Cancer incidence of 2,4-D production workers

Despite showing no evidence of carcinogenicity in laboratory animals, the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been associated with non-Hodgkin lymphoma (NHL) in some human epidemiology studies, albeit inconsistently. We matched an existing cohort of 2,4-D manufacturing employees with cancer registries in three US states resulting in 244 cancers compared to 276 expected cases. The Standardized Incidence Ratio (SIR) for the 14 NHL cases was 1.36 (95% Confidence Interval (CI) 0.74-2.29). Risk estimates were higher in the upper cumulative exposure and duration subgroups, yet not statistically significant. There were no clear patterns of NHL risk with period of hire and histology subtypes. Statistically significant results were observed for prostate cancer (SIR = 0.74, 95% CI 0.57-0.94), and "other respiratory" cancers (SIR = 3.79, 95% CI 1.22-8.84; 4 of 5 cases were mesotheliomas). Overall, we observed fewer cancer cases than expected, and a non statistically significant increase in the number of NHL cases.     

除草剂2,4-二氯苯氧乙酸正丁基酯对小鼠甲状腺及睾丸功能的影响

目的研究2,4-二氯苯氧乙酸正丁基酯(2,4-D丁酯)对小鼠甲状腺及睾丸功能的影响。方法将健康昆明种小鼠40只(雌雄各半),随机分为4组,每组10只。对照组予蒸馏水灌胃,实验组分别以40、150、300 mg/kg的2,4-D丁酯灌胃,每天1次,每周6次,实验期限为28 d。测定小鼠体重、甲状腺素(T_4)、促甲状腺激素(TSH)、胆固醇含量、睾丸脏器系数及睾丸中乳酸脱氢酶(LDH)及山梨醇脱氢酶(SDH)的活力。结果300 mg/kg组雌性小鼠体重[(20．31±1．22)g]明显低于对照组及40、150 mg/kg组,差异有统计学意义(P＜0．05)；300 mg/kg组T_4含量[(29．400±5．849)nmol/L]明显低于其他各组,差异有统计学意义(P＜0．05)；血中TSH水平各组间无明显差异；血中胆固醇含量150和300 mg/kg组明显高于40 mg/kg组及对照组,差异有统计学意义(P＜0．05)。300 mg/kg组睾丸脏器系数(0．37%±0．12%)明显低于其他各组,差异有统计学意义(P＜0．05)；各组间睾丸组织中LDH、SDH活力差异均无统计学意义(P＞0．05)。结论除草剂2,4-D丁酯可抑制雌性小鼠体重增长,并导致甲状腺功能紊乱及睾丸萎缩。     

Toxicity of three herbicides to some nitrogen-fixing cyanobacteria

The effects of some common rice field herbicides, such as 2,4-dichlorophenoxyacetic acid (2,4-D), Machete, and Saturn, on the paddy field nitrogen-fixing cyanobacteria Nostoc linckia, Nostoc calcicola, Nostoc sp., and Anabaena doliolum were studied. These cyanobacteria were found to be more tolerant to 2,4-D (lethal doses 1500-2000 micrograms/ml) than to Machete and Saturn (lethal doses 6-8 micrograms/ml). The effects of these three herbicides on some physiological processes of N. linckia were studied. The 2,4-D stimulated the growth and nitrogen fixation up to 100 micrograms/ml concentration (a dose higher than the field dose, i.e., about 40 micrograms/ml), recommended for field application. However, with Machete and Saturn this type of stimulation was not observed even at lower concentrations. Similarly, the uptake of nutrients, such as NO3- and NH+4, was also inhibited by Machete and Saturn. However, 100 micrograms/ml 2,4-D stimulated the uptake of NO3- but not of NH+4; higher doses of 2,4-D inhibited the uptake of both nutrients. Factors such as pH, organic carbon sources (glucose and acetate), and amino acids were found to regulate the toxicity of all three herbicides to N. linckia. Lower pH enhanced the toxicity of all three herbicides, whereas higher pH (up to 9.0) lowered it. Glucose and acetate (each 500 micrograms/ml) protected against the toxicity of 2,4-D and Saturn, but not against Machete. Whereas glutamine, arginine, serine, and tryptophan conferred upon N. linckia a greater protection against the toxicity of all three herbicides, methionine did not do so, and the presence of methionine with herbicide in the culture medium resulted in greater toxicity to N. linckia than that in the presence of the herbicide alone.     

Toxicity of 40 herbicides to the green alga Chlorella vulgaris

The effects on the green alga Chlorella vulgaris of 40 herbicides in 19 different chemical structure classes and with 11 dissimilar modes of action were studied through 96-h acute toxicity tests. Experimental results indicated that the average acute toxicity of acetolactate synthase (ALS)-inhibiting herbicides to C. vulgaris was close to those of the acetyl-CoA carboxylase (ACCase)-inhibiting herbicides and the lipid synthesis-inhibiting protoporphyrinogen oxidase (Protox) inhibitor. Their acute toxicities were higher than those of the microtubule process inhibitor, mitotic process inhibitor, the glutamine synthase inhibitors, and 5-enolpyruvyl-shikimate-3-phosphate synthase (EPSP synthase) inhibitors. The acute toxicities of auxin herbicides to C. vulgaris were the lowest among all herbicides tested and that of the photosynthesis-inhibiting herbicides was the highest.     

Establishing tolerable dungeness crab (Cancer magister) and razor clam (Siliqua patula) domoic acid contaminant levels.

Domoic acid has been found in razor clams (Siliqua patula) and dungeness crabs (Cancer magister) in Washington State and elsewhere on the West Coast of the United States. Due to toxic effects associated with domoic acid exposure, an effort has been made to establish tolerable domoic acid levels in crabs and clams obtained from commercial harvest and sale and from individual recreational harvesting. To accomplish this, the amount of clams and crabs consumed by populations of concern was determined, a tolerable daily intake (TDI) was developed for individuals most sensitive to effects of this compound, and the TDI was equated with consumption patterns to determine tolerable clam and crab domoic acid levels. Results indicate that the primary health effects associated with domoic acid toxicity can be averted in populations of concern and for others consuming crabs or clams less frequently (or in lesser quantity) if domoic acid contaminant concentration does not exceed 30 mg/kg in the hepatopancreas and viscera of dungeness crabs or 20 mg/kg in clams.     

Toxicity assessment of 40 herbicides to the green alga Raphidocelis subcapitata

The effects of 40 herbicides with nine modes of action on the green alga Raphidocelis subcapitata were studied by 96-h acute toxicity tests. Results showed that the EC50 of the herbicides with respect to the photosynthetic processes of R. subcapitata ranged from 0.0007 to 4.2286 mgL(-1). Photosynthesis was the process of the green alga most sensitive to the tested herbicides. The most toxic herbicides were atrazine, ametryme, simazine, prometryne, cyanazine, isoproturon, chlorotoluron, diuron, methabenzthiazuron, and paraquat. The EC50 of the protoporphyrinogen oxidase inhibitor oxadiargyl, which was the parameter least sensitive to the herbicides tested in this study, was 42.5 mgL(-1). The descending order of the average acute toxicity to R. subcapitata of herbicides with regard to the nine modes of action was as follows: photosynthetic process>cell division>lipid synthesis, acetyl-coenzyme A carboxylase>acetolactate synthase> 5-enolpyruvyl-shikimate-3-phosphate synthase, glutamine synthase, hormone synthesis>protoporphyrinogen oxidase.     

Toxicity,bioconcentration, and metabolism of the herbicide propanil (3′,4′-dichloropropionanilide) in freshwater fish

Fathead minnows (Pimephales promelas) were exposed to technical grade propanil (3′,4′-dichloropropionanilide) in a flow-through diluter system to determine acute lethality. LC₅₀ values were 11.5, 10.2, 8.6, and 3.4 mg·L^?1 at 24, 48, 96, and 192 hr, respectively. Eggs, newly hatched fry, and juvenile fish of this species were similarly exposed but at lower concentrations and for a period of 58 days. The 58-day “no effect” concentration was between 0.4 and 0.6Μg·L^?1, based upon the physiological parameters of length and dry weight of juvenile fish.¹⁴C-Propanil did not bioconcentrate significantly in fathead minnows (1.6× for parent propanil in whole body). Rainbow trout (Salmo gairdneri) readily metabolized propanil, forming at least ten products. One metabolite recovered from trout bile was identified as either 3′,4′-dichloro-2-hydroxypropionanilide or 3′,4′-dichloro-3-hydroxy-propionanilide. The technical grade propanil also contained 0.67 mg·g^?1 of 3,3′,4,4′-tetrachloroazobenzene as a contaminant.     

Using accelerated life testing procedures to compare the relative sensitivity of rainbow trout and the federally listed threatened bull trout to three commonly used rangeland herbicides (picloram, 2,4-D, and clopyralid)

We conducted 96-h static acute toxicity studies to evaluate the relative sensitivity of juveniles of the threatened bull trout (Salvelinus confluentus) and the standard cold-water surrogate rainbow trout (Onchorhyncus mykiss) to three rangeland herbicides commonly used for controlling invasive weeds in the northwestern United States. Relative species sensitivity was compared using three procedures: standard acute toxicity testing, fractional estimates of lethal concentrations, and accelerated life testing chronic estimation procedures. The acutely lethal concentrations (ALC) resulting in 50% mortality at 96 h (96-h ALC50s) were determined using linear regression and indicated that the three herbicides were toxic in the order of picloram acid > 2,4-D acid > clopyralid acid. The 96-h ALC50 values for rainbow trout were as follows: picloram, 41 mg/L; 2.4-D, 707 mg/L; and clopyralid, 700 mg/L. The 96-h ALC50 values for bull trout were as follows: picloram, 24 mg/L; 2.4-D, 398 mg/L; and clopyralid, 802 mg/L. Fractional estimates of safe concentrations, based on 5% of the 96-h ALC50, were conservative (overestimated toxicity) of regression-derived 96-h ALC5 values by an order of magnitude. Accelerated life testing procedures were used to estimate chronic lethal concentrations (CLC) resulting in 1% mortality at 30 d (30-d CLC1) for the three herbicides: picloram (1 mg/L rainbow trout, 5 mg/L bull trout), 2,4-D (56 mg/L rainbow trout, 84 mg/L bull trout), and clopyralid (477 mg/L rainbow trout; 552 mg/L bull trout). Collectively, the results indicated that the standard surrogate rainbow trout is similar in sensitivity to bull trout. Accelerated life testing procedures provided cost-effective, statistically defensible methods for estimating safe chronic concentrations (30-d CLC1s) of herbicides from acute toxicity data because they use statistical models based on the entire mortality:concentration:time data matrix.     

Cancer incidence among pesticide applicators exposed to trifluralin in the Agricultural Health Study

Trifluralin, 2,6-dinitro-N,N-dipropyl-4-trifluoromethylaniline, is a 2,6-dinitro herbicide widely used to control annual grasses and broadleaf weeds in agricultural settings. The association between trifluralin use and common cancer incidence was evaluated among 50,127 private and commercial pesticide applicators in the Agricultural Health Study (AHS), a prospective cohort study of licensed pesticide applicators and their spouses in Iowa and North Carolina. Poisson regression was used to examine internal dose-response relationships, while controlling for important lifestyle factors and other agricultural exposures. Two metrics of exposure (lifetime days and intensity-weighted lifetime days) were used in exposure-response analyses with non-exposed applicators, as well as applicators in the lowest tertile of exposure, as reference groups. Incident cancers were identified through state tumor registries from enrollment in 1993 through 2002. Trifluralin exposure was not associated with cancer incidence overall among 51% of private and commercial applicators (n=25,712) who had used trifluralin. However, there was an excess of colon cancer in the exposure category of higher half of highest tertile (rate ratios (RR) of 1.76 (95% CI=1.05-2.95) using the non-exposed as a referent and 1.93 (95% CI=1.08-3.45) using those with the lowest tertile of exposure as the referent). There was also a non-significantly elevated risk for kidney cancer and bladder cancer in the highest exposure group, although only the kidney cancer finding was consistent across exposure metrics. Although there was a possible link between trifluralin exposure and colon cancer, small numbers and inconsistencies in dose-response and subgroup analyses indicate that this may be a chance finding.     

Variety of 2,4-D metabolic pathways in plants; its significance in developing analytical methods for herbicides residues

2,4-D in plants very rapidly undergoes various transformations and its predominant metabolic pathways and rates vary with different plant species. In bean and soybean plants major 2,4-D metabolites are 4-O--D-glucosides of 4-hydroxy-2,5-dichloro- and 4-hydroxy-2,3-dichloro-phenoxy-acetic acids; in addition, considerable amounts ofN-(2,4-dichlorophenoxyacetyl)-L-aspartic andN-(2,4-dichlorophenoxyacetyl)-L-glutamic acids are accumulating in them. Among 2,4-D metabolites in cereals there prevailed 1-O-(2,4-dichlorophenoxyacetyl)--D-glucose while the glycoside of 2,4-dichlorophenol prevailed in strawberry plants.Presented in the Third International Congress of Pesticide Chemistry, Helsinki, 1974