ABSTRACT
OBJECTIVE: To compare the applicability of two risk assessment methods for occupational health risk assessment in enterprises with 1-bromopropane(1-BP) production and utilization. METHODS: Three enterprises with 1-BP production and utilization were selected as the research subjects by a typical sampling method. The exposure concentration of time-weighted average of 1-BP-exposed in worker was detected. The non-carcinogenic health risk of 1-BP was assessed using the USA Environmental Protection Agency(EPA) inhalation risk(EPA assessment model) and the Ministry of Manpower of Singapore(MOM assessment model), and the results were compared. RESULTS: When the EPA method was used for the assessment, the risk assessment results of the four posts in the manufacturing enterprises were all negligible. In the enterprises that use 1-BP, the posts of cleaning machine B and clamping were of medium risk and the other four posts were of low risk based on the occupational exposure limit(OEL) in China used as the reference exposure concentration(RfC). When the 24-hour minimal risk level of USA Agency for Toxic Substances and Disease Registry was used as the RfC, the posts of cleaning machine B and clamping were of extreme high risk; the posts in cleaning machine A and checking were of high risk; the post in the cleaning machine D was of medium risk and the post of cleaning machine C was of low risk. When the MOM assessment model was used for evaluation, the four posts were of low risk in the 1-BP production enterprises. In the enterprises that use 1-BP, the posts of cleaning machine B and clamping were of high risk; the posts of cleaning machine A, cleaning machine D and checking were of medium risk; and the post of cleaning machine C was of low risk. CONCLUSION: When the OEL value is used for risk assessment, the MOM assessment method is more suitable than the EPA assessment method to assess occupational health risks of 1-BP.
ABSTRACT
The solubility of nebivolol hydrochloride was determined in acidic aqueous media in the absence and presence of different concentration of NaCl, NaBr, or NaI at 37 ℃ in order to facilitate proper selection of dissolution media that have adequate discriminating power for enhancing the likelihood of a generic drug product to successfully pass in-vivo bioequivalence test. In the range of pH 5.0 to pH 1.0, the solubility of nebivolol hydrochloride decreased with the decrease in the pH of aqueous solution, and the solubility of nebivolol hydrochloride further decreased with the increase in the concentration of added sodium chloride. The solubility decrease of a few weakly basic drug molecules in acidic media and in higher concentration of added chloride was published previously by other researchers, and the observed decrease in the solubility in the presence of higher chloride concentration was interpreted in terms of common-ion effect. However, the results in this paper showed that the solubility of nebivolol hydrochloride also decreased when sodium chloride was replaced with sodium bromide or iodide. The approach described in this paper (i.e. substituting sodium chloride with sodium bromide or iodide) provides an effective method to verify whether common-ion effect is the true (or at least the sole) driving force behind the observed decrease in the solubility of nebivolol hydrochloride in the presence of sodium chloride. The solubility decrease reported in this paper can be interpreted in terms of salting-out effect of sodium chloride, bromide, and iodide. For hydrochloride salt of a weakly basic drug molecule like nebivolol hydrochloride, its solubility in an acidic dissolution medium can be purposely decreased to the lower end of sink condition by adding sodium chloride to make the resulting medium more discriminating. As shown in this paper, a medium at pH 1.2 with added sodium chloride is discriminating and this medium is shown to be bio-relevant to the in-vivo data collected under fasting condition (in-vivo study protocol was approved by Institutional Review Board).