Nitrophenyl Ether Research Articles

Bifenox induces programmed cell death in bovine mammary epithelial cells by impairing calcium homeostasis, triggering ER stress, and altering the signaling cascades of PI3K/AKT and MAPK

Bifenox (methyl 5-(2,4-dichlorophenoxy)-2-nitrobenzoate), a nitrophenyl ether herbicide, was first introduced in the 1980s to control broadleaf weeds. As a result of its wide and frequent application in diverse agricultural settings and reports on residual traces, potential adverse effects of bifenox have been studied extensively in rat hepatocytes, bovine peripheral lymphocytes, and mice. Despite the reported risks of bifenox exposure in dairy cows, the toxicity of bifenox on bovine lactation system has not been extensively investigated. Therefore, we used bovine mammary epithelial (MAC-T) cells to study the toxic effects of bifenox on mammary glands. We found that bifenox inhibited MAC-T cells proliferation and disturbed the cell cycle, especially in the sub-G1 and G1 phases. Bifenox also disrupted the calcium homeostasis within the cell and impaired mitochondrial membrane potential. We also examined phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling cascades. The findings indicated hyperactivation of phosphorylated protein kinase B (AKT), p70 ribosomal S6 kinase (p70S6K), S6, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and c-Jun, as well as endoplasmic reticulum (ER) stress caused by bifenox treatment. In conclusion, based on our in vitro study employing MAC-T cells, we report that bifenox can induce damage to the bovine mammary glands, potentially impacting milk production.

Preparation of new polymeric phases for thin-film liquid phase microextraction (TF-LPME) of selected organic pollutants

Thin films made of a polymer (cellulose triacetate, CTA) and a plasticizer have been studied as novel sorptive phases for chlorpyrifos, triclosan and tonalide. The preparation is reproducible and only requires the plasticizer to be added into an organic dispersion containing CTA. The evaporation of the solvent leaves an easy to manipulate continuous and homogeneous thin film, which has been investigated in terms of both composition and extraction efficiency for the different compounds. Six different plasticizers (namely dibutyl sebacate, bis(2-ethylhexyl) sebacate, bis(2-ethylhexyl) phthalate, bis(1-butylpentyl) adipate, 2-nitrophenyl octyl ether and 2-fluorophenyl 2- nitrophenyl ether) with different chemical structure and physical properties, such as lipophilicity, dielectric constant and viscosity, have been incorporated in the CTA matrix and the resulting polymeric membranes have been characterized by different techniques (scanning electron microscopy, thermal techniques, and contact angle). Preliminary tests were undertaken in 0.01 M NaCl solution enriched with 100 μg L-1 of each analyte to study the kinetics and efficiency of extraction. All analytes were effectively extracted after 6 h with all the polymeric phases, with different kinetics. Among the different elutants tested, ethyl acetate provided satisfactory recovery values. The membrane made of CTA and dibutyl sebacate has been selected and successfully applied for the microextraction of pollutants in simulated natural water, river water and a wastewater effluent with trace concentrations added (0.2–2 μg L-1) before GC–MS determination. The overall method is easy to perform and provides good reproducibility (RSD < 10%) and recoveries higher than 80%.

In-vitro assessment of the binding mechanism of oxyfluorfen (herbicide) with garlic phytocystatin: multi-spectroscopic and isothermal titration calorimetric study

Oxyfluorfen (2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene) is a nitrophenyl ether herbicide. Phytocystatins are crucial plant proteins which regulate various physiological processes and are also responsible for maintaining protease–antiprotease balance within plants. Thus, the present article deciphers the interaction of oxyfluorfen with garlic phytocystatin (GPC) through various spectroscopic and calorimetric techniques. The cysteine proteinase inhibitory assay was done to assess the inhibitory action of GPC in the presence of oxyfluorfen. The GPC loses its inhibitory activity in the presence of oxyfluorfen. The complex formation of GPC-oxyfluorfen was shown by UV absorption spectroscopy. The intrinsic fluorescence experiment affirmed the quenching of GPC in the presence of oxyfluorfen. The Stern–Volmer quenching constant and binding constant was obtained as 6.89 × 103 M−1 and 9.72 × 103 M−1, respectively. Synchronous fluorescence showed the alteration in the microenvironment around tyrosine residues. 3D fluorescence suggested the perturbation in the polarity around aromatic residues. The isothermal titration experiment suggests that the interaction of oxyfluorfen with GPC is a thermodynamically favorable reaction. Secondary structure alteration of GPC in the presence of oxyfluorfen was studied by circular dichroism (CD). The CD result showed a reduction in the α-helical content of GPC on interaction with oxyfluorfen. Consequently, all these outcomes affirmed the formation of GPC–oxyfluorfen complex along with the structural and conformational alteration. This study identifies and signifies that the exposure of oxyfluorfen induces stress within the plant system.Communicated by Ramaswamy H. Sarma

Potentiometric Response Characteristics of Membrane-BasedCs+-Selective Electrodes Containing Ionophore-Functionalized Polymeric Microspheres

Cs+-selective solvent polymeric membrane-based ion-selective electrodes (ISEs) were developed by doping ethylene glycol-functionalized cross-linked polystyrene microspheres (P-EG) into a plasticized poly(vinyl chloride) (PVC) matrix containing sodium tetrakis-(3,5-bis(trifluoromethyl)phenyl) borate (TFPB) as the ion exchanger. A systematic study examining the effects of the membrane plasticizers bis(2-ethylhexyl) sebacate (DOS), 2-nitrophenyl octyl ether (NPOE), and 2-fluorophenyl nitrophenyl ether (FPNPE) on the potentiometric response and selectivity of the corresponding electrodes was performed. Under certain conditions, P-EG-based ion-selective electrodes (ISEs) containing TFPB and plasticized with NPOE exhibited a super-Nernstian response between1×10−3and1×10−4 M Cs+, a response characteristic not observed in analogous membranes plasticized with either DOS or FPNPE. Additionally, the performance of P-EG-based ISEs was compared to electrodes based on two mobile ionophores, a neutral lipophilic ethylene glycol derivative (ethylene glycol monooctadecyl ether (U-EG)) and a charged metallacarborane ionophore, sodium bis(dicarbollyl)cobaltate(III) (CC). In general, P-EG-based electrodes plasticized with FPNPE yielded the best performance, with a linear range from 10-1–10-5 M Cs+, a conventional lower detection limit of8.1×10−6 M Cs+, and a response slope of 57.7 mV/decade. The pH response of P-EG ISEs containing TFPB was evaluated for membranes plasticized with either NPOE or FPNPE. In both cases, the electrodes remained stable throughout the pH range 3–12, with only slight proton interference observed below pH 3.

Facilitated transport of copper(II) across supported liquid membrane and polymeric plasticized membrane containing 3-phenyl-4-benzoylisoxazol-5-one as carrier

The potential of 3-phenyl-4-benzoylisoxazol-5-one (HPBI) as metal extractant has been evaluated for the first time for Cu(II) transport from aqueous nitrate solutions by supported liquid membrane (SLM) in the solvents chloroform, 2-nitro phenyl octyl ether (NPOE) and dodecyl nitro phenyl ether (DNPE). The efficiency of the membrane transport was optimized as a function of pH, temperature, aqueous phases and membrane composition. It follows the sequence CHCl 3 > DNPE > NPOE. The results suggested that the transport mechanism was mainly controlled by the diffusion of the Cu(PBI) 2 complex in the membrane core. A comparative investigation of Cu(II) transport ions has been made between SLM and polymeric plasticized membrane (PPM), containing HPBI with NPOE and DNPE as organic solvents or plasticizers in order to evaluate the feasibility of PPM with HPBI.

Temporal trends and sources of PCDD/Fs, pentachlorophenol and chlornitrofen in paddy field soils along the Yoneshiro River basin, Japan

In order to understand the long-term behaviors of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), pentachlorophenol (PCP), and 2,4,6-trichlorophenyl-4'-nitrophenyl ether (chlornitrofen, CNP) in paddy soil, we measured their concentrations in paddy soil samples collected in 1982 and 1984 (1980s) and in 2000 and 2002 (2000s) from the Yoneshiro River basin, Japan. The concentrations of PCP and CNP decreased from the 1980s to the 2000s, whereas the concentrations of PCDD/Fs and their toxic equivalency (WHO2006-TEQ) remained. The major sources of PCDD/Fs in the paddy soil samples were attributed to impurities in PCP and CNP as a result of comparisons of homologue and congener profiles and principal component analysis. Based on the results of comparison of total input and remaining amount, it is estimated that more than 99% of PCP and CNP applied to the paddy fields had disappeared, whereas most of the applied PCDD/Fs and TEQ remained.

Selective photoreduction of nitrophenyl ethers by amines in ternary β-cyclodextrin complexes. A spectroscopic and mechanistic studyDedicated to Professor Frank Wilkinson on the occasion of his retirement.

The photoreduction of nitrophenyl ethers by amines has been studied in aqueous solution in the presence of β-cyclodextrin (β-CD), and in ternary β-cyclodextrin complexes in the solid state. NMR (NOESY) and induced circular dichroism (ICD) studies in solution suggest the operation of a cooperative effect by the amine in the complexation of the nitrophenyl ether by the β-CD, evidencing the existence of interactions between complementary groups that govern the structure of the ternary complexes. Irradiation of the solutions shows an inhibitory effect of the β-CD, together with a significant increase in the chimioselectivity of the photoreaction. This tendency is confirmed by irradiation of the solid ternary complexes that show a complete selectivity, only producing the nitroso derivative. A time-resolved diffuse reflectance laser flash photolysis (DRLFP) mechanistic study on the solid complexes has demonstrated that in the ternary β-CD complexes, the evolution of the first transient (assigned to the triplet excited state of the nitrophenyl ether) is completely different than in solution or in mechanical cellulose mixtures, this approach being a very valuable tool to investigate bimolecular photoinduced reactions difficult to study in solution due to the existence of other competitive processes.

Dioxin and dioxin-like PCB impurities in some Japanese agrochemical formulations

The profile and amount of dioxin impurity in agrochemicals were studied through detailed analysis of historic Japanese formulations. The chemicals analyzed include pentachlorophenol (PCP), 2,4,6-trichlorophenyl-4 ′-nitrophenyl ether (chloronitrofen, CNP), 2,4-dichlorophenyl-4 ′-nitrophenyl ether (nitrofen, NIP), tetrachloro-iso-phthalonitrile (chlorothalonil, TPN), 2-methyl-4-chloro-phenoxyacetic acid (MCP) and 2,4-dichlorophenoxyacetic acid (2,4-D). Among the six, two herbicides, PCP and CNP, produced during the 1960s and 1970s, contained very high concentrations of PCDD/DFs and TEQ. Others contained relatively low concentrations of PCDD/DFs. Dioxin-like PCB concentrations in all chemicals studied were low and their contributions to TEQ were negligible. The total dioxin emissions from the use of agrochemicals in Japan during the past 40 years (1955–1995) were estimated to be about a few hundred thousand kg of PCDD/DFs and 250 kg of WHO-TEQ from PCP and 190×10 3 kg of PCDD/DFs and 440 kg of WHO-TEQ from CNP. The major dioxin congeners present in PCP formulations were highly chlorinated PCDD/DFs that can be formed by the coupling of PCP and/or 2,3,4,6-tetrachlorophenol, and those in the CNP formulations were tetra- to hexa-chlorinated PCDD/DFs that can be formed from 2,4,6-trichlorophenol and/or 2,3,4,6-tetrachlorophenol.

Maternal and developmental toxicity of halogenated 4′‐nitrodiphenyl ethers in mice

In an ongoing effort to delineate structure-activity relationships in the developmental toxicity of diphenyl ethers, we evaluated the maternal and developmental toxicity of 10 diphenyl ethers related to the herbicide nitrofen. All possible trichlorophenyl 4′-nitrophenyl ethers were evaluated, as were the 2,4-difluorophenyl and 2,4-dibromophenyl 4′-nitrophenyl ethers. We also evaluated bifenox and chlomethoxyfen, which are 2,4-dichlorophenyl congeners with meta-substituents on the 4′-nitrophenyl ring. Nitrofen (2,4-dichlorophenyl 4′-nitrophenyl ether) was included for comparison. Identity of the halogen affected the postnatal (but not prenatal) mortality induced by 2,4-dihalogenated 4′-nitrophenyl ethers. The presence of 3′-substituents on the 4′-nitrophenyl ring reduced both pre- and postnatal toxicity of 2,4-dichlorinated congeners. Among chlorinated 4′-nitrophenyl congeners without meta-substituents on the nitrophenyl ring, the position of chlorine substituents strongly affected the congener's potential for inducing prenatal vs. postnatal syndromes. All congeners increased liver to body weight ratios in unmated females, but such increases were not well-correlated with either prenatal or postnatal embryotoxicity. Teratology 59:69–80, 1999. © 1999 Wiley-Liss, Inc.

On the selection of the optimal plasticizer for calix[n]arene-based ion-selective electrodes: Possible correlation between the ion selectivity and the ?softness? of the plasticizer

A criterion for the selection of a suitable plasticizer for calix[n]arene-based ion-selective electrodes is discussed. The cation selectivity of plasticized membranes without the ligand was first measured as a reference. The membranes can be roughly classified into two groups. The first group shows cation selectivity in the order Cs+ K+>Na+>Li+. The membranes in the second group are made of phosphorus plasticizers, which show a selectivity in the reverse order. The plasticizers in the first group featured a linear relationship between the dipole moment of the plasticizer (calculated by a PM3 method) and the ratio of cesium selectivity to lithium selectivity. The linear relationship supports the view that the polar membrane which includes a ‘soft’ plasticizer with a large dipole moment shows selectivity for Cs+, whereas the nonpolar membrane including the ‘soft’ plasticizer with the small dipole moment shows much lower selectivity for Cs+. Next, 2-fluorphenyl-2′-nitrophenyl ether (FPNPE) which showed the highest Cs+ selectivity and tris(2-ethylhexyl)phosphate (TEHP) which showed the highest Li+ selectivity were mixed in an appropriate ratio to make membranes with a different affinity for ‘hard’ ions. The metal selectivities of several crown-based and calixarene-based ionophores were examined in these membranes. Although a few exceptions exist, the polar ‘soft’ membrane is favorable when the interfering metal ion is ‘hard”, whereas the ‘hard’ membrane is favorable when the interfering metal ion is ‘soft’.

Chronic effects of waterborne or dietary exposure to a herbicide, chlornitrofen (2,4,6-trichlorophenyl-4′-nitrophenyl ether), on reproduction of Polypedilum nubifer (Chironomidae)

Chronic effects of waterborne or dietary chlornitrofen (CNP) on the respective developmental stages of a chironomid ( Polypedilum nubifer), from hatching to emergence, and the oviposition and hatchability of its eggs, were assessed using a flowthrough aquarium. Two egg clusters, each composed of c. 500 eggs, were introduced into the aquarium. The start of emergence was delayed from one to several days as the concentration of CNP in water or food was raised. The percentage emergence success was 65, 47, 48 and 13% for control, 30, 60 and 90 μg 1 −1 CNP, respectively. The oviposition success and the hatchability of oviposited eggs decreased to about 50% of the control in midges exposed to 90 μg 1 −1 CNP, although there was no significant effect at the other concentrations. Food for the midge larvae containing 50, 160 or 560 μg CNP g −1 (wet wt) was prepared. The CNP concentration in the food did not decrease more than 30% of the initial concentration for 2 days even in the flowthrough aquaria. The emergence success was 55, 55, 40 and 22% when the midges consumed the control food and food containing 50, 160 and 560 μg CNP g −1 (wet wt), respectively. The oviposition success also decreased according to increasing CNP concentration of the food. The hatchability of oviposited eggs decreased to 0.19 at the maximum CNP concentration in the food, compared with a value of 0.67 for the control food. It is suggested that reproduction of chironomids is impaired by CNP in the food as well as that in the surrounding water, when the CNP concentration in the bottom substrate exceeds the 500 μg g −1 (wet wt).

Mechanism of Selectivity of Diphenyl Ether Herbicides Oxyfluorfen and Chlomethoxynil in Several Plants.

Selectivity mechanisms of diphenyl ether herbicide oxyfluorfen ((2-chloro-4-trifluoromethylphenyl)-3′-ethoxy-4′-nitro-phenyl ether) and chlomethoxynil (2, 4-dichlo-rophenyl-3′-methoxy-4′-nitrophenyl ether) in rice (Oryza sativa L.), barnyardgrass (Echinochloa oryzicola Vasing.), sorghum (Sorghum bicolar Moench), corn (Zea mays L.), tomato (Lycopersicon esculentum Mill), cabbage (Brassica oleracea L.), radish (Raphanus sativus L.), cucumber (Cucumis sativus L.), and buckwheat (Fiagopyrum esculentum Moench) were studied. Oxyfluorfen showed higher herbicidal activity to the plants than chlomethoxynil, and the plants absorbed more of the former. However, they metabolized 14C-chlomethoxynil more rapidly than 14C-oxyfluorfen. This greater absorption and lower metabolism of oxyfluorfen by the plants are considered main factors of its higher phytotoxicity.In oxyfluorfen treatment, rice and corn were more tolerant and absorbed less of the herbicide than other plants. Tomato showed very severe damage and had the highest absorption rate. Degradation of 14C-oxyfluorfen in the plants was very limited. Absorption of oxyfluorfen by the plants is thus possibly one factor of its selectivity.In chlomethoxynil treatment, rice and corn were more tolerant than other plants and showed the lowest absorption rate. Metabolism of 14C-chlomethoxynil was greatest in rice plants. Rates of absorption and metabolic activity of chlomethoxynil in these plants are considered to relate to its selectivity.

Accumulation, excretion and metabolism of 2,4,6-trichlorophenyl-4′-nitrophenyl ether by carp

1. 1. The bioconcentration factors (BCF) of 2,4,6-trichlorophenyl-4′-nitrophenyl ether (CNP) in carp were 334 ± 13 (mean ± SD, n = 3) for muscle, 542 for liver, 862 for kidney and 547 for gallbladder after 14 days exposure. 2. 2. The excretion rate constants ( k) of CNP by carp were 0.12 day −1 for muscle, 0.11 day −1 for liver, 0.28 day −1 for kidney and 0.14 day −1 for gallbladder assuming their processes to be first-order kinetics. 3. 3. 2,4,6-Trichlorophenyl-4′-aminophenyl ether (CNP-amino), 2,4,6-trichlorophenyl-4′-acetamide phenyl ether (CNP-acetamide) and 2,4,6-trichlorophenyl-4′-formamide phenyl ether (CNP-formamide) were detected as metabolites of CNP in muscle and viscera of carp.

Relative developmental toxicities of nine diphenyl ethers related to nitrofen

Outbred Swiss mice (Mus musculus) were treated with 2,3-dichlorophenyl 4′-nitrophenyl ether (23-DCN), 2,5-dichlorophenyl 4′-nitrophenyl ether (25-DCN), 2,6-dichlorophenyl 4′-nitrophenyl ether (26-DCN), 3,4-dichlorophenyl 4′-nitrophenyl ether (34-DCN), 3,5-dichlorophenyl 4′-nitrophenyl ether (35-DCN), 2,4,5-trichlorophenyl 4′-nitrophenyl ether (245-TCN), 2,4,6-trichlorophenyl 4′-nitrophenyl ether (CNP), 3-chlorophenyl 4′-nitrophenyl ether (3-MCN) or phenyl 4-bromophenyl ether (4-BR) at dosages that are highly teratogenic when the known teratogen nitrofen (2,4-dichlorophenyl 4′-nitrophenyl ether) is administered. The Chernoff/Kavlock screen was used to assess both prenatal and postnatal toxicity; in addition, effects of each chemical on Harderian glands were evaluated. The monochlorinated analogs and the five dichlorinated nitrofen analogs were inactive at the doses given. 4-BR was inactive at levels of up to 1,000 mg/kg/d. The trichlorinated analogs caused missing Harderian glands in pups exposed to 10 or 20 mg/kg/d 245-TCN, 50 or 100 mg/kg/d nitrofen or 250 or 500 mg/kg/d CNP; significant perinatal mortality in litters exposed to 20 mg/kg/d 245-TCN or 100 mg/kg/d nitrofen; and a high incidence of prenatal mortality in litters exposed to 500 or 750 mg/kg/d CNP. Maternal toxicity other than decreased weight gain was not seen with any compound, even at doses that caused significant prenatal or perinatal mortality. The data demonstrate that the position of chlorine substituents, as well as the number of such substituents, is critical in determining the developmental toxicity of diphenyl ethers.

Effect of a herbicide, chlornitrofen (2,4,6-trichlorophenyl-4′-nitrophenyl ether), on the growth and reproduction of the guppy ( Poecilia reticulata) through water and food

Young guppies of 30 days old ( Poecilia reticulata) were exposed to a formulation chlornitrofen (CNP) for 28 days. A cumulative number of fry decreased to 16 and 51% of the control in the 1st and 2nd parturition at 25 μg 1 −1. Normal parturition did not occur at 125 μg 1 −1. Young guppies were exposed to 200 μg 1 −1 CNP for 1 to 7 days. Number of fry decreased to 50% of the control in the guppies exposed to formulation-CNP for 1 day, while the same effect was observed with 3-days exposure in the reagent grade (99%)-CNP. However, the CNP concentration of the guppy did not differ in either case. Guppies were exposed to CNP for 30 days through a CNP-accumulated tubifex. The number of fry decreased in accordance with the CNP concentrations of tubifex. At the maximum concentration (160 μg CNP g −1, wet wt.), a cumulative number of fry decreased to 23, 43 and 49% of the control in the 1st, 2nd and 3rd month, respectively. The CNP concentration of liver and female gonad was high. The retention time of CNP accumulated in female gonad was longer than that of liver.

Biodegradation test of herbicide CNP in river water and sediment using the modified river die-away method

The biodegradation of herbicide CNP (2,4,6-trichlorophenyl 4′-nitrophenyl ether) in river waters and sediments was evaluated using a modified river die-away method. Under the test condition of this method, the biodegradability of CNP in water was different in each region. That is, the biodegradation was rapid in polluted rivers in agricultural and urban areas, but it was slow in clean rivers on the sides of mountains. In addition, seasonal variation in the CNP biodegradation in these test samples was little, though the biodegradation of CNP had a tendency to be slightly higher in June and July, after spraying CNP, in rivers in agricultural areas. It was also suggested that the potential activity of the CNP biodegradable microbes in sediment was almost similar to that in water because of easy moving of microbes between water and sediment.

Selective inhibitory action of chlomethoxynil on rice and barnyardgrass and its molecular fate in the light and dark.

Effect of light on the mode of action of diphenyl ether herbicide chlomethoxynil (2, 4-dichloropheny 1-3′-methoxy-4′-nitrophenyl ether) was investigated in rice (Oryza sativa L.) and barnyardgrass (Echinochloa oryzicola VASING.). The herbicide showed phytotoxic activity on barnyardgrass in the light, but not in the dark. Rice plant showed no phytotoxic symptoms either in light or dark.Barnyardgrass absorbed the herbicide from shoots much faster than rice, however, a little difference in rate was observed between the light and dark in the two plants. Metabolic activity of the herbicide was much greater in rice, especially in the light, compared with only slight changes in barnyardgrass. Metabolic activity and absorption by shoots were considered factors of the selective action of the herbicide. It was found that light increased the herbicidal detoxifying activity in rice plant.

Comparative studies on additive effects of sodium dodecylbenzensulfonate and sodium stearate on uptake of chemicals by willow shiner ( Gnathopogon caerulescens)

1. 1. Comparative studies between sodium dodecylbenzenesulfonate (DBS) and sodium stearate (SNa) were performed on the additive effects of the uptake of chemicals in a fresh water fish, the willow shiner ( Gnathopogon caerulescens), by the use of a continuous flow water system. 2. 2. The chemicals selected were 2,4,6-trichlorophenyl-4′-nitrophenyl ether (CNP) as a non-polar lipophilic substance and cadmium salt (Cd) as polar hydrophilic substance. 3. 3. DBS had no promotive and depressed effects on the uptake of Cd. 4. 4. SNa had no promotive and depressed effects on the uptake of CNP and Cd.

Role of structure in diphenyl ether teratogenesis

The fetotoxicity of nitrofen and 5 analogous diphenyl ethers was compared in mice, using survival on postnatal day 5 to evaluate prenatal and perinatal toxicity. The effect of each chemical on the Harderian gland weight of surviving pups was also assessed, since decreased Harderian gland weight is seen in nitrofen-exposed pups at levels of treatment that do not cause mortality. All treatments were percutaneous. 2,4,5-Trichlorophenyl 4′-nitrophenyl ether was significantly more fetotoxic than nitrofen, but 2,4,6-trichlorophenyl 4′-nitrophenyl ether (CNP) was not fetotoxic at the doses used. Neither of the 2 monochlorinated 4′-nitrophenyl ethers nor the unchlorinated 4′-nitrophenyl ether were fetotoxic at the doses tested. Absent Harderian glands resulted only from exposure to nitrofen (71% of litters) or to 2,4,5-trichlorophenyl 4′-nitrophenyl ether (22% of litters), which were also the only compounds to decrease Harderian gland weight significantly.

Teratogenicity of bifenox and nitrofen in rodents.

The teratogenicity of the diphenyl ether herbicide bifenox [2,4-dichlorophenyl 3'-carboxymethyl-4'-nitrophenyl ether] was compared to that of nitrofen [2,4-dichlorophenyl 4'-nitrophenyl ether] in rats and in mice. Neither compound increased prenatal mortality in mice. Because nitrofen causes both malformations that are compatible with survival to weaning and a high incidence of perinatal (but not of fetal) mortality, emphasis was placed on postnatal parameters of bifenox toxicity. In rats, bifenox caused a low incidence of "bloody tears", but it did not decrease survival to term or to weaning in rats or mice, and did not reduce Harderian gland weight in mice. Because the weight of the Harderian glands is a more objective measure of their status than is the presence of an eye discharge, it is concluded that bifenox is not teratogenic at the levels administered. Nitrofen decreased litter size, pup weight, and Harderian gland weight in mice.