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 MTHPA 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.     

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 MTHPA 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.     

Study on allergic rhinitis in workers exposed to methyltetrahydrophthalic anhydride

Methylterahydrophthalic anhydride (MTHPA) is used as a hardening agent in an epoxy resin system. Because work-related nasal symptoms were observed in some workers exposed toMTHPA at two condenser plants, a cross-sectional survey was performed to improve their work environment. MeanMTHPA levels in the manufacturing processes to which the workers were routinely assigned were extremely low (1.09-22.4 μg/m3). However, specific IgE antibody (S-IgE) was detected in 9 (32%) of 28 workers. Of these, 8 (89%) had nasal symptoms. An IgE-mediated mechanism seems to be associated with at least some of the cases of work-related nasal symptoms. This indicates that the occupational health administration ofMTHPA cannot be controlled simply by limiting exposure in the work environment. Total IgE (T-IgE) levels were significantly higher in S-IgE-positive workers than in S-IgE-negative workers (geometric mean, 200.5 and 51.3 IU/ml, respectively; p<0.002, unpaired t test). These findings demonstrate that workers in whom S-IgE is less likely to be produced, i.e., those in whom the T-IgE level is 80 IU/ml or less, should be assigned to work in these manufacturing processes.     

Determination of methyltetrahydrophthalic anhydride in air using gas chromatography with electron-capture detection.

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 MTHPA 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 MTHPA exposure in two condenser plants was also assessed by determining MTHPA 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.     

Methyltetrahydrophthalic acid in urine as an indicator of occupational exposure to methyltetrahydrophthalic anhydride

Objective: To investigate whether methyltetrahydrophthalic acid (MTHP acid) in urine can be used as a biomarker for exposure to methyltetrahydrophthalic anhydride (MTHPA). Methods: Workers occupationally exposed to MTHPA were studied in combination with one of the authors, who was experimentally exposed to MTHPA. Air levels of MTHPA were determined by personal sampling in the breathing zone. The MTHPA in air was sampled by silica gel and analyzed by gas chromatography (GC) with electron-capture detection. Urinary levels of MTHP acid, a metabolite of MTHPA, were determined in 15 subjects in total. Urine was collected from 14 workers immediately before the start of the work shift and then after 4 and 8 h, and from one of the authors at intervals during 24 h. MTHP acid in urine was analyzed by GC with mass spectrometric detection. Results: The time-weighted average (TWA) air levels ranged from 1.0 g to 200 g MTHPA/m³ during 8 h work shifts. The urinary levels of MTHP acid increased during exposure and decayed after the end of exposure, with an estimated half-time of about 3 h. A close correlation was found between the TWA air levels of MTHPA and creatinine-adjusted MTHP acid levels in urine collected at the end of the shift (r=0.955; P<0.0001). The current occupational exposure limit of 50 g MTHPA/m³ (Japan Society for Occupational Health) corresponded to about 1300 g MTHP acid/g creatinine, which was equivalent to about 900 nmol/mmol creatinine in the International System of Units (SI). Conclusions: These results indicate that the determination of MTHP acid in urine is suitable for use in the biological monitoring of MTHPA exposure.     

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

Objective: To examine exposure-response relationships in the occurrence of symptoms of the eyes and airways in workers exposed to methyltetrahydrophthalic anhydride (MTHPA). Methods: 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. Results: 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 MTHPA 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 μg/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 MTHPA 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 μg/m³, which was lower than the geometric mean levels detected in assembly and inspection lines in plant A. Conclusions: These results suggest that MTHPA exposure at levels above 15 μg/m³ should be avoided to prevent the development of occupational allergic diseases in most workers. Received: 4 May 1998 / Accepted: 4 August 1998     

Detection and clinical relevance of a type I allergy with occupational exposure to hexahydrophthalic anhydride and methyltetrahydrophthalic anhydride

Summary Hexahydrophthalic anhydride (HHPA) and methyltetrahydrophthalic anhydride (MTHPA) belong to the group of the acid anhydrides and, among other applications, are used in the production of epoxy resins. These substances are known as potent low-molecular allergens and induce predominantly type I allergies according to Coombs and Gell. We examined 110 employees exposed to HHPA and MTHPA. With all of them a RAST was carried out with the commercially available conjugates of phthalic anhydride (PA) and a skin prick test with 1% and 5% acetonic solutions of PA. In 109 of these sera a radio allergo sorbent test (RAST) was carried out with the not commercially available conjugates of HHPA and of MTHPA. With complaints connected with the workplace the working materials used (HHPA, MTHPA) were also checked by means of the skin prick test. With at least one positive immunological finding (in the RAST and/or skin prick test) in connection with complaints at the workplace, we performed a workplace-related inhalation test under experimental conditions. Specific IgE against acid anhydrides was detected in a total of 17 (15.4%) persons. In the challenge test, six (5.4%) sensitisations were shown to be clinically relevant. On inclusion of borderline positive findings with PA conjugates the RAST produced three false negative and one false positive finding compared with a RAST with HHPA and MTHPA conjugates. With the conjugates of trimellitic anhydride, in no case could specific IgE be detected. The skin prick test led, in comparison with the RAST, to three false positive and three false negative findings. With all clinically relevant sensitisations the skin prick test was regarded as positive. RASTs with conjugates of PA and skin prick tests with native acid anhydrides can, according to our investigations, validly ascertain workplace-related sensitisations to HHPA and MTHPA.     

Risk factors for sensitisation and respiratory symptoms among workers exposed to acid anhydrides: a cohort study

OBJECTIVES: To examine the relation between exposure to acid anhydrides and the risk of developing immediate skin prick test responses to acid anhydride human serum albumin (AA-HSA) conjugates or work related respiratory symptoms; to assess whether these relations are modified by atopy or smoking. METHODS: A cohort of 506 workers exposed to phthalic (PA), maleic (MA), and trimellitic anhydride (TMA) was defined. Workers completed questionnaires relating to employment history, respiratory symptoms, and smoking habits. Skin prick tests were done with AA-HSA conjugates and common inhalant allergens. Exposure to acid anhydrides was measured at the time of the survey and a retrospective exposure assessment was done. RESULTS: Information was obtained from 401 (79%) workers. Thirty four (8.8%) had new work related respiratory symptoms that occurred for the first time while working with acid anhydrides and 12 (3.2%) were sensitised, with an immediate skin prick test reaction to AA-HSA conjugates. Sensitisation to acid anhydrides was associated with work related respiratory symptoms and with smoking at the time of exposure to acid anhydride. When all subjects were included and all three acid anhydrides were taken into account there was no consistent evidence for an exposure-response relation, but with the analysis restricted to a factory where only TMA was in use there was an increased prevalence of sensitisation to acid anhydrides and work related respiratory symptoms with increasing full shift exposure. This relation was apparent within the current occupational exposure standard of 40 micrograms.m-3 and was not modified significantly by smoking or atopy. CONCLUSIONS: Intensity of exposure and cigarette smoking may be risk factors for sensitisation to acid anhydrides. Exposure is also a risk factor for respiratory symptoms. As there was evidence for sensitisation to TMA at full shift exposures within the occupational exposure standard this standard should be reviewed.

 

     

Risk factors for breast cancer: relevance to screening.

In a study of risk factors for breast cancer in women aged between 40 and 60 information was obtained from 236 cases identified at a diagnostic clinic and 2962 controls with no breast abnormality who attended a screening clinic. Statistical analysis of the data used information on a further 167 women who had attended both clinics to correct for possible between clinic bias in questionnaire responses. Relative risk was estimated in four 5 year age groups, and a significant excess risk was found for women under 55 who had undergone previous breast biopsy and for women aged 50-55 who were premenopausal or who had a family history of breast cancer. No significant risk was found to be associated with marital status, age at first pregnancy, breast feeding, or use of hormonal drugs. It is concluded that epidemiological information is of little value in identifying high risk groups for a screening programme in this age range.     

Risk factors for endemic giardiasis.

In a mail survey, 171 Hitchcock Clinic patients with giardiasis were compared with an age- and sex-matched control group of 684 clinic patients with respect to potential risk factors. Households with shallow well or surface water sources had an odds ratio (OR) for giardiasis of 2.1 (95% confidence interval (95%CI) 1.3-3.2) compared with households with drilled well or municipal water supply. Other observed risks include family member in day care program (OR 2.2 95%CI 1.3-3.7) and family member with diagnosed giardiasis (OR 17, 95%CI 7.4-37). Previously reported risks such as travel out of country (OR 3.2, 95%CI 1.5-7.2) and camping (OR 1.7, 95%CI 0.9-3.2) were also observed. Virtually no giardiasis risk was observed associated with report of dog or barnyard animal proximity. Control for confounding and adjustment for recall and non-response bias does not materially alter the risk estimates. We suggest that shallow well or surface household water source is an important and previously unrecognized giardiasis risk factor.     

Risk factors for surgery for prostatic hypertrophy.

The purpose of this case-control study was to evaluate potential risk factors for prostatic hypertrophy. The cases were 910 residents of Rhode Island who had a partial or total prostatectomy that was not related to cancer in the years 1985-1987. The controls were 2,003 members of the source population who were selected from a list of holders of Rhode Island driver's licenses or a roster of older Americans compiled by the Health Care Financing Administration. Cases and controls were interviewed by telephone. The risk of prostatic hypertrophy was elevated in Jewish men compared with Protestants and Catholics and in blacks compared with whites. Risk was reduced in ever-married compared with never-married men, in men who had left school at age 16 years or more compared with those who had left earlier, and in relatively tall or relatively heavy men. Coffee drinking and cigarette smoking were inversely but only weakly related to prostatic hypertrophy. There was a relatively strong, although irregular, inverse relation of beer drinking to prostatic hypertrophy. The associations of spirits and wine consumption with prostatic hypertrophy were weak.     

Risk factors for injury among veterinarians.

Work-related injuries among veterinarians are a major problem, but little is known of the specific risk factors involved. The purpose of this nested case-control study, conducted from a comprehensive population-based study of practicing Minnesota veterinarians, was to identify risk factors for job-related injuries. We questioned cases (N = 193) on exposures occurring in the month before their injury, and we questioned controls (N = 495) on exposures occurring in a randomly selected month. We used logistic regression to model the dependence of veterinary work-related injury on each exposure of interest and associated confounders. We observed increased rates for prior injuries (RR = 1.7, 95% CI = 1.1-2.6), participation in sports (RR = 1.7, 95% CI = 1.05-2.6), no sharps boxes present (RR = 1.8, 95% CI = 1.01-3.2), current smoking (RR = 4.1, 95% CI = 1.8-9.1), and 6 or fewer hours of sleep (RR = 1.8, 95% CI = 1.0-3.3). We identified a dose response for lifting patients, as follows: lifting 41-75 lb (RR = 3.1, 95% CI = 1.6-5.9), lifting 76-100 lb (RR = 3.2, 95% CI = 1.6-5.9), and lifting more than 100 lb (RR = 6.1, 95% CI = 2.5-15.0). Decreased rates were observed for participation in aerobic activities (RR = 0.6, 95% CI = 0.4-0.99), perception of lower risk (RR = 0.4, 95% CI = 0.2-0.9), and experience (RR = 0.6, 95% CI = 0.4-0.9).     

Risk factors for brain tumors in children.

An exploratory case-control study was conducted in 15 hospitals in the Baltimore, MD, SMSA of possible etiologic factors associated with brain tumors in children. Eighty-four children with brain tumors were compared to normal children and to children with other malignancies. Parents of these children were interviewed about a variety of possible etiologic factors. The findings included: 1) children with brain tumors as well as children with other cancers had a greater tendency than normal children to have been first births and to have had higher birth weights; 2) more children with brain tumors had a sibling with epilepsy or seizures than did normal children, and several of the mothers of children with brain tumors had themselves had epilepsy or a stroke at a relatively young age; 3) there were no significant differences between the groups with regard to several maternal characteristics, including smoking during pregnancy and prior radiation exposure; 4) more children with brain tumors and children with other cancers were found to have had exposures to insecticides than had normal children; 5) fewer children with brain tumors or with other cancers were reported to have had tonsillectomies than normal children; and 6) more of the children with brain tumors as well as the children with other malignancies were reported to have been exposed to farm animals and to sick pets. This exploratory study is one of the first case-control studies of the epidemiology of brain tumors in children, and the results suggest directions for future epidemiologic studies in this relatively uncharted field.     

Risk factors for breast cancer with applications to selection for the prevalence screen.

There have been many studies of individual risk factors for breast cancer; most of the factors concerned may be broadly grouped into demographic and dietary, reproductive history, endocrine related, family history of breast cancer, and previous history of breast disease. Some of these studies have examined the combined effect of these factors. The present case-control study does this in the context of a randomised controlled trial of breast cancer screening. The relative risks that we have obtained are, in general, of similar magnitude to those in other reports. The relevance of the results to a screening programme is discussed.     

Risk factors for surgical site infection in children.

OBJECTIVES: To assess the appropriateness of using the indices developed by the Study on the Efficacy of Nosocomial Infection Control (SENIC) and the National Nosocomial Infections Surveillance (NNIS) project to determine risk factors for surgical site infection (SSI) in children and, if not appropriate, to explore the factors related to SSI in children so these factors could be used in a risk index for pediatric patients. DESIGN: Cohort study during more than 4 years. SETTING: La Paz University Hospital, a national reference center that serves Health Area 5 of Madrid, Spain, which has approximately 500,000 inhabitants. PATIENTS: Convenience sample consisting of the 3,646 children admitted for surgery who had a postsurgical stay of more than 2 days. RESULTS: A model with 8 predictive factors (degree of surgical contamination; duration of surgery; type of surgery; use of a peripheral venous catheter, central venous catheter, or urinary catheter; number of diagnoses; and SSI exposition time) was created. Its relation to the SSI rate was better than that of the SENIC or NNIS indices. Its sensitivity, specificity, and area under the receiver-operating characteristic curve were higher than that of the SENIC index. CONCLUSIONS: The model that we created seems to be more adequate for predicting SSI and evaluating pediatric patients' intrinsic risk than the SENIC and NNIS indices.     

Risk factors for suicide attempts among Navajo adolescents.

BACKGROUND: Rates of adolescent suicide in the United States are highest among Native Americans but little is known about risk factors for suicide attempts in this population. METHODS: To identify risk factors for self-reported suicide attempts by Navajo adolescents, we analyzed the 1988 Indian Health Service Adolescent Health Survey that was administered to 7,254 students in grades 6 through 12 on the Navajo reservation. The responses of students reporting a past suicide attempt were compared to others. RESULTS: Nearly 15 percent (N = 971) reported a previous suicide attempt; over half of those admitted to more than one attempt. Controlling for age, a logistic regression model revealed the following associations with suicide attempts: a history of mental health problems (OR = 3.2); alienation from family and community (OR = 3.2); having a friend who attempted suicide (OR = 2.8); weekly consumption of hard liquor (OR = 2.7); a family history of a suicide or attempt (OR = 2.3); poor self-perception of health (OR = 2.2); a history of physical abuse (OR = 1.9); female gender (OR = 1.7); and sexual abuse (OR = 1.5). CONCLUSIONS: Efforts to prevent adolescent suicide attempts in this population should target individuals with those risk factors of the highest risk and prevalence of exposure.     

Risk factors for HIV-1 shedding in semen.

Semen is the body fluid most commonly associated with sexual transmission of human immunodeficiency virus type-1 (HIV-1). Because the male genitourinary tract is distinct immunologically from blood, compartment-dependent factors may determine HIV-1 shedding in semen. To identify these factors, the authors obtained 411 semen and blood specimens from 149 men seen up to three times. Seminal plasma was assayed for HIV-1 RNA and semen was cocultured for HIV-1 and cytomegalovirus (CMV), which may up-regulate HIV-1 replication. The best multivariate model for predicting a positive semen HIV-1 coculture included two local urogenital factors, increased seminal polymorphonuclear cell count (odds ratio (OR) = 12.6 for each log10 increase/mL, 95% confidence interval (CI) 12.2, 134.5) and a positive CMV coculture (OR = 3.0, 95% CI 1.2, 7.7). The best multivariate model for predicting semen HIV-1 RNA included two systemic host factors, CD4+ cell counts <200/microliter (OR = 3.0, 95 percent CI 1.3, 6.9) and nucleoside antiretroviral therapy (monotherapy: OR = 0.5, 95% CI 0.3, 1.0; combination therapy: OR = 0.4, 95% CI 0.2, 0.9), and a positive CMV coculture (OR = 1.7, 95% CI 1.0, 3.0). Thus, both systemic and local genitourinary tract factors influence the risk of semen HIV-1 shedding. These findings suggest that measures of systemic virus burden alone may not predict semen infectivity reliably.     

Risk factors for surgical-site infections following cesarean section.

OBJECTIVE: To identify risk factors associated with surgical-site infections (SSIs) following cesarean sections. DESIGN: Prospective cohort study. SETTING: High-risk obstetrics and neonatal tertiary-care center in upstate New York. PATIENTS: Population-based sample of 765 patients who underwent cesarean sections at our facility during 6-month periods each year from 1996 through 1998. METHODS: Prospective surgical-site surveillance was conducted using methodology of the National Nosocomial Infections Surveillance System. Infections were identified during admission, within 30 days following the cesarean section, by readmission to the hospital or by a postdischarge survey. RESULTS: Multiple logistic-regression analysis identified four factors independently associated with an increased risk of SSI following cesarean section: absence of antibiotic prophylaxis (odds ratio [OR], 2.63; 95% confidence interval [CI95], 1.50-4.6; P=.008); surgery time (OR, 1.01; CI95, 1.00-1.02; P=.04); <7 prenatal visits (OR, 3.99; CI95, 1.74-9.15; P=.001); and hours of ruptured membranes (OR, 1.02; CI95, 1.01-1.03; P=.04). Patients given antibiotic prophylaxis had significantly lower infection rates than patients who did not receive antibiotic prophylaxis (P=02), whether or not active labor or ruptured membranes were present. CONCLUSION: Among the variables identified as risk factors for SSI, only two have the possibility to be changed through interventions. Antibiotic prophylaxis would benefit all cesarean patients regardless of active labor or ruptured membranes and would decrease morbidity and length of stay. Women's healthcare professionals also must continue to encourage pregnant women to start prenatal visits early in the pregnancy and to maintain scheduled visits throughout the pregnancy to prevent perinatal complications, including postoperative infection.