Organic Methods Evaluation Branch
OSHA Salt Lake Technical Center
Salt Lake City, UT 84165-0200

1. General Discussion

1.1. Background

1.1.1. History of procedure

This evaluation was undertaken to develop a sampling and analytical procedure for MIAK at 50 ppm OSHA PEL (Ref. 5.1.).

1.1.2. Toxic effects (This section is for information only and should not be taken as the basis of OSHA policy.)

Eye and nose irritation are encountered at low levels. Narcosis and death can result at high concentrations. The toxic behavior would be expected to resemble that of methyl isobutyl ketone closely (Ref. 5.2.).

1.1.3. Potential workplace exposure

MIAK is used as a solvent for cellulose esters, acrylics and vinyl copolymers (Ref. 5.2. and 5.3.). No data is available on the extent of work place exposure.

1.1.4. Physical properties (Ref. 5.2., 5.3. and 5.4.)

CAS number:	110-12-3
IMIS number:	1776
Molecular weight:	114.19
Molecular formula:	C7H14O
Density:	0.888 at 20°C
Boiling point:	144°C at 101.3 kPa (760 mmHg)
Solubility:	slightly soluble in water soluble in alcohol and ether
Chemical name:	MIAK (methyl isoamyl ketone)
Synonyms:	5-Methyl-2-hexanone; 2-Methyl-5-hexanone; Methyl isopentyl ketone
Appearance:	colorless, clear liquid with a pleasant odor
Structure:	(CH3)2CHCH2CH2COCH3

1.2. Limit defining parameters

The detection limit of the analytical procedure, including a 9:1 split ratio, is 1.09 ng per injection. This is the amount of analyte which will give a peak whose height is approximately five times the baseline noise.

2. Sampling Procedure

2.1. Apparatus

2.1.1. Samples are collected by using a personal sampling pump that can be calibrated to within ± 5% of the recommended flow rate with the sampling device in line.

2.1.2. Samples are collected with 4-mm i.d. × 6-mm o.d. × 7.0 cm glass sampling tubes packed with two sections of 20/40 mesh activated charcoal separated by a 2-mm portion of urethane foam. The activated charcoal is prepared from coconut shells and is fired at 600°C prior to packing. The sampling section contains 100-mg and the back section contains 50-mg of charcoal. A 3-mm portion of urethane foam is placed between the outlet end of the tube and the backup section. A plug of Silane treated glass wool is placed in front of the sampling section.

2.2. Reagents

No sampling reagents are required.

2.3. Sampling technique

2.3.1. Immediately before sampling, break off the ends of the charcoal tube. All tubes should be from the same lot.

2.3.2. Attach the sampling tube to the sampling pump with flexible tubing. Position the tube so that sampled air first passes through the 100-mg section.

2.3.3. Attach the tube vertically in the employee's breathing zone in such a manner that it does not impede work performance.

2.3.4. After sampling for the appropriate time, remove the sampling tube and seal it with plastic caps.

2.3.5. Wrap each sample end-to-end with an OSHA seal (Form 21).

2.3.6. Record the air volume for each sample, and list any possible interferences.

2.3.7. Submit at least one blank for each set of samples. Handle the blank in the same manner as the samples, except no air is drawn through it.

2.3.8. Ship the samples to the laboratory for analysis immediately after sampling. If delay is unavoidable, store the samples at reduced temperature.

2.3.9. Submit bulk samples for analysis in a separate container. Do not ship them with air samples.

2.4. Desorption efficiency

Sixteen vials, each containing a 100-mg portion of charcoal, were divided into four groups of four vials each. Vials of the first group were liquid spiked with 2.6 µL of 10% MIAK in carbon disulfide. Vials of the other three groups were liquid spiked with 1.4, 2.6 and 5.2 µL of neat MIAK (d=0.888), respectively. These amount represent 0.1×, 0.5×, 1.0×, and 2.0× the target concentration. The vials were stored overnight in a refrigerator (0°C), desorbed with 1.0 mL of the desorbing solution, and analyzed as in Section 3. The average desorption efficiency was 96.3%. The results are listed in Table 2.4.

Table 2.4.
Desorption Efficiency

Sample #	Amount Spiked, µg	Amount Found, µg	% Recovered
D1 D2 D3 D4	229 229 229 229	214 214 222 218	93.6 93.6 97.0 95.3
		Average of 0.1× PEL = 94.9%
D5 D6 D7 D8	1231 1231 1231 1231	1145 1193 1180 1298	92.5 96.9 95.9 97.4
		Average of 0.5× PEL = 95.7%
D9 D10 D11 D12	2286 2286 2286 2286	2232 2235 2226 2221	97.6 97.8 97.4 97.1
		Average of 1× PEL = 97.5%
D13 D14 D15 D16 D17	4571 4571 4571 4571 Blank	4453 4429 4392 4438 0	97.4 96.9 96.1 97.1 Blank
		Average of 2× PEL = 96.9%

2.5. Retention efficiency

Five charcoal tubes were each liquid spiked with 2.6 µL (1× PEL) of neat MIAK. These were allowed to equilibrate for 2 hours and then 10 L of humid air (~80% relative humidity) were drawn through each tube at 0.2 L/min. Then the tubes were desorbed with 1.0 mL of desorbing solution, and analyzed as in Section 3. The results are listed in Table 2.5.

Table 2.5.
Retention Efficiency

Sample #	Amount Spiked, µg	Amount Found, µg	% Recovered
R1 R2 R3 R4 R5	2286 2286 2286 2286 2286	2131 2111 2137 2146 2133	93.2 92.4 93.5 93.9 93.3
			Average = 93.3%

2.6. Sample storage

Twelve charcoal tubes were each liquid spiked with 2.6 µL (1× PEL) of neat MIAK. These were allowed to equilibrate for 2 hours and then 10 L of humid air (~80% relative humidity) were drawn through each tube at 0.2 L/min. Half of the tubes were stored in a drawer at ambient temperature, and the other half were stored in a refrigerator (0°C). After ten days they were extracted and analyzed as in Section 3. The results are given in Tables 2.6.1. and 2.6.2.

Table 2.6.1.
Ambient Storage

Days Stored	Amount Spiked, µg	Amount Found, µg	% Recovered
10 10 10 10 10 10	2286 2286 2286 2286 2286 2286	1299 1460 1356 1526 1231 1291	56.8 63.9 59.3 66.8 53.8 56.5
			Average = 59.5%

Table 2.6.2
Refrigerator Storage

Days Stored	Amount Spiked, µg	Amount Found, µg	% Recovered
10 10 10 10 10 10	2286 2286 2286 2286 2286 2286	2183 2207 2166 2175 2178 2178	95.5 96.6 94.7 95.1 95.3 95.3
			Average = 95.4%

2.7. Recommended air volume and sampling rate

2.7.1. The recommended air volume is 10 L.

2.7.2. The recommended flow rate is 0.2 L/min.

2.8. Interferences (sampling)

It is not known if any compounds will interfere with the collection of MIAK. Any suspected interferences should be reported to the laboratory with submitted samples.

2.9. Safety precautions (sampling)

2.9.1. Attach the sampling equipment in such a manner that it will not interfere with work performance or employee safety.

2.9.2. Follow all safety practices that apply to the work area being sampled.

3. Analytical Procedure

3.1. Apparatus

3.1.1. A GC equipped with an FID. A Hewlett-Packard 5890 Gas Chromatograph equipped with a 7673A Autosampler and an FID was used in this evaluation.

3.1.2. A GC column capable of separating MIAK and the internal standard from any interferences. A 60 m × 0.32 mm i.d. (0.5 µm film) DB-WAX capillary column was used in this evaluation.

3.1.3. An electronic integrator or some other suitable means to measure detector response. A Waters 860 Networking Computer System was used in this evaluation.

3.1.4. Volumetric flasks, pipets, and syringes for preparing standards, making dilutions and performing injections.

3.1.5. Vials, 2-mL, and 4-mL, with PTFE-lined caps.

3.2. Reagents

3.2.1. MIAK. 5-Methyl-2-hexanone, 99%, was obtained from Aldrich Chemical Company.

3.2.2. Reagent grade solvent or better should be used.

3.2.3. Carbon disulfide. The carbon disulfide used in this evaluation was purchased from EM Science.

3.2.4. Dimethyl formamide (DMF). The DMF was purchased from Burdick and Jackson.

3.2.5. p-Cymene. The p-cymene used as internal standard was purchased from Aldrich Chemical Company.

3.2.6. Desorbing solution. The desorbing solution is prepared by adding 250 µL of p-cymene to 1 L of carbon disulfide/DMF (99:1, v/v).

3.3. Standard preparation

Prepare standards at concentrations of 1 µL and 4 µL of o-chloro-toluene per milliliter of desorbing solution. At least two standards at 1 µL/mL are prepared. Standards must be used the day they are prepared.

3.4. Sample preparation

3.4.1. Transfer the 100-mg section of the sampling tube to a 2-mL vial. Place the 50-mg backup section in a separate 2-mL vial.

3.4.2. Add 1.0 mL of desorbing solution to each vial and seal with a Teflon-lined cap.

3.4.3. Shake the vials vigorously several times during the next 30 min.

3.5. Analysis

3.5.1. Instrument conditions

Column:	DB-WAX, 60 m × 0.32 mm i.d., 0.5 µm film
Injector temperature:	180°C
Detector temperature:	200°C
Column temperature:	90°C (initial temp)
Temperature program:	hold initial temp 3 min, increase temp at 10 °C/min to 160°C, hold final temp 1 min
Gas flow rates:
column:     septum purge:     FID:     FID makeup:     FID:	2.0 mL/min (hydrogen) 1.2 mL/min (hydrogen) 34 mL/min (hydrogen) 30 mL/min (nitrogen) 480 mL/min (air)
Injection volume:	1 µL
Split ratio:	9:1
Retention time:	6.48 min (MIAK) 8.60 min (p-cymene)

3.5.2. Chromatogram (Figure 1.)

3.5.3. Measure detector response using a suitable method such as electronic integration.

3.6. Interferences (analytical)

3.6.1. Any collected compound which produces an FID response and has a similar retention time as MIAK or the internal standard is a potential interference.

3.6.2. GC conditions may generally be varied to circumvent interferences.

3.6.3. Retention time on a single column is not proof of chemical identity. Analysis by an alternate GC column, high performance liquid chromatography (HPLC) and confirmation by mass spectrometry are additional means of identification.

3.7. Calculations

3.7.1. An internal standard (ISTD) calibration method is used. The linear nature of FID allows the use of a point calibration, but the bracketing of samples with analytical standards is a good practice.

3.7.2. Determine the µg/mL of MIAK in both sections of each sample and blank from the calibration curve. If MIAK is found on the backup section, it is added to the amount found on the front section. Blank corrections should be performed before adding the results together.

3.7.3. Determine the air concentration by using the following formula.

mg/m3 =

(µg/mL, blank corrected) × (desorption volume, mL) (air volume, L) × (desorption efficiency, decimal)

ppm =

(mg/m)(24.46) (114.19)

where

24.46 114.19

= =

molar volume (liters) at 101.3 kPa (760 mmHg) and 25°C molecular weight of MIAK

3.8. Safety precautions (analytical)

3.8.1. Avoid skin contact and air exposure to MIAK.

3.8.2. Avoid skin contact with all solvents.

3.8.3. Wear safety glasses at all times.

4. Recommendation for Further Study

This method should be fully validated.

Figure 1. Chromatogram of MIAK at 0.5× target level

5. References

5.1. "Code of Federal Regulations", 29 CFR 1910.1000, Table Z-1-A. Limits for Air Contaminants, U.S. Government Printing Office, Washington, D.C., 1990.

5.2. Sitting, M., Handbook of Toxic and Hazardous Chemicals, Noyes Publications, Park Ridge, N.J., 1981; p 456.

5.3. Documentation of the Threshold Limit Values and Biological Exposure Indices, American Conference of Governmental Industrial Hygienist INC., 5th ed., 1986; p 400.

5.4. Weast, RC., Astle, MJ., and Beyer, WH., Handbook of Chemistry and Physics, 68th ed., CRC Press Inca, Boca Raton, Florida, 1987-88.