2-Cyanoethyl dimethyldithiocarbamate, a new contact allergen found in accelerator-free nitrile gloves.

BACKGROUND: Allergic contact dermatitis (ACD) from rubber glove usage is usually caused by rubber additives such as the accelerators. However, in analyses of the suspected gloves, ordinary rubber allergens are not always found. Accelerator-free rubber gloves are available, but some patients with accelerator allergy do not tolerate them and might also be patch test positive to them. OBJECTIVES: To identify and chemically characterize a new allergen, 2-cyanoethyl dimethyldithiocarbamate (CEDMC), in rubber gloves. We describe two patient cases: patient 1 that led us to the identification of CEDMC and patient 2 with occupational ACD caused by CEDMC. METHODS: The patients were examined with patch testing including baseline and rubber series, and their own rubber gloves. High-performance liquid chromatography (HPLC) was used for chemical analysis of rubber gloves. The allergen was synthesized and identified by nuclear magnetic resonance, mass spectrometry and infrared spectrometry, and tested on patient 2. RESULTS: CEDMC was identified by HPLC in a nitrile glove associated with hand eczema in patient 1. Patient 2 whose nitrile gloves contained CEDMC was patch test positive to CEDMC. CONCLUSIONS: CEDMC is a new contact allergen in nitrile gloves and probably forms during vulcanization from residual monomer acrylonitrile and rubber additives.

1,3-Butadiene and leukemia among synthetic rubber industry workers: exposure-response relationships.

Previous research updated the mortality experience of North American synthetic rubber industry workers during the period 1944-1998, determined if leukemia and other cancers were associated with several employment factors and carried out Poisson regression analysis to examine exposure-response associations between estimated exposure to 1,3-butadiene (BD) or other chemicals and cancer. The present study used Cox regression procedures to examine further the exposure-response relationship between several unlagged and lagged, continuous, time-dependent BD exposure indices (BD parts per million (ppm)-years, the total number of exposures to BD concentrations >100 ppm ("peaks") and average intensity of BD) and leukemia, lymphoid neoplasms and myeloid neoplasms. All three BD exposure indices were associated positively with leukemia. Using continuous, untransformed BD ppm-years the regression coefficient (beta) from an analysis that controlled only for age was 2.9 x 10(-4) (p<0.01); the regression coefficient adjusted for all covariates (age, year of birth, race, plant, years since hire and dimethyldithiocarbamate) was similar in magnitude (beta=3.0 x 10(-4), p=0.04). Lagging exposure had minimal impact on the results for leukemia for any of the three BD exposure indices. In models that controlled only for age, lymphoid neoplasms were associated with BD ppm-years and myeloid neoplasms, with BD peaks, but neither trend was statistically significant after adjusting for multiple covariates. The present results support the presence of a causal relationship between high cumulative exposure and high intensity of exposure to BD and leukemia.

An updated study of mortality among North American synthetic rubber industry workers.

This study evaluated mortality rates from leukemia and other diseases during the time period 1944 through 1998 among 17,924 men employed in the synthetic rubber industry. In this group, there were 6237 deaths, which is 14% fewer than the 7242 deaths expected based on general population rates. Numbers of observed versus expected deaths (shown hereafter as observed/expected) were 1608/1741 for all cancers combined, including 71/61 for leukemia, 53/53 for non-Hodgkin lymphoma (NHL*), and 26/27 for multiple myeloma. The higher than expected number of deaths from leukemia (16% increase) was concentrated in workers paid hourly who had started work 20 to 29 years earlier, had worked 10 or more years in the industry, and had worked in subgroups employed in polymerization, coagulation, maintenance labor, and laboratory operations. The overall higher leukemia mortality rate, as well as the higher rate in the subgroup of hourly workers who had 20 or more years since hire and 10 or more years worked, was not limited to a particular form of leukemia. Cumulative exposure to 1,3-butadiene (BD) was associated positively with all leukemias, with chronic myelogenous leukemia and, to a lesser extent, with chronic lymphocytic leukemia (CLL). Exposure to styrene or to dimethyldithiocarbamate (DMDTC) also was associated positively with leukemia. Exposures to these two agents were correlated with exposure to BD; data were limited on the independent effects of each of the three chemicals on leukemia. After controlling for the effects of BD, we found no consistent exposure-response relation between either styrene or DMDTC and all leukemias, chronic myelogenous leukemia, or CLL. However, a positive association between any exposure to DMDTC and leukemia persisted. The data from this study indicate that employment in the synthetic rubber industry is related causally to leukemia. Uncertainty remains about the specific agent or agents responsible for the association. The carcinogenic mechanisms through which BD, styrene, or DMDTC could cause leukemia in humans have not been established, and epidemiologic support for a leukemogenic role is limited for these agents. Styrene and DMDTC were associated positively with NHL. External support for this relation has not been reported from other epidemiologic studies. The study did not find any clear relation between exposure to BD, styrene, or DMDTC and multiple myeloma. Some subgroups of subjects had more than the expected number deaths from colorectal cancer, prostate cancer, and other diseases. These increases did not appear to be related to occupational exposure in the industry.

Neurotoxicity and behavioral effects of thiram in rats.

Eight of 24 female rats fed 66.9 mg/kg-day of thiram developed neurotoxicity. The neurotoxic effects were characterized by ataxia and paralysis of the hind legs. There were demyelination, degeneration of the axis cylinders, and presence of macrophages in the nerve bundle of the sciatic nerve. Degeneration in the ventral horn of the lower lumbar region of the spinal cord was evidenced by chromatolysis of motorneurons, pyknosis, and satellitosis. During a second experiment, 4 of 24 females fed 65.8 mg/kg--day also developed ataxia and paralysis. An additional 9 females showed clasping of the hind feet when picked up by the tail. Nerve conduction could not be measured for one severely ataxic rat and the electromyogram indicated a loss of motor unit function. Histopathology of this rat, along with the others, suggests the peripheral nerve as the primary site of the lesion. Thiram also caused behavioral changes in apparently normal rats. The walking pattern of the hind legs was altered with decreases in stride width and the angle between contralateral steps. These rats required significantly more shock-motivations and cleared a lower height in a jump/climb ability test. An open-field study indicated that thiram caused hyperactivity in the nonataxic rats of both sexes. Three of 24 rats fed 95.8 mg/kg-day of ferbam also developed ataxia or paralysis.