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Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting Russian Academy of Sciences, Moscow Chapaevsk Central Hospital

Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Page 1: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

Boris Revich Oleg Sergeev

Dioxins, PCB and human effects in some

cities of Russia

Center for Demography and Human Ecology of Institute for Forecasting

Russian Academy of Sciences, Moscow

Chapaevsk Central Hospital

Page 2: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins in Environment of Chapayevsk

• Air. The average concentration in 1994 was 0.116 pg/m3

• Soil.

Distance from plant, km

Dioxin, ng/kg:

3 36.8

5 - 7 3.9

10 - 15 0.9

Germany act 5.0

Page 3: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins in Environment of Chapayevsk

• Cow milk. Dioxins were

found in all samples:

2,3,7,8-TCDD was 17.32

pg/TEQ/g fat that was

significantly higher

than the accepted

regulatory standard in

Russia (5.2 pg TEQ/g

fat)

Page 4: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins in Blood pg WHO-TEQ98/g lipids

Distance from Plant Groups N Average

0 km (1997) Workers 4 412

1 – 3 km General 6 75.2

5 – 8 km [Revich et al., 1999, 2001]

-”- 44 24.5

< 5 km (1998) -”- 13 75.7

> 5 km [Akhmed-khanov, Revich et al., 2002]

11 44.1

Japan [Matsueda et al., 1999; Iida et al., 1999]

63 15.0 - 16.0

USA, residents near Great Lakes [Anderson et al., 1999]

39.4

Page 5: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins in Breast Milk, pg TEQ/g fat

City, Country N Average concentration

Russian cities with chlorine production:

Chapayevsk, 1998 [Revich et al., 1999]

40 43.3

Usolye-Sibirskoye [A.Schecter et al., 1999]

11 23.7

Kazakhstan, area near cotton fields [Hooper et al., 1999]

16 74.0

Uzbekistan [Hooper et al., 1999]

9 24.2

Japan [Iida et al., 1999]

125 16.0

South Korea, Seoul [Shin et al., 1999]

11 24.1

Page 6: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxin Health Effects in Chapayevsk

Studies on dioxins exposure in this

city population’ health developed in

following directions:

•Estimation of newborns sex ratio

•Estimation of boys’ physical

growth and sexual maturation

•Estimation of medical-genetic

parameters

•Estimation of dioxins as a risk

factor of breast cancer development

•Estimation of human emotional

stress

Page 7: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins As An Endocrine Disruptors

Page 8: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Sex Ratio

The range of sex ratio among

newborns in Chapaevsk city

(1983 – 1997) (boys/girls) was

from 0.79 to 1.27 with mean

value of 1.03. These results

match with the results of Seveso

incident (Italy, 1976), seem to be

associated with fewer males

born than were expected

[P.Mocarelli, 1996].

Dioxin Health Effects in Chapayevsk

Page 9: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Sex Ratio (Ufa Study)

•Investigated the sex ratio of children of pesticide workers who produced the biocide trichlorophenol and the herbicide 2,4,5-trichlorophenoxy acetic acid from 1961 to 1988 in the city of Ufa, Bashkortostan, Russia.

Page 10: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Sex Ratio (Ufa Study)

•The sex ratio (fraction male) of the combined cohort of 227 children from 150 male and 48 female workers was 0.40, significantly lower (z-test for proportions = 3.21; p < 0.001) than those for the city of Ufa (0.512) and elsewhere worldwide.

J.J.Ryan, Z.Amirova, and G.Carrier: Environmental Health Perspectives Volume 110, Number 11, November 2002

Page 11: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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• The data on Chapayevsk and Ufa have confirmed the hypothesis that the decrease in the ratio of male to female births in industrial countries was caused by dioxins.

Sex Ratio

Page 12: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxin Health Effects in ChapayevskSemen Quality

Semen Analysis in Workers of Chemical Plant in Chapayevsk and in Controls

[N.Goncharov et al., 1999]

Semen parameters

Chapaevsk Controls P-value

Volume (ml) 2.6 1.7 3.1 1.3 0.242

pH 7.5 0.3 7.4 3.0 0.115

Concentra-tion (million/ml)

87 70 71 58 0.344

Motility (% motile)

61 8 64 10 0.428

Vitality (% live)

69 13 64 12 0.786

Morphology (% normal)

17 10 42.8 9 0.000

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Animal studies have shown effects of dioxins on sexual development, serum concentrations of sex hormones and gonadotropins, and developmental malformations

However, the relationship between dioxin exposure and human sexual development has not been well studied. There is epidemiological evidence of an association between dioxins and decreased levels of testosterone, as well as increased levels of LH and FSH in occupationally exposed adults.

Page 14: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxin Health Effects in ChapayevskSEXUAL AND PHYSICAL MATURATION

OF MALE ADOLESCENTS

Participants from USA

Paige Williams, Susan Korrick, Mary M. Lee, Larisa Altshul,Jennifer Adibi, Russ Hauser

Harvard School of Public Health, Biostatistics Department, Boston, MA, USA

Harvard School of Public Health, Environmental Health Department, Boston, MA, USA

Pediatric Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA

Grant of EPA and CRDF

Page 15: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxin Health Effects in ChapayevskSEXUAL AND PHYSICAL MATURATION OF MALE

ADOLESCENTSMethods and Materials

• The first phase of the study conducted in 1999 consisted of a survey of 10-16 year old boys in Chapaevsk.

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Dioxin Health Effects in ChapayevskSEXUAL AND PHYSICAL MATURATION OF MALE

ADOLESCENTSMethods and Materials

• Cryptorchidism (undescended testicles) and hypospadias are common minor congenital anomalies of male reproductive tract development. Recently, the possibility that these minor reproductive tract abnormalities may be related to exposure to environmental contaminants, such as the hormonally active dioxins, has been raised.

Page 17: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxin Health Effects in ChapayevskSEXUAL AND PHYSICAL MATURATION

OF MALE ADOLESCENTS

• Among the 2580 children examined in phase one, the residential distribution for the 45 cases of cryptorchidism (1,7%), 16 cases of hypospadias (0,6%) and 139 cases of delayed sexual development (5,4%).

Page 18: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxin Health Effects in ChapayevskSEXUAL AND PHYSICAL MATURATION

OF MALE ADOLESCENTS

• In phase two, information on the residential address of the mother during her pregnancy and the work history of both parents prior to and during the pregnancy was available in 95 cases and 113 controls.

Page 19: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Preliminary results showed

that a high proportion of the

boys consumed locally grown or

raised foods during their

lifetime: over 70% consumed

locally produced dairy

products, over 50% consumed

locally raised chickens or eggs,

and over 80% consumed locally

caught fish during their lifetime.

Dioxin Health Effects in ChapayevskSEXUAL AND PHYSICAL MATURATION

OF MALE ADOLESCENTS

Page 20: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Morphogenetic Homeostasis

Fluctuating asymmetry - The Health of the Environmental

Congenital morphogenetic options - The Environmental Human

N.Zhuchenko, I.Ivanova

Moscow Medical Academy

Page 21: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Congenital morphogenetic options (CMGO)

Complete examination of children was carried out with a view to reveal congenital morphogenetic options. 369 children (5-7 age), who visited kindergartens of Chapaevsk town located in different districts, were examined.

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Congenital morphogenetic options (CMGO)

87 clearly discern, according to the international criteria, CMGO were recorded. The alternative evaluation of each traits was accomplished in the survey, that is, the extreme forms of a manifestation of one attribute or another without anthropometry were taken into account.

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The CMGO number per one child varied from 0 to10. The average number of CMGO per one child was equal to 4,5 for boys and 4,4 for girls, and these values were more than those obtained in other ecologically unfavorable regions in Russia Chernobyl area.

Congenital morphogenetic options (CMGO)

Page 24: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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The following attributes are among the most frequently occuring ones: sandals chack, epicantus, shawl scrotum (for boys), clinodactyly, broad first fingers of hands and others.

Damages of skin and trunk are among the most frequently encountered, but damages of the mouth are met rarely.

Congenital morphogenetic options (CMGO)

Page 25: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Cytogenetic Homeostasis

J.Revazova et al.

Cytogenetic Investigation of Women Exposed to Different Levels of Dioxins in Chapayevsk Town

Chemosphere. – 2001. – vol.43. – PP.999 – 1004

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The highest mean number of metaphases with CA (5.84%) was in the “Workers” group, “1 – 3 km” – 5.35% and “5 – 8 km” – 4.91%. The tendency to decrease of the total number of chromosome aberrations per 100 cells among the groups “Workers” – “1 – 3 km” – “5 – 8 km” was similar to that for the number of cells with chromosome aberrations and was expressed more clearly.

Cytogenetic Homeostasis

Page 27: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Cytogenetic Homeostasis

Group N. of sub-jects

N. of meta-pha-ses

N. of meta-phases with aberra-tions(% SE)

Total of aberra-tions(10-2±SE)

“Workers” 15 4,500 5.840.48

6.220.54

“1 – 3 km” 16 4,800 5.350.43

5.710.54

“5 – 8 km” 14 4,015 4.910.40

5.110.41

Results of analysis of CA in peripheral blood lymphocytes of women exposed to

different levels of dioxins

Page 28: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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It was noted that the most number of individuals with the frequency of aberrant cells more than 5.0% was observed in the group “Workers”. The number of persons with aberrant metaphases more than 5% was significantly higher in “Workers” compared to “5 – 8 km” (χ2 = 4.24; p < 0.05).

Cytogenetic Homeostasis

Page 29: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins and Breast Cancer

Page 30: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins and Breast Cancer

Epidemiological evidence

supports the link between

exposure to organochlorines

and breast cancer. The results

of epidemiological research on

environment risk factors and

breast cancer vary, but in

certain case - control studies

the role of these factors has

been confirmed.

Page 31: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins and Breast Cancer

Organochlorines simulate or

mimic sex hormones that may be

mentioned as causes of some types

of cancer. However, one point on

which all investigators agree at

this time is that the greater the

lifetime exposure to estradiol, the

greater the risk of breast cancer

developing. An increase in risk is

seen if the estrogen exposure

occurs during the fetal, rapid

breast formation time, pregnancy

or menopause periods.

Page 32: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins and Breast Cancer

In Chapayevsk all alive

breast cancer patients born

after 1940 year were included

in the case-control study to

investigate the role of

established breast cancer risk

factors and to estimate the

possible dioxin exposure. The

response in case group was 65

persons.

Page 33: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins and Breast Cancer

The selection of

controls was taken from

the general medical

insurance database.

This group will be

matched by age. For the

higher reliability the

ratio of number

cases/controls was 2:1.

Page 34: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins and Breast Cancer

A special questionnaire

was developed and it

included questions on

birthplace, occupation and

residence of women and

their parents, diet,

lifestyle, reproductive

function, medical history

and other questrions.

Page 35: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Dioxins and Breast Cancer

Factors OR P

Oral contraception 2.4[1.03–5.5]

0.042

Breast cancers in relatives

9.0[1.85–43.6]

0.006

Usage more than 50% of pork from farms in the Chapaevsk region

5.7[1.3–25.5]

0.021

- fish from the nearest lakes or rivers

2.3[1.13–4.80]

0.022

Odds Ratios (OR) for breast cancer risk factors

Page 36: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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PCB and Environmental Health

• PCB exposure on health is studied in details in Serpukhov, where condensers infill with PCB had taken place. Even 10 years after the use of PCBs at the plant had been banned, the levels of soil and produce contamination are still extremely high.

Page 37: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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• Near the plant, the maximum PCB concentration in soil was 30 mg/kg dry weight. The PCB content in carrots (washed) grown on the polluted soils was 2350 g/kg wet weight and 1500 g/kg in peeled carrots. Very high concentrations were found in leafy vegetables: 2500 and 1490 g/kg wet weight in celery and parsley, respectively.

PCB and Environmental Health

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• The admissible daily dose of PCB intake is 5 g/kg human body weight (WHO, 1988). The greatest concern is caused by contamination of carrots. Consumption of 250 – 300 g of carrots grown on the soils near the plant was equal to a daily PCB dose.

PCB and Environmental Health

Page 39: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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Resi-dence area

N Sponta-neous abortions

Low-birth weight

Birth defects

Near the plant

177 4,1(2,6–6,0 )

1,4(0,6–3,4)

0,7(0,2–2,2)

2 – 5km from the plant

1344 1,9(1,3–3,0)

1,1(0,6–2,1)

1,0(0,5–1,9)

More than 5km from the plant

377 1,0 1,0 1,0

Relative risk of disruptions in reproductive function and newborn’s health defects in

various parts of Serpukhov

PCB and Environmental Health.Serpukhov Study

Page 40: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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• Cases had significantly higher mean serum PCB concentrations compared with controls (2.0 versus 1.5 ng/g, p=0.03).

• When adjusted for serum lipid, age, and frequency of intercourse, the mean PCB serum concentration for cases was 465 ± 39 ng/g lipid compared to 429 ± 38 ng/g lipid for controls (p=0.54).

PCB and Infertility. Serpukhov Study

Page 41: Boris Revich Oleg Sergeev Dioxins, PCB and human effects in some cities of Russia Center for Demography and Human Ecology of Institute for Forecasting

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• In logistic regression models adjusted for age and frequency of intercourse, there was a 1.7 increased odds (95% CI 0.9 to 3.3) of being a case for each ng/g increase in serum PCB and a 1.1 (95% confidence interval 0.9 to 1.4) increased odds of being a case for each ng/g lipid increase in serum PCB [S.Korrick, B.Revich et al., 1998].

PCB and Infertility. Serpukhov Study