Hans Welinder

Mortality and cancer morbidity in cohorts of asbestos cement workers and referents

Total and cause specific mortality and cancer morbidity were studied among 1929 asbestos cement workers with an estimated median cumulative exposure of 2.3 fibre (f)-years/ml (median intensity 1.2 f/ml, predominantly chrysotile). A local reference cohort of 1233 industrial workers and non-case referents from the exposed cohort were used for comparisons. The risk for pleural mesothelioma was significantly increased (13 cases out of 592 deaths in workers with at least 20 years latency). No case of peritoneal mesothelioma was found. A significant dose response relation was found for cumulative exposure 40 years or more before the diagnosis, with a multiplicative relative risk (RR) of 1.9 for each f-year/ml. No relation was found with duration of exposure when latency was accounted for. There was a significant overrisk in non-malignant respiratory disease (RR = 2.6). The overall risks for respiratory cancer, excluding mesothelioma, and for gastrointestinal cancer were not significantly increased. Surprisingly, colorectal cancer displayed a clear relation with cumulative dose, with an estimated increase of 1.6% in the incidence density ratio for each f-year/ml (but not with duration of exposure).

Specific antibodies to methyltetrahydrophthalic anhydride in exposed workers

A group of 145 workers exposed to methyltetrahydrophthalic anhydride (MTHPA) was investigated. They were working in a plant which, since 1983, handled an epoxy resin with MTHPA as a hardener. Specific IgE antibodies (RAST) to a conjugate between MTHPA and human serum albumin (HSA) were statistically significantly increased (P= 0·001; 26 subjects = 18% positive) in the exposed group, compared to a non‐exposed control group (n= 33). One positive worker was only exposed for 2 months. Twenty‐three exposed subjects were also skin‐prick test positive to MTHPA‐HSA. The exposed group was divided into three different exposure categories, according to their contact with the epoxy resin. The average exposure levels at the time of the investigation were, in zone 10·085 mg/m3, in zone II0·014 mg/m3, and in zone III 0·010 mg/m3, though the exposure probably had been higher earlier. There was an association between exposure intensity and RAST‐positive persons (P= 0·0025, chi‐square trend test). Forty‐four persons (30%) were smokers, and 16(11%) atopics. No association between sensitization and either atopy or smoking was found. There was an association between exposure intensity and specific IgG antibodies (P= 0·0003, chi‐square trend test). Specific IgG4 antibodies were closely related to specific total IgG antibodies (P= 0·0001). These findings demonstrate that MTHPA is a sensitizing agent at low levels of exposure.

A reduced capacity for unscheduled DNA synthesis in lymphocytes from individuals exposed to propylene oxide and ethylene oxide

Propylene oxide (PO) has been produced commercially since 1925. The main uses of PO are (1) as intermediates in the synthesis of polyurethane foams and polyester resins (via propylene glycol), and (2) as a fumigant for sterilizing plastic medical equipment and foodstuffs (IARC, Vol. 11, 1976). PO has (a) rate constants for chemical reactivity with water and other nucleophils, (b) mutagenicity, and (c) estimates of risk to man, all similar to those observed for ethylene oxide (EO). (For detailed review, see Ehrenberg and Hussain, 1981.) Both PO and EO are carcinogenic in mammals, and EO has also been implicated as a human carcinogen (Hogstedt et at., 1979a, b). Recently we have shown that exposure, both in vivo and in vitro, of an individuals lymphocytes to EO inhibited unscheduled DNA synthesis (UDS), a step in the enzymatic repair of DNA lesions (Pero et al., 1981). Here we report a verification of these earlier results of EO exposure, and further extend our results to include another closely related epoxide, PO, which we have now found also caused inhibition of UDS after occupational exposure. According to our knowledge, this is the first report of the genotoxic effects of PO in man.

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.

IgG antibodies against polyisocyanates in car painters

A group of thirty car painters exposed to vapours and aerosols of paint containing prepolymer and monomer of hexametylene diisocyanate (HDI) was investigated. Specific antibodies against monomer HDI and prepolymerized HDI were analysed with RAST (IgE) and ELISA (IgG) assays after conjugation of the haptens with human serum albumin. There was no significant increase of serum IgG antibodies against HDI monomer, nor of specific IgE antibodies against HDI monomer or prepolymer. Specific IgG antibodies against prepolymerized HDI were significantly increased, as compared with non‐exposed referents (medians 0.11 vs 0.03 absorbance (A)). Six car painters were found to have specific IgG antibodies of subclass 4 against HDI prepolymer, four also against HDI monomer. This shows an association between exposure and specific IgG antibodies. Thirteen subjects had suffered symptoms of rhinitis and/or conjunctivitis, and ten had symptoms from the bronchi (two asthma). There was no significant association between symptoms and levels of specific antibodies. Most of the symptoms were slight and unspecific, probably due to irritative effects of the exposure.

Cadmium metabolism in man

ABSTRACT Twenty-one high frequency solderers, who had been exposed to cadmium (Cd) from a solder for periods ranging from 1 month to 18 years (median 8 months; present time-weighted average 30 nmol/m3; particle size below 1μm) had Cd levels ranging from < 10 to 440 nmol/l in blood and from < 0·5 to 27 μmol/mol creatinine in urine. Individual workers showed considerable variations in blood Cd levels with time, but less variation in urine levels. There was a statistically significant (p < 0·001) increase of Cd in urine with increasing exposure time. Four gas solderers, who had been intermittently exposed for 8-20 years (median 17 years) had Cd levels ranging from 45 to 150 nmol/l and urine levels of from 2 to 20 μmol/mol creatinine. There was no correlation between Cd levels in blood and urine during exposure. After exposure had ceased there was a considerable decay of blood Cd in most subjects. The half-time in 11 people ranged from 25 to 146 days (median 41 days). After the decay blood levels reached a steady state. Concentrations in urine did not decrease, or did so only very slowly. There was a significant increase of levels in urine (p < 0·001) with increasing post-decay levels in blood. There was also a significant increase (0·01 < p < 0·05) of excretion of ß2-microglobulin in urine (range 1·1-18 mg/mol creatinine, median 4·7 mg/mol creatinine) measured 11-15 months after exposure had ceased, with increasing Cd levels in urine. This may indicate an effect on renal tubular function even at kidney Cd loads corresponding to Cd levels in urine of the order of as little as 10 μmol/mol creatinine.

Association of HLA‐DQ5 and HLA‐DR1 with sensitization to organic acidanhydrides

Background Organic acid anhydrides are low molecular weight industrial chemicals, able to cause rhinoconjunctivitis and asthma associated with specific IgE against hapten–carrier protein conjugate. Only a proportion of exposed workers develop IgE‐associated allergy to acid anhydrides.

Are occupational, hobby, or lifestyle exposures associated with Philadelphia chromosome positive chronic myeloid leukaemia?

OBJECTIVES To investigate a broad range of occupational, hobby, and lifestyle exposures, suggested as risk factors for Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML). METHODS A case-control study, comprising 255 Ph+CML patients from southern Sweden and matched controls, was conducted. Individual data on work tasks, hobbies, and lifestyle exposures were obtained by telephone interviews. Occupational hygienists assessed occupational and hobby exposures for each subject individually. Also, occupational titles were obtained from national registries, and group level exposure—that is, the exposure proportion for each occupational title—was assessed with a job exposure matrix. The effects of 11 exposures using individual data and two exposures using group data (organic solvents and animal dust) were estimated. RESULTS For the individual data on organic solvents, an effect was found for moderate or high intensity of exposure (odds ratio (OR) 3.4, 95% confidence interval (95% CI) 1.1 to 11) and for long duration (15–20 years) of exposure (OR 2.1, 95% CI 1.1 to 4.0). By contrast, the group data showed no association (OR 0.69, 95% CI 0.27 to 1.8; moderate or high intensity versus no exposure). For extremely low frequency electromagnetic fields (EMFs), only individual data were available. An association with long occupational exposure to EMFs was found (OR 2.3, 95% CI 1.2 to 4.5). However, no effect of EMF intensity was indicated. No significant effects of benzene, gasoline or diesel, or tobacco smoking were found. OR estimates below unity were suggested for personal use of hair dye and for agricultural exposures. CONCLUSIONS Associations between exposure to organic solvents and EMFs, and Ph+CML were indicated but were not entirely consistent.

Relationship between IgG1 levels and airway responses in guinea pigs actively and passively sensitized to hexahydrophthalic anhydride.

Organic acid anhydrides (OAAs) are industrial chemicals that may cause induction of specific IgE and airway symptoms in exposed workers. They are a good model for studies of relationships between chemical structure and the sensitizing potential of reactive low‐molecular‐weight compounds. Hexahydrophthalic anhydride (HHPA) is such a compound. This study aimed to evaluate the relationship between specific IgG1 levels and airway responses in a model to predict the sensitizing potential of OAAs. Guinea pigs were either actively or passively sensitized to HHPA. For active sensitization, guinea pigs were injected i.d. with 0.1 ml of olive oil (vehicle) or 0.05, 0.5, or 5% HHPA in olive oil. Passive sensitization was performed by i.p. injection of different volumes of antisera (0.75–6 ml, either unheated to keep IgE or heated to destroy IgE) taken form HHPA‐sensitized guinea pigs. Specific antibody levels were evaluated with ELISA and passive cutaneous anaphylaxis. Animals were challenged 16–18 days after active sensitization, or 2 days after passive sensitization, by interatracheal instillation with HHPA conjungated to guinea pig serum albumin (HHPA‐GPSA; 0.05% in saline), and the immediate effects on lung resistance (R1), and plasma extravasation, measured as Evans blue dye extravasation, for up to 6 min were recorded. Active sensitization caused production of specific IgG1. Provocation with HHPA‐GPSA caused an increase of both (R1), and Evans blue dye extravasation, which was dependent upon the active sensitization dose. Challenge with HHPA‐GPSA in passively sensitized guinea pigs also produced an increase in both (R1), and Evans blue dy extravasation which was related to IgG1 level. In the guinea pig model of HHPA‐induced airway allergy, the airway responses are closely related to the serum levels of specific IgG1. Thus, the IgG1 levels induced by the immunization may reflect the sensitizing potential of HHPA.

Mortality and cancer morbidity among cement workers

OBJECTIVE--To explore associations between exposure to cement dust and cause specific mortality and tumour morbidity, especially gastrointestinal tumours. DESIGN--A retrospective cohort study. SUBJECTS AND SETTING--2400 men, employed for at least 12 months in two Swedish cement factories. MAIN OUTCOME MEASURES--Cause specific morality from death certificates (1952-86). Cancer morbidity from tumour registry information (1958-86). Standardised mortality rates (SMRs; national reference rates) and standardised morbidity incidence rates (SIRs; regional reference rates) were calculated. RESULTS--An increased risk of colorectal cancer was found > or = 15 years since the start of employment (SIR 1.6, 95% confidence interval (95% CI) 1.1-2.3), mainly due to an increased risk for tumours in the right part of the colon (SIR 2.7, 95% CI 1.4-4.8), but not in the left part (SIR 1.0, 95% CI 0.3-2.5). There was a numerical increase of rectal cancer (SIR 1.5, 95% CI 0.8-2.5). Exposure (duration of blue collar employment)-response relations were found for right sided colon cancer. After > or = 25 years of cement work, the risk was fourfold (SIR 4.3, 95% CI 1.7-8.9). There was no excess of stomach cancer or respiratory cancer. Neither total mortality nor cause specific mortality were significantly increased. CONCLUSIONS--Diverging risk patterns for tumours with different localisations within the large bowel were found in the morbidity study. Long term exposure to cement dust was a risk factor for right sided colon cancer. The mortality study did not show this risk.