The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Anil Kumar Nain - One of the best experts on this subject based on the ideXlab platform.
-
Molecular interactions of drug Semicarbazide Hydrochloride in aqueous-D-xylose/L-arabinose solutions at different temperatures: Volumetric, acoustic and viscometric study
The Journal of Chemical Thermodynamics, 2020Co-Authors: Ankita, Dinesh Chand, Anil Kumar NainAbstract:Abstract The interactions of drug Semicarbazide Hydrochloride in water and in aqueous-carbohydrate (D-xylose/L-arabinose) solutions from their physicochemical behaviour are studied. Density, ρ, ultrasonic speed, u and viscosity, η of the drug Semicarbazide Hydrochloride in water and in aqueous-D-xylose/L-arabinose (5 wt% and 10 wt% of D-xylose/L-arabinose in water, w/w) solvents were measured as functions of concentrations at temperatures, T = (293.15 – 318.15) K and at atmospheric pressure, p = 101 kPa. The measured data have been utilized to calculate various properties like the apparent molar volume, V φ from density measurements while apparent molar compressibility, K s , ϕ , acoustic impedance, Z and intermolecular free length, Lf from ultrasonic speed measurements. The values obtained from these parameters indicate strong solute–solvent interactions within the solutions. The viscosity data have been analyzed using Jones-Dole equation and coefficients A and B were evaluated. The temperature derivative of B-coefficient, dB/dT together with activation parameters of viscous flow have also been determined. The results are discussed in terms of hydrophilic-hydrophilic and hydrophilic-hydrophobic interactions in these systems along with the structure breaking/making ability of the drug.
-
correlation between physicochemical properties and non covalent interactions involving l arginine l histidine and Semicarbazide Hydrochloride at temperatures from 293 15 to 318 15 k
The Journal of Chemical Thermodynamics, 2020Co-Authors: Jyoti Gupta, Anil Kumar NainAbstract:Abstract Physicochemical properties and the nature of interaction of drug-amino acid have been investigated from the experimentally measured values of densities, ρ, ultrasonic speed, u and viscosities, η of l-arginine and l-histidine in aqueous-Semicarbazide Hydrochloride (1 wt% and 2 wt% Semicarbazide Hydrochloride in water, w/w) solvents over the temperature range of 293.15 K to 318.15 K at an interval of 5 K and at atmospheric pressure. From the experimental densities, the apparent molar volume, V φ , limiting apparent molar volume, V ϕ o and transfer volume, V ϕ , t r o were obtained. Further from the ultrasonic data, thermo-acoustical parameters, such as apparent molar compressibility, K s , ϕ , limiting apparent molar compressibility, K s , ϕ o and transfer compressibility, K s , ϕ , t r ° have been evaluated. The viscosity data have been used to determine Falkenhagen Coefficient, A, Jones-Dole coefficient, B, free energy of activation of viscous flow per mole of solvent, Δ μ 1 o # and solute, Δ μ 2 o # , entropies, Δ S o # and enthalpies, Δ H o # of activation of viscous flow. The results have been interpreted in terms of plausible molecular interactions. The cosphere overlap model has been used to interpret the positive V ϕ , t r o values. These amino acids act as structure maker in aqueous-Semicarbazide Hydrochloride solvents.
-
molecular interactions of drug Semicarbazide Hydrochloride in aqueous d xylose l arabinose solutions at different temperatures volumetric acoustic and viscometric study
The Journal of Chemical Thermodynamics, 2020Co-Authors: Dinesh Chand, Anil Kumar NainAbstract:Abstract The interactions of drug Semicarbazide Hydrochloride in water and in aqueous-carbohydrate (D-xylose/L-arabinose) solutions from their physicochemical behaviour are studied. Density, ρ, ultrasonic speed, u and viscosity, η of the drug Semicarbazide Hydrochloride in water and in aqueous-D-xylose/L-arabinose (5 wt% and 10 wt% of D-xylose/L-arabinose in water, w/w) solvents were measured as functions of concentrations at temperatures, T = (293.15 – 318.15) K and at atmospheric pressure, p = 101 kPa. The measured data have been utilized to calculate various properties like the apparent molar volume, V φ from density measurements while apparent molar compressibility, K s , ϕ , acoustic impedance, Z and intermolecular free length, Lf from ultrasonic speed measurements. The values obtained from these parameters indicate strong solute–solvent interactions within the solutions. The viscosity data have been analyzed using Jones-Dole equation and coefficients A and B were evaluated. The temperature derivative of B-coefficient, dB/dT together with activation parameters of viscous flow have also been determined. The results are discussed in terms of hydrophilic-hydrophilic and hydrophilic-hydrophobic interactions in these systems along with the structure breaking/making ability of the drug.
-
Correlation between physicochemical properties and non-covalent interactions involving l-arginine/l-histidine and Semicarbazide Hydrochloride at temperatures from 293.15 to 318.15 K
The Journal of Chemical Thermodynamics, 2020Co-Authors: Jyoti Gupta, Anil Kumar NainAbstract:Abstract Physicochemical properties and the nature of interaction of drug-amino acid have been investigated from the experimentally measured values of densities, ρ, ultrasonic speed, u and viscosities, η of l-arginine and l-histidine in aqueous-Semicarbazide Hydrochloride (1 wt% and 2 wt% Semicarbazide Hydrochloride in water, w/w) solvents over the temperature range of 293.15 K to 318.15 K at an interval of 5 K and at atmospheric pressure. From the experimental densities, the apparent molar volume, V φ , limiting apparent molar volume, V ϕ o and transfer volume, V ϕ , t r o were obtained. Further from the ultrasonic data, thermo-acoustical parameters, such as apparent molar compressibility, K s , ϕ , limiting apparent molar compressibility, K s , ϕ o and transfer compressibility, K s , ϕ , t r ° have been evaluated. The viscosity data have been used to determine Falkenhagen Coefficient, A, Jones-Dole coefficient, B, free energy of activation of viscous flow per mole of solvent, Δ μ 1 o # and solute, Δ μ 2 o # , entropies, Δ S o # and enthalpies, Δ H o # of activation of viscous flow. The results have been interpreted in terms of plausible molecular interactions. The cosphere overlap model has been used to interpret the positive V ϕ , t r o values. These amino acids act as structure maker in aqueous-Semicarbazide Hydrochloride solvents.
-
effect of concentration and temperature on apparent molar properties of homologous α amino acids in aqueous Semicarbazide Hydrochloride solutions a quest on the concept of kosmotropic chaotropic behaviour of amino acids
The Journal of Chemical Thermodynamics, 2019Co-Authors: Jyoti Gupta, Anil Kumar NainAbstract:Abstract Various non-covalent interactions can be scrutinized by the measurement of physical properties. The nature of interactions between drugs and amino acids governs the functionalization process, so a better understanding demands reliable thermophysical data. Keeping this in mind, we report herein the densities, ρ, ultrasonic speed, u and viscosities, η of glycine, l-alanine, l-valine and l-isoleucine in aqueous-Semicarbazide Hydrochloride (1 wt% and 2 wt% Semicarbazide Hydrochloride in water) solvents in the temperature range of 293.15–318.15 K at an interval of 5 K and at atmospheric pressure. The density data have been used to calculate the apparent molar properties like Vϕ, V ϕ ° and transfer volume, V ϕ , t r ° . From the ultrasonic speed data, thermo-acoustical parameters, such as K s , ϕ , K s , ϕ ° and transfer compressibility, K s , ϕ , t r ° have been evaluated. The viscosity data have been used to calculate Falkenhagen Coefficient, A, Jones-Dole coefficient, B. The hydration numbers, n H has also been evaluated. The entropies, Δ S ° # and enthalpies, Δ H ° # activation parameters, Δ μ 1 ° # and Δ μ 2 ° # were also calculated. The co-sphere overlap model was used to interpret the positive V ϕ , t r ° values. In addition, the values of V ϕ ° , K s , ϕ ° , B and Δ μ 2 ° # have been split into groups’ contributions of the amino acids.
Akiyoshi Nishikawa - One of the best experts on this subject based on the ideXlab platform.
-
chronic toxicity and carcinogenicity of Semicarbazide Hydrochloride in wistar hannover galas rats
Food and Chemical Toxicology, 2014Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi Nishikawa, Kumiko OgawaAbstract:Abstract We performed a combined study to determine the chronic toxicity and carcinogenicity of Semicarbazide Hydrochloride (SEM-HCl). Male and female Wistar Hannover GALAS rats were fed a diet containing SEM-HCl at 0, 10, 50, and 250 ppm for 52 weeks (10 rats/sex/group) or for 104 weeks (50 rats/sex/group). Enlargement of the knee joints was apparent in both sexes at 250 ppm. Reduced body weight was observed at 250 ppm from week 76 only in males. SEM-HCl exerted no toxic effects on hematology, serum biochemistry, or organ weights. Histopathologically, disarrangement of chondrocytes accompanied by increased connective tissues, and degeneration of articular cartilage were found in males at 50 ppm and above and in females at 250 ppm. Mild changes in the elastic laminae were observed at 250 ppm for both sexes in the chronic toxicity study. There were no significant intergroup differences in the incidences or types of any tumors. Taken together, toxicological effects of chronic exposure to SEM-HCI mainly occurred in the bone, cartilage, and aorta. Based on histopathological findings, the no-observed-adverse-effect-level was 10 ppm in males and 50 ppm in females (equal to 0.6 mg/kg/day in males and 3.9 mg/kg/day in females). SEM-HCl was not carcinogenic in rats.
-
age related susceptibility to induction of osteochondral and vascular lesions by Semicarbazide Hydrochloride in rats
Toxicologic Pathology, 2010Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi NishikawaAbstract:To compare the susceptibility to toxicity of Semicarbazide Hydrochloride (SEM-HCl) between young and adult rats, 3- and 20-week-old female SD rats were given a diet containing SEM-HCl at 0, 500, or 1,000 ppm and 0 or 1,000 ppm, respectively, for 4 weeks. Half of the animals were then maintained on basal diet for a further 2 weeks as recovery groups. Only in young rats was deformation of the knee joints as well as thorax and tail observed at 500 and 1,000 ppm. Histopathologically, severe osteochondral lesions, such as disarrangement and thickening of the epiphyseal cartilage and deformation of articular cartilage, were observed, but the severity of these lesions became reduced during the recovery period. In adult rats, osteochondral lesions were relatively mild. Fissures in the cartilage matrix of the tibia were characteristic of adult rats, and in these, reduction of severity was not obvious in the recovery group. In the thoracic aorta, the appearance of elastic laminae was altered only in young rats in both the 4-week treatment and recovery groups. These results suggest that growing animals are more susceptible to toxicity of SEM-HCl than adults are. Effects and the induced lesions link to the developing stage of the target organs.
-
a ninety day toxicity study of Semicarbazide Hydrochloride in wistar hannover galas rats
Food and Chemical Toxicology, 2009Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi NishikawaAbstract:A ninety-day toxicity study of Semicarbazide Hydrochloride (SEM-HCl) was conducted in male and female Wistar Hannover GALAS rats fed diet containing the compound at concentration of 0, 250, 500 and 1000 ppm. Suppression of body weight gain and food consumption was found in both sexes at 1000 ppm throughout the study. Enlargement and deformation of knee joints were obvious at 500 and 1000 ppm from week 3, together with deformation of the thorax and tail. Histopathologically, disarrangement of chondrocytes and fissures in the cartilage matrix were apparent at all doses tested in epiphyseal and articular cartilage. The severity of these lesions increased dose-dependently, accompanied by increased connective tissues and bone deformation at high doses. Additionally, compact bones at 1000 ppm became thin, suggesting loss of bone mass. In the thoracic aorta, the edges of elastic laminae became rough and the interlaminar spaces were altered from a fibrillar to a rod or globular appearance. No abnormalities were detected in any other organs. Taken together, toxicological effects of subchronic exposure to SEM-HCI were mainly observed in bone, cartilage and the aorta, with the no-observed-adverse-effect-level estimated from the present histopathological examination of less than 250 ppm in both sexes.
Miwa Takahashi - One of the best experts on this subject based on the ideXlab platform.
-
chronic toxicity and carcinogenicity of Semicarbazide Hydrochloride in wistar hannover galas rats
Food and Chemical Toxicology, 2014Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi Nishikawa, Kumiko OgawaAbstract:Abstract We performed a combined study to determine the chronic toxicity and carcinogenicity of Semicarbazide Hydrochloride (SEM-HCl). Male and female Wistar Hannover GALAS rats were fed a diet containing SEM-HCl at 0, 10, 50, and 250 ppm for 52 weeks (10 rats/sex/group) or for 104 weeks (50 rats/sex/group). Enlargement of the knee joints was apparent in both sexes at 250 ppm. Reduced body weight was observed at 250 ppm from week 76 only in males. SEM-HCl exerted no toxic effects on hematology, serum biochemistry, or organ weights. Histopathologically, disarrangement of chondrocytes accompanied by increased connective tissues, and degeneration of articular cartilage were found in males at 50 ppm and above and in females at 250 ppm. Mild changes in the elastic laminae were observed at 250 ppm for both sexes in the chronic toxicity study. There were no significant intergroup differences in the incidences or types of any tumors. Taken together, toxicological effects of chronic exposure to SEM-HCI mainly occurred in the bone, cartilage, and aorta. Based on histopathological findings, the no-observed-adverse-effect-level was 10 ppm in males and 50 ppm in females (equal to 0.6 mg/kg/day in males and 3.9 mg/kg/day in females). SEM-HCl was not carcinogenic in rats.
-
age related susceptibility to induction of osteochondral and vascular lesions by Semicarbazide Hydrochloride in rats
Toxicologic Pathology, 2010Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi NishikawaAbstract:To compare the susceptibility to toxicity of Semicarbazide Hydrochloride (SEM-HCl) between young and adult rats, 3- and 20-week-old female SD rats were given a diet containing SEM-HCl at 0, 500, or 1,000 ppm and 0 or 1,000 ppm, respectively, for 4 weeks. Half of the animals were then maintained on basal diet for a further 2 weeks as recovery groups. Only in young rats was deformation of the knee joints as well as thorax and tail observed at 500 and 1,000 ppm. Histopathologically, severe osteochondral lesions, such as disarrangement and thickening of the epiphyseal cartilage and deformation of articular cartilage, were observed, but the severity of these lesions became reduced during the recovery period. In adult rats, osteochondral lesions were relatively mild. Fissures in the cartilage matrix of the tibia were characteristic of adult rats, and in these, reduction of severity was not obvious in the recovery group. In the thoracic aorta, the appearance of elastic laminae was altered only in young rats in both the 4-week treatment and recovery groups. These results suggest that growing animals are more susceptible to toxicity of SEM-HCl than adults are. Effects and the induced lesions link to the developing stage of the target organs.
-
a ninety day toxicity study of Semicarbazide Hydrochloride in wistar hannover galas rats
Food and Chemical Toxicology, 2009Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi NishikawaAbstract:A ninety-day toxicity study of Semicarbazide Hydrochloride (SEM-HCl) was conducted in male and female Wistar Hannover GALAS rats fed diet containing the compound at concentration of 0, 250, 500 and 1000 ppm. Suppression of body weight gain and food consumption was found in both sexes at 1000 ppm throughout the study. Enlargement and deformation of knee joints were obvious at 500 and 1000 ppm from week 3, together with deformation of the thorax and tail. Histopathologically, disarrangement of chondrocytes and fissures in the cartilage matrix were apparent at all doses tested in epiphyseal and articular cartilage. The severity of these lesions increased dose-dependently, accompanied by increased connective tissues and bone deformation at high doses. Additionally, compact bones at 1000 ppm became thin, suggesting loss of bone mass. In the thoracic aorta, the edges of elastic laminae became rough and the interlaminar spaces were altered from a fibrillar to a rod or globular appearance. No abnormalities were detected in any other organs. Taken together, toxicological effects of subchronic exposure to SEM-HCI were mainly observed in bone, cartilage and the aorta, with the no-observed-adverse-effect-level estimated from the present histopathological examination of less than 250 ppm in both sexes.
Midori Yoshida - One of the best experts on this subject based on the ideXlab platform.
-
chronic toxicity and carcinogenicity of Semicarbazide Hydrochloride in wistar hannover galas rats
Food and Chemical Toxicology, 2014Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi Nishikawa, Kumiko OgawaAbstract:Abstract We performed a combined study to determine the chronic toxicity and carcinogenicity of Semicarbazide Hydrochloride (SEM-HCl). Male and female Wistar Hannover GALAS rats were fed a diet containing SEM-HCl at 0, 10, 50, and 250 ppm for 52 weeks (10 rats/sex/group) or for 104 weeks (50 rats/sex/group). Enlargement of the knee joints was apparent in both sexes at 250 ppm. Reduced body weight was observed at 250 ppm from week 76 only in males. SEM-HCl exerted no toxic effects on hematology, serum biochemistry, or organ weights. Histopathologically, disarrangement of chondrocytes accompanied by increased connective tissues, and degeneration of articular cartilage were found in males at 50 ppm and above and in females at 250 ppm. Mild changes in the elastic laminae were observed at 250 ppm for both sexes in the chronic toxicity study. There were no significant intergroup differences in the incidences or types of any tumors. Taken together, toxicological effects of chronic exposure to SEM-HCI mainly occurred in the bone, cartilage, and aorta. Based on histopathological findings, the no-observed-adverse-effect-level was 10 ppm in males and 50 ppm in females (equal to 0.6 mg/kg/day in males and 3.9 mg/kg/day in females). SEM-HCl was not carcinogenic in rats.
-
age related susceptibility to induction of osteochondral and vascular lesions by Semicarbazide Hydrochloride in rats
Toxicologic Pathology, 2010Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi NishikawaAbstract:To compare the susceptibility to toxicity of Semicarbazide Hydrochloride (SEM-HCl) between young and adult rats, 3- and 20-week-old female SD rats were given a diet containing SEM-HCl at 0, 500, or 1,000 ppm and 0 or 1,000 ppm, respectively, for 4 weeks. Half of the animals were then maintained on basal diet for a further 2 weeks as recovery groups. Only in young rats was deformation of the knee joints as well as thorax and tail observed at 500 and 1,000 ppm. Histopathologically, severe osteochondral lesions, such as disarrangement and thickening of the epiphyseal cartilage and deformation of articular cartilage, were observed, but the severity of these lesions became reduced during the recovery period. In adult rats, osteochondral lesions were relatively mild. Fissures in the cartilage matrix of the tibia were characteristic of adult rats, and in these, reduction of severity was not obvious in the recovery group. In the thoracic aorta, the appearance of elastic laminae was altered only in young rats in both the 4-week treatment and recovery groups. These results suggest that growing animals are more susceptible to toxicity of SEM-HCl than adults are. Effects and the induced lesions link to the developing stage of the target organs.
-
a ninety day toxicity study of Semicarbazide Hydrochloride in wistar hannover galas rats
Food and Chemical Toxicology, 2009Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi NishikawaAbstract:A ninety-day toxicity study of Semicarbazide Hydrochloride (SEM-HCl) was conducted in male and female Wistar Hannover GALAS rats fed diet containing the compound at concentration of 0, 250, 500 and 1000 ppm. Suppression of body weight gain and food consumption was found in both sexes at 1000 ppm throughout the study. Enlargement and deformation of knee joints were obvious at 500 and 1000 ppm from week 3, together with deformation of the thorax and tail. Histopathologically, disarrangement of chondrocytes and fissures in the cartilage matrix were apparent at all doses tested in epiphyseal and articular cartilage. The severity of these lesions increased dose-dependently, accompanied by increased connective tissues and bone deformation at high doses. Additionally, compact bones at 1000 ppm became thin, suggesting loss of bone mass. In the thoracic aorta, the edges of elastic laminae became rough and the interlaminar spaces were altered from a fibrillar to a rod or globular appearance. No abnormalities were detected in any other organs. Taken together, toxicological effects of subchronic exposure to SEM-HCI were mainly observed in bone, cartilage and the aorta, with the no-observed-adverse-effect-level estimated from the present histopathological examination of less than 250 ppm in both sexes.
Kaoru Inoue - One of the best experts on this subject based on the ideXlab platform.
-
chronic toxicity and carcinogenicity of Semicarbazide Hydrochloride in wistar hannover galas rats
Food and Chemical Toxicology, 2014Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi Nishikawa, Kumiko OgawaAbstract:Abstract We performed a combined study to determine the chronic toxicity and carcinogenicity of Semicarbazide Hydrochloride (SEM-HCl). Male and female Wistar Hannover GALAS rats were fed a diet containing SEM-HCl at 0, 10, 50, and 250 ppm for 52 weeks (10 rats/sex/group) or for 104 weeks (50 rats/sex/group). Enlargement of the knee joints was apparent in both sexes at 250 ppm. Reduced body weight was observed at 250 ppm from week 76 only in males. SEM-HCl exerted no toxic effects on hematology, serum biochemistry, or organ weights. Histopathologically, disarrangement of chondrocytes accompanied by increased connective tissues, and degeneration of articular cartilage were found in males at 50 ppm and above and in females at 250 ppm. Mild changes in the elastic laminae were observed at 250 ppm for both sexes in the chronic toxicity study. There were no significant intergroup differences in the incidences or types of any tumors. Taken together, toxicological effects of chronic exposure to SEM-HCI mainly occurred in the bone, cartilage, and aorta. Based on histopathological findings, the no-observed-adverse-effect-level was 10 ppm in males and 50 ppm in females (equal to 0.6 mg/kg/day in males and 3.9 mg/kg/day in females). SEM-HCl was not carcinogenic in rats.
-
age related susceptibility to induction of osteochondral and vascular lesions by Semicarbazide Hydrochloride in rats
Toxicologic Pathology, 2010Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi NishikawaAbstract:To compare the susceptibility to toxicity of Semicarbazide Hydrochloride (SEM-HCl) between young and adult rats, 3- and 20-week-old female SD rats were given a diet containing SEM-HCl at 0, 500, or 1,000 ppm and 0 or 1,000 ppm, respectively, for 4 weeks. Half of the animals were then maintained on basal diet for a further 2 weeks as recovery groups. Only in young rats was deformation of the knee joints as well as thorax and tail observed at 500 and 1,000 ppm. Histopathologically, severe osteochondral lesions, such as disarrangement and thickening of the epiphyseal cartilage and deformation of articular cartilage, were observed, but the severity of these lesions became reduced during the recovery period. In adult rats, osteochondral lesions were relatively mild. Fissures in the cartilage matrix of the tibia were characteristic of adult rats, and in these, reduction of severity was not obvious in the recovery group. In the thoracic aorta, the appearance of elastic laminae was altered only in young rats in both the 4-week treatment and recovery groups. These results suggest that growing animals are more susceptible to toxicity of SEM-HCl than adults are. Effects and the induced lesions link to the developing stage of the target organs.
-
a ninety day toxicity study of Semicarbazide Hydrochloride in wistar hannover galas rats
Food and Chemical Toxicology, 2009Co-Authors: Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi NishikawaAbstract:A ninety-day toxicity study of Semicarbazide Hydrochloride (SEM-HCl) was conducted in male and female Wistar Hannover GALAS rats fed diet containing the compound at concentration of 0, 250, 500 and 1000 ppm. Suppression of body weight gain and food consumption was found in both sexes at 1000 ppm throughout the study. Enlargement and deformation of knee joints were obvious at 500 and 1000 ppm from week 3, together with deformation of the thorax and tail. Histopathologically, disarrangement of chondrocytes and fissures in the cartilage matrix were apparent at all doses tested in epiphyseal and articular cartilage. The severity of these lesions increased dose-dependently, accompanied by increased connective tissues and bone deformation at high doses. Additionally, compact bones at 1000 ppm became thin, suggesting loss of bone mass. In the thoracic aorta, the edges of elastic laminae became rough and the interlaminar spaces were altered from a fibrillar to a rod or globular appearance. No abnormalities were detected in any other organs. Taken together, toxicological effects of subchronic exposure to SEM-HCI were mainly observed in bone, cartilage and the aorta, with the no-observed-adverse-effect-level estimated from the present histopathological examination of less than 250 ppm in both sexes.
