Propylene glycol monomethyl ether occupational exposure (PGME). 4. Analysis of 2-methoxypropionic acid in urine

Abstract

Objective: The two isomers propylene glycol monomethyl ether [PGME-a (1-methoxy-2-propanol, M2P) and PGME-b (2-methoxy-1-propanol)] have different toxicities due to the different ways they are metabolised. The higher toxicity of PGME-b has been attributed to the formation of 2-methoxypropionic acid (2-MPA) as a metabolite of primary alcohol. Six healthy male volunteers were exposed to PGME-a vapour (15, 50 and 95 ppm) with and without respiratory protection for 6 h, including a 30-min break. They were also exposed to PGME-a liquid (10% or 30% in water), via one hand, for 30 min or 1 h. Commercial products of M2P always contain a small quantity of the b isomer, and GC analysis has shown that the product used for this human volunteer exposure contained approximately 0.3% of the b isomer. The objective of this study was to determine the levels of 2-MPA in urine after these exposures to 99.7% PGME-a. Method: An analytical method developed by Laitinen [6] was used for the determination of 2-MPA in the urine of exposed volunteers. Results: End exposure levels of 2-MPA were found to reach from 1.19 to 3.29 mg/l for inhalation and dermal exposure to PGME-a vapour and from under the detection limit to 2.10 mg/l for exposure of one hand in PGME-a liquid. 2-MPA concentrations in urine samples from a nonexposed person or from a person exposed to PGME-a vapour at 15 ppm (inhalation and dermal exposure) and also from a person exposed to PGME-a vapour up to 95 ppm with respiratory protection (dermal-only exposure) all varied from under the detection limit to 0.30 mg/l and are then not significant.

Final Report on the Safety Assessment of Methoxyisopropanol and Methoxyisopropyl Acetate as Used in Cosmetics

“…Methoxyisopropanol vapor was apparently not absorbed through the skin, as no Methoxyisopropanol was detected in the blood, urine, or expired air after 6 h of exposure (Devanthéry et al 2002). Devanthéry et al (2003) used a study design similar to the one described above (in Devanthéry et al 2002) to determine the amount of the β-isomer metabolite 2-methoxypropionic acid in urine after 6-h exposures to 15, 50, and 95 ppm Methoxyisopropanol α-isomer. The concern was that commercially available Methoxyisopropanol α-isomer contains small amounts of the β-isomer.…”

“…The surprisingly high concentrations of 2-methoxypropionic acid in urine after Methoxyisopropanol α-isomer exposure was attributed to the way the two isomers of Methoxyisopropanol are metabolized. Approximately 2% of the α-isomer is excreted unchanged in the urine, whereas 68% of the β-isomer is released as 2-methoxypropionic acid (Devanthéry et al 2003). Domorandzki et al (2003) incubated human whole blood and liver homogenate with 5 or 50 μg/ml Methoxyisopropyl Acetate and measured the in vitro hydrolysis rate of Methoxyisopropyl Acetate to Methoxyisopropanol in each tissue type.…”

Sensitive headspace gas chromatography analysis of free and conjugated 1-methoxy-2-propanol in urine

“…In spite of some work [7,8] showing the validity of urinary alkoxypropionic acids as biomarker of 1M2P exposure, the need to analyse unmetabolized 1M2P in urine as free or conjugated products is also becoming more interesting for the exposure assessment [9,10], since the conjugated 1M2P fraction appeared to be between 30% and 65% [3]. Moreover, different countries have published a biological exposure index for urinary 1M2P at the end of the work shift, fixed at 15 mg/L by the German Research Foundation [11] and 20 mg/L by the Swiss National Accident Insurance Fund [12].…”