Methyltetrahydrophthalic anhydride:determination and its effect

Introduction

Methyltetrahydrophthalic anhydride (MTHPA) (Fig. 1) is a viscous liquid (b.p. >200°C) and a well-known industrial inhalant allergens) with a molecular weight of 166. The commercial product is a mixture of isomers.Methyltetrahydrophthalic anhydride, an organic anhydride, is a sensitizing agent even at low air concentrations. Aggressive control of exposure to methyltetrahydrophthalic anhydride in the workplace can minimize the potential for sensitization or occupational allergy. Thus,air monitoring is very important. A method for the air monitoring of methyltetrahydrophthalic anhydride has previously been described, in which methyltetrahydrophthalic anhydride was sampled in Amberlite XAD-2 tubes,eluted in toluene and analyzed by gas chromatography (GC) with flame ionization detector (FID). The method is not sufficiently sensitive and thus requires a long sampling time when low exposure levels are expected. Clearly, there is a need for more sensitive methods of measuring MTHPA at very low concentrations in air. [1]

Isomers of Methyltetrahydrophthalic anhydride

Industrial methyltetrahydrophthalic anhydride is generally produced by a Diels-Alder reaction of hydrocarbons with five carbon atoms (mainly isoprene and pentadiene) and MA. The Diels-Alder adduct may be further modified by isomerization to obtain properties suitable for the epoxy systems. Thus, technically methyltetrahydrophthalic anhydride is a mixture of several isomers. At least three isomers of MTHPA were found by GC-MS.There is reason to believe, by GC retention-time analysis of the pure isomers, that the first two isomers are 3-methyl-cyclohexene-4-1,2-dicarboxylic anhydride and4-methyl-cyclohexene-4-l,2-dicarboxylic anhydride, respectively. The third isomer has not yet been identified.[2]

Determination of methyltetrahydrophthalic anhydride in air

Methyltetrahydrophthalic anhydride (MTHPA) stimulates the production of specific IgE antibodies which can cause occupational allergy even at extremely low levels of exposure (15-22 micrograms/m³). Safe use in industry demands control of the levels of exposure causing allergic diseases. Thus, the air monitoring of MTHPA is very important, and sensitive methods are required to measure low air concentrations or short-time peak exposures. This paper outlines the use of silica-gel tubes for sampling airborne methyltetrahydrophthalic anhydride vapour, followed by analysis using gas chromatography with electron-capture detection. No breakthrough was observed at 113, 217, 673 and 830 micrograms/m³ (sampling volume 30, 60, 60 and 20 l, respectively; relative humidity 40-55%). Concentrations > 1.0 microgram/m³ could be quantified at 20-min sampling with a sampling rate of 1 l/min. The present method can also be applied to measurements of exposure to hexahydrophthalic and methylhexahydrophthalic anhydride. The risk of methyltetrahydrophthalic anhydride exposure in two condenser plants was also assessed by determining methyltetrahydrophthalic anhydride levels in air of the workplace. In conclusion, our method was found to be reliable and sensitive, and can be applied to the evaluation of MTHPA exposure.[1]

Effect of methyltetrahydrophthalic anhydride on humans or animals

Allergy to methyltetrahydrophthalic anhydride in epoxy resin workers

One hundred and forty four current and 26 former workers in a plant producing barrels for rocket guns from an epoxy resin containing methyltetrahydrophthalic anhydride (MTHPA; time weighted average air concentration up to 150 micrograms/m3) were studied. They showed higher frequencies of work related symptoms from the eyes (31 v 0%; p < 0.001), nose (53 v 9%; p < 0.001), pharynx (26 v 6%; p < 0.01), and asthma (11 v 0%; p < 0.05) than 33 controls. Also they had higher rates of positive skin prick test to a conjugate of methyltetrahydrophthalic anhydride and human serum albumin (16 v 0%; p < 0.01), and more had specific IgE and IgG serum antibodies (18 v 0%; p < 0.01 and 12 v 0%; p < 0.05 respectively). There were statistically significant exposure-response relations between exposure and symptoms from eyes and upper airways, dry cough, positive skin prick test, and specific IgE and IgG antibodies. There was a non-significant difference in reaction to metacholine between exposed workers and non-smoking controls. In workers with and without specific IgE antibodies, differences existed in frequency of nasal secretion (54 v 23%; p < 0.05) and dry cough (38 v 12%; p < 0.05). Workers with specific IgG had more dry cough (38 v 12%; p < 0.05), but less symptoms of non-specific bronchial hyperreactivity (0 v 26%; p < 0.05). Atopic workers sneezed more than non-atopic workers (65 v 30%; p < 0.01). In a prospective study five sensitised workers who left the factory became less reactive to metacholine, and became symptom free. In 41 workers who stayed, there was no improvement, despite a 10-fold reduction in exposure. The results show the extreme sensitising properties of MTHPA.[3]

Specific antibodies against methyltetrahydrophthalic anhydride

Occupational exposure to methyltetrahydrophthalic anhydride (MTHPA) from an epoxy resin was studied to evaluate the nature of reported ocular and nasal complaints and some risk factors for sensitization. Methods: Seventy-three current and 22 former workers underwent a questionnaire survey and serologic investigations. Total and MTHPA-specific immunoglobulin (Ig)E levels were measured by means of a Pharmacia CAP system, and MTHPA-specific immunoglobulin (Ig)E levels were measured by enzyme immunoassay. Forty-six (63%) of the currently exposed workers has positive MTHPA-specific IgE, and no significant difference was found between those continuously or intermittently exposed (58% and 71%, respectively). Work-related ocular or nasal symptoms were significantly associated with specific IgE but not with specific IgG4. This finding indicates that there is an IgE-mediated mechanism in most cases of work-related symptoms associated with methyltetrahydrophthalic anhydrid exposure. The total IgE levels were significantly (P < 0.005) higher in the specific IgE-positive workers than in the specific IgE-negative workers (geometric mean 101 IU/ml and 44.8 IU/ml, respectively). Multiple logistic regression analysis also revealed that the group with high total IgE levels (> or = 80 IU/ml) had a significant relative risk (RR 4.7) of producing MTHPA-specific IgE as compared with the group with low total IgE levels (< 80 IU/ml). These results show that methyltetrahydrophthalic anhydrid has a high sensitizing ability and that a high total IgE level is the most significant risk factor for workers exposed to MTHPA. However, to evaluate conclusively the effect of high total IgE levels on sensitization, further prospective studies are necessary.[4]

References

[1]Johyama Y, Yokota K, Fujiki Y, Takeshita T, Morimoto K. Determination of methyltetrahydrophthalic anhydride in air using gas chromatography with electron-capture detection. Ind Health. 1999;37(4):364-368. doi:10.2486/indhealth.37.364

[2]Welinder H, Gustavsson C. Methyltetrahydrophthalic anhydride in air--sampling and analysis. Ann Occup Hyg. 1992;36(2):189-197. doi:10.1093/annhyg/36.2.189

[3]Nielsen J, Welinder H, Horstmann V, Skerfving S. Allergy to methyltetrahydrophthalic anhydride in epoxy resin workers. Br J Ind Med. 1992;49(11):769-775. doi:10.1136/oem.49.11.769

[4]Yokota K, Johyama Y, Yamaguchi K, Fujiki Y, Takeshita T, Morimoto K. Specific antibodies against methyltetrahydrophthalic anhydride and risk factors for sensitization in occupationally exposed subjects. Scand J Work Environ Health. 1997;23(3):214-220. doi:10.5271/sjweh.201

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