Very Toxic Substances

Substances which have lethal effects in very low amounts or can lead to very severe diseases are regarded as very toxic. For labeling very toxic substances and preparations, the relevant R-phrases, the skull-and-crossbones danger symbol, T+ , and the indication of danger very toxic are used. The scientific criteria for the classification are summarized in Table 3.1. 

The following R-phrases have to be used in order to express the application route  

R 27 Very toxic in contact with skin. R 28 Very toxic if swallowed. 

The lethal doses of the various very toxic compounds can vary over a wide range the LD50 value of the well-known Seveso poison 2,3,7,8-tetrachloro-di-benzo-dioxin (TCDD) indicates higher toxicity than potassium cyanide by a factor of 10 000, but it is less toxic than botulinus toxin by nearly the same factor. 

Natural compounds, as well as chemicals, can have very toxic properties. Indeed, many very toxic substances are natural toxins. Table 3.2 shows a selection of very toxic toxins and their occurrence in nature. 

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H6 Toxic substances and preparations (including very toxic substances and preparations) which, if they are... 

The city of Los Angeles issues a smog alert when the ozone in its atmosphere reaches 0.5 ppm. This means that in every mole of air, there is 0.5 X 10 mol of ozone. This may not seem like much, but ozone is a very toxic substance that is particularly damaging to soft tissue such as the lungs. 

Segregation is practised to allow for housekeeping, construction and maintenance requirements and to reduce the risk of an accident resulting in a domino effect , e.g. from a fire, explosion or toxic release. For very toxic substances, e.g. prussic acid (HCN) or tetraethyl lead, this may involve isolating the entire manufacturing operation in a separate unoccupied building or sealed-off area. 

Table 6.1 illustrates standard toxicity ratings that are used to describe estimated toxicities of various substances to humans. Reference is made to them in this book to denote toxicities of substances. Their values range from one (practically nontoxic) to six (supertoxic). In terms of fatal doses to an adult human of average size, a taste of a supertoxic substances (just a few drops or less) is fatal. A teaspoonful of a very toxic substance could have the same effect. However, as much as a quart of a slightly toxic substance might be required to kill an adult human. 

SeMet is classified as a very toxic substance. It should be stored in closed containers below 4°C in the freezer. SeMet should only be handled in a well-ventilated hood with rubber gloves, protective goggles and facial mask. To reduce the risk of accidental poisoning in the food and feed industry, pre-... 

Phosgene gas, COCI2, which is a very toxic substance used to make pesticides and herbicides, is made by passing carbon monoxide gas and chlorine gas over solid carbon, which acts as a catalyst. 

The carbamates are also typical xenobiotics. One important exception is eserine (physostigmine), a very toxic substance that is present in Calabar beans, the seeds of a Leguminosae from West Africa. Calabar beans were used in legal matters in West Africa. Suspected persons were given a drug made from the beans, and if they survived, they were not guilty. Eserine was... 

Octamethylpyrophosphoramide, when very pure, is a colorless somewhat viscous oil with the following physical constants b.p. 120 to 122° at 0.5 mm. 154° at 2 mm. sp. gr., 1.09. Normally the color is yellow to amber. The compound is miscible with water, soluble in most organic solvents, and insoluble in higher aliphatic hydrocarbons. It is a very toxic substance with a MLD50 to white mice of 17 mg./kg. by intraperitoneal injection. 

For example, metallic mercury is insoluble in the stomach and intestinal tract and is excreted almost completely as a result of this non-bioavailability. In contrast, inhaled mercury vapor is incorporated very effectively via the lungs and is strongly toxic in a systemic way. Organic mercury compounds (e.g., methyl mercuric chloride) when in the intestinal tract are sufficiently soluble to behave as orally very toxic substances. 

Substances which lead to severe, non-lethal health effects on an acute exposure in the same doses as those mentioned in Table 3.3 are also classified as toxic. To distinguish them from the lethal effects, they are classified with the R-phrase R 39/. In order to distinguish them from very toxic substances, the R-phrases for toxic have to follow the R 39, as can be seen in the following example ... 

A preparation has to be classified as very toxic if the sum of the quotients of the concentrations of the very toxic substances divided by their classification limits is equal or greater than one (see Fig. 3.25). 

PT+ = is the percentage by weight or by volume of each very toxic substance in the preparation, LT+ = is the very toxic limit specified for each very toxic substance, expressed as a percentage by weight or by volume... 

Chemical substances called inhibitors decrease the rates of enzyme-catalyzed reactions. Irreversible inhibitors render enzymes permanently inactive and include several very toxic substances such as the cyanide ion and heavy-metal ions. Reversible inhibitors are of two types competitive and noncompetitive. 

FIGURE 4.1.1.1 Dose-Response Curve. This is a generic dose-response curve for a toxic substance. The threshold is the dose below which no effect is detected. The x-axis can range from micrograms (for very toxic substances) to grams (for less toxic substances). The y-axis is the percentage of a population that exhibits some iUness or death. 

Camphor is a cyclic ketone of the hydroaromatic terpene group. It is an ingredient of a large number of over-the-counter topical remedies (with a camphor content of 1-20%) taken especially for symptomatic relief of chest congestion and muscle aches but its effectiveness is of some doubt. Camphor is readily absorbed from all sites of administration, including topical application to the skin. The compound is classified as a class-IV chemical, i.e. a very toxic substance. Hundreds of cases of intoxication have been reported, usually after accidental ingestion by children (Skoglund et al. 1977 Kopelman 1990). 

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