Toxicity to mammals

QSAR models describing phytotoxicity (Table 5.12) are limited to a few chemical classes, mostly those with relatively well-understood modes of action such as herbicidal compounds. 

Small laboratory rodents are the established surrogate test species for terrestrial wildlife. For reasons of expediency, the laboratory rat Rattus norvegicus is most commonly used in toxicity tests to record adverse effects on mammalian species. The toxicity is generally described in terms of the LD50 that is, the single dose of the toxicant (mg/kg) which is acutely lethal after 24-96 h for 50% of the individuals exposed, regardless of how mortality is evoked. The toxicants are administered orally with food to at least six (three 

Benzenes, phenols, anilines 8 Lactuca sativa growth 16/21 d xmol/l 

Life stage of the species the toxicity of xenobiotics towards organisms varies with age relative to lifespan and their sex, size, lipid content, etc. 

Duration of the test sensitivity to chemicals may increase or decrease with changes in the test period due to alterations in the catabolic status and in the defence mechanisms of the animals. 

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Phosphoric Acid and Phosphorothioic Acid Anhydrides. The aUphatic organophosphoms esters originally developed by Schrader (27) are extremely toxic to mammals and are largely of historic interest. Tetraethyl pyrophosphate [107-49-3] (40) (bp 104—110°C at 10.7 Pa, d 1.185, vp 6.1 mPa at 30°C) is miscible with water and hydrolyzes very rapidly with a half-life of 6.8 h at 25°C. The rat LD qS ate 1.1 (oral) and 2.4 (dermal) mg/kg. 

The development of malathion in 1950 was an important milestone in the emergence of selective insecticides. Malathion is from one-half to one-twentieth as toxic to insects as parathion but is only about one two-hundredths as toxic to mammals. Its worldwide usage in quantities of thousands of metric tons in the home, garden, field, orchard, woodland, on animals, and in pubHc health programs has demonstrated substantial safety coupled with pest control effectiveness. The biochemical basis for the selectivity of malathion is its rapid detoxication in the mammalian Hver, but not in the insect, through the attack of carboxyesterase enzymes on the aUphatic ester moieties of the molecule. 

Health and Environment. Manganese in trace amounts is an essential element for both plants and animals and is among the trace elements least toxic to mammals including humans. Exposure to abnormally high concentrations of manganese, particulady in the form of dust and fumes, is, however, known to have resulted in adverse effects to humans (36,37) (see Mineral nutrients). 

The sulfonamides impede this synthesis and are therefore toxic to those bacteria that synthesize thek own foHc acid. Mammals cannot synthesize this and related vitamins and depend on food sources for them the sulfas are therefore not toxic to mammals in this regard. 

Pharmacology. Lycorine was first examined by Morishima wl found it relatively non-toxic to mammals. Given per os or subcutaneous, to the dog or cat, it causes, in small doses, salivation and in large dos vomiting and diarrhoea. It has no special effect on the blood pressure death seems to be due to a generalised collapse. Post mortem —hyper m and ecchymoses in the stomach, intestine, pulmonary pleura and end... 

Methylparathion is the corresponding dimethyl derivative. Later (1952) malathion found favour because of its decreased toxicity to mammals it is readily made in 90% yield by the addition of dimethyidithiophosphate to diethylmaleate in the presence of NEtr as a cataly.st and hydroquinone as a polymerization inhibitor ... 

Many isocj anidea are reported to exhibit no appreciable toxicity to mammals See J. A. Green, II and P. T. Hoffmann m Isonitrile Chemistry, I. Ugi (Ed.), Academic Press, New York, 1971, p. 2. However, since certain isocyamdes are highly toxio (e.g., 1,4 dnsocyanobutane), the checkers recommend that all isocyamdes bo handled with due oaution. 

Kerr SH, Brogdon JE. 1959. Relative toxicity to mammals of 40 pesticides. Agricultural Chemicals 14 44-45, 135. 

Different from the use of ordinal insecticides, this disruption method has high target selectivity and, as would be desired, ensures the survival of natural enemies. The sex pheromone, which shows no toxicity to mammals, is an ideal insect-behavior regulator (IBR). Table 8 shows the application areas of main mating disruptants for lepidopteran insects. In addition to the use of the synthetic pheromone of P. gossypiella in large cotton fields, many disruptants are... 

Tables 14.6, 14.7, 14.8, 14.9 and 14.10 provide further insight into the comparative properties and toxicity of pesticides applied on organic and conventional farms to treat a given type of pest. Table 14.6 lists the primary pesticides approved for use on organic farms and their uses and target pests. Tables 14.7-14.10 again list the major organic pesticides, along with two or three conventional pesticide alternatives that are used by conventional farmers to manage the same pest problems. Tables 14.7 and 14.8 summarize the rates of application of these pesticides, while Tables 14.9 and 14.10 focus on relative measures of toxicity to mammals and other organisms.

Focusing on furan ring compounds, Katsuda [28] developed furamethrin (18) in 1966, which was suitable as an active ingredient of electric vaporizing insecticides due to its extremely low toxicity to mammals and its high volatility. Almost simultaneously, resmethrin (19) was reported by Elliott et al. [29] in 1967 as possessing a powerful lethal effect, and has been used in aerosol formulations. 

Pyrethroids have low oral toxicity to mammals, and in general their insect (topical) to mammal (oral) toxicity ratio is much higher than that of the other major classes of insecticides [25]. As the reason, at least the following mechanisms are conceivable (1) negative temperature dependence - differences in body temperature between insects and mammals makes the insect nerves much more sensitive, (2) metabolic rate - insects metabolize the insecticide more slowly than mammals, and the metabolizing enzyme systems are different, and (3) differences in body size - insects will have less chance to metabolize the insecticides before reaching the target site [26]. 

The insecticide if used on food crops should be non-toxic to mammals or broken down at such a rate as to be innocuous when the crop is harvested. 

Insects are very sensitive to fluorophosphonates, so that the compound parathion was synthesised and used as an insecticide soon after the Second World War. However, it entered the food chain and eventually found its way into mammals and caused death. An important breakthrough occurred with the synthesis of malathion, an insecticide which has high toxicity to insects, where it is converted to malaoxon, a potent acetylcholinesterase inhibitor. However, malathion is much less toxic to mammals, since it is readily detoxified (Appendix 3.8). 

Insecticide, thought to be less acutely toxic to mammals than DDT. Also used to treat cancer of the adrenal gland. Not specifically banned under the Stockholm convention, but is no longer manufactured in most countries... 

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