Amine-curing agent for epoxy resin, bis (4-amino-3-methylcyclohexyl) methane, has been suspected of inducing toxic symptoms in man which resemble collagen disease such as scleroderma or polymyositis.
We studied subacute toxicity of this agent by repeated oral administrations to rats. The agent was administered 25, 37.5, 50, 75 or 100 mg/kg per one dose, 8 times in 10 days or 17 times in 4 weeks or 20-22 times in 4 weeks. When administration had been completed, clinical biochemical tests and histopathological examinations were carried out.
Animals of high dosage group showed suppression of body weight increase and loss of muscular strength of limbs in the administration period. By clinical biochemical tests, elevation of blood components from muscle (CPK, GOT, creatine) was noticed. Also, increase of monoamine oxidase and decrease of alkaline phosphatase were revealed. By histological examinations, skeletal muscle and choroid plexus of brain showed noticeable changes. In muscles of high dosage group, atrophy, degeneration and regeneration of muscle fibers were observed and an increase of fibroblasts was also seen. In choroid plexus, vacuolar changes in epithelial cells were observed, being clearly dose-dependent. No particular change was recognized in skin.
Though scleroderma-like change was not observed in the skin histologically, our results suggest that this amine-curing agent was greatly associated with muscle symptoms in the workers who handled epoxy resin and that it was one of causative agents which induced toxic symptoms like those of collagen disease.

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Adjustments of urinary ALA concentrations as to urinary specific gravity and creatinine were examined for workers exposed to lead and heat. Judging from our findings, we suggested that it was preferable to adopt the specific gravity (UG) at 1.020 as the adjustment value to obtain the correct urinary ALA concentration.
Though corrected values thus obtained were found adequate for urine in the normal range of specific gravity, they failed to be adequate for concentrated urine samples higher than UG 1.025. Urinary volume adjustment was found to be necessary for these concentrated urine in stead of urinary specific gravity adjustment. For the practical purposes, we postulated urinary volume coefficients, which were estimated to be 0.5 for samples ranging from UG 1.026 to 1.030, 0.4 for samples from UG 1.031 to 1.035 and 0.3 for samples from UG 1.036 to 1.040, respectively.

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Workers, who had been exposed to cadmium oxide fume, i.e., engaged in welding work with cadmium containing silver solder in an automobile parts manufacturing factory, were examined in 1975. Twenty two male welders were 22 to 55 years old and exposed to cadmium for periods ranging from 7 months to 23 years.
Excreted urinary cadmium levels varied from 5.7 μg to 184.9 μg per day, and these values were useful indices of most recent exposures in workshop environments. The examinees were divided into three groups according to excreted urinary cadmium levels: five of them in high, eleven in middle, and six in low group, respectively. Workers in high-excretion group complained of considerable subjective symptoms and their urinary protein showed a remarkable increase, compared to middle- and low-excretion groups, and the electrophoretic pattern of urinary proteins showed preponderance of globulins.
Urinary calcium and β₂-microglobulin in the high-excretion group showed a remarkable increase. In all examinees, urinary phosphate, calcium, and β₂-microglobulin were significantly correlated with urinary excreted cadmium.
Furthermore, in the high-excretion group showed a considerable increase of serum creatinine values and reduction of creatinine clearance, and percent tubular reabsorption of phosphate, calcium and β₂-microglobulin decreased. In all examinees, creatinine clearance and percent tubular reabsorption of both phosphate and calcium were significantly negatively correlated with urinary cadmium excretion.
Therefore, five high-excretion workers showed evidence of chronic renal tubular dysfunction and one of these was particularly recoginized as having remarkable renal damage.
The possibility to affirm the effects of exposure to cadmium was suggested on hematological findings related to anemia. Liver function abnormalities were not recoginized. A slight reduction of the respiratory function was found in one worker of the high-excretion group, but radiological examination of chest showed no abnormalities in all examinees.

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The effects of beryllium on cultured cells were investigated. Three cell-lines (HeLa-S3, Vero, HEL-R66) were used in these experiments and they were cultured in Eagle's MEM plus 5 or 10% FBS (Fetal Bovine Serum) containing beryllium in various concentrations. HeLa cells or Vero cells were able to grow in the medium with 10 μg Be/ml (1.1 mM). On the other hand, the growth of HEL cells were strongly inhibited, even when cultured in the medium with 1 μg Be/ml (1.1×10^-1 mM) and the number of living cells showed markedly low level as compared to that of the control samples cultured in the medium without beryllium.
The cytotoxic effects of beryllium on these cells, which were cultured for three days in the medium with beryllium, were observed. None of cytotoxic effects were found on HeLa cells cultured with 0.5 μg/ml (5.5×10^-2 mM) and on Vero cells cultured with 0.05 μg Be/ml (5.5×10^-3 mM), while HEL cells received cytotoxic effects even when cultured in the medium containing 0.05 μg Be/ml (5.5×10^-3 mM), and these effects on the cells appeared strong when cultured in the medium without FBS.
It was revealed from these experiments that HEL cells are very sensitive in terms of toxic effects of beryllium. Therefore, there cells can be used for the toxicological study on low level concentrations of the metal.

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