Studies on the Adverse Effects of Methyltetrahydrophthalic Anhydride exposure

Introduction

Acid anhydrides are widely used in the production of alkyd resins and as curing agents for epoxy resins. The major health hazards are mucosal and skin irritation and sensitisation of the respiratory tract.[1] Organic acid anhydrides such as methyltetrahydrophthalic anhydride (MTHPA;Figure 1) are used in the production of alkyd and polyester resins and as curing agents for epoxy resins. Studies of effects from exposure to acid anhydrides have mainly been concerned with symptoms from the lower airways.[2] 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.

Risk factors for sensitisation to methyltetrahydrophthalic anhydride

To examine an association between specific IgE to methyltetrahydrophthalic anhydride (MTHPA) and exposure time, atopic history, smoking habits, and total IgE concentrations. A cross sectional survey was carried out on a population of 148 workers from two condenser plants using epoxy resin with methyltetrahydrophthalic anhydride, an acid anhydride curing agent known to cause allergy. Using a Pharmacia CAP system with a methyltetrahydrophthalic anhydride human serum albumin conjugate, specific IgE antibody was detected in serum from 97 (66%) out of the 148 workers exposed to MTHPA. Stepwise multiple linear regression analysis showed a striking relation between log concentrations of specific and total IgE (P < 0.0001). Furthermore, when the workers were divided into two groups according to a cut-off point (100 IU/ml) between low and high total IgE, current smoking was significantly (P = 0.025) associated with specific IgE production only in the group with low total IgE (< 100 IU/ml). Smoking is the most significant risk factor for raising specific IgE to methyltetrahydrophthalic anhydride in the group with low total IgE concentrations.[1]

The relationship of atopy, smoking, and sensitization to methyltetrahydrophthalic anhydride

Yokota K et al. investigated the association of smoking, atopy and helper T (Th) cytokines with sensitization to methyltetrahydrophthalic anhydride (MTHPA) in occupationally exposed subjects. A population of 147 workers from two condenser plants using epoxy resin with MTHPA underwent a questionnaire survey and serologic investigation. Total and methyltetrahydrophthalic anhydride-specific IgE levels were measured by the Pharmacia CAP system, and serum levels of interleukin (IL)-4, IL-13, and interferon-gamma (IFN-g) by enzyme immunoassay. The Pharmacia CAP-Phadiatop test, which detects serum IgE specific to most common aeroallergens, was also used. Ninety-six (65%) of the currently exposed workers had positive methyltetrahydrophthalic anhydride-specific IgE. A significant difference was found in the frequency of positive specific IgE between atopic and non-atopic subjects (P<0.01), but not between smokers and non-smokers. As for smoking, the frequency of positive specific IgE was significantly (P<0.005) higher in smokers than that in non-smokers in non-atopic subjects. Multiple logistic regression analysis also confirmed significant contribution of atopy and smoking to the development of specific IgE (odds ration=3.2 and 10.5, respectively), suggesting that atopic subjects who became sensitized to P<0.01 may become sensitized to common aeroallergens. On the other hand, none of the Th cytokines contributed to the elevation of specific IgE levels. These results suggest that atopic subjects and non-atopic smokers are at increased rist of sensitization by P<0.01. However, to evaluate conclusively the effect of atopy on sensitization, further prospective studies are necessary.[3]

Exposure-response relationships in rhinitis and conjunctivitis caused by methyltetrahydrophthalic anhydride

To examine exposure-response relationships in the occurrence of symptoms of the eyes and airways in workers exposed to methyltetrahydrophthalic anhydride (MTHPA). A population of 111 workers from 2 condenser plants (A and B) using epoxy resin with MTHPA underwent a questionnaire survey and serology investigations, and data obtained on 95 subjects in assembly and inspection lines were analyzed for this study. In all, 24 (65%) of 37 workers in plant A and 38 (66%) of 58 workers in plant B had positive MTHPA-specific IgE. The air levels of methyltetrahydrophthalic anhydride detected in assembly and inspection lines were higher in plant A than in plant B (geometric mean 25.5-63.9 and 4.93-5.49 microg/m3, respectively). IgE-sensitized workers in each plant had significantly (P < 0.05) more complaints regarding the eyes and nose than did unsensitized workers, suggesting that there is an IgE-mediated mechanism in most of these symptoms. The sensitized workers in plant A had higher frequencies for symptoms of the eyes, nose, and pharynx than did those in plant B (P < 0.02). Furthermore, only 15% of persons often displayed work-related symptoms among the 20 symptomatic workers in plant B as compared with 73% of the 26 symptomatic workers in plant A (P < 0.0001). These results can be explained by the difference in the methyltetrahydrophthalic anhydride levels measured in the lines between the two plants. In plant B the minimal level of MTHPA that was associated with work-related symptoms was 15-22 microg/m3, which was lower than the geometric mean levels detected in assembly and inspection lines in plant A. These results suggest that methyltetrahydrophthalic anhydride exposure at levels above 15 microg/m3 should be avoided to prevent the development of occupational allergic diseases in most workers.[4]

References

[1]Yokota K, Johyama Y, Yamaguchi K, Fujiki Y, Takeshita T, Morimoto K. Risk factors for sensitisation to methyltetrahydrophthalic anhydride. Occup Environ Med. 1997;54(9):667-670. doi:10.1136/oem.54.9.667

[2]Nielsen J, Welinder H, Bensryd I, Andersson P, Skerfving S. Symptoms and immunologic markers induced by exposure to methyltetrahydrophthalic anhydride. Allergy. 1994;49(4):281-286. doi:10.1111/j.1398-9995.1994.tb02661.x

[3]Yokota K, Johyama J, Yamaguchi K, Takeshita T, Morimoto K. The relationship of atopy, smoking, and sensitization to methyltetrahydrophthalic anhydride. Int J Immunopathol Pharmacol. 2004;17(2 Suppl):83-90. doi:10.1177/03946320040170S214

[4]Yokota K, Johyama Y, Yamaguchi K, Takeshita T, Morimoto K. Exposure-response relationships in rhinitis and conjunctivitis caused by methyltetrahydrophthalic anhydride. Int Arch Occup Environ Health. 1999;72(1):14-18. doi:10.1007/s004200050328

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