A study of the urinary cotinine in the employees deriving from the exposure to nicotine at the Nicorette patch and the Nicorette gum production at Pfizer Health AB, Helsingborg

Abstract: Air sampling and biological sampling have been performed to examine the exposure to nicotine in the Nicorette patch and Nicorette gum production at Pfizer Health AB in Helsingborg, Sweden. For this purpose stationary and personal sampling equipment have been used. At the Nicorette patch production, XAD-2 tubes were used to sample nicotine vapor and at the Nicorette gum production Teflon filters were used to sample the Nicotine Resin Complex 20% IRP (NRC) in the air. NRC is an ion exchange resin that carries the nicotine in the Nicorette gums. Specimens of urine from the presumably not exposed employees, from another source than at in the Nicorette production room, have been examined into the concentration of cotinine, a primary metabolite to nicotine. Cotinine is a reliable substance of measuring the exposure to nicotine. For the nicotine vapor extraction, a slightly modified NIOSH's method NMAM-2544 has been used. The extraction of nicotine from the NRC and the Teflon filters was done with Pfizer's method NM-080-3 and an extra liquid-liquid nicotine extraction has been done as well. The same program, in a liquid chromatograph with tandem mass spectrometry (LC-MS/MS), was used for analyzing both the nicotine from the NRC and the nicotine vapor. The specimens of urine were worked up and the urinary cotinine was isolated and transferred to an organic phase and analyzed in an LC-MS/MS. The average concentration of nicotine in the ambient air in the Nicorette patch manufacturing room is low, 2 ?g/m3. But at the reception position, where the employees collect the Nicorette patches, the concentration of nicotine is 30 ?g/m3 on average. An average of the estimated nicotine exposure, based on the concentration of nicotine in the air samples for the employees, is 70 ?g'h/m3. It is also very obvious, from the urinary cotinine analysis, that there are persons who are exposed to more nicotine than from the nicotine vapor. This may be due to the fact that nicotine has penetrated through the skin when the employees have not used sufficient protection clothes. In the Nicorette gum production room, the concentration of nicotine in the air for a whole working day is measured to an average value of 4 ?g/m3, which is equal to 20 ?g/m3 of NRC. The employees are exposed to the irritating NRC dust, which has on average a concentration of 35 ?g/m3 of nicotine, which equals 175 ?g/m3 of NRC. That gives an estimated average exposure of 90 ?g'h/m3 of nicotine, which equals 450 ?g'h/m3 of NRC, which comes from the nicotine measured in the air samples. The exposure is very well connected to the working procedures. In the Nicorette gum production site, the concentration of cotinine varied very much in relation to the amount of nicotine that the employees were exposed to from the air. The NRC is very irritating and affects the upper respiratory region and causes coughs and sour throats. Irritation from the NRC is noticed in concentrations in the range from 13 ?g/m3 up to 600 ?g/m3. Measured in the concentration of nicotine, the range of the level, in which the irritation is noticed, corresponds to between 2.5 and 120 ?g/m3. That is many times lower than the stated Threshold Limit Value (TLV) for nicotine, 500 ?g/m3.