シロマジン

１．品目名：シロマジン（CYROMAZINE）

２．用　途：殺虫剤（トリアジン系）

３．安全性

（１）単回投与試験

　急性経口LD₅₀はマウスで2,029 mg/kg、ラットで3,530～4,050 mg/kgと考えられる。

（２）反復投与／発がん性試験

　CD-1マウスを用いた混餌（50、1,000、3,000 ppm）投与による24ヶ月間の反復投与／発がん性併合試験において、1,000 ppm以上の投与群で体重増加抑制、肝比重量の増加等が認められる。本試験における無毒性量は50 ppm（6.5 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（30、300、3,000 ppm）投与による104週間の反復投与／発がん性併合試験において、3,000 ppm投与群で摂餌量減少、300 ppm以上の投与群で体重減少が認められる。本試験における無毒性量は30 ppm（1.8 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混餌（30、300、3,000 ppm）投与による26週間の反復投与試験において、3,000 ppm投与群で体重増加抑制、赤血球数、ヘマトクリット値、ヘモグロビン値の低下等が認められる。本試験における無毒性量は300 ppm（8.86 mg/kg）と考えられる。

（３）繁殖試験

　SDラットを用いた混餌（30、1,000、3,000 ppm）投与による２世代繁殖試験において、3,000 ppm投与群F0雄に受胎率低下、F1及びF2世代の出生児に生存率低下、体重増加抑制が、1,000 ppm以上の投与群のF0及びF1世代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30 ppm（2.0 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（100、300、600 mg/kg）投与による催奇形性試験において、600 mg/kg投与群の胎児動物で平均体重減少、300 mg/kg以上投与群母動物で体重増加抑制、胎児動物で化骨遅延が認められる。本試験における無毒性量は母動物、胎児動物とも100 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（5.0、10、30 mg/kg）投与による催奇形性試験において、30 mg/kg投与群母動物で体重減少、摂餌量減少が、10 mg/kg以上の投与群母動物で便量及び尿量の減少が認められる。胎児動物では、対照群を含む全ての群に、自然発生と同種類の奇形が用量相関なく散発性に認められる。出生児の観察では、30 mg/kg投与群に死亡児の軽度の増加が認められるが、他の群には投与に起因する異常所見は認められない。本試験における無毒性量は母動物5 mg/kg、胎児動物30 mg/kg、出生児10 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、酵母を用いた突然変異試験、V79培養細胞を用いた突然変異試験、マウスリンパ腫細胞を用いた突然変異試験、ヒトリンパ球を用いた染色体異常試験、ラット及びマウス肝培養細胞を用いた不定期DNA合成試験は、ハムスター骨髄細胞を用いた核異常試験、マウスを用いた小核試験、マウス優性致死試験の結果は、いずれも陰性と認められる。

（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　　　　　　　　　　　　　1.8 mg/kg/日
　　　　　　　　　　　　　　　　　　　　動物種　　　ラット
　　　　　　　　　　　　　　　　　　　　投与量／投与経路　30 ppm／混餌
　　　　　　　　　　　　　　　　　　　　試験期間　　104週間
　　　　　　　　　　　　　　　　　　　　試験の種類　反復投与／発がん性併合試験
　安全係数　　　　　　　　　　　　　100
　ＡＤＩ　　　　　　　　　　　　　　　　0.018 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、12.7％である。

･･･････････････････････････････････････････････････････････････････････････････
（＊）催奇形性試験として、上述のほか、ニュージーランドホワイトウサギを用いた強制経口（5、10、30、60 mg/kg）投与による試験成績が提出されており、対照群を含むすべての群に水頭症をはじめ、各種の奇形が用量相関なく散発的に認められる。これらの奇形発生の遺伝要因を検討するため、奇形胎児の父親を用いた交配試験を行ったところ、検体投与試験と同種類の奇形の同程度の散発が認められた。これらの奇形は、このウサギ繁殖コロニーに自然発生する奇形と同様のため、検体投与に起因するものではないと考えられる。

（別添１）

REFERENCES

Bathe, R. and Sachsse, K,(1978a). Acute oral LD50 in the mouse of technical CGA 72662. Unpublished report, project no.Siss 6446 from CIBA-GEIGY Ltd., Basle, Switzerland.

Bathe, R. and Sachsse, K,(1978b). Acute oral LD50 in the rat of technical CGA 72662. Unpublished report, project no.Siss 6446 from CIBA-GEIGY Ltd., Basle, Switzerland.

Bathe, R. and Sachsse, K,(1978c). Acute dermal LD50 in the rat of technical CGA 72662. Unpublished report, project Siss 6446 from CIBA-GEIGY Ltd., Basle, Switzerland.

Beilstein, P. and Muller, D.,(1985). L5178Y/TK+/- Mouse Lymphoma mutagenicity test. Unpublished report, project no.840942 from CIBA-GEIGY Ltd., Basle, Switzerland.

Blair, M. and Hardisty, J.F.,(1982a). Oncogenicity study with CGA 72662 technical in albino mice. Unpublished report, project no.382-082 from International Research and Development Corporation, Mattawan, Mi., USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Blair, M. and Hardisty, J.F.,(1982b). 2-year chronic and oncogenicity study with CGA-72662 technical in albino rats. Unpublished report, project no.382-081 from International Research and Development Corporation, Mattawan, Mi., USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Blair, M., McMeekin, S.O. and Schardein, J.L.,(1981a). CGA-72662 technical-teratoloty study in rabbits. Unpublished report, study no.382-072/072a from International Research and Development Corporation, Mattawan, Mi, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.


Blair, M., Slezak, S.E. and Schardein, J.L.,(1981b). Two generation reproduction study with CGA-72662 in albino rats. Unpublished report, project no.382-086 from International Research and Development Corporation, Mattawan, Mi, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Boone, T. and Cheung, M.W.,(1985). Residues of cyromazine and melamine in chicken tissues and eggs resulting from the feeding of cyromazine in the diet. Unpublished report no.ABR-84082 from CIBA-GEIGY Corporation, Greensboro, NC, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Burdock, G.A., Weatherholtz, W.M., Alsaker, R.D., Brown, H.R., Dawkins, B.G., Voelker, R.W., Dawkins, K.K. and Marshall, P.M.,(1980). Subchronic toxicity study in dogs - CGA-72662 technical - final report. Unpublished report, project no.483-180 from Hazleton Laboratories America, Vienna, VA, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Deparade, E. and Arni, P.,(1988). Salmonella/microsome mutagenicity test (OECD - conform) - CGA 72662 tech. Unpublished report, project no.871713 from CIBA-GEIGY Ltd., Basle, Switzerland.

Dollenmeier, P. and Muller, D.,(1986). V79 Chinese hamster point mutation test (with and without metabolic activation) - CGA 72662 techn. Unpublished report, project no.840798 from CIBA-GEIGY Ltd., Basle, Switzerland.

Goldenthal, E.L. and Hughes, R.,(1979). 90 day subacute toxicity study with CGA-72662 in albino rats. Unpublished report, project no.382-052 from International Research and Development Corporation, Mattawan, MI., USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Hartmann, H.R., Schneider, M., Gretener, P., Froehlich, E., Malinowske, W., Krinke, A. and Gfeller, W.,(1988). CGA-72662 tech. - 28 day aerosol inhalation toxicity in the rat - final report. Unpublished report, project no.861472 from CIBA-GEIGY Ltd., Basle, Switzerland.

Hool, G. and Arni, P.,(1984). Saccharomyces cerevisiae D7/mammalian-microsome mutagenicity test in vitro (Test for mutagenic properties in yeast cells) - CGA 72662 techn. Unpublished report, project no.831167 from CIBA-GEIGY Ltd., Basle, Switzerland.

Hool, G., Langauer, M. and Muller, D.,(1980). Nucleus anomaly test in somatic interphase nuclei - CGA 72662 - Chinese hamster (Test for mutagenic effects on bone marrow cells). Unpublished report, project no.791347 from CIBA-GEIGY Ltd., Basle, Switzerland.

Hool, G. and Muller, D.,(1981). Dominant lethal study - CGA 72662 - mouse (Test for cytotoxic or mutagenic effects on male germinal cells). Unpublished report, project no.790033 from CIBA-GEIGY Ltd., Basle, Switzerland.

Jessup, D.C. and Hughes, R.,(1979). 90 day subacute oral toxicity study with CGA-72662 in purebred beagle dogs. Unpublished report no.382-048 from International Research and Development Corporation, Mattawan, MI., USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Murphy, T.G. and Simoneaux, B.,(1985). Percutaneous absorption of cyromazine in rats. Unpublished report no.ABR-85035 from CIBA-GEIGY Corporation, Greensboro, NC, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Murphy, T.G., Brown, K. and Doornheim, D.,(1987). Dermal absorption of cyromazine in rats. Unpublished report no.ABR-86069 from CIBA-GEIGY Corporation, Greensboro, NC, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Nemec, M.D. and Rodwell, D.E.,(1985). A teratology study (segment Ⅱ) in albino rabbits with cyromazine technical-final report. Unpublished report, project no.WIL-82001 from WIL Reserch Laboratories Inc., Ashland, OH, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Nemec, M.D. and Rodwell, D.E.,(1986a) A study of the incidence of foetal malformations in the control population of BUK:(CRL) NZWfBR rabbits. Unpublished report, project no.WIL-82005 from WIL Research Laboratories Inc., Ashland, OH, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Nemec, M.D. and Rodwell, D.E.,(1986b) A teratoloty and postnatal study in albino rabbits with cyromazine technical-final report. Unpublished report, project no.WIL-82008 from WIL Reserch Laboratories Inc., Ashland, OH, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

NTP/NIH, 1983. Carcinogenesis bioassay of melamine in F344/N rats and B6C3F1 mice (feed study). US NIH Publication No.83-2501, March,(1983).

Rodwell, D.E., Tasher, E.J. and Jessup, D.C.,(1979) CGA-72662 technical-teratoloty study in rats. Unpublished report, study no.382-070 from International Research and Development Corporation, Mattawan, MI, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.


Sabol, R.J.,(1987). Acute oral toxicity study in rats - EPA guidelines no.81-1. Unpublished report, project no.5020-87 from Stillmeadow Inc., Houston, TX., USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Schardein, J.L., Aldridge, D. and Blair, M.,(1985). Cyromazine-teratology study in rabbits. Unpublished report, study no.382-104 from International Research and Development Corporation, Mattawan, MI, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Simoneaux, B.,(1981). Identification of a major metabolite of 14C-CGA-72662 in chickens. Unpublished report no.ABR-81035 from CIBA-GEIGY Corporation, Greensboro, NC, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Simoneaux, B. and Cassidy, J.E.,(1978). Metabolism and balance study of 14C-CGA 72662 in the rat. Unpublished report no.ABR-78072 from CIBA-GEIGY Corporation, Greensboro, NC, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Simoneaux, B. and Cassidy, J.E.,(1979). Metabolism and balance study of 14C-CGA 72662 in a chicken. Unpublished report no.ABR-79043 from CIBA-GEIGY Corporation, Greensboro, NC, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Simoneaux, B. and Cassidy, J.E.,(1981). Metabolism and balance study of 14C-CGA 72662 in a mature sheep. Unpublished report no.ABR-80055 from CIBA-GEIGY Corporation, Greensboro, NC, USA. Submitted by CIBA-GEIGY Ltd., Basle, Switzerland.

Simoneaux, B. and Marco, G.,(1984). Balance and metabolism of 14C-cyromazine in lactating goats. Unpublished report no.ABR-84067 from CIBA-GEIGY Corporation, Greensboro, NC, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Smith, J., Boone, T. and Harper, J.,(1983). Residues in rat tissues resulting from the feeding of cyromazine. Unpublished report no.ABR-83088 from CIBA-GEIGY Corporation, Greensboro, NC, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Staley, J.A.,(1986). Distribution and characterization of 14C-labelled cyromazine in monkeys. Unpublished report no.ABR-85100 from CIBA-GEIGY Corporation, Greensboro, NC, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.


Staley, J.A. and Simoneaux, B.,(1986). Distribution and characterization of 14C-labelled cyromazine in monkeys. Unpublished report no.ABR-86008 from CIBA-GEIGY Corporation, Greensboro, NC, USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Strasser, F. and Arni, P.,(1985). Chromosome studies on human Lymphocytes in vitro with CGA 72662 techn. Unpublished report, project no.850013 from CIBA-GEIGY Ltd., Basle, Switzerland.

Strasser, F. and Arni, P.,(1986). Mammalian spot test, mouse, 8 weeks - CGA 72662 techn. Unpublished report, project no.850616 from CIBA-GEIGY Ltd., Basle, Switzerland.

Strasser, F., Langauer, M. and Arni, P.,(1987). Micronucleus test (mouse) - CGA 72662 tech. Unpublished report, project no.861345 from CIBA-GEIGY Ltd., Basle, Switzerland.

Tong, C.,(1982). The hepatocyte primary culture/DNA repair assay on compound CGA-72662 using rat hepatocytes in culture. Unpublished report, project no.042782 from Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, N.Y. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Tong, C.,(1983). The hepatocyte primary culture/DNA repair assay on compound CGA-72662 using mouse hepatocytes in culture. Unpublished report, project no.050382 from Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, N.Y.. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

Ullmann, L. and Sachsse, K.,(1978a). Eye irritation in the rabbit of technical CGA 72662. Unpublished report, project no.6446 from CIBA-GEIGY Ltd., Basle, Switzerland.

Ullmann, L. and Sachsse, K.,(1978b). Skin irritation in the rabbit of single application of technical CGA 72662. Unpublished report, project no.6446 from CIBA-GEIGY Ltd., Basle, Switzerland.

Ullmann, L. and Sachsse, K.,(1978c). Skin sensitizing (contact allergenic) effect in guinea pigs of technical CGA 72662. Unpublished report, project no.6446 from CIBA-GEIGY Ltd., Basle, Switzerland.


Ullmann, L. and Sachsse, K.,(1978d). Acute oral LD50 in the rabbit of technical CGA 72662. Unpublished report, project no.Siss 6446 from CIBA-GEIGY Ltd., Basle, Switzerland.

Ulrich, C.E. and Blair, M.,(1979). Acute inhalation study on CGA-72662 tech. Unpublished report no.382-075 from International Reserch and Development Corporation, Mattawan, MI., USA. Submitted to WHO by CIBA-GEIGY Ltd., Basle, Switzerland.

WHO (1990). The WHO recommended classification of pesticides by hazard and guidelines to classification 1990-1991 (WHO/PCS/90.1). Available from the International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland.


（別添２）

食　品　規　格　（案）

（注）イ：イタリア　　　　フ：フランス
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