Tests on animals

Health and Safety Factors. Boron trifluoride is primarily a pulmonary irritant. The toxicity of the gas to humans has not been reported (58), but laboratory tests on animals gave results ranging from an increased pneumonitis to death. The TLV is 1 ppm (59,60). Inhalation toxicity studies in rats have shown that exposure to BF at 17 mg/m resulted in renal toxicity, whereas exposure at 6 mg/m did not result in a toxic response (61). Prolonged inhalation produced dental fluorosis (62). High concentrations bum the skin similarly to acids such as HBF and, if the skin is subject to prolonged exposure, the treatment should be the same as for fluoride exposure and hypocalcemia. No chronic effects have been observed in workers exposed to small quantities of the gas at frequent intervals over a period of years. 

The inherent toxicity of a material is measured by tests on animals. It is usually expressed as the lethal dose at which 50 per cent of the test animals are killed, the LD50 (lethal dose fifty) value. The dose is expressed as the quantity in milligrams of the toxic substance per kilogram of body weight of the test animal. 

Some values for tests on rats are given in Table 9.1. Estimates of the LD50 for man are based on tests on animals. The LD50 measures the acute effects it gives only a crude indication of the possible chronic effects. 

The acceptable limits for toxic exposure depend on whether the exposure is brief or prolonged. Lethal concentration for airborne materials and lethal dose for non-airbome materials are measured by tests on animals. The limits for brief exposure to toxic materials that are airborne are usually measured by the concentration of toxicant that is lethal to 50% of the test group over a given... 

Testing on animals may provide initial information on the effect of a possible shortterm exposure on human health. Acute toxicity is defined as the toxic effect of a substance after a single oral, dermal, or inhalative application. For acute oral toxicity, for instance, LD50 is defined as the amount of substance expressed in mg per kg body weight which has a lethal effect on 50% of the test animals after a single oral application. Such tests are useful in that they assess the toxicity of a material relative to that of other known compounds. 

I will try to cover only the synthesis of the known indole type derivatives known to be hallucinogenic. You may notice that the primary amine used in these syntheses may be substituted with many other primary amines, much like the reaction of lysergic acid with a primary amine in LSD formulas. The potencies of the primary amines used in LSD are not the same as for the indole derivatives. According to tests on animals, the duration and potency of indole derivatives are as follows. 

In order to reduce animal testing under REACH, and also because of the ban on the marketing of cosmetic products/ingredients tested on animals, a broader strategy for risk assessment has been suggested. One element suggested in this strategy is the TTC concept. 

The Committee had required as a minimum, teratogenicity testing in two species, one of which should preferably be a non-rodent, for one generation only. They also recognised the limitations of teratogenicity tests in animals but emphasised that only in the most exceptional circumstances would they release any drug for clinical trial in women of child-bearing age rmtil the appropriate tests on animals had been carried out satisfactorily. 

Moreover, in view of such an universal activity of MYKO 63, EORTC decided in May 1980 to extend to 1982 the period during which this drug will be tested on animal tumors. To date new results increase still further the spectrum of effectiveness of MYKO 63 successful experiments were performed — or are in progress - on tumors such as lymphomas and lymphosarcomas, either radioresistant or radio-sensitive, on neuroblastomas (acute brain tumors, mainly in children), fibroblastomas (muscles tumors) and HeLa (from Helen Lattimer, the first patient who died from this tumor) cervix carcinoma (uterus tumor). 

The NCI scientists discovered that extracts of the bark and needles of a yew tree, Taxus brevifolia of the Pacific Northwest, killed trunor cells. Fresh samples were obtained from the forests in the state of Washington in August 1962. Paclitaxel was first isolated from yew tree extract in 1967, and retested on cells in the laboratory. After it was found to be effective in tests on animals with tmnors, paclitaxel was studied in a large munber of human cancer patients and finally approved by the Food and Drug Administration (FDA) in 1992 for use in treating cancer in people. 

Swiss chemist Albert Hofmann at Sandoz Laboratories synthesizes LSD. After initial testing on animals, Hoffman s subsequent accidental ingestion of the drug in 1943 reveals LSD s hallucinogenic properties. 

By the early nineteenth century, the medicinal use of cannabis spread from Asia and the Middle East to Europe, and finally to the Americas by the mid 1800s. A Western physician named W.B. O Shaughnessey who was working in Calcutta, India, observed the use of cannabis there. After performing tests on animals, the doctor assured himself that cannabis was safe. He developed a solution of cannabis in alcohol, known as a tincture. When placed in the mouth, this tincture proved an effective analgesic (pain reliever). The doctor was also impressed with its muscle relaxant and... 

Before a drug may be tested on humans, it must first be tested on animals. Tests on humans are called clinical trials, and animal trials are often referred to as preclinical trials. Preclinical trials differ from the animal tests mentioned earlier in this chapter. The previously discussed animal tests help the drug discovery team determine and optimize the pharmacodynamic and pharmacokinetic behavior of a hit or lead. Preclinical trials, in contrast, are standardized, industrywide tests. The preclinical tests have technical names such as Segment II Reproductive Study in Rabbits or 6-Month Toxicity Study in Rats. The specific names suggest the exact nature of each study. Each trial seeks to answer predefined safety questions concerning a drug candidate. Preclinical trials do not address the therapeutic effectiveness of the drug candidate in any way. Preclinical trials examine exclusively safety issues. 

The final principle is that there should be no additional unnecessary testing on animals. 

The ingredients used are considered environmentally friendly, mild and not tested on animals. No animal-derived ingredients are used. 

REACH will oblige producers to register all chemical substances produced in or imported into the EU, above a total quantity of 1 tonne per year. Authorisation will be required for certain hazardous substances. The most dangerous substances will either be banned or progressively substituted by safer alternatives. REACH should ensure a high level of protection of human health and the environment as well as the free movement of substances, on their own, in preparations, or in articles, while enhancing competitiveness and innovation. It should also promote the development of alternative methods for the assessment of hazards of substances in order to avoid unnecessary testing on animals. 

Like Rohypnol, GHB is a central nervous system (CNS) depressant, which, when tested on animals, induces a sleep-like state in doses ranging from 0.1 to 1.5 milligrams per kilogram.33 Although many neurotransmitter systems are affected by treatment with GHB, evidence supports the hypothesis that GHB itself acts as a neurotransmitter. This implies that GHB is a naturally occurring chemical in the body that is necessary for normal nervous system functions. Administered as a drug, GHB has been shown to temporarily inhibit the release of dopamine in the brain.34 This inhibition is followed by a marked increase in the release of both dopamine and naturally occurring opioids, such as endorphins.35... 

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