Boris Revich Oleg Sergeev

1
Boris Revich Oleg Sergeev
Center for Demography and Human Ecology of
Institute for Forecasting Russian Academy of
Sciences, Moscow Chapaevsk Central Hospital

• Dioxins, PCB and human effects in some cities of
  Russia

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Dioxins in Environment of Chapayevsk

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

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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)

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Dioxins in Blood pg WHO-TEQ98/g lipids
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Dioxins in Breast Milk, pg TEQ/g fat
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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

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Dioxins As An Endocrine Disruptors
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Sex Ratio
Dioxin Health Effects in Chapayevsk

• 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.

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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.

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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 lt 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

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Sex Ratio

• 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.

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Dioxin Health Effects in ChapayevskSemen Quality
Semen Analysis in Workers of Chemical Plant in
Chapayevsk and in ControlsN.Goncharov et al.,
1999
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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.

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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
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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.

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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).

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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.

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Dioxin Health Effects in ChapayevskSEXUAL AND
PHYSICAL MATURATION OF MALE ADOLESCENTS

• 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.

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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
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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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Congenital morphogenetic options (CMGO)

• 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.

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Congenital morphogenetic options (CMGO)

• 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.

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Cytogenetic Homeostasis
Cytogenetic Investigation of Women Exposed to
Different Levels of Dioxins in Chapayevsk Town
J.Revazova et al.
Chemosphere. 2001. vol.43. PP.999 1004
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Cytogenetic Homeostasis

• 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.

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Cytogenetic Homeostasis
Results of analysis of CA in peripheral blood
lymphocytes of women exposed to different levels
of dioxins
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Cytogenetic Homeostasis

• 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 (?2 4.24 p lt 0.05).

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Dioxins and Breast Cancer
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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.
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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.
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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.
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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 21.
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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.
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Dioxins and Breast Cancer
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.

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PCB and Environmental Health

• 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.

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PCB and Environmental Health

• 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.

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PCB and Environmental Health.Serpukhov Study
Relative risk of disruptions in reproductive
function and newborns health defects in various
parts of Serpukhov
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PCB and Infertility. Serpukhov Study

• Cases had significantly higher mean serum PCB
  concentrations compared with controls (2.0 versus
  1.5 ng/g, p0.03).
• 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 (p0.54).

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PCB and Infertility. Serpukhov Study

• 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.