Results of a two-year chronic toxicity and oncogenic study of rats ingesting diets containing 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)

Kociba, R.J.; Keyes, D. G.; Lisowe, R.W.; Kalnins, R.; Dittenber, D.D.; Wade, C. E.; Gorzinski, S.J.; Mahle, Nels H.; Schwetz, Bernard A.

doi:10.1016/0015-6264(79)90283-9

Cited by 39 publications

(6 citation statements)

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“…The daily oral dose levels in the three treated groups, calculated on the basis of food intake and body weight, were 0.1, 1, and 100 mg/kg body weight, respectively. The highest dose caused toxic effects in a chronic feeding study [25]. The control group received untreated chow.…”

Section: Dominant Lethal Test On Female Ratsmentioning

confidence: 99%

Mutagenicity studies with 2,4,5-T on bacteria and mammalian germ cells

Herbold

Machemer

Röhrborn

1982

Teratog. Carcinog. Mutagen.

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The herbicide 2,4,5-T (2,4,5-trichlorophenoxyacetic acid) was evaluated for potential mutagenicity by a Salmonella/mammalian-microsome test, a dominant lethal test on female rats, and by a cytogenetic assay on spermatogonia of Chinese hamster. In the Salmonella/mammalian-microsome test on four Salmonella typhimurium strains (TA 1535, TA 100, TA 1537, and TA 98), doses of up to and including 2500 micrograms/plate did not cause any mutagenic effects. In a dominant lethal test on female rats, 8-week dietary administration of 2,4,5-T at doses of up to and including 10 mg/kg/day did not cause any increase in preimplantation loss or the rate of dead implants, and did not have any effect on the fertilization quota. Cytogenetic analysis of the spermatogonia of male Chinese hamsters orally dosed five times at 24-hr intervals with 2,4,5-T at levels of up to and including 100 mg/kg did not provide any indication of 2,4,5-T having chromosome-damaging effects. Therefore, none of the three test systems provided any indication of 2,4,5-T having a mutagenic effect.

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Section: Dominant Lethal Test On Female Ratsmentioning

confidence: 99%

Mutagenicity studies with 2,4,5-T on bacteria and mammalian germ cells

Herbold

Machemer

Röhrborn

1982

Teratog. Carcinog. Mutagen.

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“…[27] Furthermore, 2,4-D and 2,4,5-T, the 2 main ingredients in the mixture of AO, demonstrated no apparent oncogenic effect in experimental animals. [28,29] Several studies reported an earlier age of onset for PC among AO-exposed patients. [6,13,14] However, there was no change in overall survival among patients exposed to AO.…”

Section: Discussionmentioning

confidence: 99%

How Agent Orange impacts prostate cancer risk, pathology, and treatment outcomes

Paracha,

Siddiqui,

Abid

et al. 2024

Curr Urol

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Between 2.6 and 3.8 million veterans served in Vietnam while the US military dispersed Agent Orange (AO), although the exact number of exposed individuals is unknown. Agent Orange, an herbicide, is a known risk factor for various cancers, including sarcoma and leukemia, but less is known about its link with prostate cancer (PC). Prostate cancer is the most commonly diagnosed malignancy in men and the fifth most common cause of cancer-related death in men worldwide. In 2023, approximately 288,300 patients will be given a diagnosis of PC, and an estimated 34,700 fatalities will occur in the United States. However, whether the pathologic characteristics of PC among those exposed to AO differ from those in the general population remains unclear. Our review synthesizes the literature regarding the impact of AO exposure on PC incidence and disease course. A comprehensive PubMed literature search of articles published beginning in 1950 was performed using the primary search terms “Agent Orange,” “TCDD,” and “tetrachlorodibenzodioxin” and the secondary search terms “prostate cancer” or “prostate neoplasm.” The search was limited to studies that focused on human participants and were published in English. Four authors thoroughly reviewed the retrieved articles for relevancy to the study aims: discussion of PC diagnosis, prognosis, or management among patients exposed to AO. Of 108 studies identified in our search, 13 were included in this systematic review. Findings within studies concerning AO exposure with relation to PC incidence, age at diagnosis or treatment initiation, and PC severity seemed to be mixed and generally conflicting. However, the literature seems to indicate that there are no significant differences in survivorship between exposed and unexposed veterans who are given a diagnosis of PC. Given these heterogeneous outcomes, the evidence does not encourage a significantly different approach to the diagnosis and management of PC for veterans exposed to AO. Clinicians should make case-by-case decisions regarding PC screening and potential treatment options for this patient group, weighing clinical suspicion against the harms of diagnostic workup and treatment.

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“…Specifically, although TCDD promotes a variety of tumors in different strains of rats, mice, and hamsters through a non-genotoxic mechanism believed to involve the Ah receptor [ 11 , 12 , 14 – 16 ], benign or malignant tumors of the prostate are not among those observed in excess in experimental animals. 2,4,5-T itself, in the absence of TCDD, has been found not to increase tumor incidence in experimental rodents [ 154 ]. Similarly, 2,4-D—the other ingredient of Agent Orange—demonstrates no apparent oncogenic effect in experimental animals [ 155 – 157 ].…”

Section: Discussionmentioning

confidence: 99%

A critical review of the epidemiology of Agent Orange/TCDD and prostate cancer

et al. 2014

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To inform risk assessment and regulatory decision-making, the relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and prostate cancer requires clarification. This article systematically and critically reviews the epidemiologic evidence on the association between exposure to TCDD or Agent Orange, a TCDD-contaminated herbicide used during the Vietnam War, and prostate cancer risk. Articles evaluated include 11 studies of three cohorts, four case–control or cross-sectional studies, and three case-only studies of military veterans with information on estimated Agent Orange or TCDD exposure; 13 studies of seven cohorts, one case–control study, and eight proportionate morbidity or mortality studies of Vietnam veterans without information on Agent Orange exposure; 11 cohort studies of workers with occupational exposure to TCDD; and two studies of one community cohort with environmental exposure to TCDD. The most informative studies, including those of Vietnam veterans involved in Agent Orange spraying or other handling, herbicide manufacturing or spraying workers with occupational TCDD exposure, and community members exposed to TCDD through an industrial accident, consistently reported no significant increase in prostate cancer incidence or mortality. Only some potentially confounded studies of Vietnam veterans compared with the general population, studies with unreliable estimates of Agent Orange exposure, and analyses of selected subgroups of Vietnam veterans reported positive associations. Overall, epidemiologic research offers no consistent or convincing evidence of a causal relationship between exposure to Agent Orange or TCDD and prostate cancer. More accurate exposure assessment is needed in large epidemiologic studies to rule out a causal association more conclusively.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-014-9931-2) contains supplementary material, which is available to authorized users.

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Results of a two-year chronic toxicity and oncogenic study of rats ingesting diets containing 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)

Cited by 39 publications

References 4 publications

Mutagenicity studies with 2,4,5-T on bacteria and mammalian germ cells

Mutagenicity studies with 2,4,5-T on bacteria and mammalian germ cells

How Agent Orange impacts prostate cancer risk, pathology, and treatment outcomes

A critical review of the epidemiology of Agent Orange/TCDD and prostate cancer

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