equipment, except for the natural rubber gloves, contained
the peak B material, and the polyethylene bags used in this
process contained peak C and peak D material!
The gloves were used to prevent contamination from
human skin, and the material of the gloves was polyethylene
in runs 1-3 and natural rubber in run 4 (Tables 1 and 3).
The wet cake contacted the natural rubber gloves during
transfer to the dryer pans. Thus, the wet cake of AlaGln
during run 4 (Tables 1 and 3) contained peak B material at
high concentration (runs 1 and 3 were treated with polyeth-
ylene gloves). However, the concentration of peak B changed
with the location of the crystal of the wet cake. Peak B
content on the surface of the lump crystal was 32 ppm, but
only 5 ppm in the central part. Such distribution was evidence
of the fact that peak B represented contamination from the
surface of the crystal. It was found that a pair of natural
rubber gloves released more than 2 g of the peak B material
6
with EtOH (about 10 ppm in 200 kg production ap-
proximately).
Peak C and peak D were found in polyethylene bags. The
manufacturer of the polyethylene bags used 5 ppm of these
two reagents as stabilizers. Polyethylene bags were used as
containers for the wet cake storage. The polyethylene bag
was changed in plant production. The bag size was 200 L
on the plant scale but 90 L in the pilot plant.
Each polyethylene was a low-density type, and the bags
and the “stabilizers” were from different manufacturers.
During the wet cake storage, these stabilizer compounds
transferred from the polyethylene to the cake. The experi-
ments on storage of the wet cake using miniature bags,
prepared from the same polyethylenes of real bags, were
carried out, and the results are shown in Table 4. 200 g of
AlaGln wet cake, prepared from 100 g of AlaGln dry cake
and 100 g of EtOH, was packed into a polyethylene bag
Figure 1. HPLC chart of MeOH. Washing the filter is
described in the text; run 2 is listed in Tables 1 and 3.
and B (BHT and DOP) were supposedly from the filter itself
because the blank test (see Experimental Section) also
showed peaks A and B. Peak B was from a widely used
polymer plasticizer, and it was easily detected from vinyl
4
tape, the electric wire peel, a neutral filter, and so on. The
concentrations of these compounds were measured by HPLC
analysis (Table 3). Fundamentally, peak A (BHT) and peak
B (DOP) were found in MeOH treated with a blank filter.
The measured value was revised with the blank filter
concentration.
2
revised to 30-cm size. It was stored in an isothermal box at
5
0°C for 5 h, followed by drying the cake and analyzing
the concentration of impurities. The transfer of the polymer
stabilizer to the product by the organic solvent media is a
7
widely known phenomenon in the food area. In this case,
8
the temperature of the filtered cake was high, and EtOH
Study on the Turbidity Compounds
was used in the crystallization. The compounds causing
turbidity were transferred very easily from the gloves and
bags to the cake.
During runs 2 and 3 in Table 1, the turbidity was caused
by the 200-L polyethylene bag. It was caused by natural
rubber gloves during run 4 (Tables 1 and 3). To prevent the
turbidity, the process has been changed as follows: the
material of the gloves was returned to polyethylene. In this
case, the contact time with the wet cake is very short;
therefore, there is no worry about turbidity. The containers
Prior to the purification, the crude AlaGln cake showed
no turbidity In this purification, during the treatment with
the resin column followed by activated carbon, no turbidity
was found in the water.5
From these results (the wet cake showed turbidity), the
product did not become contaminated with turbidity com-
pounds before the activated carbon treatment or after drying.
Therefore, all of the equipment, crystallizer, feed pipe,
pressure filter, pumps, clothes, gloves, and storage bags were
checked. That is, those components were rinsed with MeOH,
and the MeOH was analyzed by HPLC. After that, no
(
6) A pair of natural rubber gloves (20 g) was soaked in 300 mL of EtOH for
0 min under reflux conditions, and the EtOH was evaporated. The residual
was peak B material, and the weight was 2.2 g.
1
(
4) The operation rooms for this process have HEPA filters. DOP was used
for the tracer for the HEPA filter ability (“DOP filter test”). However, the
tested HEPA filter never spreads DOP.; Irie, T.; Mitui, Y.; Saiki, A.; Suzuki,
M.; Shionozuka, M.; Otake, N. EValuation of organic components in clean
(7) For example: Bourges, F.; Bureau, G.; Pascat, B. Food Addit. Contam.
1993, 10, 443. Sarbach, C.; Yagoubi, N.; Sauzieres, J.; Renaux, D.; Ferrir,
D.; Postaire, E. Int. J. Parm. 1996, 140, 169. We searched the database
“CA File” on CAS on line (April, 1998, updated) for the words
“polyethylene” and “transfer”; all of the literature sources were within the
food area.
room air using atmospheric pressure ionization mass spectrometer, The
th
1
0
Symposium of air cleaning and contamination control Japan, 1991.
(5) Before the resin treatment, the water solution (about 30 wt %) of the crude
cake did not show turbidity in an optical view check.
(8) The temperature of the filtration cake was maintained over 40 °C because
of polymorphism.
350
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