Number
088-EN
Section
General Section
Use
Sector
Manufacture of bulk, large scale chemicals (including petroleum products)
Manufacture of fine chemicals
Health services
Scientific research and development
Function
Processing aid
Process
Chemical production or refinery in closed process without likelihood of exposure or processes with equivalent containment conditions.
Product category
Processing aids such as pH-regulators, flocculants, percipitant, neutalization agents
Pharmaceuticals
Application
Production of penicillin
Abstract
4-methylpentan-2-one (MIBK) was used for purification of penicillin in a pharmaceutical production. As an alternative the company used a method, where penicillin becomes water soluble through pH adjustment and then the purification can be made by ultra filtration. In this way MIBK was totally phased out.
Substituted substances
4-Methylpentan-2-one
CAS No. 108-10-1 EC No. 203-550-1 Index No. 606-004-00-4
Chemical group
Ketones
Classification: hazard statements
H225 Highly flammable liquid and vapour
H351 Suspected of causing cancer
H332 Harmful if inhaled
H336 May cause drowsiness or dizziness
H319 Causes serious eye irritation
Other adverse effects
The substance is: 2B carcinogen (IARC) as listed in the Substance Database according to SUBSPORT Screening Criteria (SDSC).
Alternative Substances
Water
CAS No. 7732-18-5 EC No. 231-791-2 Index No.
Chemical group
Non-metal oxides
Reliability of information
Evidence of implementation: there is evidence that the solution was implemented and in use at time of publication
Reason substitution
skin/respiratory sensitizing
Hazard Assessment
Substance to be substituted: 4-methylpentan-2-one (MIBK) is possibly carcinogenic to humans (Group 2B), according to the IARC Monographs. Alternative substances: The alternative is water and an unknown pH-adjusting agent. » Check the Substance Database according to SUBSPORTplus Screening Criteria (SDSC)
Description of Substitution
In the manufacturing process of penicillin, the company previously used 4-methylpentan-2-one (methyl isobutyl ketone - MIBK) for purification. Through optimisation and systematic review of well-defined and publicly available "unit operations" for the chemical industry a new method was found. Using pH adjustment penicillin becomes soluble in water. It can thereafter be purified using ultrafiltration. There are several advantages with the new method. MIBK has several properties of concern regarding occupational health and safety. It was replaced by water. Moreover, the new method is performed in a closed system and thereby the employees do not get in contact with the product. Formerly, MIBK was regenerated to be reused. This process is also eliminated. The new method can also be used for purification of other antibiotics. A disadvantage with the new method is that it has been necessary to reengineer production equipment. This investment was, however, quickly recovered, since the new process ensures a higher yield as compared to the old one. The new method has a larger water consumption than before, but the waste water is clean, so that it can be headed directly to the sewers without prior treatment.
Case/substitution evaluation
The alternative was assessed against hazards in hazardous Substance Database according to SUBSPORT Screening Criteria (SDSC) and is not listed in the database. Information is missing for a complete evaluation. But the substitution of a carcinogenic substance is necessary.
State of implementation
Full capacity
Date and place of implementation
1990 Denmark
Type of information supplier
User
Contact
Date, reviewed
December 11, 2020