N., and Bakry, N. M. (2006)

Ioannou, Yiannakis M., Dauterman, Walter C., and Tucker, William P. (1980). Degradation of diazinon by 2,4-dihydroxy-7-methoxy-2h-1, 4-benzoxazin-3(4h)-one in maize. Phytochemistry 19: 1607-1611.
Chem Codes: Chemical of Concern: DZ Rejection Code: METABOLISM.

A cyclic hydroxamate, 2,4-dihydroxy-7-methoxy-2H- 1,4-benzoxazin-3(4H)-one (DIMBOA), was isolated and identified from shoots of 6-day-old corn seedlings grown in the dark. From 100 g of plant tissue 100 mg of DIMBOA were isolated. This hydroxamate was very effective in catalysing the hydrolysis of the pyrimidinyl organophosphate insecticide, diazinon (O, O-diethyl- O-[6- methyl-2-(1-methylethyl)-4-pyrimidinyl] phosphorothioate) to 6- methyl-2-(1-methylethyl)-4-hydroxypyrimidine and diethyl phosphorothioic acid. The optimum pH for hydrolytic activity was 5 and at pH values equal to or higher than the pKa of the hydroxamic group (6.95) most of the activity was lost. Zea mays/ Gramineae/ corn/ diazinon/ degradation.

Iriarte Capaccio, Christian A. and Varela, Oscar (2000). Enantiospecific synthesis of a glycoside of -epi-purpurosamine. Tetrahedron: Asymmetry 11: 4945-4954.
Chem Codes: Chemical of Concern: DZ Rejection Code: METHODS.

2-Propyl -epi-purpurosaminide dihydrochloride 14 and its di-N-acetylated derivative 15 were synthesized by an enantiospecific sequence which involves the 2-propyl 6-O-acetyl-3,4-dideoxy-[alpha]--erythro-hex-3-enopyranosid-2-ulose 2 as the key precursor. The first approach through the saturated diol 4, prepared by reduction of the enone system of 2, was unsuccessful as the C-2 position of 2,6-di-O-sulfonyl derivatives 5 and 6 resisted substitution by azide. Therefore, an alternative sequence starting from the allylic alcohol 3, also derived from 2, was developed. In this case, the 2,6-di-O-tosyl derivative 9 gave the expected 2,6-diazide 10 with additional unwanted rearrangement of the double bond to the 2-propyl 4,6-diazido-2,3,4,6-tetradeoxy-[alpha]--threo-hex-2-enopyranoside 11 isomer. However, the ditriflate derivative 13, analogous to 9, underwent substitution to afford the diazide 10 in good yield. Upon reduction of the azide functions and saturation of the double bond of 10 by catalytic hydrogenation under acidic conditions, the dihydrochloride salt 14 was obtained as a crystalline product (43% overall yield from 3).

Ishiwata, Shigemasa and Kamiya, Mamoru (1999). Cyclodextrin inclusion: catalytic effects on the degradation of organophosphorus pesticides in neutral aqueous solution. Chemosphere 39: 1595-1600.
Chem Codes: Chemical of Concern: DZ Rejection Code: FATE.

[alpha] -,[beta]- and [gamma]-Cyclodextrins were found to have promotive inclusion-catalytic effects on the degradation of organophosphorus pesticides solubilized in neutral aqueous media. Pesticide degradations were especially accelerated in such systems as [alpha] -cyclodextrin plus diazinon and [beta]-cyclodextrin plus chloropyrifos. The above findings are in contrast with the inhibitive catalytic effects of cyclodextrins on pesticide degradations in alkaline media.Cyclodextrin catalytic effects found here were considerably affected by differences in the substitutional and hetero-cyclic properties of the aromatic rings of pesticides and also by the sizes of cyclodextrin cavities. Cyclodextrin inclusion-catalytic effects/ organophosphorus pesticide degradation/ diazinon/ chloropyrifos

Itoh, Toyofumi, Hisada, Hiroyuki, Usui, Yoshiharu, and Fujii, Yuki (1998). Hydrolysis of phosphate esters catalyzed by copper(II)-triamine complexes. The effect of triamine ligands on the reactivity of the copper(II) catalysts. Inorganica Chimica Acta 283: 51-60.
Chem Codes: Chemical of Concern: DZ Rejection Code: METHODS.

Hydrolysis/ Phosphate esters/ Copper complexes/ Triamine complexes/ Kinetics and mechanism Hydrolyses of lithium 2,4-dinitrophenyl ethyl phosphate (7) and 2,4-dinitrophenyl diethyl phosphate (8) catalyzed by copper(II)--triamine complexes (triamine = cis,cis-triaminocyclohexane (1), 1,5,9-triazacyclododecane (2), 1,4,7-triazacyclononane (3), dipropylenetriamine (4), N-(2-aminoethyl)-1,3-propanediamine (5), diethylenetriamine (6)) were investigated at pH 7.0-9.5, and the reactivity of the catalysts was found to increase in the order 5 ~ 6 ~ 4 3 1 2. From the pH dependence of the apparent rate constants, and the deprotonation constant (pKa) of the coordinated water, the active species was confirmed to be CuL(OH)+ for all of the catalysts. Furthermore, the reactions were confirmed to proceed via a phosphate ester-coordinated intermediate on the basis of a good fit between the reciprocal of the stability constant (Kester-1) of a mixed complex of CuL(OH)+ with diethyl phosphate (9) and the Michaelis constant KM for 1-4, and of crystal structure analysis of [mu]-(diethyl phosphato)-(dipropylenetriamine)copper(II) hexafluorophosphate (10). In addition, it was found that the increasing order (5 ~ 6 ~ 4 ) in the estimated rate constant (kcat) corresponded closely to the decreasing order in the coordination strength of triamine ligands. The effect of triamine ligands was discussed in relation to the Lewis acidity of central copper(II) ion and the reaction mechanism.

Iverson, F., Grant, D. L., and Lacroix, J. (1975). Diazinon Metabolism in the Dog. Bull.Environ.Contam.Toxicol. 13: 611-618.

EcoReference No.: 37257

Chemical of Concern: DZ; Habitat: T; Effect Codes: BCM,ACC; Rejection Code: NO ENDPOINT(DZ).

Iyaniwura, T. T. (1990). In vitro toxicology of organophosphorus pesticide combinations. In Vitro Toxicology [IN VITRO TOXICOL.]. Vol. 3, no. 4, pp. 373-377. 1990.

Chem Codes: Chemical of Concern: DZ Rejection Code: IN VITRO.

ISSN: 0888-319X

Descriptors: enzymes
Descriptors: toxicology
Descriptors: diazinon
Descriptors: malathion
Descriptors: organophosphorus compounds
Abstract: The anticholinesterase effects of four organophosphate pesticides were studied in vitro: these include azinphosethyl, azinphosmethyl, diazinon, and malathion. All compounds inhibited the cholinesterase enzyme dose dependently, but malathion inhibited the cholinesterase enzyme to less than 10% at all concentrations studied ranging from 10- super(10) - 10- super(5)M. A combination of equal proportions of azinphosethyl and azinphosmethyl acted additively, while malathion and diazinon combinations were synergistic. The potentiation of malathion toxicity by diazinon was underscored.
Language: English
English
Publication Type: Journal Article
Classification: X 24135 Biochemistry
Classification: H SE5.23 ORGANOPHOSPHATES
Subfile: Health & Safety Science Abstracts; Toxicology Abstracts

Jaaskelainen, Ilpo, Monkkonen, Jukka, and Urtti, Arto (1994). Oligonucleotide-cationic liposome interactions. A physicochemical study. Biochimica et Biophysica Acta (BBA) - Biomembranes 1195: 115-123.

Chem Codes: Chemical of Concern: DZ Rejection Code: METHODS.

Cationic liposomes are effective in delivering antisense oligonucleotides into cells in culture, but their interactions with the oligonucleotides are poorly understood. We studied the aggregation and fusion reactions during the formation of cationic lipid/oligonucleotide complexes in solution and their interactions with lipid bilayers. Phosphorothioate oligonucleotides (15-mer) were complexed with cationic liposomes composed of dimethyldioctadecylammonium bromide (DDAB) and dioleoylphosphatidylethanolamine (DOPE) at 8:15 molar ratio or of a commercial formulation DOTAP (N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammoniummethylsulfate), at different ratios with apparent -/+ charge ratios of 0.03-5.6. Mean size of the complexes increased with -/+ ratio so that at charge ratios 0.4-2.0 the size increased by at least an order magnitude due to the oligonucleotide induced aggregation. Resonance energy transfer experiments showed that in addition to aggregation oligonucleotides induced fusion of cationic liposomes, but the fusion was rate-controlled by the initial aggregation step. Rate constants for oligonucleotide induced aggregation were dependent on lipid concentration and were in the range of (0.2-1) [middle dot] 107 M-1 s-1 and (1-10) [middle dot] 107 M-1 s-1 for DDAB/DOPE and DOTAP, respectively. Increase in oligonucleotide concentration induced the aggregation and fusion until at high -/+ ratios electrostatic repulsion of negative surfaces inhibited further aggregation and fusion. DOTAP/oligonucleotide complexes did not induce leakage of calcein from neutral EPC liposomes, but did cause leakage at -/+ charge ratios of 2.0 from EPC/DOPE liposomes. Also at -/+ charge ratios below 0.8 DOTAP/oligonucleotide complexes induced leaking from negatively charged DPPC/DPPG liposomes. These results indicate that either phosphatidylethanolamine or negative charge are required in the cell membrane for fusion of cationic liposome-oligonucleotide complexes. The ratio of oligonucleotide to cationic lipid is critical in determining the physicochemical properties of the mixture. Cationic lipid/ Oligonucleotide/ Particle size/ Calcein leakage/ Fusion/ Aggregation

Jabbari, Esmaiel and Khakpour, Maziar (2000). Morphology of and release behavior from porous polyurethane microspheres. Biomaterials 21: 2073-2079.
Chem Codes: Chemical of Concern: DZ Rejection Code: METHODS.

A novel biomaterial application of porous microspheres is for sustained delivery of biologically active agents. Recent studies have pointed out the importance of biomaterial porosity in promoting biocompatibility and controlling release rate of active agents. The objective of this research was to investigate the effect of chain-extending agent on the porosity and release behavior of polyurethane (PU) microspheres prepared using a two-step suspension polycondensation method with methylene diphenyl diisocyanate (MDI) as the isocyanate, polyethylene glycol (PEG400) as the diol, and 1,4-butanediol as the chain-extending agent. Chain-extending agent was used to increase the ratio of hard to soft segments of the PU network, and its effect on microsphere morphology was studied with scanning electron microscopy. According to the results, porosity was significantly affected by the amount of chain-extending agent. The pore size decreased as the concentration of chain-extending agent increased from zero to 50 mole%. With further increase of chain-extending agent to 60 and 67%, PU chains became stiffer and formation of pores was inhibited. Therefore, pore morphology was significantly affected by variations in the amount of chain-extending agent. The release behavior of microspheres was investigated with diazinon as the active agent. After an initial burst, corresponding to 3% of the incorporated amount of active agent, the release rate was zero order. Polyurethane microspheres/ Suspension polycondensation/ Morphology/ Pore size/ Chain-extending agent

Jackson, D. M. and Lam, J. J. Jr. (1989). Jalysus wickhami (Hemiptera: Berytidae): Toxicity of Pesticides Applied to the Soil or in the Transplant Water of Flue-Cured Tobacco. J.Econ.Entomol. 82: 913-918.

EcoReference No.: 68596

Chemical of Concern: ADC,CBF,PRN,FNF,MLX,OML,EP,CPY,DZ,ACP; Habitat: T; Effect Codes: MOR; Rejection Code: LITE EVAL CODED(CBF,ADC),OK(ALL CHEMS),OK TARGET(DZ).

JACOBS RM and YESS NJ (1993). Survey of imported green coffee beans for pesticide residues. FOOD ADDIT CONTAM; 10 575-577.

Chem Codes: Chemical of Concern: DZ Rejection Code: SURVEY.

BIOSIS COPYRIGHT: BIOL ABS. The US Food and Drug Administration carries out incidence/level monitoring in order to acquire data on the presence and amounts of pesticide residues in particular commodity/chemical combinations. In the survey reported here, imported green coffee beans were analysed for a variety of pesticide chemicals. A total of 60 green coffee samples were collected from 21 countries that are major exporters of coffee to the United States. The samples were analysed for organochlorine/organophosphorus, N-methyl carbamate, benomyl group and EBDC residues. Four samples had detectable residues: chlorpyrifos, 0.01, 0.02 and 0.04 ppm and pirimiphos-methyl, 0.01 ppm. The majority (93%) of the green coffee samples analysed in this survey had no detectable pesticide residues. Biochemistry/ Food Technology/ Food Analysis/ Food Technology/ Food-Processing Industry/ Food Technology/ Food Additives/Poisoning/ Food Additives/Toxicity/ Food Contamination/ Food Poisoning/ Food Preservatives/Poisoning/ Food Preservatives/Toxicity/ Public Health Administration/ Statistics/ Herbicides/ Pest Control/ Pesticides

Jacoby, P. W., Slosser, J. E., and Meadors, C. H. (1983). Vegetational responses following control of sand shinnery oak with tebuthiuron. Journal of Range Management. Vol. 36, no. 4, pp. 510-512. 1983.
Chem Codes: Chemical of Concern: DZ Rejection Code: NO COC.

ISSN: 0022-409X

Descriptors: chemical control
Descriptors: vegetation patterns
Descriptors: Quercus havardii
Abstract: Tebuthiuron (N-(5-1,1-dimethylethyl)-1,3,4-thia-diazol-2-yl)-N,N'-dimethylurea ) pellets were applied aerially in April 1979 at rates of 0.5 and 1.0 kg ai./ha to rangelands supporting a uniform stand of sand shinnery oak (Quercus havardii Rybd.) near Andrews (Texas). Tebuthiuron pellets were applied at 1.1 kg ai/ha to a second location near Jayton, Texas, in March 1980. Sand shinnery oak was significantly reduced in treated plots at both locations. Yield of annual and perennial grasses were significantly greater and those of forbs significantly less on tebuthiuron-treated plots at Andrews. Untreated plots at Andrews had more bare soil than those treated with tebuthiuron after 18 and 30 months. Grass yields at the Jayton site were greater, although no significant differences occurred with forb yields.
Language: English
English
Publication Type: Journal Article
Classification: D 04700 Management
Subfile: Ecology Abstracts

JAMAL GA (1997). NEUROLOGICAL SYNDROMES OF ORGANOPHOSPHORUS COMPOUNDS. ADVERSE DRUG REACTIONS AND TOXICOLOGICAL REVIEWS; 16 133-170.

Chem Codes: Chemical of Concern: DZ Rejection Code: REVIEW.

BIOSIS COPYRIGHT: BIOL ABS. RRM LITERATURE REVIEW TOXICOLOGY ORGANOPHOSPHORUS COMPOUNDS NEUROLOGICAL SYNDROMES JITTER NERVE CONDUCTION NEUROMUSCULAR JUNCTION INSECTICIDES EVOKED POTENTIALS COGNITIVE DYSFUNCTION NERVOUS SYSTEM TOXICITY NERVOUS SYSTEM DISEASE NERVOUS SYSTEM Diagnosis/ Nervous System/ Pharmacology/ Poisoning/ Animals, Laboratory

James, D. G. (2003). Pesticide Susceptibility of Two Coccinellids (Stethorus punctum picipes and Harmonia axyridis) Important in Biological Control of Mites and Aphids in Washington Hops. Biocontrol Sci.Technol. 13: 253-259.

EcoReference No.: 76934

Chemical of Concern: CPY,MLN,PSM,DZ,DMT,CBL,PIM,MOM,ES,IMC,TMX,BFT; Habitat: T; Effect Codes: MOR; Rejection Code: TARGET(BFT,DZ).

James, D. G. and Rayner, M. (1995). Toxicity of Viticultural Pesticides to the Predatory Mites Amblyseius victoriensis and Typhlodromus doreenae. Plant Prot.Q. 10: 99-102.

EcoReference No.: 67984

Chemical of Concern: CaPS,BMY,CBD,CTN,MZB,FRM,IPD,MLX,Cu,PCZ,TDM,VCZ,Zineb,Ziram,CuOH,AZ,CBL,CPY,DZ,DMT,ES,MLN,MDT,DCF; Habitat: T; Effect Codes: MOR; Rejection Code: LITE EVAL CODED(CaPS),OK(ALL CHEMS),OK TARGET(DZ).

James, P. J., Mitchell, H. K., Cockrum, K. S., and Ancell, P. M. C. (1994). Controlled release insecticide devices for protection of sheep against head strike caused by Lucilia cuprina. Veterinary Parasitology 52: 113-128.

Chem Codes: Chemical of Concern: DZ Rejection Code: MIXTURE.

The effectiveness of polymer matrix tags containing (w/w) 8.5% cypermethrin, 7.5% flucythrinate, 13.7% tetrachlorvinphos or 20.0% diazinon in protecting sheep against head strike by the sheep blowfly (Lucilia cuprina Wiedemann) was investigated in larval implant, fly cage and field studies.Tags impregnated with cypermethrin reduced the total number of egg masses deposited on the heads of sheep in fly cage studies over a 6 week period by 73.3% compared with no treatment. Tags impregnated with flucythrinate reduced the number of egg masses by 25.3% over 21 weeks but there were no significant differences (P L. cuprina larvae by either cypermethrin or flucythrinate tags.Tags impregnated with diazinon gave longer protection than treatment with a liquid formulation containing 400 ppm diazinon in larval implant, fly cage and field studies. Over a 12 week period in field studies, 6.6% of rams treated with diazinon tags became struck compared with 30% treated by diazinon jetting 35.7% treated with plastic tags not impregnated with insecticide and 24.2% of untreated rams. When the rams were exposed to high populations of L. cuprina in an exposure house from 13 to 18 weeks after treatment, 3.3% of rams treated with diazinon tags, 57.1% treated by diazinon jetting, 43.8% treated with plastic tags and 23.5% of untreated rams became struck. Most strikes in the diazinon tagged sheep occurred at sites which were not contacted by the tags. Tags impregnated with tetrachlorvinphos reduced the number of strikes in comparison with no treatment in larval implant and fly cage studies but the results were inconsistent and not as good as those from diazinon tags.It is concluded that well designed controlled release devices that reliably contact the wool on the heads of sheep at sites of flystrike risk and which are able to withstand damage from rams fighting may be able to give prolonged protection against head strike. Lucilia cuprina/ Sheep-Arthropoda/ Controlled release technology/ Head strike/ Cypermethrin/ Flucythrinate/ Tetrachlorvinphos/ Diazinon/ Control methods-Arthropoda

Jamnback, H. and Frempong-Boadu, J. (1966). Testing Blackfly Larvicides in the Laboratory and in Streams. Bull.W.H.O. 34: 405-421.

EcoReference No.: 2837

Chemical of Concern: CBL,CPY,DMT,DZ,MDT,Naled,ATN; Habitat: A; Effect Codes: BEH,POP; Rejection Code: NO ENDPOINT(ALL CHEMS).

Jeffery, John C., Liard, Davina J., and Ward, Michael D. ( A very strong metal-metal interaction in a dinuclear ruthenium(II) complex with the dianion of 2,3-dihydroxy-but-2-enal as a compartmental bridging ligand. Inorganica Chimica Acta 251: 9-12.

Chem Codes: Chemical of Concern: DZ Rejection Code: METHODS.

An unexpected reaction between [Ru(bipy)2Cl2] (bipy=2,2′-bipyridine) and ethylene glycol at high temperatures affords the dinuclear complex [{Ru(bipy)2}2([mu]-C4H4O3)][PF6]2 (1), in which the compartmental bridging ligand is the dianon of 2,3-dihydroxy-but-2-enal. Electrochemical and spectroscopic properties indicate a very strong electronic interaction between the metals across the delocalised bridge, with a 0.77 V separation between the Ru(II)/Ru(III) couples and a strong near-IR transition ([lambda]max=1210 nm; [epsilon]=5000 dm3 mol-1 cm-1) in the mixed-valence state. Crystal structures/ Metal-metal interaction/ Ruthenium complexes/ Compartmental ligand complexes/ Dinuclear complexes

Jenkins, D., Klein, S. A., Yang, M. S., Wagenet, R. J., and Biggar, J. W. (1978). The Accumulation, Translocation and Degradation of Biocides at Land Wastewater Disposal Sites: the Fate of Malathion, Carbaryl, Diazinon and 2,4-D Butoxyethyl Ester. Water Res. 12: 713-723.
Chem Codes: Chemical of Concern: CBL,MLN,DZ Rejection Code: NO SPECIES.

Jenkins, David, Klein, Stephen A., Yang, M. S., Wagenet, R. J., and Biggar, James W. (1978). The accumulation, translocation and degradation of biocides at land wastewater disposal sites: the fate of malathion, carbaryl, diazinon and 2,4-D butoxyethyl ester. Water Research 12: 713-723.

Chem Codes: Chemical of Concern: DZ Rejection Code: FATE.

Waste disposal on the land has been practiced since pre-Biblical times and the capacity of the land to purify wastewater has often been demonstrated. It is, however, necessary to examine the large-scale and widespread use of land wastewater disposal in the context of current regulatory attitudes, for its effect on both the land, the water quality of adjacent or underlying waters, and for associated risks (public health or otherwise). This research addresses the specific problem of translocation and accumulation of biocides during the spray irrigation of wastewater.

Jensen, I. H. and Bile, N. (1993). Scientific and Technical Work. 6. Flies. Dan.Pest Infest.Lab.Annu.Rep. 1992: 36-85.
Chem Codes: EcoReference No.: 70762
Chemical of Concern: DDT,HCCH,DZ,MTPN,PPB,ATN,DMT,MOM,CYP,DFT,PPC,BDL,BRSM,TVP,BDF Rejection Code: ABSTRACT/REVIEW.

Jensen, I. H. and Bile, N. (1994). Scientific and Technical Work. 6. Flies. Dan.Pest Infest.Lab.Annu.Rep. 1993: 35-74.

Chem Codes: EcoReference No.: 70763
Chemical of Concern: DDT,HCCH,DZ,PPB,ATN,DMT,MOM,CLC,BDL,CYP,MTPN,TVP,BRSM,BDF Rejection Code: ABSTRACT/REVIEW.

Jensen, I. H. and Bile, N. (1995). Scientific and Technical Work. 6. Flies. Dan.Pest Infest.Lab.Annu.Rep. 1994: 35-80.

Chem Codes: EcoReference No.: 70764
Chemical of Concern: DDT,HCCH,DZ,PPB,ATN,MOM,BDL,CLC,BRSM,MTPN,BDF,BDL,TVP Rejection Code: REVIEW.

Jensen, I. H. and Bile, N. (1996). Scientific and Technical Work. 6. Flies. Dan.Pest Infest.Lab.Annu.Rep. 1995: 37-71.

Chem Codes: EcoReference No.: 70761
Chemical of Concern: DDT,HCCH,DZ Rejection Code: REVIEW.

JENSEN IH and BILE, N. (1996). DANISH PEST INFESTATION LABORATORY ANNUAL REPORT 1995. DANISH PEST INFESTATION LABORATORY ANNUAL REPORT; 1995 I-II, 1-85.

Chem Codes: Chemical of Concern: DZ Rejection Code: REVIEW.

BIOSIS COPYRIGHT: BIOL ABS. RRM ANNUAL REPORT CHECKLIST ANNUAL REPORT INSECT PESTS RODENT PESTS STORED PRODUCTS PESTS PESTICIDES EFFICACY PEST MANAGEMENT AGRICULTURE GOVERNMENT AND LAW NATIONAL AGENCY OF ENVIRONMENTAL PROTECTION DANISH PEST INFESTATION LABORATORY DENMARK EUROPE Legislation/ Organization and Administration/ Biology/ Plants/Growth & Development/ Soil/ Herbicides/ Pest Control/ Pesticides

Jeong, T. a. e. Cheon, Jordan, S. D., Matulka, R. A., Stanulis, E. D., Kaminski, E. J., and Holsapple, M. P. *. (1995). Role of metabolism by esterase and cytochrome P-450 in cocaine-induced suppression of the antibody response. Journal of Pharmacology and Experimental Therapeutics [J. PHARMACOL. EXP. THER.]. Vol. 272, no. 1, pp. 407-416. 1995.
Chem Codes: Chemical of Concern: DZ Rejection Code: MIXTURE.

ISSN: 0022-3565

Descriptors: immune response (humoral)
Descriptors: immunosuppression
Descriptors: antibody response
Abstract: To investigate the role of metabolism in cocaine-induced immunosuppression, diazinon and beta -ionone were administered as an esterase inhibitor and a cytochrome P-450 (P-450) inducer, respectively, to B6C3F1 female mice. When 10 or 30 mg/kg of diazinon was administered 30 min before cocaine (30 mg/kg) was administered i.p. for 7 consecutive days, the suppression of the T-dependent antibody response to sheep red blood cells was potentiated greatly when compared to the suppression by cocaine alone. Spleen and thymus weights were decreased significantly and serum glutamate-pyruvate transaminase activities were elevated dramatically when cocaine and diazinon were administered together. beta -Ionone was administered s.c. for 7 consecutive days and the P-450 activities were determined 3 days after the last administration. beta -Ionone induced cocaine N-demethylation, which is the first step in the activation of cocaine to the metabolites capable of producing hepatotoxicity, as well as P-450IA1- and P-450IIB1-specific monooxygenases. The inductive effects of beta -ionone on P-450IA1/2 and P-450IIB1/2 proteins were confirmed by using Western immunoblotting with selective monoclonal antibodies. In addition, when beta -ionone (600 mg/kg) was administered with cocaine for 7 days, the suppression of the antibody response was potentiated greatly, thymus weight was decreased significantly and serum glutamate-pyruvate transaminase was elevated. Our present results suggest that inhibition of the esterase pathway of cocaine shunts the metabolism of cocaine into an immunotoxic pathway, and that the metabolism of cocaine by P-450 may be the critical pathway for the generation of the metabolites capable of suppressing the antibody response.