1.1 Background

1.1.1 History of procedure

Butyl butyrate and isobutyl isobutyrate have been proposed as a replacement for the cellosolves in the manufacturing of circuit boards. Sampling for butyl butyrate and isobutyl isobutyrate using charcoal tubes had good retention and storage efficiencies. Desorption of both butyl butyrate and isobutyl isobutyrate with carbon disulfide showed nonconstant desorption ranging from 91.5% to 97.6% for loadings of 0.592 to 11.85 mg butyl butyrate and 91.8% to 98.9% for loadings of 0.59 to 11.8 mg isobutyl isobutyrate. The butyl butyrate and isobutyl isobutyrate desorption efficiency using 1:99 dimethyl formamide:carbon disulfide was constant and averaged 101% for butyl butyrate and 100% for isobutyl isobutyrate.

1.1.2 Potential workplace exposure (Ref. 5.1)

Butyl butyrate is used in the manufacture of circuit boards, and in the flavoring and fragrance industries.

1.1.3 Toxic Effects (This section is for information purposes and should not be taken as the basis for OSHA policy.) (Ref. 5.2)

Butyl butyrate and isobutyl isobutyrate are moderate eye, mucous membrane, and respiratory irritants. An exposure of 5000 ppm for 6 hours killed two out of three rats exposed, but there was no exposure symptoms when rats were exposed to 500 ppm for 6 hours. Isobutyl isobutyrate exposure of 5000 ppm for 6 hours killed half the rats exposed.

1.1.4 Physical properties:

Butyl butyrate (Ref. 5.1):

Compound: Synonyms: Molecular weight: Density: Freezing point: Boiling point: Flash point: Color: Molecular formula: CAS: IMIS: RTECS: DOT:

CH3(CH2)2COO(CH2)3CH3 butyl butanoate; butanoic acid butyl ester; butyric acid butyl ester; n-butyl n-butyrate 144.21 0.871 -91.5°C 166°C  53.5°C (128°F) (open cup) clear liquid  C8H16O2 109-21-7  SLC1 22464; ES8120000 UN 2528

Isobutyl isobutyrate (Ref. 5.3):

Compound: Synonyms:  Molecular weight: Density:  Freezing point: Boiling point: Flash point:  Color: Molecular formula: CAS: IMIS: RTECS: DOT:

(CH3)2CHCOOCH2CH(CH3)2 2-Methylpropyl isobulyrate; 2-Methylpropyl 2-methylpropanoate; Isobutyric acid, isobuutyl ester; 2-Methylpropyl 2-methypropionate 144.21  0.855  -81°C  148°C 37°C (99°F) (open cup) clear liquid C8H16O2  97-85-8 1537 44147; NQ5250000  UN 2528

1.2 Limit defining parameters

1.2.1 The detection limit of the analytical procedure for both compounds is 5 ng with a 1 µL injection or 5 µg/mL. This is the smallest amount that could be detected under normal operating conditions.

1.2.2 The overall detection limit for both compounds are based on a 10 liter air volume.

1.3 Advantages

1.3.1 The sampling procedure is convenient.

1.3.2 The analytical method is reproducible and sensitive.

1.3.3 Reanalysis of samples is possible.

1.3.4 It may be possible to analyze other compounds at the same time.

1.3.5 Interferences may be avoided by proper selection of column and GC parameters.

1.4 Disadvantages

none known

2.1 Apparatus

2.1.1 A calibrated personal sampling pump, the flow of which can be determined within ±5% at the recommended flow.

2.1.2 Charcoal tubes, lot 120, containing 100 mg adsorbing section with a 50 mg backup section separated by a 2 mm portion of urethane foam, with a silanized glass wool plug before the adsorbing section and a 3 mm plug of urethane foam at the back of the backup section. The ends are flame sealed and the glass tube containing the adsorbent is 7 cm long, with a 6 mm O.D. and 4 mm I.D., SKC tubes or equivalent.

2.2 Sampling technique

2.2.1 Open the ends of the charcoal tube immediately before sampling.

2.2.2 Connect the charcoal tube to the sampling pump with flexible tubing.

2.2.3 Place the tubes in a vertical position to minimize channeling, with the smaller section towards the pump.

2.2.4 Air being sampled should not pass through any hose or tubing before entering the charcoal tube.

2.2.5 Seal the charcoal tube with plastic caps immediately after sampling. Seal each sample lengthwise with OSHA Form-21 sealing tape.

2.2.6 with each batch of samples, submit at least one blank tube from the same lot used for samples. This tube should be subjected to exactly the same handling as the samples (break ends, seal, & transport) except that no air is drawn through it.

2.2.7 Transport the samples (and corresponding paperwork) to the lab for analysis.

2.2.8 Bulks submitted for analysis must be shipped in a separate mailing container from other samples.

2.3 Desorption efficiency

2.3.1 Six tubes were spiked at each loading of 0.52 mg (10.0 ppm), 2.96 mg (50.1 ppm), 5.92 mg (100 ppm), and 11.9 mg (201 ppm) butyl butyrate, and 0.59 mg (10.0 ppm), 2.95 mg (50.0 ppm), 5.9 mg (100 ppm), and 11.8 mg (200 ppm) isobutyl Isobutyrate. They were allowed to equilibrate overnight at room temperature. They were opened, each section placed into a separate 2 mL vial, desorbed with 1 mL carbon disulfide for 30 minutes with occasional shaking, and analyzed by GC-FID. The desorption for butyl butyrate was non-constant ranging from 91.5% to 97.6%. (Table 2.3.1.1)

2.3.2 Six tubes were spiked at each loading of 0.5,)2 mg (10.0 Ppm), 2.96 mg (50.1 ppm), 5.92 mg (100 ppm), and 11.9 mg (201 ppm) butyl butyrate, and 0.19 mg (10.0 ppm), 2.95 mg (50.0 ppm), 5.9 mg (100 lipm), and 11.8 mg (200 ppm) isobutyl isobutyrate. They were allowed to equilibrate overnight at room temperature. They were opened, each section placed into a separate 2 mL vial, desorbed with 1 mL, 1:99 dimethyl formamide:carbon disulfide, for 30 minutes with occasional shaking, and were analyzed by GC-FID. The desorption efficiency averaged 101% for butyl butyrate and 100% for isobutyl isobutylrate. (Tables 2.3.2.1 and 2.3.2.2)

Table 2.3.2.1 Butyl Butyrate  1:99 DMF:Carbon Disulfide Desorption Efficiency
Tube #		%	Recovered
	0.592mg	2.96mg	5.92mg	11.8mg
1 2 3 4 5 6	97.4 100 100 97.5 100 101	101 100 101 102 102 101	102 102 102 102 102 101	102 102 102 103 102 102
average	99.3	101	102	102
overall average: 101%
standard deviation: ±1.41

Table 2.3.2.2 Isobutyl Isobutyrate 1:99 DMF:Carbon Disulfide Desorption Efficiency
Tube #		%	Recovered
	0.59mg	2.95mg	5.9mg	11.8mg
1 2 3 4 5 6	101 101 100 99.2 100 100	102 101 100 101 99.2 99.9	100 100 99.7 100 100 100	101 101 101 100 101 100
average	100	100	99.9	101
overall average: 100%
standard deviation: ±0.763

2.4 Retention efficiency

Six tubes were spiked with 5.92 mg (100 ppm) butyl butyrate and 5.9 mg (100 ppm) isobutyl isobutyrate, allowed to equilibrate overnight, and had 10 liters humid air (90% RH) pulled through them. They were opened, desorbed, and analyzed by GC-FID. The retention efficiency averaged 101% for butyl butyrate and 99.5% isobutyl isobutyrate. There was no butyl butyrate or isobutyl isobutyrate found on the backup portions of the tubes. (Tables 2.4.1 and 2.4.2) 

2.5 Storage

Tubes were spiked with 5.92 mg (100 ppm) butyl butyrate (BUBU) and 5.9 mg (100 ppm) isobutyl isobutyrate (IBUIBU), and stored at room temperature until opened and analyzed. The recoveries averaged 100% for the 14 days stored for both compounds. (Table 2.5)

2.6 Precision

The precision was calculated using the area counts from six injections of each standard at concentrations of 0.592, 2.96, 5.92, and 11.8 mg/mL butyl butyrate acid 0.59, 2.95, 5.9, and 11.8 mg/mL isobutyl isobutyrate in the desorbing solution. The pooled coefficient of variation for butyl butyrate was 0.000499 and for isobutyl isobutyrate was 0.00473. (Tables 2.6.1 and 2.6.2)

where:

A(1), A(2), A(3), A(4) = # of Injections at each level
CVl, CV2, CV3, CV4 = Coefficients at each level

2.7 Air volume and sampling rate studied

2.7.1 The air volume studied was 10 liters.

2.7.2 The sampling rate studied was 0.2 liters per minute.

2.8 Interferences

Suspected interferences should be listed on sample data sheets.

2.9 Safety precautions

2.9.1 Sampling equipment should be placed on an employee in a manner that does not interfere with work performance or safety.

2.9.2 Safety glasses should be worn at all times In designated areas.

2.9.3 Follow all safety practices that apply to the workplace being sampled.

3.1 Apparatus

3.1.1 Gas chromatograph equipped with a flame ionization detector. A HP5890 gas chromatograph was used in this study.

3.1.2 GC column capable of separating the analyte and an internal standard from any interferences The column used in this study was a 15 meter DB-WAX capillary column 0.32 mm I.D. with a O.25 µm film thickness. Other columns that can be used are a longer DB-WAX column, such as a 60 meter column, or a 60 meter DB-1 capillary column 0.32 mm I.D. with a 1.0 µm film thickness.

3.1.3 An electronic integrator or some other suitable method of measuring peak areas.

3.1.4 Two milliliter vials with Teflon-lined caps.

3.1.5. A 10 µL syringe or other convenient size for sample injection.

3.1.6. Pipets for dispensing the desorbing solution. The Glenco 1 mL dispenser was used in this method.

3.1.7 Volumetric flasks - 5 mL and other convenient sizes for preparing standards.

3.2 Reagents

3.2.1 Purified GC grade nitrogen, hydrogen, and air.

3.2.2 Butyl butyrate, Reagent grade

3.2.3 Isobutyl isobutyrate, Reagent grade

3.2.4 Dimethyl formamide, Reagent grade

3.2.5 Carbon disulfide, Reagent grade

3.2.6 n-Hexylbenzene Reagent grade

3.2.7 The desorbing solution is prepared by adding 250 mL n-hexylbenzene to 1 liter of a 1:99 dimethyl formamide:carbon disulfide solution to obtain a concentration of 0.25 µL/mL n-hexylbenzene in the solution. The n-hexylbenzene is used as the internal standard.

3.3 Sample preparation

3.3.1 Sample tubes are opened and the front and back section of each tube are placed in separate 2 mL vials.

3.3.2 Each section is desorbed with 1 mL of the desorbing solution.

3.3.3 The vials are sealed immediately and allowed to desorb for 30 minutes with occasional shaking.

3.4 Standard preparation

3.4.1 At least two separate standards are prepared by diluting a known quantity of butyl butyrate and isobutyl isobutyrate with the desorbing solution.

3.4.2 A third analytical standard should be prepared at a higher concentration to check the linearity of the detector. For this study two standard at 1 µL/mL (0.871 mg/mL butyl butyrate and 0.855 mg/mL isobutyrate), one standard at 4 µL/mL (3.48 mg/mL butyl butyrate and 3.42 mg/mL isobutyl isobutyrate), one standard at 8 µL/mL (6.97 mg/mL butyl butyrate and 6.84 mg/mL isobutyl isobutyrate), and one standard at 14 µL/mL (12.2 mg/mL butyl butyrate and 11.97 mg/mL isobutyl isobutyrate) were used.

3.5 Analysis

3.5.1 Gas chromatograph conditions.

Flow rates (mL/min.)	Temperature (°C)
Nitrogen (make-up): 30 Hydrogen (carrier): 2 Hydrogen (detector): 30 Air: 350	Injector: 181 Detector: 221 Column: 60  10°/min to 130

Injection size: 1µL 
Chromatogram:see Figure 1

3.5.2 Gas chromatograph conditions for 60 meter DB-1 capillary column.

Flow rates (mL/min.)	Temperature (°C)
Nitrogen (make-up): 30  Hydrogen (carrier): 2  Hydrogen (detector): 60 Air: 420	Injector: 180 Detector: 220 Column: 50  10°/min to 180

Injection size: 1 µL 
Chromatogram: see Figure 2

3.5.3 Peak areas are measured by an integrator or other suitable means.

3.6 Interferences (analytical)

3.6.1 Any compound having the general retention time of the analyte or the internal standard used is an interference. Possible interferences should be listed on the sample data sheet. GC parameters should be adjusted if necessary so these interferences will pose no problems.

3.6.2 Retention time data on a single column is rot considered proof of chemical identity. Samples over the target concentration should be confirmed by GC/Mass Spec or other suitable means.

3.7 Calculations

3.7.1 The instrument is calibrated with a standard of 0.871 mg/mL (1 µL/mL) butyl butyrate and 0.855 mg/mL (1 µL/mL) isobutyl isobutyrate in the desorbing solution. The linearity of the calibration is checked with a standard of 3.48 mg/mL (4 µL/mL) butyl butyrate and 3.42 mg/mL(4 µL/mL) isobutyl isobutyrate in the desorbing solution.

3.7.2 If the calibration is non-linear, two more standards must be analyzed so a calibration curve can be plotted and sample values obtained.

3.7.3 To calculate the concentration of analyte in the air sample the following formulas are used:



3.7.4 The above equations can be consolidated to form the following formula. To calculate the ppm of analyte in the sample based on a 10 liter sample:

µg/mL  24.45 MW DV 10 L DE

= = = = = =

concentration of analyte in sample or standard Molar volume (liters/mole) at 25°C and 760 mm Hg.  Molecular weight (g/mole) Desorption volume 10 liter air sample Desorption efficiency

3.7.5 This calculation is done for each section of the sampling tube and the results added together.

3.8 Safety precautions

3.8.1 All handling of solvents should be done in a hood.

3.8.2 Avoid skin contact with all chemicals.

3.8.3 Wear safety glasses, gloves and a lab coat at all times.

Figure 1. An analytical standard containing 871 µg/mL butyl butyrate and 855 µg/mL isobutyl isobutyrate in 1:99 dimethylformamide:carbon disulfide with 0.25 µL/mL n-hexylbenzene internal standard, analyzed on a 15 meter DB-WAX capillary column.

Figure 2. An analytical standard containing 871 µg/mL butyl butyrate and 855 µg/mL isobutyl isobutyrate in 1:99 dimethyl formamide:carbon disulfide with 0.25 µL/mL n-hexylbenzene internal standard, analyzed on a 60 meter DB-1 capillary column.

5.1 Windholz, M., "The Merck Index", Eleventh Edition, Merck Co., Rahway N.J., 1989, p. 239.

5.2 Clayton, G.D.t Clayton, F.E., "Patty's Industrial Hygiene and Toxicology", Third Edition, Volume 2A, John Wiley & Sons, New York N.Y., 1981, p. 2286.

5.3 Sax, N., Lewis, R., "Hawley's Condensed Chemical Dictionary", Eleventh Edition, Van Nostrand Reinhcld Co., New York, 1987, p. 654.