Metabolism and Placental Transfer of Stereoisomers of Tetramethrin Isomers in Pregnant Rats

Abstract

isomers labeled with 14C in the acid moiety to 13-day pregnant rats at 300 mg/kg, the radiocarbon was rapidly eliminated into the urine and feces, and almost completely recovered within 7 days. The 14C tissue residue levels were very low with the four labeled preparations. The major metabolic reactions for the four isomers were cleavage of the ester linkage and oxidation at the isobutenyl group of the acid moiety. The traps isomers underwent ester cleavage to larger extents than the cis isomers. There were no significant differences in the 14C excretion, 14C tissue residue levels and the nature and amounts of metabolites between the [1 R]-and [1 RS]-traps isomers. The absorption in the gastrointestine, however, seemed to differ between the [1 R, cis]-and [1 RS, cis]-isomers, although once entering into the blood stream, the [1 R]-and [1 RS]-cis isomers appeared to receive the same matabolic fates. When 13-day pregnant rats were treated with single or 5 consecutive daily oral administrations of each of 14C-Neopynamin® (1 RS, traps/cis, 8/2) and Neopynamin Forte® (1 R, traps/ cis, 8/2) preparations labeled with 14C in the acid moiety at 300 mg/kg or 300 mg/kg/day, the radiocarbon transferred to the fetus were less than 0.004% of the dose and there were no significant differences in the 14C levels and the transfer ratio (14C tissue levels/14C maternal blood) for the fetus between the two preparations.Moreover, the major metabolites in the fetus and maternal blood with the two preparations were the same, and identified as chrysanthemic acids and their hydroxymethyl or carboxylic acid derivatives.

Metabolism of (Z)-(1R,3R)-Profluthrin in Rats

“…In urine and feces, 55% to 58% of dosed 14 C was excreted as ester-cleaved metabolites, while 1% to 12% (not including unchanged ( Z )-(1 R ,3 R )-profluthrin in feces) was confirmed to be ester-retaining. As we indicated above, the existence or nonexistence of cyano moiety on its α-position of the alcohol side and the stereochemical conformations of the 1- and 3-positions of cyclopropane can affect the ratio of ester linkage-retained metabolites. ,,− Since ( Z )-(1 R ,3 R )-profluthrin does not have cyano moiety on its α-position of the alcohol side and its steric conformation about the substituent of 1- and 3-cyclopropane is trans , it was supposed to be easily hydrolyzed. Actually, the amount of ester metabolites in excreta was between 1 and 16%, relatively low, and thus in agreement with the known rules for pyrethroid metabolism.…”

“…There are many pyrethroids with chrysanthemic acid as an acid moiety, i.e., tetramethrin, phenothrin, cyphenothrin, empenthrin, and allethrin. The metabolic fate of chrysanthemic acid is well characterized. − In short, the ω-position of chrysanthemic acid is oxidized to alcohol and carboxylic acid, and/or conjugated to glucuronide, and rapidly excreted mainly in urine. These previous reports, including the metabolism of chrysanthemic acid, provide sufficient basis on which to estimate the metabolic pathways of the acid side of ( Z )-(1 R ,3 R )-profluthrin; however, further experimentation with acid side labeled ( Z )-(1 R ,3 R )-profluthrin or other compound that has the same substructure is considered to be prudent to elucidate the whole metabolic fate of ( Z )-(1 R ,3 R )-profluthrin.…”

“…It has also been revealed that the stereochemical conformations of 1and 3-positions of the cyclopropane ring can affect the efficiency of esterase, and the trans isomers generally cleave more easily than the cis isomers. 7,8 Profluthrin does not have a cyano group on its α-position of the alcohol moiety and thus can be regarded as a type I pyrethroid. Since it has a unique alcohol moiety, it evokes our interest to clarify the metabolic features.…”

“…Conventional synthetic pyrethroids such as tetramethrin, phenothrin, cyphenothrin, empenthrin, cypermethrin, and allethrin are easily cleaved at the ester linkage followed by oxidation and conjugation with glucuronic acid. ,, The rate of ester cleavage is lower for the type II pyrethroids such as cyphenothrin and cypermethrin, which consist of secondary alcohol with cyano group on its α-position, than for the type I pyrethroids such as tetramethrin and phenothrin, which consist of primary alcohol, ,, probably due to the difference of accessibility of esterase to the target site. It has also been revealed that the stereochemical conformations of 1- and 3-positions of the cyclopropane ring can affect the efficiency of esterase, and the trans isomers generally cleave more easily than the cis isomers. , Profluthrin does not have a cyano group on its α-position of the alcohol moiety and thus can be regarded as a type I pyrethroid. Since it has a unique alcohol moiety, it evokes our interest to clarify the metabolic features.…”

Bioconcentration and metabolism of <i>trans</i>-tetramethrin in fish

“…[18][19][20][21][22][23][24][25][26] These circumstances suggest that for its bioconcentration in fish as well as its metabolism behavior, tetramethrin is one of the most suitable pyrethroids to have been investigated in detail. In order to obtain the relevant information of I on metabolism and bioconcentration in fish, we have conducted an in vivo fish study using 1RS-trans isomers of I (trans-I).…”