ENFERMEDADES GENERADAS POR CONTAMINANTES. CONTAMINANTES QUE GENERAN ENFERMEDADES.

ENFERMEDADES GENERADAS POR CONTAMINANTES

CONTAMINANTES QUE GENERAN ENFERMEDADES

EL PROBLEMA TAMBIÉN ES LA DOSIS

EL PROBLEMA TAMBIÉN ÉS EL TIEMPO

ORGANOCHLORINE COMPOUNDS ARE TOXIC COMPOUNDS AT HIGH CONCENTRATIONS

HEXACHLOROBENZENE

CHLORACNE by EXPOSURE TO DIOXINS

AUGUST 2004 NOVEMBER 2004 V. Yushchenko

Newborn with in-utero growth delay and skin hyperigmentation due to in-utero exposure to PCBs (Kyushu, Japan, 1968)

ORGANOCHLORINE COMPOUNDS WERE NOT PRESENT IN THE ENVIRONMENT NOR IN HUMAN

BODIES SIXTY YEARS AGO

THEREFORE

OUR METABOLISM IS NOT READY TO HANDLE THEM

(which is not the case for PAH)

POLYCYCLIC AROMATIC HYDROCARBONS

– 1-naphthol 1-naphthol

– 2-fluorenol2-fluorenol

– 9-phenanthrol 9-phenanthrol

– 1-pyrenol 1-pyrenol

– 3-benzo[a]pyrenol3-benzo[a]pyrenol

• PAH metabolites

1-PYRENOL

0

0.5

1

1.5

2

2.5

3

3.5

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33

ng

/ml

MEASUREMENTS OF EXPOSURE TO PAH IN WOMEN FROM VALENCIA

urine values normalized to creatinine

WHAT IS THE PROBLEM AT LOW CONCENTRATIONS?

WE NEED TO ESTIMATE WHAT ARE THE DELETERIOUS EFFECTS OF EXPOSURE AT LOW

AMOUNTS

BUT

FOR LONG PERIODS ENCOMPASSING ALL LIFE AND ALL GROWTH STAGES (INCLUDING IN UTERO

DEVELOPMENT)

Development of neural system in children

Decrease of brain cells with age

Small increases of cell losses (0.1 or 0.3% per year) may give rise to clinic emergencies at younger age. Levels of loss of 40% are probable causes of illness

ESCALA DE ACTIVIDAD CARCINOGÉNICA GRUPO 1. CARCINOGÉNICO EN HUMANOS. COMPUESTOS SOBRE LOS QUE HAY EVIDENCIA SUFICIENTE DE SU CARCINOGENICIDAD EN HUMANOS. GRUPO 2A. PROBABLE CARCINÓGENO EN HUMANOS. COMPUESTOS EN LOS QUE HAY EVIDENCIA EXPERIMENTAL DE SU CARCINOGENICIDAD EN ANIMALES PERO LA EVIDENCIA DE SU ACTIVIDAD EN HUMANOS ES LIMITADA. GRUPO 2B. POSIBLE CARCINOGÉNICO EN HUMANOS. COMPUESTOS CON POCA EVIDENCIA DE CARCINOGENICIDAD EN HUMANOS E INSUFICIENTE DE SU ACTIVIDAD EN ANIMALES. GRUPO 3. NO DEFINIBLE COMO CARCINOGÉNICO EN HUMANOS. GRUPO 4. COMPUESTOS PROBABLEMENTE NO CARCINOGÉNICOS EN HUMANOS.

TÉRMINOS EPIDEMOLÓGICO-TOXICOLÓGICOS

EXPOSICIÓN. SUCESO QUE PONE EN CONTACTO UN SER HUMANO CON UN CONTAMINANTE PRESENTE EN EL MEDIO AMBIENTE DURANTE UN CIERTO TIEMPO EXPOSICIÓN TOTAL. EXPOSICIÓN ACUMULADA INDEPENDIENTEMENTE DEL MEDIO AMBIENTAL O VÍA DE ENTRADA (INHALACIÓN, INGESTIÓN, DÉRMICA). DOSIS. CANTIDAD DE UN CONTAMINANTE ADSORBIDA O DEPOSITADA EN EL CUERPO DURANTE UN CIERTO TIEMPO, USUALMENTE DESDE UN ÚNICO MEDIO. DOSIS INTERNA. CANTIDAD ADSORBIDA DE UN CONTAMINANTE EN UN TEJIDO DEL CUERPO DURANTE UN CIERTO TIEMPO. DOSIS BIOLÓGICA EFECTIVA. CANTIDAD DE UN CONTAMINANTE O SUS METABOLITOS DEPOSITADA O ADSORBIDA QUE INTERACCIONA CON UN TEJIDO U ÓRGANO DETERMINADO DURANTE UN CIERTO

TÉRMINOS EPIDEMIOLÓGICOS BIAS. ERROR EN LA MEDIDA DE LOS EFECTOS DE LA EXPOSICIÓN A UN CONTAMINANTE. ÍNDICE DE MORTALIDAD. NÚMERO DE MUERTES EN UNA POBLACIÓN DURANTE UN INTÉRVALO DE TIEMPO ESPECÍFICO. PREVALENCIA. PROPORCIÓN DE LA POBLACIÓN AFECTADA EN UN TIEMPO DETERMINADO.

TÉRMINOS EPIDEMIOLÓGICOS ASOCIACIÓN. MANIFESTACIÓN NO ALEATORIA DE UNA ENFERMEDAD RELACIONADA CON LA EXPOSICIÓN A UN CONTAMINANTE. ESTUDIO CASO CONTROL. COMPARACIÓN ENTRE DOS POBLACIONES, ENFERMA Y DE CONTROL, EN RELACIÓN CON LA EXPOSICIÓN A UN CONTAMINANTE. ESTUDIO EN COHORTE. ESTUDIO DE COLECTIVOS EXPUESTOS Y NO EXPUESTOS A UNO O VARIOS CONTAMINANTES Y SEGUIMIENTO DE SUS ENFERMEDADES. ESTUDIO CROS-SECCIONAL. ESTUDIO DE UN COLECTIVO EN EL QUE EN UN MOMENTO DETERMINADO SE IDENTIFICA EL NIVEL DE EXPOSICIÓN A UNO O VARIOS CONTAMINANTES EN CADA INDIVIDUO Y SU ESTADO DE SALUD. ÍNDICE DE INCIDENCIA. RELACIÓN ENTRE EL NÚMERO DE CASOS EN UNA POBLACIÓN DE RIESGO Y EN LA POBLACIÓN GENERAL

ESTUDIO CROS-SECCIONAL

PUEBLO DE FLIX

AREA DE ESTUDIO

• Comarca de la Ribera d’Ebre• Ubicada en el curso del río• 4500 habitantes• Industria electroquímica• Agricultura de frutas y

hortalizas, almendras, aceite y vino.

FLIX

•FLIX

Población rural expuesta acontaminación específica

Chlorine

Organochlorinated solvents trichloroethylene

tetrachloroethylene dichlorometane chloroform...

NaOH, HCl, H2

ACTIVITIES IN THE ELECTROCHEMICAL PLANT

Products synthesized

Average 24-hr air concentrations of organochlorine compounds in Flix and the reference community (Barcelona)

COMPOUND Flix Barcelona

ng/m3 average range average range

HCB 35 11-44 0.3 0.25-0.4

PCBs 1 0.1-2 0.7 0.1-1

pp'-DDE 0.2 0.02-0.5 0.1 0.06-0.3

608 Residents from Flix gave biologic samplesage: 48.8 years

84.3% lived for more than 20 years in Flix

SEX

41%59%

MEN WOMEN

OCCUPATION

69%21%

10%

PRESENT WORKERSPREVIOUS WORKERSNON WORKERS

TOTAL 421338 women

83 men46 years

TOTAL 5951 men

8 women40 years

TOTAL 128115 men

13 women62 years

36 +/- 104

4.3 +/- 2.3

9.2 +/- 15

1.6 +/- 1.2

9.6 +/- 14

3.7 +/- 4.4

0.6 +/- 0.9

0.2 +/- 0.4

1.2 +/- 2.4

0.3 +/- 0.4

1.1 +/- 1.9

0.5 +/- 0.4

1.6 +/- 3.4

0.5+/-0.4

0

2

4

6

8

10

12

14

16

18

20

c (

ng

/ml)

PeCB HCH HCH op'DDE op'DDD op'DDT PCB 28 PCB101

PCB153

PCB180

POBLACIÓ TOTAL (N=625)

8 times higher in the population of Flix than in Barcelona

100 times higher than in the USA rural population (Sther-Green y cols, 1988)

23 times higher than in USA general population (Murphy y cols.,1985)

1.4 times higher than Slovakian population (Koçan y cols.1994)

De l’ordre o inferiors a altres publicadesnferiors o De l’ordre o inferiors a altres publicadesnferiors o In the order or lower than other reported

Levels in sera by occupational groups

0,6

4,2

0,5

6,4

0,4

0,1

1,1

0,1

13

0,2

13

0,7

0,3

2,3

3,2

0,04

8,8

0,1

9,1

0,6

0,1

0,9

0,8

1,2

0,9

1,1

64

2.0

17

0 5 10 15 20 25 30 35 40 45 50 55 60 65

PeCB

HCB

HCH

OCS

pp' DDE

pp' DDT

PCB 118

PCB 153

PCB 138

PCB 180

Present workers Previous workers Non workers

0.1 - 1510.4 - 234

0.3 - 22

5.3 - 1485

2.4 - 953

1.1 - 222

0.1 - 223

0.3 - 67

0.7 - 38

C (ng/ml)

• Criterio OMS (IPCS 1994)

adulto 64 Kg --- 22m3 aire

4 horas/día en el exterior

• Concentraciones medias

Cint = 51 ng/m3

Cext = 26 ng/m3

Estimación de la inhalación de HCB

1.13 g HCB /dia

Referencia:

0.4 10-4 - 2 10-3 g/día

CANCER INCIDENCE BY DETAILED CAUSE AND SEX IN A COMMUNITY HIGHLY EXPOSED TO HCB (1980-1989) CAUSE MALE, N INCIDENCE

RATIO FEMALE, N INCIDENCE

RATIO THYROID 2 6.7 1 1 SOFT-TISSUE 3 5.5 1 2.2 BRAIN 4 2.7 1 0.93 UNKNOWN 10 2.3 4 1.2 BREAST 0 - 19 1.3 TOTAL 74 0.96 55 0.93

•Reference values:• TSH 0.25-5 mIU/ml; Total T4: 4.7-12.4 mg/ml; Free T4: 0.8-2.0 ng/dl; AST: 10-38 UI/l; ALT: 7-33 UI/l; GGT in men: 10-50 UI/l; GGT in women: 5-35 UI/l.

Description of TSH, total T4, free T4, AST (Aspartate aminotransferase, ALT (Alanine aminotransferase and GGT (Gamma Glutamil Transpeptidase serum levels, by sex and occupational status. Flix, Catalonia

Men Women Ever worker Never worker Ever worker Never worker TSH (n=608) Median (maxi-min) Age adjusted mean % > 5lU/ml*

1.2 (0.0;3.5) 1.2 0.6

1.5 (0.2;29.3) 1.3 1.2

1.5 (0.7;5.3) 1.6 4.5

1.4 (0.0;36.9) 1.3 2.1

Total T4 (n=192) Median (max-min) Age adjusted mean % < 4.7 g/dl*

6.4 (2.9;9.8) 6.2 14.7

7.1 (5.0;10.0) 7.1 0

5.5 (3.8;7.7) 6.2 30.0

7.4 (4.2;11.3) 7.7 1.1

Free T4 (n=192) Median (max-min) Age adjusted mean % < 0.8 ng/dl*

1.3 (0.9;1.8) 1.3 0

1.4 (1.1-2.0) 1.4 0

1.2 (1.0-1.3) 1.2 0

1.3 (0.8;1.7) 1.3 0

AST (n=192) Median (maxi-min) Age adjusted mean % > 38 IU/l*

21 (9.0;34.0) 21.2 0

23.0 (14.0;35.0) 22.4 0

19.0 (15.0,22.0) 19.0 0

19.0 (11.0;33.0) 18.9 0

ALT (n=192) Median (maxi-min) Age adjusted mean % > 33 IU/l*

13.0 (6.0;49.0) 10.1 5.3

11.0 (6.0;50.0) 11.8 5.9

10.0 (6.0,16.0) 9.9 0

10.0 (5.0;38.0) 10.1 1.1

GGT (n=192) Median (maxi-min) Age adjusted mean % > 50 IU/l (men)* % > 35 IU/l (women)*

23.0 (9.0;255.0) 26.2 17.3 -

17.0 (11.0;44.0) 17.5 0 -

13.0 (9.0; 32.0) 15.0 - 0

15.0 (8.0;110.0) 15.2 - 3.4

Ln TSH Total T4 Free T4 Ln AST Ln ALT Ln GGT

Ln HCB -0.08 -0.28* 0.02 0.10 0.17** 0.34*

Ln PCBs -0.07† -0.01 0.09 0.03 0.05 0.19

* p<0.001

** p = 0.02; † p = 0.05

Correlación entre los niveles de HCB y las desviaciones de T4, ALT y GGT

CONCLUSIONES DEL ESTUDIO

• Los niveles de HCB aumentan:

- con el tiempo de residencia,

- con el consumo local de pescado.

- con la edad de las mujeres

- en el grupo de edad media en los hombres

• Los niveles de HCB en los extrabajadores > 60 años son similares a los no trabajadores.

• La salud percibida no difiere del resto de Catalunya.

• Riesgo superior para la totalidad de las enfermedades asociadas al HCB para los que han trabajado alguna vez en la electroquímica.

• No se ha registrado ningún caso de Porfíria Cutanea Tarda.

• Seis personas con exceso de porfirinas totales en la orina.

• Cinco personas con anomalías en el perfil de porfirinas excretadas.

• Determinación de la ruta metabólica de el HCB: conjugado del glutatión en la orina.

• Correlación entre el Pentaclorobenzotiol y el HCB en el suero: r2=0.78

ESTUDIO CASO-CONTROL

ENFERMOS DE CÁNCER DE PÁNCREAS

HUMAN SERUM CONCENTRATIONS COMPOUND CONTROL

(n = 26) POSITIVE non mutated (n = 17)

POSITIVE mutated (n = 34)

HCB 9.22.1 124.0 9.92.6 -HCH 153.8 8.42.9 123.0 -HCH 2.90.84 1.20.62 0.750.37 pp'-DDE 9.42.7 124.8 227.5 pp'-DDT 0.530.26 0.610.46 1.70.51 PCB-52 0.040.053 0.350.38 0.210.14 PCB-138 1.10.28 0.940.62 1.70.41 PCB-153 1.30.24 1.00.30 1.90.41 PCB-180 1.30.22 1.350.35 2.30.58 Concentration ng/ml. Interval: 95% confidence

TERTILES COMPOUND POSITIVE

non mutated (n = 17)

POSITIVE mutated (n = 34)

pp'-DDE <7.4 7.4-21 >21

9 (53%) 5 (29%) 3 (18%)

8 (23%) 12 (35%) 14 (41%)

pp'-DDT nd+dnq <1.9 >1.9

12 (71%) 3 (18%) 2 (12%)

9 (26.5%) 12 (35%) 13 (38%)

HUMAN SERUM CONCENTRATIONS IN CONTROLS AND CASES OF EXOCRINE PANCREATIC CANCER WITH AND WITHOUT A MUTATION IN THE K-RAS GENE

INMA – INfancia y Medio Ambiente (Environment and

Childhood) is a NETWORK born in 2003 funded by the

Spanish Ministry of Health.

The project brings together different working groups

from different universities, research centers, hospitals

and Health administration.

INMA aims to study the role of the most important

environmental pollutants in air, water and diet and

their effects on child growth and development.

Overview

The INMA project aims to

Objectives

•To describe the degree of individual prenatal exposure to environmental pollutants present in the air and water, and the internal dose of chemicals during pregnancy and at birth

•To evaluate the impact of the exposure to different contaminants on infants’ growth, health and development

•To evaluate the role of diet and fatty acids on infants’ growth, health and development

INMA participants

PopulationInclusion

Year

Target

number

Flix

Menorca

Granada

Madrid

Valencia

Sabadell

Asturias

Guipuzkua

1997-99

1997-98

2001-2002

2003

2003-2005

2004-2006

2004-2006

2005-2007

92

492

668

50*3

800

800

400

600

Carrizo et al., Environmental Science and Technology, 40, 1420-1426 (2006)

MA

TE

RN

AL

FE

ED

ING

AR

TIF

ICIA

L F

EE

DIN

G

CONCENTRATIONS BUDGET

-2.2

-1.7

-1.2

-0.7

-0.2

0.3

0.8

PeC

B

HC

B

BH

CH

PC

B28

PC

B52

PC

B10

1

4,4'

-DD

E

PC

B11

8

PC

B15

3

4,4'

-DD

T

PC

B13

8

PC

B18

0

tPC

B

ng

/ml

-2.2

-1.7

-1.2

-0.7

-0.2

0.3

0.8

PeC

B

HC

B

BH

CH

PC

B28

PC

B52

PC

B10

1

4,4'

-DD

E

PC

B11

8

PC

B15

3

4,4'

-DD

T

PC

B13

8

PC

B18

0

tPC

B

ng

/ml

-0.2

0.3

0.8

1.3

1.8

2.3

PeC

B

HC

B

BH

CH

PC

B28

PC

B52

PC

B10

1

4,4'

-DD

E

PC

B11

8

PC

B15

3

4,4'

-DD

T

PC

B13

8

PC

B18

0

tPC

B

ug

-0.2

0.3

0.8

1.3

1.8

2.3

PeC

B

HC

B

BH

CH

PC

B28

PC

B52

PC

B10

1

4,4'

-DD

E

PC

B11

8

PC

B15

3

4,4'

-DD

T

PC

B13

8

PC

B18

0

tPC

B

ug

INTAKE OF ORGANOCHLORINE COMPOUNDS THROUGH MATERNAL AND ARTIFICIAL FEEDING IN THE COHORT OF MENORCA

DIFFERENCES BETWEEN BIRTH AND FOUR YEARS

POLYBROMODIPHENYL ETERS

Carrizo et al. Environ. Sci. Technol. 41, 4907-4912 (2007)


Carrizo et al. Environ. Sci. Technol. 41, 4907-4912 (2007)

EFFECTS

Exposure to hexachlorobenzene during pregnancy and social behavior at age 4 years

Ribas-Fito et al., Environmental Health Perspectives, 115, 447-450 (2007)

Prenatal exposure to current concentrations of HCB is associated with a decrease in the Social Competence and an increase of the Attention-Deficit Hyperactivity Disorder at preschooler ages.

These results suggest that some infants may be at risk from the developmental neurotoxicity of HCB due to relatively high concentrations of HCB detected in cord serum and breast milk from women in certain parts of the world.

Ribas-Fito et al., Environmental Health Perspectives, 115, 447-450 (2007)

Ribas-Fito et al., American Journal of Epidemiology, 164, 955-962 (2006)

Early exposure to DDE and asthma

Early exposure to DDE and asthma

Sunyer et al., Clinical and Experimental Allergy 36, 1236–1241 (2006)

Wheezing occurring at four (odds ratio = 1.13 (1.01-1.26) per each increase in 1 ng/ml) as well as asthma diagnosed at six (1.18 (1.01-1.3)) showed a statisticaly significant association with DDE measured at birth.

Early exposures to DDE seems to play a role in asthma, but not exposures occurring during breastfeeding or later

Sunyer et al., Environmental Health Perspectives 113, 1787-1790 (2005) Sunyer et al., Clinical and Experimental Allergy 36, 1236–1241 (2006)

Delays in cognitive skills and In utero exposure to DDT

Prenatal exposure to background low-level concentrations of DDT is associated with a decrease in the cognitive skills among preschoolers



4,4-DDT incorporation by breastfeeding

77DDT prenatal exposure and cognitive development at 4 years

0

20

40

60

80

100

120

<0.05 0.05-0.20 >0.20

No BF

Short BF

Long BF (>20w)

Ribas-Fitó, Am J Epidemiol 2007

DDT exposure at birth (ng/ml)

McC

arth

y ge

nera

l cog

niti

ve s

cale

*

* p<0.05

Ribera d’Ebre y Menorca (n=391)

Ribas-Fito et al., American Journal of Epidemiology, in press

Children who were breastfed for more than 20 weeks had better cognitive performance regardless of their in utero exposure to DDT.

A linear dose response between breastfeeding and cognition was observed in all DDT groups.

Ribas-Fito et al., American Journal of Epidemiology, in press

Despite the possibility of harm from environmental contaminants in breast milk, breastfeeding for long periods should still be recommended as the best infant feeding method

Thyroid disruption and organochlorine compounds. Four-year-old children.

Alvarez-Pedrerol et al., Occupational and Environmental Medicine 65, 452-457 (2008)Alvarez-Pedrerol et al., Environment International 34, 737-740 (2008)

Background levels of OCs at four years-old children affect their thyroid function.

Children with higher levels of p,p’-DDT, β -HCH and PCBs (138, 153 and 118) had lower concentrations of T3, while freeT4 was only negatively associated with PCB-118.

As thyroid hormones are essential for normal brain development, the lower levels of T3 or free T4 observed in children with higher exposure to OCs may affect cognitive function.

Levels of PCB-153 and β-HCH in utero are positively related to TSH concentrations. Association between β-HCH and TSH confirmed in the Valencian cohort.

Levels of DDE in mothers are positively correlated to TSH and negatively to free T4.

Alvarez-Pedrerol et al., Occupational and Environmental Medicine 65, 452-457 (2008)Alvarez-Pedrerol et al., Environment International 34, 737-740 (2008)

ORGANOCHLORINE COMPOUNDS AND CHILDREN SIZE

Exposure to hexachlorobenzene and risk of overweight

Smink et al., Acta Pædiatrica 97, 1465-1469 (2008)

High exposure of HCB prenatal (level in cord blood > 1.03 ng/mL) is associated with an increase of BMI and overweight in girls and boys at age 6.5 years.

Children from normal weight mothers also presented an increased risk of having higher BMI with increasing concentrations of HCB in cord serum.

Smink et al., Acta Pædiatrica 97, 1465-1469 (2008)

Compound Exposure Effect ReferencesHCB In utero Poor social behaviour Ribas-Fito et al., Environ. Health Perspect. 115, 447-450 (2007)

HCB In utero ADHD Ribas-Fito et al., Environ. Health Perspect. 115, 447-450 (2007)

HCB 4 years Alteration of thyroid hormones (T3 and T4)

Alvarez-Pedrerol et al., Occup.Environ. Med. 65, 452-457 (2008)Alvarez-Pedrerol et al., Environ. Int. 34, 737-740 (2008)

HCB In utero Overweight Smink et al., Acta Pædiatrica 97, 1465-1469 (2008)

HCB adults Thyroid cancer Grimalt et al., Int. J. Cancer 56, 200-203 (1994)

HCB 4 years Alteration of thyroid hormones (T3 and T4)

Sala et al., Occup. Environ. Med. 58, 172-177 (2001)

HCB In utero Birth size Lopez-Espinosa et al., Pediatrics 128, e127-e134 (2011)

DDE In utero Asthma Ribas-Fito et al., Am. J. Epidemiol. 164, 955-962 (2006)Sunyer et al., Clin. Exp. Allergy 36, 1236–1241 (2006)

DDE 4 years

mothers

Alteration of thyroid hormones (TSH, T3 and T4)

Alvarez-Pedrerol et al., Occup. Environ. Med. 65, 452-457 (2008)Alvarez-Pedrerol et al., Environ. Int. 34, 737-740 (2008)Lopez-Espinosa et al., Environ. Res. 109, 479-485 (2009)

DDE In utero Increase in urinary coproporphyrins

Sunyer et al., Environ. Health Perspect. 116, 1407-1410 (2008)

DDE In utero Birth weight Lopez-Espinosa et al., Pediatrics 128, e127-e134 (2011)

DDT In utero Decrease of cognitive skills. Higher for children with GSTP1 Val-105 allele

Ribas-Fito et al., Am. J. Epidemiol. 164, 955-962 (2006)Morales et al. Environ. Health Perspect.116, 1581-1585 (2008)

DDT In utero Birth weight Lopez-Espinosa et al., Pediatrics 128, e127-e134 (2011)

PCB-118, PCB-153 4 years

In utero

Alteration of thyroid hormones (T4 and TSH)

Alvarez-Pedrerol et al., Occup. Environ. Med. 65, 452-457 (2008)Alvarez-Pedrerol et al., Environ. Int. 34, 737-740 (2008)

Β-HCH 4 years

In utero

Alteration of thyroid hormones (T4 and TSH)

Alvarez-Pedrerol et al., Occup. Environ. Med. 65, 452-457 (2008)Alvarez-Pedrerol et al., Environ. Int. 34, 737-740 (2008)Lopez-Espinosa et al., J. Exp. Sci. Environ. Epidemiol. 20, 579-588 (2010)

BDE-47 4 years Poor social behaviour Gascon et al., Environ. Int. 37, 605-611 (2010)

BDE-47 4 years Postnatal attention deficit Gascon et al., Environ. Int. 37, 605-611 (2010)

ENFERMEDADES GENERADAS POR CONTAMINANTES. CONTAMINANTES QUE GENERAN ENFERMEDADES.

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