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PubMed1988

Identification of the hepatic cytochrome P-450 isozymes induced and decreased by picloram.

Microsomes from male rats treated with picloram (100 mg/kg/day) for 7 days showed a 48% decrease in 16 alpha-hydroxylase activity when incubated with (4-14C) androstenedione. These data are consistent with the assertion that picloram decreases the titer of hepatic male specific cytochrome P-450h. Several lines of evidence suggested that picloram is an inducer of hepatic cytochrome P-450 in male rats. First, SDS polyacrylamide gel electrophoresis revealed an intensified hepatic microsomal polypeptide (MW 54,000) following picloram pretreatment. This polypeptide co-migrated with protein bands which were correspondingly intensified after pretreatment with known inducers of cytochrome P-450d (3-methylcholanthrene and isosafrole). Second, no increase in the binding of metyrapone to picloram treated microsomes was noted compared with controls, suggesting no increase in phenobarbital-inducible forms of cytochrome P-450. Third, hepatic microsomes from picloram treated rats activated 2-amino-3-methylimidazo [4,5-f] quinoline (a cytochrome P-450d mediated catalysis) causing a 5-fold increase in the number of induced Salmonella typhimurium TA98 revertant colonies formed compared with control microsomes. Fourth, the binding of n-octylamine to hepatic microsomes from picloram-treated rats showed, like microsomes from 3-methylcholanthrene-treated rats, an increase in the proportion of high-spin cytochrome P-450 present. Cytochrome P-450d is known to be a high spin haemoprotein.

Androstenedione↗

PubMed1987

Effects of picloram on xenobiotic biotransformation in rat liver.

1. The effect of picloram on model xenobiotic substrate biotransformation in vivo was studied in female and male rat liver. 2. Treatment with picloram had little effect on epoxide hydratase and glutathione S-transferase activity, but caused a dose-dependent increase in ethoxyresorufin-O-deethylase activity and a concomitant decrease in aldrin epoxidase activity in male rats. 3. Treatment of male rats with equivalent doses of 2-acetylaminofluorene, 2-amino-anthracene and picloram induced ethoxyresorufin-O-deethylase activity to the same degree. 4. Treatment of female rats with picloram resulted in dose-dependent increases in ethoxyresorufin and ethoxycoumarin-O-deethylation without decreasing aldrin epoxidase activity. 5. Picloram binds to liver microsomal preparations from rats pretreated with phenobarbitone and/or 3-methylcholanthrene, giving a type I spectrum. 6. The results indicate that picloram is a 3-methylcholanthrene-type inducer, and the implications are discussed.

Animals↗

PubMedDate not supplied

Persistence and lateral movement of 2,4-dichlorophenoxy acetic acid and picloram on power line rights-of-way.

Soil persistence and lateral movement of 2,4-D (2,4-dichlorophenoxy acetic acid) and picloram (4-amino-3,5,6-trichloropicolinic acid) were examined following their application as a stem-foliage spray for brush control on two power line rights-of-way. Ditches to collect runoff water were located 3, 10, 20, and 30 m downslope from the treated areas. Runoff water and soil samples were collected after 0.14, 0.43, 0.57, 1, 2, 4, 7, 8, 11, 15, 16, and 48 weeks and were analyzed for picloram and 2,4-D residues. Only 3 of 85 soil samples downslope from the target areas contained residues of 2,4-D, and only 1 of 85 down slope samples contained a detectable residue of picloram. Of 56 runoff water samples, only 11 contained 2,4-D residues and only 1 contained residues of picloram. The greatest distances down-slope at which residues were detected in runoff water were 20 and 10 m for 2,4-D and picloram, respectively. No residues of either herbicide were recovered in soil or water at 15 weeks or 48 weeks after spraying. Despite normal rainfall frequency and amounts in the first several weeks after spraying in mid-June, significant runoff of either herbicide was not evident at either study site.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1990

Chronic toxicity and oncogenicity of picloram in Fischer 344 rats.

The chronic toxicity and oncogenicity of the herbicide picloram was studied in male and female Fischer 344 rats administered 0, 20, 60, or 200 mg/kg.d technical-grade picloram via their feed for 2 yr. A comprehensive set of in-life and clinical pathology parameters was measured and an extensive list of tissues was examined grossly and by light microscopy from control and treatment groups of animals. The primary treatment-related effect observed in the study was hepatocellular swelling and altered tinctorial properties in the central regions of the liver lobules of both sexes of rats ingesting 60 or 200 mg/kg.d picloram. Males were more affected than females. Increases in liver weights accompanied these changes in both sexes of rats ingesting the high dose level of picloram. All other histopathologic lesions observed were typical of those that normally occur in aged Fischer 344 rats. There were no treatment-related increases in the incidence of any particular tumor type or in total tumors. No treatment-related effects were observed in rats ingesting 20 mg/kg.d of the test material.

Animals↗

PubMed1986

Acute, 14-day repeated dosing, and 90-day subchronic toxicity studies of potassium picloram.

Potassium picloram was administered either by gavage (acute studies) or in drinking water to male and female Sprague-Dawley-derived rats (14-day and 90-day studies). The acute oral LD50 was 950 mg/kg (812-1120) for males and 686 mg/kg (599-786) for females. Depression, prostration, ataxia, tremors, and convulsions preceded death. There were no consistent biologically significant compound-related effects in rats that received 60, 190, 600 mg potassium picloram/kg/day for 14 days. In the subchronic study, rats received 60, 190, 600, or 1070 mg potassium picloram/kg/day in drinking water for 90 consecutive days. There were only 4 male and 2 female survivors out of 20 rats of each sex at the 1070 mg/kg dose and 16 male and 18 female survivors at the 600 mg/kg dose. Mortality was dose dependent. Administration of picloram appeared to exacerbate renal and hepatic lesions commonly noted in rats of this age. For example, at levels up to 1070 mg/kg mild lesions in the kidney of treated rats, especially in males at 600 mg/kg, were noted. Also noted were an increased incidence of mononuclear liver foci in male rats that received 190 and 600 mg/kg and an increased severity of mononuclear liver foci in females that received 600 mg/kg. There were no other consistent biologically significant compound-related effects. No specific organ site toxicity could be identified in these studies. Toxicity from exposure to picloram in drinking water is apparently low.

Animals↗

PubMed1985

Teratological evaluation of picloram potassium salt in rabbits.

The embryotoxic and teratogenic potential of orally administered picloram potassium salt was evaluated in New Zealand white rabbits. Artificially inseminated rabbits were given 0, 40, 200 or 400 mg picloram acid equivalent/kg body weight/day in the form of picloram potassium salt in aqueous solution on days 6 to 18 of gestation. The foetuses were removed for examination on day 29 of gestation. Transient weight loss was observed among rabbits given 200 or 400 mg/kg/day of the test material, though the total weight gain of the treated groups during gestation was comparable to that of controls. A few isolated, sporadic cases of foetal malformations were observed in the dosed groups, but there was no indication of a dose-related embryotoxic or teratogenic response to treatment.

Abnormalities, Drug-Induced↗

PubMed1991

Effects of 2,4-dichlorophenoxyacetic acid and picloram on biotransformation, peroxisomal and serum enzyme activities in channel catfish (Ictalurus punctatus).

Channel catfish (Ictalurus punctatus) exposed to a mixture of picloram and 2,4-dichlorophenoxyacetic acid (2,4-D) for 10 days displayed increased activities of hepatic ethoxyresorufin O-deethylase (EROD), decreased serum chloride concentrations and decreased liver/body weight ratios. These changes were not observed in fish exposed to either compound alone. Neither compound, nor their mixture, increased hepatic peroxisomal catalase or lauroyl CoA oxidase activities. The results of this study indicate that 10-day exposure of 2,4-D or picloram does not induce peroxisomal enzymes in channel catfish; however, exposure to a mixture of 2,4-D and picloram may cause physiological effects to catfish not observed with either compound alone.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1987

Dietary toxicity of picloram herbicide in rats.

The toxicity of orally administered technical-grade picloram was evaluated in male and female Fischer 344 rats. Dietary dose levels were up to 2000 mg/kg body weight (bw) X d for 2 wk, 500 mg/kg bw X d for 13 wk, or 200 mg/kg bw X d for 12 mo. Routine indices of toxicity were evaluated at all of the respective time periods. Body weight, food consumption, clinical chemistries, urinalyses, and hematological determinations were considered unaffected by treatment. The only treatment-related effect, regardless of the duration of exposure, was in the liver of both male and female rats. This was generally manifested as an increase in the liver-to-body weight ratio and slight hypertrophy and pallor of the centrilobular hepatocytes. These effects were consistently present in rats receiving 1000 mg/kg bw X d for 2 wk, 300 mg/kg bw X d for 13 wk, or 200 mg/kg bw X d for 6 or 12 mo. Similar effects were marginally evident for rats receiving 500 mg/kg bw X d for 2 wk, 150 mg/kg bw X d for 13 wk, or 60 mg/kg bw X d for 6 or 12 mo. At 60 mg/kg bw X d, the effects were not progressive from 6 to 12 mo. The no-observable-effect level (NOEL) was 20 mg/kg bw X d for male and female rats fed picloram for 12 mo.

Administration, Oral↗

PubMedDate not supplied

Gas chromatographic determination of picloram in fish.

A simple method for determining picloram in fish is described. The sample is homogenized with ethyl acetate, acidified with 1N HCl, and extracted twice more with ethyl acetate. Ethyl acetate fractions are pooled, derivatized with diazomethane, cleaned up by column chromatography, and analyzed by electron capture gas chromatography. Rainbow trout exposed to 14C-picloram were used to evaluate the efficiency of 2 methods of extraction and to provide data on the rate of uptake and the bioconcentration factor. The detection limit for this method is 5 ng/g, using a 4 g sample.

Animals↗

PubMed1978

Hatching success and early performance of chicks from eggs sprayed with 2,4-D,2,4,5-T and picloram at various stages of embryonic development.

Aqueous solutions of 2,4-D, 2,4-5-T and picloram were sprayed on hens' eggs at 10x normal rate (11.2 kg/ha). Eggs used were stored prior to incubation over a 24 day period and application on each age egg occurred at the start as well as 4 and 18 days after the onset of embryonic development. No adverse effects on any parameter used to evaluate either incubation or subsequent live performance could be attributed to either spray treatment or embryonic age when applied. Although extended preincubation storage significantly reduced hatching success, it was independent of herbicide contact and germ stage when contaminated. Chicks derived from eggs stored 1--2 and 23--24 days before incubation performed comparably and were uninfluenced by all treatments during incubation.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMed1976

[Ultrastructural changes caused by a herbicide, picloram in technical dosage (70,4%), in a plankton alga, Dunaliella bioculta (Volvocales)].

A study on the effects of an auxin-like herbicide-picloram (techinical grade 70,4%)--was carried out on a planktonic green Alga, Dunaliella bioculata. At concentrations about 250 mug/ml, the cellular growth decreases while at 400 mug/ml it is completely inhibited. Concentrations of 250-300 mug/ml induce the fall of flagella and an increase of the cellular volume; granulous inclusions-nuclear bodies-are observed inside the nucleus; Golgi apparatus is abnormally developed. The vascuolar system is particularly disturbed: its volume increases; vesicles, cytoplasmic and membrane fragments and osmiophilic granulations can be observed inside vacuoles under the electron microscope.

Cell Division↗

PubMed1986