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Promoting gender-based analysis in
environmental health research
Donna Mergler PhD
Professor emerita
Center for interdisciplinary studies on health, well-being, society
and environment
University of Quebec at Montreal
Principal Investigator
Canadian Institutes for Health Research Team on Gender,
Environment and Health

CEC, 2014
Lead poisoning in the 1920’ and
1930’s in the United States
– Alice Hamilton (1869 – 1970), the mother of modern occupational
health, did much work on lead poisoning
– Studies showed women workers had higher lead levels compared to
men and the prevalent notion was that women workers were more
susceptible to lead poisoning than male workers.
– By taking into account job category and socio-economic status, she
showed that when men and women were doing the same job, there
was no difference in their blood lead levels
– Since more women worked in the poorer paying jobs with higher
exposures, overall, women had higher blood lead levels as compared
to men1.
Hamilton A. Exploring the Dangerous Trades, Little Brown & Co., 1943
Photo: Hanna-Andrea Rother

A similar situation today for
pesticide poisonings?

• In 2002, enhanced surveillance of pesticide poisonings in South Africa
revealed that, contrary to the official statistics, women had a higher
prevalence of pesticide poisonings compared to men1:
– higher exposures in women, who did more seasonal work with high exposures
and were likewise more exposed in the home.
– women’s pesticide-related health problems were often misdiagnosed because
of the dominant belief that women were not exposed ‘like men’ to pesticides

• In 2004, a field study of 488 migrant workers in Mexico:
– women were six times more likely than men to have anemia and asthma,
twice more likely to have parasites and respiratory and gastrointestinal
diseases and 38% more likely to suffer from heart disease. Significantly more
women than men reported symptoms associated with pesticide poisoning2
1. London et al. Int J Occup Environ Health 2002; 8:46-59
2. Palacios-Nava et al. Salud pública de México 2004; 46: 286-293
Women Farmworkers in North America
• The percentage of women farm workers is increasing.
– In Mexico, in 1985, the number of women in the total population of
agricultural workers was about 20%, by 2004 it was estimated at 42.6%1.
– In California, women make up 26% of the seasonal agricultural workers2

• An important percentage of farming is done by migrant workers (from
one state to another or from one country to another), whose working
and living conditions are generally very poor. Researchers from Guelph
University have carried out studies with women migrant workers in
Ontario3 and produced a fact sheet…
1. cited in Ojinaga et al. in Genero, Ambiente y Contaminación por Sustancías Químicas 2012 p 67-78;
2. cited in Habib and Fathallah, Work 2012;41 Suppl 1:4356-62 2012
3. Preibisch & Encalada Grez, 2010; Journal of Women in Culture and Society 35: 289-316
• “In 2006, there were 15,576 SAWP workers in
Ontario, 393 were women; 75% came from Mexico
• Most of them are single mothers, in part due to
recruitment practices that limit placements in
Canada to this group.
• They value highly the wages they earn in Canada;
the money serves to support their family in Mexico.
• Women accede to their employers’ demands in order to maintain their
employers’ approval and preserve their tenure in the SAWP, even when
these put their health and safety at risk or violate their rights.
• Migrant women face greater restrictions on their mobility than men.
• They face considerable barriers in accessing public health care and other
social services required to address their gender‐specific needs
• They face a number of challenges when trying to parent across borders
• Migrant women are resilient, innovative individuals pioneering a new life
for their families”.
Preibisch & Encalada Grez Migrant Workers Fact Sheet,
Univerisity of Guelph – Rural Women Making Change 2008
Same sex, no sex, and unaware sex in
neurotoxicology (Weiss, 2011)

• “Males predominate in behavioral experiments, few such
experiments study both sexes, some investigators fail to even
describe the sex of their subjects, and in vitro studies tend to wholly
ignore sex, even for model systems aimed at neurological disorders
that display marked sex differences”.
• “In Volume 29 of Neurotoxicology (2008), the male:female ratio of
whole-animal, single sex studies was 40:1. Four were on both sexes”.

Weiss B. Neurotoxicology. 2011; 32:509-17
Articles in recent volumes of environmental
health journals
No. of
studies

No sex

Stratified
for
sex/gende
r

Animal
studies

17

2
(12%)

13
(76%)

1
(6%)

1
(6%)

0

Human
studies

25

3
(12%)

4
(16%)

5*
(20%)

13
(52%)

6
(24%)

* 3 were pregnant women
Neurotoxicology : vol 39 (2013); vol 40 (2014)
Environmental Health Perspectives: vol 121 (1) (2013)
Environmental Research: vol 129 (2014)
Consequences of not examining
gender and sex differences
• Under-estimation of the environment-related health problems in
one sex or the other (usually women) or both
• Health problems are attributed to other causes (susceptibility,
hysteria, complaining)
• Cycle of ignorance : There is less research on the particular situation
because it is not viewed as an environmentally-related problem and
thus not a “research priority” and thus not studied and if it’s not
studied, it’s not a problem
• Prevention strategies that target the source, the transmission or the
effects of environmental hazards do not necessarily address the
entire population.
Gender Differences in
Susceptibility to
Environmental
Factors: A Priority
Assessment

Scientific Group on
Methodologies for the Safety
Evaluation of Chemicals
(SCOPE, WHO, UNEP, IPCS)

1998

2012
Sex and gender
• In 2001, a committee from the Institute of Medicine
provided the following definitions:
– Sex: The classification of living things, generally as male or
female, according to their reproductive organs and functions
assigned by chromosomal complement. In most studies of
nonhuman animals, the term "sex" should be used.
– Gender: A person's self-representation as male or female, or
how that person is responded to by social institutions based on
the individual's gender presentation. Gender is rooted in biology
and shaped by environment and experience
1. Exploring the Biological Contributions to Human Health: Does Sex Matter?
Institute of Medicine, 2001
Gender and sex interact throughout the life
span
CONTACT WITH THE
ENVIRONMENT

GENDER

Infant and childhood
experiences
Adolescence

fetal growth and
development

Puberty

Childhood
growth and
development

SEX

Working and family life
Retirement

Menopause
Andropause
Reproduction,
pregnancy, breastfeeding,
Reproduction

Decline of
biological
functions
Fetal growth and
development
Childhood
growth and
development

•

DBCP, a pesticide used extensively in
banana plantations rendered men
sterile; until the cause was known
women were often “accused” of
infertility

•

In utero exposure to many toxics
commonly found in our
environments will affect developing
boys and girls differently

•

Childhood playing activities and
household chores may differ
between boys and girls translating
into different exposure patterns

•

Several toxic substances modify the
chronology of puberty…..

Infant and childhood
experiences

Puberty
Adolescence
Reproduction
Pregnancy
Breast-feeding

Working and family
life

Menopause
Andropause
Decline of biological
functions

Retirement
Fetal growth and
development
Childhood
growth and
development
Puberty

Pregnancy
Breast-feeding

Early breast development in girls after
prenatal exposure to non-persistent
pesticides
Mean age at breast development was
8.9 years in exposed girls vs. 10.4 years
in non-exposed.
Wohlfahrt-Veje et al, Int J Andrology 2012; 35: 272-282

Mothers working in
greenhouses with exposure
to pesticides in Denmark
Childhood growth,
development and puberty

Childhood experiences

• Menarche is occurring at a
younger age
• The period between the
appearance of secondary sexual
characteristics and menarche is
increasing
• Secondary sexual characteristics
are appearing much younger in
girls
• Endocrine modifiers may
contribute to these changes

Pinto, K.. J. Early Adolescence 2007; 27:509-544
Some examples of sex differences in animal
studies with pre-natal exposures
• Lead (Pb)
•

In rats, lead and maternal stress interact differently on male and female
offsprings’ corticosteroid levels, neurotransmitters and behavior. (Cory-Slechta
et al, 2005)

•

In mice, low level prenatal Pb exposure showed male-specific effects in 1 year
old offspring, for motor activity and brain dopamine metabolism; effects were
non-linear, with the largest effects at the lower doses (Leasure et al, 2011)

• Polychlorinated Biphenyl (PCB) congeners
•

Sex-specific differences have been reported for motor activity and
neurotransmission (Boix et al, 2011), as well as on the retina (Kremer et al, 1999)

• Polybrominated diphenyl ethers (PBDE)
•

No sex differences were observed in male and female mice prenatally
exposed to PBDE (Viberg et al, 2004)
Birth cohort studies
• Some studies have examined sexes separately and reported
differences for some functions but not for others.
– Several studies have reported stronger associations between prenatal
Pb exposure and poorer cognitive performance and behavioral
disorders for boys compared to girls1,2; others have not observed
differences3
– Poorer motor performance was reported in relation to prenatal
mercury in boys, while other functions were similar4
– Boys presented greater risk for behavioral disorders in relation to
prenatal exposure to phthaltes5.
– Boys presented greater risk for early childhood symptoms of attention
disorders in relation to mothers’ exposure to pesticides6,7, while others
have not observed differences8

.
1. Ris et al, 2004; 2. Jedrychowski et al, 2009; 3. Kim et al, 2001; 4. Grandjean et al, 1998 ; 5.
Engel et al, 2010; 6. Marks et al, 2010; 7. Fortenberry et al. 2014; 8. Bouchard et al, 2010
Intellectual deficits and behavioural
disorders in children

Percentage
of children

50

75

100

125

150

median score
(adapted from Rice, 1998)
Cognitive performance and environmental Mn
exposure in primary school children
Country

Mn source

Quebec1

Well water

Brazil2

Airborne (Mn alloy
production)

Mexico3

Airborne (mines and
transformation)

1. Bouchard et al, 2011

2. Menezes-Filho et al, 2011

3. Riojas-Rodriguez et al. 2010
Low hair manganese : <2µg/g
Quebec
Brazil
Mexico

High hair manganese : ≥2µg/g
Quebec
Brazil
Mexico
Combined analysis of the relation between
hair Mn and Full IQ in primary school children
Quebec
(n = 377)

Mexico
(n = 195)

Brazil
(n – 82)

p

% girls

53.7

48.7

46.3

ns

Age

9.1 ± 1.78

9.42 ± 1.45

8.74 ± 1.61

0.007

Full IQ

104 ± 12

78.5 ± 14

85.2 ± 14

0.0001

• Adjusted Full IQ Score for each study separately on mothers’ Raven score,
mothers’ education, z-score of height for age
• Examined association with hair Mn, taking into account study, age and sex
• Stratified for sex, taking into account study and age
Estimate : -2.62 (-4.10 - -1.13)

Estimate boys: - 1.08 (-3.21 – 1.05)
Estimate girls: - 4.19 (-6.19 - -2.07)

In a recent study in the same region in Brazil, externalizing behaviors and
attention problem scores were significantly associated with girls' hair
manganese levels but not with boys’ (Menezes filho et al. In press)
In a study of manganese-exposed adult mice, long-lasting differences in neuronal
morphology were observed in females, but not in males, in the absence of
differences in manganese accumulation in the brain (Madison et al., 2011).
The cycle of
environmental
disease

Newborn
underweight

0 – 6 months
Further exposure
through breast milk,
but also benefits

Mothers’ exposures,
working and living
conditions

For boys and men, this can likewise translate into
For teenage girls, this
higher prevalence of anti-social, delinquent and
often translates into
criminal behavior
early pregnancies
Ex: In a longitudinal study of crime arrests in
young adults in relation to prenatal and
childhood Pb : the attributable risk for 6-y blood
lead rate was 0.85 arrests/year for males and
0.18 for females (Wright et al, 2008).

Using Indicators to Mesure
Progress on Environmental
Health, WHO ,UNEP, 2002

Teenager to adult :
school drop-out, low
paid job, further
exposure

Age 6 Lack of energy,
poor school
performance

6 months – 2 y
Poverty and lack of
parental
knowledge.
Environmental
exposure

Age 3
Developmental
delays. Child does
not demand
stimulation.
Frequent illnesses
Childhood exposures
• Toddlers’ activities may differ between boys and girls
– A study of farm workers’ children showed that boys had more
frequent contacts with their environment while girls contact objects
for longer durations.
– The authors point out that “Understanding how frequency and
duration contribute to dermal and non-dietary ingestion exposure
could increase understanding of the potential difference in exposure
between the genders”. (Beamer et al, 2008)

• Childhood playing activities and household chores may differ
between boys and girls translating into different exposure
patterns:
• In a study around a dumpsite, boys roamed in contaminated areas
more than girls (Steegmann and Hewner, 2000)
• Girls may be more exposed to more household contaminants.
Childhood socialization : gender identity
• Googled boys and girls e-games

Tank 2008
Choose-your-weapon

Extreme Hair Make Over

Spider-3-rescue

Rock Star Make Over
Room Clean-up

http://www.free-online-games-to-play.net/games/girlgames/page/3/
Biologic differences and exposure
• A study of serum PCB concentration in adolescents1:
– Girls : positively with milk consumption fat intake , the
duration of breast-feeding, and the concentrations of serum
triglycerides and cholesterol and negatively with body fat,
– Boys: fat intake and serum triglycerides, and marginally with
the duration of breast-feeding and negatively with body fat.
– Similar and significant estimates for external exposure
– Sex-related differences in the serum PCB concentration
disappeared after allowing for calculated body fat content
– The authors discuss the role of changes in body fat and PCB
concentrations throughout the lifespan in women
1. Nawrot et al, 2002
Gender, sex or both?
• Analysis of Data from the Canadian Health
Measures Survey: Bisphenol A (BPA)
– Males had higher volume-based urinary BPA
concentrations than did females, but lower creatininestandardized urinary concentrations of BPA.
– The reversal in the sex difference was attributed to the
higher urinary creatinine concentrations
– The authors conclude : “Differences between the sexes in
urinary BPA concentrations may reflect differences in
exposure and in pharmacokinetic factors, the relevance of
which is not currently known”
Bushnik et al, 2010
Urinary Bisphenol-A: data from the
Canadian Health Measures Survey
(geometric means)
2

µg/L

2

1.5

1.5

1

1

0.5
0

2.5

µg/g cr

0.5
6 - 11y 12- 19y 20 - 39y 40 - 59y 60- 79y

0

6 - 11y 12- 19y 20 - 39y 40 - 59y 60- 79y
Different functions/different exposures
Men

Women

70.0

70.0

60.0

60.0

50.0

50.0

40.0

Series2

30.0

Series3

40.0

unpaid
Series1

30.0

20.0

10.0

0.0

total
Series5

Series6 20.0

10.0

paid
Series4

0.0
15 - 24 25 - 34 35 - 44 45 - 54 55 - 64 65 - 74 75 years
years years years years years years old and
over

15 - 24 25 - 34 35 - 44 45 - 54 55 - 64 65 - 74 75 years
years years years years years years old and
over

Table 638. Average Hours pers Week Spent Doing Unpaid Household Work and Paid Work by Sex and
Age (US Census Bureau, The 2011 Statistical Abstract; The National Data Book)
http://www.census.gov/compendia/statab/cats/labor_force_employment_earnings.html
From the Hänninen twin study

Hänninen et al, 1991
Informal work
• A surprising result from our studies on mercury exposure in the
Brazilian Amazon : high blood Pb: mean: 13.1 µg/dL range: 0.59 - 48.3
µg/dL
• Highest levels were observed among young men and older
women
• Partition analysis identified activities with respect to blood Pb

Barbosa et al, 2009
Working together
Community

Natural Sciences &
Engineering

Health Sciences

Social Sciences & Humanities
Cancer among women plastics workers:
an interdisciplinary study1
• Breast cancer risk in relation to occupations with exposure to carcinogens and
endocrine disruptors: a Canadian case–control study (Brophy et al 2012)1,2
– Many investigators (researchers and community) from different disciplines
– Mixed-method research approach (quantitative and qualitative)2
• women in the study area held a wide range of jobs in the plastics industry
dating back to the 1960s;
• the majority of automotive plastics manufacturing workers in the study area
are women;
• the work environment is heavily contaminated with dust, vapours and fumes;
• there has been a historic failure by government regulators to control
exposures;
• workers receive a steady dose of mixtures of chemicals through inhalation,
absorption and ingestion;
• workers are getting sick; and society is largely unaware of their plight.
1. De Matteo et al, New Solutions 2012: 22:427-448
2. Brophy et al. Environmental Health. 2012; 11:87.
3. Winner of the American Public Health Association Scientific Award in Occupational Health
Gender and sex: not an afterthought
• Taking gender and sex into account begins with the
research question
• Some questions …
– Are different disciplines and concerned parties providing input?
– Is the situation similar for both sexes ?
– What are the differences and similarities ?
– If just one sex is involved, this should be stated up front
(including animal and cell studies1)

1. Ritz et al. First steps for integrating sex and gender considerations into basic experimental
biomedical research FASEB J. 2014;28:4-13
Study or Intervention Design:
a non-exhaustive list of questions

• If there is exposure assessment, are the activities and habits of both
genders adequately considered?
• If it involves working populations (including informal work), is there a good
description of the work activities?
• Is the sample size sufficient to demonstrate possible differences?
• Are there sex and/or gender-related factors that could influence the
relation between exposure and biomarkers of exposure?
• Are the outcome measurements relevant for males and females?
• Could gender differences influence the outcomes?
• Have the individual outcome measures been validated for males and
females?
• Are the social consequences of effects equally relevant for both genders?
Data presentation & analyses
Report on Urinary Bisphenol A
(µg/g creatinine)
( Urinary Bisphenol A geometric means)
USA National Health and
µg/L
2 Survey (2009)
Nutrition
1.5
1
0.5
0

6 - 11y 12- 19y 20 39y

40 - 60- 79y
59y

2.5
2
1.5
1
0.5
0

Canadian Health
Measures Survey
(2010)

6 - 11y 12- 19y 20 39y

µg/g cr

40 - 60- 79y
59y
Complex analyses
• In studies seeking to examine the associations between exposure
and health outcomes, sex/gender is included in multiple regression
analyses as any other co-variable like: age, income, and many
others…
• Some studies suggest that this may not fully capture the sex/gender
differences.
• Stratifying analyses by sex/gender can help to understand both
similarities and differences (both exposure patterns and effect can
be different)
• Mixed methods, cluster analysis, multi-level analyses have been
proposed to examine the complex interrelations between social,
physical and biological factors and health outcomes
Sources of
exposure

Biomarkers
of
exposure

Biomarkers
of effect

Health
outcomes

Social
impact

• There is growing awareness of the importance of including gender.
• There is no simple "recipe" for integrating gender and sex in
environmental health research - or in examining these complex
interrelationships
• It requires a change in paradigm to take into account and to promote a
bettering understanding of sex and gender in environmental health
An
Ecosystem
Approach
to Human
Health

biosphere
global ecosystem
regional ecosystem
local ecosystem
community
workplace
biological factors

home
Health & wellbeing

economy

geophysical milieu
culture
toxic substances
socio-political situation

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Promoting gender-based analysis in environmental health research

  • 1. Promoting gender-based analysis in environmental health research Donna Mergler PhD Professor emerita Center for interdisciplinary studies on health, well-being, society and environment University of Quebec at Montreal Principal Investigator Canadian Institutes for Health Research Team on Gender, Environment and Health CEC, 2014
  • 2. Lead poisoning in the 1920’ and 1930’s in the United States – Alice Hamilton (1869 – 1970), the mother of modern occupational health, did much work on lead poisoning – Studies showed women workers had higher lead levels compared to men and the prevalent notion was that women workers were more susceptible to lead poisoning than male workers. – By taking into account job category and socio-economic status, she showed that when men and women were doing the same job, there was no difference in their blood lead levels – Since more women worked in the poorer paying jobs with higher exposures, overall, women had higher blood lead levels as compared to men1. Hamilton A. Exploring the Dangerous Trades, Little Brown & Co., 1943
  • 3. Photo: Hanna-Andrea Rother A similar situation today for pesticide poisonings? • In 2002, enhanced surveillance of pesticide poisonings in South Africa revealed that, contrary to the official statistics, women had a higher prevalence of pesticide poisonings compared to men1: – higher exposures in women, who did more seasonal work with high exposures and were likewise more exposed in the home. – women’s pesticide-related health problems were often misdiagnosed because of the dominant belief that women were not exposed ‘like men’ to pesticides • In 2004, a field study of 488 migrant workers in Mexico: – women were six times more likely than men to have anemia and asthma, twice more likely to have parasites and respiratory and gastrointestinal diseases and 38% more likely to suffer from heart disease. Significantly more women than men reported symptoms associated with pesticide poisoning2 1. London et al. Int J Occup Environ Health 2002; 8:46-59 2. Palacios-Nava et al. Salud pública de México 2004; 46: 286-293
  • 4. Women Farmworkers in North America • The percentage of women farm workers is increasing. – In Mexico, in 1985, the number of women in the total population of agricultural workers was about 20%, by 2004 it was estimated at 42.6%1. – In California, women make up 26% of the seasonal agricultural workers2 • An important percentage of farming is done by migrant workers (from one state to another or from one country to another), whose working and living conditions are generally very poor. Researchers from Guelph University have carried out studies with women migrant workers in Ontario3 and produced a fact sheet… 1. cited in Ojinaga et al. in Genero, Ambiente y Contaminación por Sustancías Químicas 2012 p 67-78; 2. cited in Habib and Fathallah, Work 2012;41 Suppl 1:4356-62 2012 3. Preibisch & Encalada Grez, 2010; Journal of Women in Culture and Society 35: 289-316
  • 5. • “In 2006, there were 15,576 SAWP workers in Ontario, 393 were women; 75% came from Mexico • Most of them are single mothers, in part due to recruitment practices that limit placements in Canada to this group. • They value highly the wages they earn in Canada; the money serves to support their family in Mexico. • Women accede to their employers’ demands in order to maintain their employers’ approval and preserve their tenure in the SAWP, even when these put their health and safety at risk or violate their rights. • Migrant women face greater restrictions on their mobility than men. • They face considerable barriers in accessing public health care and other social services required to address their gender‐specific needs • They face a number of challenges when trying to parent across borders • Migrant women are resilient, innovative individuals pioneering a new life for their families”. Preibisch & Encalada Grez Migrant Workers Fact Sheet, Univerisity of Guelph – Rural Women Making Change 2008
  • 6. Same sex, no sex, and unaware sex in neurotoxicology (Weiss, 2011) • “Males predominate in behavioral experiments, few such experiments study both sexes, some investigators fail to even describe the sex of their subjects, and in vitro studies tend to wholly ignore sex, even for model systems aimed at neurological disorders that display marked sex differences”. • “In Volume 29 of Neurotoxicology (2008), the male:female ratio of whole-animal, single sex studies was 40:1. Four were on both sexes”. Weiss B. Neurotoxicology. 2011; 32:509-17
  • 7. Articles in recent volumes of environmental health journals No. of studies No sex Stratified for sex/gende r Animal studies 17 2 (12%) 13 (76%) 1 (6%) 1 (6%) 0 Human studies 25 3 (12%) 4 (16%) 5* (20%) 13 (52%) 6 (24%) * 3 were pregnant women Neurotoxicology : vol 39 (2013); vol 40 (2014) Environmental Health Perspectives: vol 121 (1) (2013) Environmental Research: vol 129 (2014)
  • 8. Consequences of not examining gender and sex differences • Under-estimation of the environment-related health problems in one sex or the other (usually women) or both • Health problems are attributed to other causes (susceptibility, hysteria, complaining) • Cycle of ignorance : There is less research on the particular situation because it is not viewed as an environmentally-related problem and thus not a “research priority” and thus not studied and if it’s not studied, it’s not a problem • Prevention strategies that target the source, the transmission or the effects of environmental hazards do not necessarily address the entire population.
  • 9. Gender Differences in Susceptibility to Environmental Factors: A Priority Assessment Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SCOPE, WHO, UNEP, IPCS) 1998 2012
  • 10. Sex and gender • In 2001, a committee from the Institute of Medicine provided the following definitions: – Sex: The classification of living things, generally as male or female, according to their reproductive organs and functions assigned by chromosomal complement. In most studies of nonhuman animals, the term "sex" should be used. – Gender: A person's self-representation as male or female, or how that person is responded to by social institutions based on the individual's gender presentation. Gender is rooted in biology and shaped by environment and experience 1. Exploring the Biological Contributions to Human Health: Does Sex Matter? Institute of Medicine, 2001
  • 11. Gender and sex interact throughout the life span CONTACT WITH THE ENVIRONMENT GENDER Infant and childhood experiences Adolescence fetal growth and development Puberty Childhood growth and development SEX Working and family life Retirement Menopause Andropause Reproduction, pregnancy, breastfeeding, Reproduction Decline of biological functions
  • 12. Fetal growth and development Childhood growth and development • DBCP, a pesticide used extensively in banana plantations rendered men sterile; until the cause was known women were often “accused” of infertility • In utero exposure to many toxics commonly found in our environments will affect developing boys and girls differently • Childhood playing activities and household chores may differ between boys and girls translating into different exposure patterns • Several toxic substances modify the chronology of puberty….. Infant and childhood experiences Puberty Adolescence Reproduction Pregnancy Breast-feeding Working and family life Menopause Andropause Decline of biological functions Retirement
  • 13. Fetal growth and development Childhood growth and development Puberty Pregnancy Breast-feeding Early breast development in girls after prenatal exposure to non-persistent pesticides Mean age at breast development was 8.9 years in exposed girls vs. 10.4 years in non-exposed. Wohlfahrt-Veje et al, Int J Andrology 2012; 35: 272-282 Mothers working in greenhouses with exposure to pesticides in Denmark
  • 14. Childhood growth, development and puberty Childhood experiences • Menarche is occurring at a younger age • The period between the appearance of secondary sexual characteristics and menarche is increasing • Secondary sexual characteristics are appearing much younger in girls • Endocrine modifiers may contribute to these changes Pinto, K.. J. Early Adolescence 2007; 27:509-544
  • 15. Some examples of sex differences in animal studies with pre-natal exposures • Lead (Pb) • In rats, lead and maternal stress interact differently on male and female offsprings’ corticosteroid levels, neurotransmitters and behavior. (Cory-Slechta et al, 2005) • In mice, low level prenatal Pb exposure showed male-specific effects in 1 year old offspring, for motor activity and brain dopamine metabolism; effects were non-linear, with the largest effects at the lower doses (Leasure et al, 2011) • Polychlorinated Biphenyl (PCB) congeners • Sex-specific differences have been reported for motor activity and neurotransmission (Boix et al, 2011), as well as on the retina (Kremer et al, 1999) • Polybrominated diphenyl ethers (PBDE) • No sex differences were observed in male and female mice prenatally exposed to PBDE (Viberg et al, 2004)
  • 16. Birth cohort studies • Some studies have examined sexes separately and reported differences for some functions but not for others. – Several studies have reported stronger associations between prenatal Pb exposure and poorer cognitive performance and behavioral disorders for boys compared to girls1,2; others have not observed differences3 – Poorer motor performance was reported in relation to prenatal mercury in boys, while other functions were similar4 – Boys presented greater risk for behavioral disorders in relation to prenatal exposure to phthaltes5. – Boys presented greater risk for early childhood symptoms of attention disorders in relation to mothers’ exposure to pesticides6,7, while others have not observed differences8 . 1. Ris et al, 2004; 2. Jedrychowski et al, 2009; 3. Kim et al, 2001; 4. Grandjean et al, 1998 ; 5. Engel et al, 2010; 6. Marks et al, 2010; 7. Fortenberry et al. 2014; 8. Bouchard et al, 2010
  • 17. Intellectual deficits and behavioural disorders in children Percentage of children 50 75 100 125 150 median score (adapted from Rice, 1998)
  • 18. Cognitive performance and environmental Mn exposure in primary school children Country Mn source Quebec1 Well water Brazil2 Airborne (Mn alloy production) Mexico3 Airborne (mines and transformation) 1. Bouchard et al, 2011 2. Menezes-Filho et al, 2011 3. Riojas-Rodriguez et al. 2010
  • 19. Low hair manganese : <2µg/g Quebec Brazil Mexico High hair manganese : ≥2µg/g Quebec Brazil Mexico
  • 20. Combined analysis of the relation between hair Mn and Full IQ in primary school children Quebec (n = 377) Mexico (n = 195) Brazil (n – 82) p % girls 53.7 48.7 46.3 ns Age 9.1 ± 1.78 9.42 ± 1.45 8.74 ± 1.61 0.007 Full IQ 104 ± 12 78.5 ± 14 85.2 ± 14 0.0001 • Adjusted Full IQ Score for each study separately on mothers’ Raven score, mothers’ education, z-score of height for age • Examined association with hair Mn, taking into account study, age and sex • Stratified for sex, taking into account study and age
  • 21. Estimate : -2.62 (-4.10 - -1.13) Estimate boys: - 1.08 (-3.21 – 1.05) Estimate girls: - 4.19 (-6.19 - -2.07) In a recent study in the same region in Brazil, externalizing behaviors and attention problem scores were significantly associated with girls' hair manganese levels but not with boys’ (Menezes filho et al. In press) In a study of manganese-exposed adult mice, long-lasting differences in neuronal morphology were observed in females, but not in males, in the absence of differences in manganese accumulation in the brain (Madison et al., 2011).
  • 22. The cycle of environmental disease Newborn underweight 0 – 6 months Further exposure through breast milk, but also benefits Mothers’ exposures, working and living conditions For boys and men, this can likewise translate into For teenage girls, this higher prevalence of anti-social, delinquent and often translates into criminal behavior early pregnancies Ex: In a longitudinal study of crime arrests in young adults in relation to prenatal and childhood Pb : the attributable risk for 6-y blood lead rate was 0.85 arrests/year for males and 0.18 for females (Wright et al, 2008). Using Indicators to Mesure Progress on Environmental Health, WHO ,UNEP, 2002 Teenager to adult : school drop-out, low paid job, further exposure Age 6 Lack of energy, poor school performance 6 months – 2 y Poverty and lack of parental knowledge. Environmental exposure Age 3 Developmental delays. Child does not demand stimulation. Frequent illnesses
  • 23. Childhood exposures • Toddlers’ activities may differ between boys and girls – A study of farm workers’ children showed that boys had more frequent contacts with their environment while girls contact objects for longer durations. – The authors point out that “Understanding how frequency and duration contribute to dermal and non-dietary ingestion exposure could increase understanding of the potential difference in exposure between the genders”. (Beamer et al, 2008) • Childhood playing activities and household chores may differ between boys and girls translating into different exposure patterns: • In a study around a dumpsite, boys roamed in contaminated areas more than girls (Steegmann and Hewner, 2000) • Girls may be more exposed to more household contaminants.
  • 24. Childhood socialization : gender identity • Googled boys and girls e-games Tank 2008 Choose-your-weapon Extreme Hair Make Over Spider-3-rescue Rock Star Make Over Room Clean-up http://www.free-online-games-to-play.net/games/girlgames/page/3/
  • 25. Biologic differences and exposure • A study of serum PCB concentration in adolescents1: – Girls : positively with milk consumption fat intake , the duration of breast-feeding, and the concentrations of serum triglycerides and cholesterol and negatively with body fat, – Boys: fat intake and serum triglycerides, and marginally with the duration of breast-feeding and negatively with body fat. – Similar and significant estimates for external exposure – Sex-related differences in the serum PCB concentration disappeared after allowing for calculated body fat content – The authors discuss the role of changes in body fat and PCB concentrations throughout the lifespan in women 1. Nawrot et al, 2002
  • 26. Gender, sex or both? • Analysis of Data from the Canadian Health Measures Survey: Bisphenol A (BPA) – Males had higher volume-based urinary BPA concentrations than did females, but lower creatininestandardized urinary concentrations of BPA. – The reversal in the sex difference was attributed to the higher urinary creatinine concentrations – The authors conclude : “Differences between the sexes in urinary BPA concentrations may reflect differences in exposure and in pharmacokinetic factors, the relevance of which is not currently known” Bushnik et al, 2010
  • 27. Urinary Bisphenol-A: data from the Canadian Health Measures Survey (geometric means) 2 µg/L 2 1.5 1.5 1 1 0.5 0 2.5 µg/g cr 0.5 6 - 11y 12- 19y 20 - 39y 40 - 59y 60- 79y 0 6 - 11y 12- 19y 20 - 39y 40 - 59y 60- 79y
  • 28. Different functions/different exposures Men Women 70.0 70.0 60.0 60.0 50.0 50.0 40.0 Series2 30.0 Series3 40.0 unpaid Series1 30.0 20.0 10.0 0.0 total Series5 Series6 20.0 10.0 paid Series4 0.0 15 - 24 25 - 34 35 - 44 45 - 54 55 - 64 65 - 74 75 years years years years years years years old and over 15 - 24 25 - 34 35 - 44 45 - 54 55 - 64 65 - 74 75 years years years years years years years old and over Table 638. Average Hours pers Week Spent Doing Unpaid Household Work and Paid Work by Sex and Age (US Census Bureau, The 2011 Statistical Abstract; The National Data Book) http://www.census.gov/compendia/statab/cats/labor_force_employment_earnings.html
  • 29. From the Hänninen twin study Hänninen et al, 1991
  • 30. Informal work • A surprising result from our studies on mercury exposure in the Brazilian Amazon : high blood Pb: mean: 13.1 µg/dL range: 0.59 - 48.3 µg/dL • Highest levels were observed among young men and older women • Partition analysis identified activities with respect to blood Pb Barbosa et al, 2009
  • 31. Working together Community Natural Sciences & Engineering Health Sciences Social Sciences & Humanities
  • 32. Cancer among women plastics workers: an interdisciplinary study1 • Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case–control study (Brophy et al 2012)1,2 – Many investigators (researchers and community) from different disciplines – Mixed-method research approach (quantitative and qualitative)2 • women in the study area held a wide range of jobs in the plastics industry dating back to the 1960s; • the majority of automotive plastics manufacturing workers in the study area are women; • the work environment is heavily contaminated with dust, vapours and fumes; • there has been a historic failure by government regulators to control exposures; • workers receive a steady dose of mixtures of chemicals through inhalation, absorption and ingestion; • workers are getting sick; and society is largely unaware of their plight. 1. De Matteo et al, New Solutions 2012: 22:427-448 2. Brophy et al. Environmental Health. 2012; 11:87. 3. Winner of the American Public Health Association Scientific Award in Occupational Health
  • 33. Gender and sex: not an afterthought • Taking gender and sex into account begins with the research question • Some questions … – Are different disciplines and concerned parties providing input? – Is the situation similar for both sexes ? – What are the differences and similarities ? – If just one sex is involved, this should be stated up front (including animal and cell studies1) 1. Ritz et al. First steps for integrating sex and gender considerations into basic experimental biomedical research FASEB J. 2014;28:4-13
  • 34. Study or Intervention Design: a non-exhaustive list of questions • If there is exposure assessment, are the activities and habits of both genders adequately considered? • If it involves working populations (including informal work), is there a good description of the work activities? • Is the sample size sufficient to demonstrate possible differences? • Are there sex and/or gender-related factors that could influence the relation between exposure and biomarkers of exposure? • Are the outcome measurements relevant for males and females? • Could gender differences influence the outcomes? • Have the individual outcome measures been validated for males and females? • Are the social consequences of effects equally relevant for both genders?
  • 35. Data presentation & analyses Report on Urinary Bisphenol A (µg/g creatinine) ( Urinary Bisphenol A geometric means) USA National Health and µg/L 2 Survey (2009) Nutrition 1.5 1 0.5 0 6 - 11y 12- 19y 20 39y 40 - 60- 79y 59y 2.5 2 1.5 1 0.5 0 Canadian Health Measures Survey (2010) 6 - 11y 12- 19y 20 39y µg/g cr 40 - 60- 79y 59y
  • 36. Complex analyses • In studies seeking to examine the associations between exposure and health outcomes, sex/gender is included in multiple regression analyses as any other co-variable like: age, income, and many others… • Some studies suggest that this may not fully capture the sex/gender differences. • Stratifying analyses by sex/gender can help to understand both similarities and differences (both exposure patterns and effect can be different) • Mixed methods, cluster analysis, multi-level analyses have been proposed to examine the complex interrelations between social, physical and biological factors and health outcomes
  • 37. Sources of exposure Biomarkers of exposure Biomarkers of effect Health outcomes Social impact • There is growing awareness of the importance of including gender. • There is no simple "recipe" for integrating gender and sex in environmental health research - or in examining these complex interrelationships • It requires a change in paradigm to take into account and to promote a bettering understanding of sex and gender in environmental health
  • 38. An Ecosystem Approach to Human Health biosphere global ecosystem regional ecosystem local ecosystem community workplace biological factors home Health & wellbeing economy geophysical milieu culture toxic substances socio-political situation