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Four groups of Wistar rats were exposed either to saccharin + 2,4,5-T (taste-aversion group, T-A), saccharin + oil vehicle (taste-aversion control, T-A C), water + 2,4,5-T (enhanced neophobia, E-N), or water + oil (neophobia, N). Rats in the T-A group evidenced a marked aversion to saccharin in 3 consecutive preference tests, performed every third day, starting 3 days after exposure. The aversion was less pronounced, although statistically significant in 2 additional preference tests, performed respectively after a 9-day rest period of ad lib water drinking, and a 24 hr period of forced exposure to saccharin. An enhanced neophobia effect was found in the E-N group in the first preference test. Suggestions are made concerning the possible long-term effects on food preferences among wild-living animals as a result of large-scale application of 2,4,5-T-containing herbicides. more...

The effects of 2,4,5-T on the hepatic cell in the 13 day old quail embryo have been studied. When injected at the dose level of 80 or 240 mg/kg into non-incubated eggs, this herbicide induces a proliferation of the smooth endoplasmic reticulum. The ergastoplasmic cisternae are dilated and feature a decrease in ribosomic covering. The mitochondria are swollen showing a pale matrix and a deficiency in cristae. One also observes an increase in the amount and size of lipidic inclusions and a dilatation of bile canaliculi. Moreover, biochemical analysis reveals a significant decrease in the glycogen content indicating that 2,4,5-T disturbs the glycogenic function of the liver. more...

The herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and two structurally related compounds, phenoxyacetic acid and 2,4,5-trichlorophenol, were suspended in a 1:1 solution of honey:water and administered by gavage to pregnant mice on one of gestation days 8-15 (copulation plug day = day 1) or on three consecutive days (7-9, 10-12, or 13-15). Doses were 800-900 mg/kg for single and 250-300 mg/kg/day for multiple treatments. With the exception of 2,4,5-trichlorophenol treatment on day 14, only 2,4,5-T treatment significantly increased prenatal mortality, and only 2,4,5-T was associated with decreased fetal weight when comparisons were made with the solvent controls. Although low incidences were seen in all treatment groups, only 2,4,5-T significantly increased cleft palate or other gross malformations. Significant skeletal, visceral or histopathological defects were not observed. These results indicate that both the carboxyl group and chlorination of the aromatic ring are essential for an unambiguous teratogenic response. more...

The Evatt Royal Commission Report on the Use and Effects of Chemical Agents on Australian Personnel in Vietnam has authoritatively rejected the substantive claims that were made by the Vietnam Veterans' Association of Australia about the adverse effects of exposure to phenoxy herbicides in Vietnam on the health of Vietnam veterans and their families. The Commission concluded that Vietnam veterans were not exposed to toxic levels of chemicals in Vietnam; that they are not at any increased risk of fathering children with birth defects, or contracting cancer; and that, although they have slightly higher rates of psychiatric disorder, heart disease, alcoholism and alcohol-related disease, these effects are unconnected with exposure to chemicals in Vietnam. The reasons for these findings deserve to be given the widest possible publicity. Only by doing so is there any prospect of dissolving the misapprehension that Vietnam veterans have been poisoned by herbicides. more...

Fertility and sperm number, motility, and morphology were analyzed in male C57BL/6 mice exposed to various mixtures of 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlor-ophenoxyacetic acid (2,4,5-T), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet for 8 wk. Somatic cell (bone marrow) sister chromatid exchange frequencies were also evaluated in mice injected with similar chemical mixtures. The concentration of the test chemicals was such that the average daily feeding dose in the three mixtures or control was 40 mg/kg 2, 4-D, 40 mg/kg 2,4,5-T, and 2.4 micrograms/kg TCDD; 40 mg/kg 2,4-D, 40 mg/kg 2,4,5-T and 0.16 microgram/kg TCDD; 20 mg/kg 2, 4-D, 20 mg/kg 2,4,5-T, and 1.2 micrograms/kg TCDD; or no chemical added (control). No significant dose-related effects were observed in the treated mice compared to the control group. more...

1 The minimum toxic dose of tetrachloro-dibenzo-p-dioxin (TCDD) for man has been calculated from monkey and human data to be 0.1 microgram kg-1. 2 The amount of TCDD which man takes in from his environment is about 1/2050 of that present in one square metre of his immediate environment. 3 The average concentration of TCDD present in Vietnam immediately after spraying Agent Orange was 8 microgram m-2. 4 A soldier directly sprayed would attain an internal body concentration of 7 X 10(-5) microgram kg-1 or 1/1750 of the minimum toxic dose; soldiers moving through previously sprayed areas would ingest much less. 5 These quantitative aspects indicate that the dioxin sprayed with Agent Orange in Vietnam cannot have caused systemic illnesses in Vietnam veterans or birth defects in their children. more...

At toxic doses in rats, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4-chlorophenoxyacetic acid (MCPA) caused injuries in blood vessels in the brain. 2. 2,4-D caused extravasations of the circulating Evans blue-albumin complex also in the spinal cord. 3. By contrast, potency in damaging cerebral vessels was almost non-existent with 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). 4. None of the three chlorophenoxyacetic acids caused such cerebrovascular injuries in mice, guinea pigs, Syrian hamsters, rabbits and chickens. more...

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. more...

The carcinogenic effect of a herbicide trichlorophenoxyethanol (TCPE) was investigated. The substance always contains 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) as a trace contaminant. Outbred Swiss-H/Riop mice were treated for 1 year with different doses of the various admixtures of the two compounds and those of dioxin alone to determine whether their carcinogenic effects are dose-dependent. Observation time after TCPE treatment was 1 and 2 years. The maximum tolerable dose of TCPE (70 mg/kg) with a dioxin concentration of 7.10(-6) mg/kg doubled the number of liver tumours as compared to the controls. The occurrence of liver tumours decreased at the administration of lower doses of the two compounds. No change in tumour frequency could be detected when the level of dioxin as a trace contaminant was raised, either (10 ppm). According to our preliminary results, dioxin has a more toxic than carcinogenic effect. The use of TCPE as a herbicide in accordance with the proper factory regulations and the consumption of products treated with it does not seem to bear a carcinogenic risk for the consumer. more...

In an earlier study 2,4,5-trichlorophenoxythanol (TCPE) contaminated with dioxin, a component of the Hungarian herbicide Buvinol, was found to be hepatocarcinogenic. In the present work, the hepatocarcinogenicity of TCPE was compared to its possible genotoxicity in vitro, using the Salmonella/microsome test for mutagenicity and for its DNA-damaging effect, the induction of sister chromatid exchanges (SCE) in Chinese hamster cells in vitro. It was found that purified TCPE (with 0.1 ppm dioxin content) was under no conditions mutagenic by the Ames test, i.e., it belongs to the group of false-negative chemicals. TCPE was, however, genotoxic; its DNA-damaging effect was demonstrated by an increase in the frequency of SCE, while pure dioxin of corresponding amount was ineffective. However, elevated SCE frequency and the toxicity on bacteria and mammalian cells by TCPE were significantly decreased by the metabolic activation system (S-9 mix) isolated from liver. This observation indicates that in the detoxication of TCPE in vitro, a key role is to be attributed to the hepatic microsomal enzymes. It is presumed that TCPE is hepatocarcinogenic only in a dose range which has exhausted the detoxicating capacity of the liver. more...

The possible association between exposure to phenoxy herbicides and development of soft tissue sarcomas has been studied in both case-control and cohort studies. In these studies soft tissue sarcoma cases have been identified from either deaths with malignant neoplasms of the connective tissue (ICD-8 171) as the underlying cause of death, from incident cancer cases with the same topography code, or from incident cases of extraskeletal sarcomas, excluding lympho and reticulosarcomas. The current study shows that the choice of source material has a considerable influence on the registered occurrence of soft tissue sarcomas in a well defined population. In 1978 to 1982 an annual number of 33 deaths from ICD-8 171 was registered in Denmark, whereas the annual number of diagnosed extraskeletal sarcomas was 231. The distribution over histologic types differed between tumours coded to the connective tissue and extraskeletal sarcomas coded to specific organs. Furthermore, during the period 1943 to 1982 the mortality from ICD-8 171 increased slightly, whereas the incidence from all extraskeletal sarcomas decreased slightly, except for males since 1970. Time trends based on any of the three source materials should, however, be interpreted with caution. more...

Using the Chinese hamster V79 in vitro cell system designed to measure intercellular communication, 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and several mixtures of these compounds were tested for their ability to inhibit this biological process. The ability of these chemicals to inhibit colony-forming ability of these cells was tested prior to the studies to measure intercellular communication. 2,4-D was less cytotoxic than 2,4,5-T. Both 2,4,5-T and 2,4-D were able to inhibit intercellular communication at their respective noncytotoxic dose ranges. Various mixtures of both chemicals were also able to inhibit intercellular communication, showing some kind of additivity. No-effect levels were also noted in the intercellular communication assay. These results were interpreted as being consistent with the hypothesis that these compounds might be teratogenic by their ability to inhibit intercellular communication during development. more...

This article discusses the use of sprayed herbicides during the Vietnam conflict and the health problems exhibited by the veterans exposed to these chemicals. A short history of health problems attributed to herbicide exposure is given. Experimental research on the effects of dioxin, a byproduct in the manufacture of some herbicides, is limited to laboratory animals. In every instance the tested animal exhibited some ill effects following exposure. The research has shown that the lethal dose varies according to animal species and that the effects of dioxin exposure are cumulative. Reasons are given for the lack of research on the effects of human exposure. Numerous physical and psychological signs and symptoms attributed to agent orange exposure are listed. The stresses on the veteran with these health problems are discussed. The nurse practitioner may be the first health care professional to see these patients. Specific interventions are suggested for the nurse to incorporate into practice. more...

Chloracne was found in 52% of 226 workers in a 1979 cross-sectional survey at a plant where 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) had been manufactured from 1948 to 1969. Mean duration of residual chloracne was 26 years, and in 29 subjects, it had been present for 30 years. A significant increased prevalence of abnormal gamma-glutamyl transpeptidase (GGT) and higher mean GGT were found in those with chloracne, compared to those without. Although mean triglyceride values were higher in those with chloracne, the difference was not statistically significant. Neurological examination showed a statistically significant higher prevalence of abnormal sensory findings in those with chloracne. Increased prevalence of angina and reported myocardial infarction in those with chloracne was not significant when age-adjusted. Increased prevalence of reported sexual dysfunction and decreased libido in those with chloracne compared to those without was statistically significant after age adjustment. No differences were found between those with and without chloracne in serum cholesterol, total urinary porphyrins, or in reproductive outcome. more...

Practical grade 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), dissolved in dimethylsulfoxide (DMSO), was injected into the air space of fertilized chicken eggs prior to incubation. Doses of 2,4,5-T administered were 12.5, 25, 50, 75, 100, and 125 mg/kg to determine herbicide toxicity on the first day of incubation. A similar group was studied on day 5 of incubation with doses of 2,4,5-T at 50, 75, 100 and 250 mg/kg. LD50 was estimated to be 62 mg/kg on day zero and 68 mg/kg on day 5. Additionally, embryos were exposed to 2,4,5-T at 50 mg/kg on day zero of gestation and sacrificed after 48 h of incubation. Serial sections were examined for teratological and developmental anomalies. None were found. more...

Male C57BL/6 mice were given feed containing various concentrations of 2,4,-dichlorophenoxyacetic acid (2,4-D),2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to provide daily doses of approximately 40 mg/kg 2,4,-D, 40 mg/kg 2,4,5-T, and 2.4 micrograms/kg TCDD (group II): 40 mg/kg 2,3-D, 40 mg/kg 2,4,5-T, and 0.16 micrograms/kg TCDD (group III); and 20 mg/kg 2,4-D, 20 mg/kg 2,4,5-T, and 1.2 micrograms/kg TCDD (group IV). The chemical mixtures were chosen to approximate the concentrations of the components of Herbicide Orange. Controls (group I) were given a diet with only the corn oil vehicle added to the feed. In the treated animals, liver enlargements, hepatocellular toxicity, and reduced thymus size were found an body weight gain was significantly less than that of the control animals. Significant of complete recovery from liver and thymus toxicity was observed when the mice were returned to a control diet. The thymic toxicity and hepatotoxicity seemed to be related to TCDD levels, while the decrease in body weight gain was more closely associated with phenoxy acid concentrations. All effects attributed to the mixture were elicited by individual compounds in the mixture in previous studies. more...

Since amino acid conjugates are plant metabolites of the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), 5 amino acid conjugates (aspartic acid, glutamic acid, leucine, methionine and tryptophan) of 2,4,5-T were tested for possible mutagenic activity utilizing 5 strains of Salmonella typhimurium (TA97, TA98, TA100, TA1535 and TA1538) with and without rat-liver microsomal and cytosolic enzymes. These compounds did not cause any significant increase in reversions when compared with controls in the presence or absence of the activating system. Further, linear regression analysis showed no significant (p less than 0.05) dose-response relationships. Thus, it was concluded that the tested amino acid conjugates of 2,4,5-T are not mutagens or promutagens in these assays. more...