カズサホス

１．品目名：カズサホス（CADUSAFOS）

２．用　途：殺虫剤（有機リン系）

３．安全性

（１）単回投与試験

　急性経口LD50はマウスで71 mg/kg、ラットで30～182 mg/kgと考えられる。

（２）反復投与／発がん性試験

　スイスマウスを用いた混餌（0.1、0.5、1、5 ppm）投与による２年間の反復投与／発がん性併合試験において、5 ppm投与群で血漿・赤血球中のコリンエステラーゼ活性低下、副腎皮質萎縮、脳コリンエステラーゼ活性低下等が、1 ppm以上の投与群で腎の壊死性動脈炎が認められる。本試験における無毒性量は0.5 ppm（0.072 mg/kg）と考えられる。発がん性は認められない。

　SDラットを用いた混餌（0.1、0.5、1、5 ppm）投与による２年間の反復投与／発がん性併合試験において、5 ppm投与群で、行動減少、血漿・赤血球中コリンエステラーゼ活性低下が認められる。本試験における無毒性量は1 ppm（0.05 mg/kg）と考えられる。発がん性は認められない。

　ビーグル犬を用いた強制経口（10、30、90 μg/kg）投与による91日間の反復投与試験において、血漿中コリンエステラーゼ活性低下を除き、検体投与に起因した影響は認められていない。また、ビーグル犬を用いた強制経口（0.2、1、5、20 μg/kg）投与による１年間の反復投与試験において、5μg/kg以上の投与群における血漿中コリンエステラーゼ活性低下を除き、検体投与に起因した影響は認められない。

　なお、ニワトリを用いた強制経口（8 mg/kg、21日間隔で２回）投与による急性遅発性神経毒性試験において、遅発性神経毒性は認められない。

（３）繁殖試験

　SDラットを用いた混餌（0.1、0.5、5 ppm）投与による２世代繁殖試験において、5 ppm投与群のF0、F1親動物で体重増加抑制、血漿・赤血球中のコリンエステラーゼ活性低下が認められる。本試験における無毒性量は0.5 ppm（0.025 mg/kg）と考えられる。

（４）催奇形性試験

　SDラットを用いた強制経口（2、6、18 mg/kg）投与による催奇形性試験において、6 mg/kg以上の母動物で振せん、歩行運動の低下、摂餌量の低下が、胎児動物で体重増加抑制が認められる。本試験における無毒性量は母動物、胎児動物とも2 mg/kgと考えられる。催奇形性は認められない。

　ニュージーランドホワイトウサギを用いた強制経口（0.1、0.3、0.9 mg/kg）投与による催奇形性試験において、0.3 mg/kg以上の投与群母動物で死亡、流産、下痢、神経過敏等が認められる。胎児動物では、検体投与に起因した影響は、認められない。本試験による無毒性量は母動物で0.1 mg/kg、胎児動物で0.9 mg/kgと考えられる。催奇形性は認められない。

（５）変異原性試験

　細菌を用いた復帰変異試験、CHO培養細胞を用いた前進突然変異試験、CHO培養細胞を用いた染色体異常試験、ラット肝培養細胞を用いた不定期DNA合成試験は、いずれも陰性と認められる。BALB/3T3マウス培養細胞を用いた形質転換試験は、代謝活性下で陽性と認められる。

（６）その他

　上記を含め、別添１に示した試験成績が提出されている。

４．ＡＤＩの設定

　以上の結果を踏まえ、次のように評価する。

無毒性量　　　　　　　　　　　0.025 mg/kg/日
　　　　　　　　　　　　　　　　　動物種　　　ラット
　　　　　　　　　　　　　　　　　投与量／投与経路　0.5 ppm／混餌
　　　　　　　　　　　　　　　　　試験の種類　繁殖試験
　　　　　　　　　　　　　　　　　試験期間　　２世代
安全係数　　　　　　　　　　　100
ＡＤＩ　　　　　　　　　　　　　　0.00025 mg/kg/日

５．基準値案

　別添２の基準値案のとおりである。基準値案の上限まで本農薬が残留したすべての農作物を摂食すると仮定した場合、国民栄養調査結果に基づき試算すると、摂取される農薬の量（理論最大摂取量）のＡＤＩに対する比は、8.1％である。

（別添１）

REFERENCES

FMC (1990a) FMC 67825 Technical Material Cadusafos. Mammalian Toxicology Overview prepared by Toxicology Department FMC Corporation Chemical Research and Development Center, Princeton, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Dalgard, D.W. (1988) 13-Week Comparative Oral Toxicity Study in Dogs with FMC 67825 (techn.). Project Number A87-2531. Unpublished report prepared by Hazleton Laboratories, America, inc. for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

De Prospo, J.R.et al. (1987) Multi-Generation Reproduction Study with FMC 67825 Technical in Rats. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

De Prospo, J.R. (1986) Acute Oral Toxicity in Rats with FMC 67825 Technical Material. Study Number A85-1796. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Dudek, B.R. (1984) Four Hour Acute Aerosol Inhalation Toxicity Study in Rats with FMC 67825 Technical Material. Study Number A84-1231. Unpublished report prepared by ToxiGenies, Inc., Illinois for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Freeman, Ch. (1985) Teratology Study in Rats with FMC 67825 Technical. Study Number A84-1173. Unpublished report prepared by FMC Toxicology Laboratory Princeton, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Freeman, Ch. (1985) Teratology Study in Rabbits with FMC 67825 Technical. Study Number A84-1175. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey.

Freeman, Ch. (1987a) Acute Dermal Toxicity in Rabbits with FMC 67825 Technical Material. Study Number A86-2190. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Freeman, Ch. (1987b) Acute Oral Toxicity in Rats with FMC 67825 Technical. Study Number A86-2191. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Geiger, L.E.et al. (1986) Cholinesterase Inhibition Titration Study in Rats with FMC 67825 (techn.). Study Number A84-1169. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Haworth, St.R.et al. (1984) Salmonalla/Mammalian Microsome Plate Incorporation Mutagenicity Assay (Ames Test). With FMC 67825 D (techn.). Study Number A83-1155. Unpublished report prepared by Microbiological Associates, Bethesda, Maryland for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Kedderis, L.B. (1988a) FMC 67825 Technical: Antidotal Study in Rats with Atropine and/or 2-PAM. Study Number A86-2222. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Kedderis, L.B. (1988b) FMC 67825 Technical: Antidotal Study in Rats with Atropine and/or 2-PAM. Study Number A86-2222A. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Lawlor, T.E.et al. (1985) Salmonalla/Mammalian-Microsome Plate Incorporation Mutagenicity Assay (Ames Test) with FMC 67825 (techn.). Study Number A85-1797. Unpublished report prepared by Microbiological Associates, Inc., Bethesda, Maryland for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

McCarty, J.D. (1984a) Primary Eye Irritation in Rabbits with FMC 67825 (techn.). Study Number A83-1154. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

McCarty, J.D. (1984b) Primary Skin Irritation in Rabbits with FMC 67825 (techn.). Study Number A84-1238. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

McCarty, J.D. (1984c) Acute Oral Toxicity in Rats with FMC 67825 Technical Material. Study Number A83-1164. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

McCarty, J.D. (1984d) Skin Sensitization Study in Guinea Pigs with FMC 67825 Technical Material. Study Number A84-1271. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.


McCarty, J.D.et al. (1985) Ninety Day Feeding Study in Rats with FMC 67825 (techn.). Study Number A84-1232. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

McCarty, J.D.et al. (1986) Twenty-Eight Day Range-finding Study with FMC 67825 Technical in Mice. Study Number A83-1153. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

McCarty, J.D.et al. (1987) Chronic Oncogenicity Study in Mice with FMC 67825 Technical. Study Number A84-1437. Unpublished report prepared by FMC Corp Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Puhl, R.J. (1987) FMC 67825 (techn.). Rat Metabolism Single and Multiple Low-Dose Test Regimen. Unpublished Report prepared by Hazelton Laboratories America Inc. Wisconsin. (HLA Study No.6124-105; FMC Report No.PC-0077) Submitted to FMC Corporation, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Putman, D.L.et al. (1984) Activity of FMC 67825 (techn.),(RUGBY) in the Morphological Transformation of BALB/3T3 Mouse Embryo Celles in Presence and Absence of Exogenous Metabolic Activation. Study Number A83-1158. Unpublished report prepared by Microbiological Associates Inc., Bethesda, Maryland for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Rand, G.M. (1986) Twenty-Eight Day Range-finding Study in Rats with FMC 67825 (techn.). Study Number A83-1146. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Rand, G.M. (1983a) Acute Dermal Toxicity in Rabbits with FMC 67825 Technical Material. Study Number A83-916. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Rand, G.M. (1983b) Acute Oral Toxicity in Mice with FMC 67825 Technical Material. Study Number A83-915. Unpublished report prepared by FMC Toxicology Laboratory, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.

Roberts, N.L.et al.(1984) Acute Delayed Neurotoxicity Study in the Domestic Hen with FMC 67825. Study Number A84-1246. Unpublished report prepared by Huntingdon Research Centre England for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Seely, J.C.et al.(1985a) 14-Day Range-finding Oral Toxicity Study in Dogs with FMC 67825 (techn.). Study Number A84-1203. Unpublished report prepared by Pharmacopathics Research Laboratories, Inc. Laurel, Maryland for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Seely, J.C.et al.(1985b) 91-Day Subchronic Oral Toxicity Study in the Dog with FMC 67825 Technical. Study Number A84-1204. Unpublished report prepared by Pharmacopathics Research Laboratories, Inc. Laurel, Maryland for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Selim.S. (1984) Rat Balance Study and Tissue Distribution of 14CLabelled FMC 67825 (techn.). Report (Nr.FM-175T) of the Primate Research Institute, New Mexico State University, submitted to FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Shellenberger,Th.E. (1986) One Year Oral Toxicity Study in the Dog with FMC 67825 (techn.). Study Number A84-1538. Unpublished report prepared by Tegeris Laboratories Inc.(formerly:Pharmacopathics Research Laboratories, Inc.), Laurel, Maryland for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Stankowski, L.F.et al.(1985) Mammalian Cell Forward Gene Mutation Assay with FMC 67825 (techn.). Study Number A85-1601. Unpublished Report prepared by Pharmakon Research International, Inc., Waverly, Pennsylvania for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Thilagar, A.et al.(1984a) Chromosome Aberrations Assay in Chinese Hamster Ovary (CHO) Cells. With FMC 67825 (techn.). Study Number A83-1157. Unpublished report prepared by Microbiological Associates, Bethesda, Maryland for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Thilagar, A.et al.(1984b) Unscheduled DNA Synthesis in Rat Primary Hepatocytes with FMC 67825 (techn.). Study Number A83-1159. Unpublished report prepared by Microbiological Associates, Bethesda, Maryland for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Thilagar, A.et al.(1984c) CHO/HGPRT Mutation Assay in Chinese Hamster Ovary (CHO) Cells. With FMC 67825 (techn.)(RUGBY). Study Number T-2199-332. Unpublished report prepared by Microbiological Associates Inc., Bethesda, Maryland for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Weiner, M.et al.(1986) Chronic Oral toxicity/Oncogenicity Study in Rats with FMC 67825 Technical.Study Number A84-1287.Unpublished report prepared by Hazleton Laboratories America Inc., Virginia for FMC Corporation. Submitted to WHO by FMC Corporation, NJ, USA.

Wu, J.(1988) FMC 67825 (techn.). Rat Metabolism: Metabolite Identification and Distribution.10 Unpublished report prepared by FMC Corporation, Metabolism Laboratories, New Jersey. Submitted to WHO by FMC Corporation, NJ, USA.


（別添２）

食　品　規　格　（案）

（注）オ：オーストラリア