Epidemiological cohort-analytical prospective study was conducted to investigate possible late sequelae in workers exposed to MMA. Personal of MMA producing, polymers (on base of MMA) producing, polymethyl methacrylate and organic polymer glass processing plants was investigated. Persons who had worked at least 3 years in the period from 1938 to 1985 were included in experimental cohort. The experimental cohort consisted of 3914 persons: 1151 male and 2763 female. Death indexes were calculated on sum "person-observation years". Average levels of sex-age-specific death rate for 1959, 1969, 1979 (in the town where those plants situated) were taken as a standard for calculation. Risk was detected on the base of standardized death ratios (SDR). SDR is calculated as a percentage ratio of deaths in experimental cohort to expected number of deaths. Evidence of differences is evaluated by confidence intervals of malignant tumor rate fluctuation.

MMA individual cumulative doses (ICD) were calculated for every person taking into consideration the duration of work at every workplace and occupational history. MMA exposure levels evaluation method was taken as a base for ICD calculation. The method consists in multiplication MMA exposure levels on exposure duration (in years). ICD value is expressed in conditional units [3]. Correlation-regression analysis is used to detect the strenght of association between MMA exposure intensity and MN prevalence level.

Female group was formed to investigate the possible MMA remote genetic effects. The group consisted of 219 women worked from 1976 to 1985. Data on obstetrical history, gestation, delivery and newborns' condition were collected from maturnity house archives. The data were compared with formal statistical data for the same time period (control group).

Higher death risk of a various MN localizations in exposed persons, than in general population was revealed by epidemiological study. In general relative death risk is lower in the cohort, than in general population; it may be due to "healthy worker effect". But if as a control group were used persons worked at the same time period in methylacrylate, butylacrylate and methacryl acid producing, it would revealed statistically significant higher MN death rate in "MMA" group in 1.4 times (P < 0.05).

It should be noted increasing of MN deaths portion in experimental cohort as compared with general population: 23.7% to 19.3% in male and 34.1% to 19.2% in female, respectively.

Deepen analysis of air pollution data allowed to distinguish 7 MMA exposure levels that were marked from 0 to 6. The marks were used to calculate ICD in workers exposed to MMA. All contingent was arbitarly divided in 4 groups with ICD fluctuations: 1 group - from 0 to 14, 2 group - from 15 to 28, 3 group - from 29 to 56, 4 group - from 57 to 170 conditional units.

MN rate analysis in those groups provides evidence that the risk increases with MMA dose increasing - 2.7%; 4.6%; 4.6% and 7.2%, respectively. Positive correlation (r = 0.956; P < 0.05) provides evidence that exist enough great possibility of association between MN prevalence level and MMA dose. Various localization cancer analysis showed that MN risk increases with MMA dose increasing in female only in relation to reproductive system cancer and in male only in relation to lung cancer (r = 0.961 and r = 0.963, P < 0.05).

Spontaneous miscarriges (SM) rate at early pregnancy (under 12 weeks) in women exposed to MMA at 2-6 marks level (i.e. concentrations higher, than MAC in 2 and more times) was 6.3% as compared with 2.5% in women exposed to MMA at 0-1 marks level (P < 0.05). Statistically significant higher rate of inborn defects (ID) and hypoxia in babies of studied women in first group as compared with second group was revealed by health condition and physical development newborn investigation (62.01 and 8.6; 99.2 and 13.5 0/00 , respectively)(P < 0.001). The number of stillborn babies in the first group was in 1.5 times higher, than in second group (P < 0.05).

Comparison of recorded indexes values in female groups with different MMA exposure intensity and duration allowed to establish that at 2-6 marks level and lenght of service - 5 years and more there were more premature babies and babies with hypotrophia (weight-height index < 65). The level of other negative indexes (encephalopathies, hypoxia of newborns, inborn defects, still-born rate) is higher in group with 0-1 marks and the highest ID and hypoxia rates were in this group at lenght of service - under 5 years.

Although experts of IARC have not recognized MMA as a human cancerogen yet [4]. Obtained data allow to consider MMA exposure as a modification factor in cancerogenic process. With reference to higher women reproductive system risk, it may be suggested that unfavourable hormon background due to high MMA exposure - predominance of estrus-type reactions [1] is an initial mechanism in pathogenesis of hormone-depending organ MN development [2]. MMA exposure in lung cancer development could play a role as a factor aggravating smoking effect. 74% of male and 4% of female were smokers.

It is necessary to take into consideration MMA exposure late sequelae on posterity. High intensive MMA exposure on mothers leads to increasing of SM rate, but lower intensive exposure (MAC and a few higher) leads increasing of ID, still-born, newborn hypoxia number. In first case it seems to be associated with more pronounced embryotoxic MMA effect leading to fetus death at early pregnancy. The number of SM does not exceed control level at lower MMA exposure, but teratogenic effect begins to play a main role. Statistically significant higher ID rate provides evidence of teratogenic effect.

Since positive correlation between MMA dose and MN rate is revealed, measures to decrease MMA concentrations in workplace air may be play a decisive role in prevention of late sequelae in workers.

1. Blagodatin VM Hygiene, industrial toxicology and occupational pathology in production of polyacrylates and raw materials for them. Moscow, FF Erisman Research Institute of Hygiene (1984).

2. Volkova OV Functional morphology of female reproductive system. Moscow, Meditsina (1983).

3. Davydova NN, Diatlova LA Establishing of cause-effect relations between labor conditions and morbidity of miners in Kuzbass. Zdravookhranenie Rossiyskoy Federatsii 1991; (8): 9-11.

4. IARC monographs on the evaluation of the cancerogenic risk of chemicals to humans. Lyon. Centre international de recherche sur le cancer (CIR C/IARC), 1994. V.60. P. 445-474.