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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
2
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
3
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)
4
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
5
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
6
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
7
Dioxins As An Endocrine Disruptors
8
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
9
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.
10
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
11
• 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
12
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
13
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.
14
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
15
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.
16
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.
17
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%).
18
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.
19
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
20
Morphogenetic Homeostasis
Fluctuating asymmetry - The Health of the Environmental
Congenital morphogenetic options - The Environmental Human
N.Zhuchenko, I.Ivanova
Moscow Medical Academy
21
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.
22
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.
23
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)
24
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)
25
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
26
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
27
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
28
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
29
Dioxins and Breast Cancer
30
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.
31
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.
32
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.
33
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.
34
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.
35
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
36
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.
37
• 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
38
• 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
39
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
40
• 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
41
• 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