toxicological evaluations of the sclerotium of Lignosus rhinocerus (Cooke), the Tiger Milk mushroom.

Lee SS, Enchang FK, Tan NH, Fung SY, Pailoor J.SourceCENAR and Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Journal of ethnopharmacology.J Ethnopharmacol.2013 May 2;147(1):157-63. doi: 10.1016/j.jep.2013.02.027. Epub 2013 Feb 28.
ETHNOPHARMACOLOGICAL RELEVANCE: Lignosus rhinocerus (Tiger Milk mushroom) is distributed in South China, Thailand, Malaysia, Indonesia, Philippines and Papua New Guinea. In Malaysia, it is the most popular medicinal mushroom used by the indigenous communities to relieve fever, cough, asthma, cancer,
PMID 23458920

Single and 90-day repeated oral dose toxicity studies of fermented Rhus verniciflua stem bark extract in Sprague-Dawley rats.

Shin SH, Koo KH, Bae JS, Cha SB, Kang IS, Kang MS, Kim HS, Heo HS, Park MS, Gil GH, Lee JY, Kim KH, Li Y, Lee HK, Song SW, Choi HS, Kang BH, Kim JC.SourcePreclinical Research Center, ChemOn Inc., 334 Jeil-ri, Yangji-myeon, Cheoin-gu, Yongin-si, Gyeonggi-do 449-826, Republic of Korea; College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.Food Chem Toxicol.2013 May;55:617-26. doi: 10.1016/j.fct.2013.01.043. Epub 2013 Feb 15.
Fermented Rhus verniciflua stem bark (FRVSB) extract, an urushiol-free extract of Rhus verniciflua Stokes (RVS) fermented with Fomitella fraxinea, has various biological activities. The present study was carried out to investigate the potential toxicity of the FRVSB extract following single and repe
PMID 23416650

Japanese Journal

F344ラットにおけるホウセンカ抽出物の13週間亜慢性毒性試験

豊田武士,高見成昭,今井俊夫,〓永晩,蓮村麻衣,水田保子,大波冴子,鈴木勇,廣瀬雅雄,西川秋佳,小川久美子
日本食品化学学会誌 20(1), 52-60, 2013-04-22
… 以上の結果から、一部の血清電解質において変動が認められたものの、毒性学的意義は乏しいと考えられ、ホウセンカ抽出物の無毒性量(NOAEL)は雌雄ともに5.0%以上(雄:3997mg/kg bw/day、雌:4577mg/kg bw/day)と判断された。 …
NAID 110009603497

日本における農薬等の急性参照用量設定の基本的考え方

吉田緑,鈴木大節,松本清司,代田眞理子,井上薫,高橋美和,森田健,小野敦
食品衛生学雑誌 54(4), 331-334, 2013
ヒトが農薬等を24時間以内に経口摂取した場合の急性暴露による悪影響の指標として急性参照用量（Acute Reference Dose; ARfD）を設定する基本的考え方をSolecki et al.（2005）の指針を基にまとめた．ARfDの評価はすべての農薬を対象とし，急性影響とは単回投与で発現する毒性を指す．カットオフ値以上であればARfD設定の必要はないと判定すべきである．基本的にはすべての …
NAID 130003369311

Adverse Effects of Excessive Leucine Intake Depend on Dietary Protein Intake: A Transcriptomic Analysis to Identify Useful Biomarkers

IMAMURA Wataru,YOSHIMURA Ryoji,TAKAI Marie,YAMAMURA Junki,KANAMOTO Ryuhei
Journal of Nutritional Science and Vitaminology 59(1), 45-55, 2013
… In conclusion, the gene-marker panel suggested that for male rats dietary Leu supplementation of 2% is the NOAEL dose in low-protein (6%) diets. …
NAID 130003368148