ISSN:0265-203X    

DOI:10.1080/02652038909373749

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

ISSN:0265-203X    

DOI:10.1080/02652038909373750

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

ISSN:0265-203X    

DOI:10.1080/02652038909373751

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

ISSN:0265-203X    

DOI:10.1080/02652038909373752

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

ISSN:0265-203X    

DOI:10.1080/02652038909373753

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

Exposure to pesticides as a result of their use in agriculture will vary according to the type of formulation, the method of application and the protective measures used. Quantitation of external exposure does not on its own predict the amount absorbed nor does it allow the toxic hazard to be assessed; information on skin penetration is also required. With the use of a suitable generic database for exposure, the assessment of many compounds would only require the measurement of skin penetration. With the knowledge of human dermal pharmacokinetics a field study can be performed which measures the absorbed dose directly and avoids the need for exposure measurement.

ISSN:0265-203X    

DOI:10.1080/02652038909373754

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

ISSN:0265-203X    

DOI:10.1080/02652038909373755

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

Metabolic and kinetic data on pesticides are now becoming an important part of the toxicological dossier required for product registration. In this paper the approach by one agrochemical company to generating such data is discussed. Metabolic data for the acaricide clofentezine are presented to illustrate why such data should be regarded as not only an important registration requirement, but also as integral to understanding the toxicological profile of pesticides.

ISSN:0265-203X    

DOI:10.1080/02652038909373756

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

In toxicological studies, the test compound FOE 3440 A, a [(3,5‐dichloro‐2‐pyridyl)oxy]phenoxypropanoate with herbicidal properties, produced a severe increase in weight and an intensive induction of monooxygenases activity in the mouse, but not in the rat. Comparative subacute studies were performed with oral administration of 0, 5, 20 and, in some instances, 80 mg kg−1body weight to mice, rats, hamsters, dogs and rhesus monkeys. Liver enzyme activities were measured. The evaluationofthe enzyme activity results showed an unusually severe dose‐related induction of the monooxygenases [7‐ethoxycoumarin‐O‐deethylase (EOD), 7‐ethoxyresorufin‐O‐deethylase (EOR) and aldrin epoxidase (ALD)] in the mouse and a much weaker reaction in the other species tested.

ISSN:0265-203X    

DOI:10.1080/02652038909373757

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

To date, studies on the mechanism of toxicity of pesticides are not yet an integral part of the toxicological evaluation process. However, in recent years mechanistic studies have played an increasing role in the assessment of toxicological hazards to man, and in this paper we have described two examples where an understanding of mechanism has contributed positively to risk assessment or has provided a surer scientific basis for the judgement of whether a potential hazard will be expressed in man. In the first example, an evaluation of the scientific literature leads to the conclusion that hepatic peroxisome proliferation in rats and mice is directly, or indirectly, related to the development of hepatocellular tumours. A wide range of non‐mutagenic chemicals elicit peroxisome proliferation in mouse and rat liver, but not the guinea pig or marmoset liver. Using one of the diphenyl ether herbicides, fomesafen, we have shown that isolated hepatocytes from mice and rats, but not those from guinea pigs, marmosets and significantly man, undergo peroxisome proliferation. Therefore, it seems reasonable to conclude that although fomesafen causes peroxisome‐related tumours in the mouse, man is neither susceptible nor sensitive to this mechanism. Consequently, we can conclude that fomesafen will not cause liver tumours in humans exposed to this herbicide. The herbicide paraquat, although safe in normal agricultural use, has been responsible for numerous human fatalities, almost exclusively as a result of the intentional ingestion of the concentrated commercial product. In this, the second example, studies on the mechanism of paraquat toxicity have provided a rational scientific basis for the evaluation of putative treatments and provide a framework for the development of novel approaches to reduce its toxicity. Also, a study of its mechanism of toxicity revealed that paraquat was selectively accumulated into the lung (in comparison with other tissues) by a previously unknown polyamine transport process. It was possible to determine the apparent kinetic constants for this uptake and use these pharmacokinetic parameters to predict that spray operators exposed to paraquat would not be at risk of lung injury. This scientific argument reinforced the epidemiological evidence that spray operators were clinically indistinguishable from an appropriate control population. In conclusion, mechanistic studies can contribute to the weight of evidence that is required in order to make scientific judgements on the hazards and risks that an individual pesticide will pose to man.

ISSN:0265-203X    

DOI:10.1080/02652038909373758

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor