**7. References**

286 Toxicity and Drug Testing

shown in Figure 7. But even in this situation a general equation (or general line) might be used to correlate both sets of data, albeit with an increase in the regression standard deviation. It remained to be seen exactly how much error was introduced by use of a general

**N**

(47)

**0 2 4 6 8 10**

Fig. 7. Plots of VOC activity, **Y**, against VOC carbon number, **N**, showing how a general equation may be used to correlate two sets of data that give rise to lines of different slope. Various sets of data on toxicological and biological activity, **Y**, for a number of processes were used to construct an equation in which a number of indicator variables, **I**, were used in order to fit all the sets of data into one equation. The result was Eqn. 51 (Abraham *et al*., 2010c).

The 'standard' process was taken as eye irritation thresholds, as log (1/EIT) for which no indicator variable was used. The given processes and the corresponding indicator variables

There are two processes listed in Table 5 that have not been considered here. The data on gaseous anesthesia on tadpoles were derived from aqueous anesthesia together with water to gas partition coefficients, and so are indirect data, and the compounds in the data set for inhalation anesthesia on mice cover a very restricted range of descriptors. Of the 720 data points, 77 were outliers. Nearly all of these were VOCs classed as 'reactive' or 'chemical' in respiratory tract irritation in mice, or VOCs that acted by specific effects in odor detection thresholds. The remaining 643 data points all refer to nonreactive VOCs or to VOCs that act through selective and not specific effects. The SD value of 0.357 in Eqn. 47 is quite good by comparison to the various SD values for individual processes, suggesting that the general equation has incorporated these with little loss in accuracy; the predicted standard deviation in Eqn. 47 is only 0.357 log units. The equation is scaled to eye irritation thresholds, but it is noteworthy that the coefficient for the NPT indicator variable is nearly zero. Thus EIT and NPT can be estimated through Eqn. 48 for any nonreactive VOC for which the relevant

**Y** = -7.805 + 0.056 · **E** + 1.587 · **S** + 3.431· **A** + 1.440· **B** + 0.754 · **L +** 0.553· **Idr + +** 2.777 ·**Iodt** -0.036· **Inpt** + 6.923· **Imac** + 0.440· **Ird50** + 8.161· **Itad** + 7.437· **Icon** +

equation.

+ 4.959· **Idav** 

are shown in Table 5.

descriptors are available.

**Y**

**30**

**25**

**20**

**15**

**10**

**5**

**0**

(N = 643, SD = 0.357, R2 = 0.992, F = 6083.0)


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**13** 

*Brazil* 

*Mikania glomerata* **and** *M. laevigata***:** 

**Clinical and Toxicological Advances** 

Thais M. Guimarães de Francisco and Francinete Ramos Campos

*Mikania laevigata* and *M. glomerata*, commonly known as guaco, are important medicinal plant species used in South America for the treatment of respiratory diseases. In folk medicine, their leaves have ample use due to their balsamic, antiophidic, appetite stimulant, antispasmodic, expectorant, and antimalarial properties, among others (Coimbra, 1942; Lucas, 1942; Neves & Sá, 1991; Alice et al., 1995; Gasparetto et al., 2010; Napimoga &

There is also pre-clinical evidence of the anti-inflammatory, anti-allergy, and bronchodilation activities of these species (Fierro et al., 1999; Moura et al., 2002; Suyenaga et al., 2002; Graca et al., 2007a). Due to their important effects, pharmaceutical preparations, including syrup and oral solutions, are freely distributed through various government phytotherapy programs and, thus, are widely used by the population (Gasparetto et al.,

The pharmacological effects of guaco are attributed mainly to the presence of coumarin (1,2 benzopyrone); however, other metabolites have been shown to produce significant pharmacological effects. Studies that have evaluated isolated markers in the mouse model of allergic pneumonitis have demonstrated that coumarin and *o*-coumaric acid are part of the phytocomplex that is responsible for the therapeutic activities of guaco species (Santos et al., 2006). In addition, dihydrocoumarin and syringaldehyde have antioxidant, immunologic and anti-inflammatory properties (Farah & Samuelsson, 1992; Hoult & Paya, 1996; Bortolomeazzi et al., 2007; Stanikunaite et al., 2009; Gu & Xue, 2010). Finally, kaurenoic acid, isolated in high quantities from both species (Fierro et al., 1999; Veneziani et al., 1999; Yatsuda et al., 2005), has been shown to contribute to the effects of guaco through its antimicrobial, antinociceptive, anti-inflammatory and smooth muscle relaxant activities (Block et al., 1998; Costa-Lotufo et al., 2002; Wilkens et al., 2002; Cunha et al., 2003; Cotoras

The presence of these metabolites is directly related to the benefits of guaco, but studies have shown them to be toxic. Dihydrocoumarin administered to groups of rodents led to carcinogenic activity, ulcers, forestomach inflammation, parathyroid gland hyperplasia and increased nephropathy (National Toxicology Program, 1993a). Kaurenoic acid has been shown to kill sea urchin embryos and to cause hemolysis in mouse and human erythrocytes

et al., 2004; Tirapelli et al., 2004; Cavalcanti et al., 2006).

**1. Introduction** 

Yatsuda, 2010).

2010).

João Cleverson Gasparetto, Roberto Pontarolo,

*Department of Pharmacy, Universidade Federal do Paraná,* 

