Authors
Ryan, JJ., Amirova, Z., Carrier, G.

Title
Sex ratios of children of Russian pesticide producers exposed to dioxin.

Journal
Environmental Health Perspectives, 110: A699-A701. 2002.

Summary
Change in birth sex ratio has been documented in North America and Europe. However, an explanation for the observed change is unknown. Exposure to environmental contaminants is thought by some to be causally associated although a biologically plausible mechanism of action has yet to be provided. The present study therefore explored the potential association between exposure to several toxicants and birth sex ratio. The Khimprom agrochemical plant is situated in the city of Ufa in the Bashkortostan Republic of Russia. Between the years of 1961 and 1988 approximately 600 workers at these plants produced the wood preservative 2,4,5-trichlorophen (TrCP), the germicide hexachlorophene and the phenoxy herbicide 2,4,5-trichlrorphenoxy acetic acid (2,4,5-T). A cohort of over 250 workers produced 2,4,5-T itself between 1964 and 1967. During production of these chlorinated compounds, the by-product 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was produced. Workers may have come into contact with TCDD through breathing contaminated air or by direct skin contact with materials containing TCDD. Some previous studies have shown that serum TCDD levels may be associated with altered sex ratio of offspring. There was an increasing probability of female births with increasing TCDD concentrations in the blood serum samples from the fathers between the years of 1977 and 1996 following the accidental explosion of a chemical plant in Seveso, Italy in 1976. However, other studies of TCDD exposed populations have failed to show an alteration in the sex-ratio of offspring.

The objective of the current study was to report the offspring sex-ratio for the chemical plant workers in Ufa. In September 1992, blood samples were collected and analyzed for close to 60 men, women and children from the factory and the city of Ufa. Further to this, the current study collected 20 blood samples from the cohort of workers who produced 2,4,5-T and 23 samples from the cohort of workers who produced TrCP between the years of 1997-2001. In total, 84 blood samples were measured and expressed in TCDD dioxin toxic equivalents (TEQ). Company archival records of individual workers were consulted for age, sex and dates working in the designated shops, as well as the number, sex and date of birth of their children. A personal or telephone interview was done with each individual or a relative to confirm the sex and number of live-born children. All live born children born after the worker had been employed for 9 months or more in either of the two factories were included in the analysis. The sex ratio for the city of Ufa (0.51) was used as a comparison for that obtained from the workers. The sex ratio is calculated by taking the number of males born and dividing it by the total number of males and females born. Normally the sex ratio is 0.51 (105 males to 100 females).

The sex ratio for the combined cohorts (0.40) was statistically different from the comparison group (p<0.001). Fathers who were exposed to TCDD had a sex ratio of 0.38 verses 0.50 if the mother was exposed. The results of the blood analysis showed that blood lipid TEQ values were virtually the same for mothers and fathers in both groups but were over 3 times higher in the TrCP cohort (672 median TEQ) than the 2,4,5-T group (177 median TEQ). The sex ratio was as low as 0.23 (7males/23 females) for fathers who were in the TrCP cohort with measured blood values with a median of 715 ppt TEQ blood lipid.

The strength of this study is that it used direct blood lipid levels as a measure of exposure. However, a major limitation of this study is the small sample size employed making it difficult to translate these observations to the population level where contaminant exposure is much lower. A further limitation was that the blood measurements were taken from the subjects several years (23 year median) after being exposed to TCDD, making the exposure levels inaccurate. The half-life of TCDD (time required for half the quantity TCDD in humans to be metabolized or eliminated by normal biological processes) has been estimated around 7 to 12 years. Therefore, the blood levels in this study would have also depended on how long ago the subject worked in the plant. In addition, the biological mechanisms through which TCDD acts on altered sex ratio in offspring are not yet fully understood and require further study.