# Acute and Repeated Toxicological Study of Anti-Inflammatory Herbal Formula, Yeosinsan, in Rats
## 3 Results
### Chronic oral Toxicity
#### 3.2.6 Gross Autopsy and Histopathological Examinations
In the spleen observation, in the female 500 mg\(\cdot\)kg\({}^{-1}\cdot\)d\({}^{-1}\) group and all dose groups at 1000 and 2000 mg\(\cdot\)kg\({}^{-1}\cdot\)d\({}^{-1}\), extramedullary hematopoiesis was observed to be very weak (minimal) to weak (slight). In the dose groups at or over 500 mg\(\cdot\)kg\({}^{-1}\cdot\)d\({}^{-1}\), increased pigmentation was observed to be very weak (minimal) to weak (slight). In addition, in the male control group and the male 500 mg\(\cdot\)kg\({}^{-1}\cdot\)d\({}^{-1}\) dose group, extramedullary hematopoiesis was observed to be very weak (minimal) in 1 and 10 cases, respectively. This was judged to be a change within the normal range. In the observation of the female genitalia (ovary, uterus, and vagina), changes associated with the test substance were not observed. Other observed findings were judged to be spontaneous or accidental changes observed in animals of similar age, given the incidence (Table 7). Regarding the photomicrographs shown in Figure 4, the chronic high-dose group showed extramedullary hematopoiesis and increased pigmentation in the spleen. The chronic high-dose group showed squamous cell hyperplasia in the forestomach (Figure 4L,R). \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Dosage Group (mg\(\cdot\)kg\({}^{-1}\cdot\)d\({}^{-1}\))** & **0** & **500** & **1000** & **2000** \\ \hline \multirow{5}{*}{**Spleen**} & Number examined & 10 & 10 & 10 & 10 \\  & Number unremarkable & 9 & 9 & 5 & 0 \\  & 1\textgreater{} & 1 & 1 \({}^{\text{a}}\) & 3 \({}^{\text{a}}\) & 3 \({}^{\text{a}}\) \\  & 2\textgreater{} & 0 & 0 & 0 & 1 \({}^{\text{a}}\) \\  & Total finding incidence & 1 & 1 \({}^{\text{a}}\) & 3 \({}^{\text{a}}\) & 4 \({}^{\text{a}}\) \\  & Increased pigmentation & 1\textgreater{} & 0 & 1 \({}^{\text{a}}\) & 3 \({}^{\text{a}}\) & 7 \({}^{\text{a}}\) \\  & 2\textgreater{} & 0 & 0 & 1 & 3 \({}^{\text{a}}\) \\  & Total finding incidence & 0 & 1 \({}^{\text{a}}\) & 4 \({}^{\text{a}}\) & 10 \({}^{\text{a}}\) \\ \hline \multirow{5}{*}{**Male**} & **Sternum/Marrow** & Number examined & 10 & 0 & 0 & 10 \\  & Number unremarkable & 10 & 0 & 0 & 10 \\ \hline \multirow{5}{*}{**Sqamous cell hyperplasia, forestomach**} & Number examined & 10 & 10 & 10 & 10 \\  & Number unremarkable & 10 & 10 & 10 & 9 \\  & 1\textgreater{} & 0 & 0 & 0 & 1 \\  & Total finding incidence & 0 & 0 & 0 & 1 \\ \hline \multirow{5}{*}{**Tests**} & Number examined & 10 & 0 & 0 & 10 \\  & Number unremarkable & 10 & 0 & 0 & 9 \\  & 2\textgreater{} & 0 & 0 & 0 & 1 \\  & Total finding incidence & 0 & 0 & 0 & 1 \\ \hline \multirow{5}{*}{**Skin, inguinal**} & Number examined & 10 & 0 & 0 & 10 \\  & Number unremarkable & 10 & 0 & 0 & 10 \\ \hline \multirow{5}{*}{**Spinal cord, cervical**} & Number examined & 10 & 0 & 0 & 10 \\  & Number unremarkable & 10 & 0 & 0 & 10 \\  & Number examined & 10 & 0 & 0 & 10 \\  & Number unremarkable & 10 & 0 & 0 & 10 \\  & Number unremarkable & 10 & 0 & 0 & 10 \\ \hline \multirow{5}{*}{**Female**} & **Spleen** & Number examined & 10 & 10 & 10 & 10 \\  & Number unremarkable & 10 & 4 & 1 & 0 \\  & Extramedullary hematopoiesis & 1\textgreater{} & 0 & 2 \({}^{\text{a}}\) & 4 \({}^{\text{a}}\) & 4 \({}^{\text{a}}\) \\  & Total finding incidence & 0 & 2 \({}^{\text{a}}\) & 4 \({}^{\text{a}}\) & 4 \({}^{\text{a}}\) \\  & Increased pigmentation & 1\textgreater{} & 0 & 5 \({}^{\text{a}}\) & 8 \({}^{\text{a}}\) & 5 \({}^{\text{a}}\) \\  & & 2\textgreater{} & 0 & 0 & 0 & 5 \({}^{\text{a}}\) \\  & Total finding incidence & 0 & 5 \({}^{\text{a}}\) & 8 \({}^{\text{a}}\) & 10 \({}^{\text{a}}\) \\ \hline \multirow{5}{*}{**Sternum/marrow**} & Number examined & 10 & 0 & 0 & 10 \\  & Number unremarkable & 10 & 0 & 0 & 10 \\ \hline \multirow{5}{*}{**Stomach**} & Number examined & 10 & 10 & 10 & 10 \\  & Number unremarkable & 10 & 10 & 10 & 7 \\ \cline{1-1}  & Total finding incidence & 1\textgreater{} & 0 & 0 & 0 & 2 \\ \cline{1-1}  & 2\textgreater{} & 0 & 0 & 0 & 1 \\ \cline{1-1}  & Total finding incidence & 0 & 0 & 0 & 3 \\ \hline \hline \end{tabular}
\end{table}