High levels of manganese exposure and neurobehavioral effects on children

José Antonio Menezes‐FilhoLaboratory of Toxicology ‐ College of Pharmacy

Federal University of BahiaBrazil

1

Background

• High levels of waterborne manganese have been associated with problematic behaviors in school‐aged children (Bouchard, 2007 & Khan, 2011)

• So far, this has not been reported with respect to airborne manganese. 

• Lucchini (2011) observed tremor, olfactory and motor changes in adolescents in Brescia, Italy.

2

Background• In Bahia, Brazil a ferro‐manganese alloy plant has been

emitting tons of MnO particulate matter since 70’s.

• High exposure levels has been evidenced (Menezes‐Filho, 2009).– Air Mn in PM2.5: 0.151 µg/m3 (range 0.011–0.439 µg/m3 ) (0.05 µg/m3 

EPA urban air)

– MnH levels: 15.20 µg/g (1.10–95.50 µg/g) gradient related to atmospheric dispersion.

– Mn water levels: low compared to the WHO guidelines of 400 µg/L (WHO, 2006).

• Inverse associations between LogMnH and intellectualfunction of children and their mothers: (Menezes‐Filho, 2011).– Full‐Scale IQ: β= ‐5.78 (95%CI ‐10.71 to ‐0.21)/ Adj. Nut.St. & Mat. IQ.

– Raven Score: β= ‐2.69(95%CI ‐5.43 to 0.05)/Adj. Age, Income & Educ.3

Objectives

4

• We report here the results of the evaluation of children of two communities exposed to airborne Mnfrom a ferro‐manganese alloy plant and its relation with behavioral changes in children.

Methods• Cross‐sectional design• Seventy children (34 boys) age range 6 to 12 years, living in two 

communities close to a ferro‐manganese alloy plant in Bahia, Brazil were evaluated.  

5

Simões Filho Town

Santa Luziavillage

Cotegipe village

Ferro‐alloy Plant

• Hair manganese (MnH) and blood lead levels (BLL) were measured by GF‐AAS (Wright 2006, Montes, 2009).

• The Children’s Behavior Check List (CBCL) Portuguese version validated in Brazil was administered to parents or caregivers and teachers. 

• Trained psychologist generated behavioral indices:• Internalizing: withdrawn, somatic complaints, and 

anxious/depressed scales) • Externalizing: combines disruptive and aggressive behaviors • Scale for inattention. • Maternal estimated IQ (WAIS‐III)

• Socioeconomic questionnaires were applied to volunteers, after giving consent to participate.

• The study approved by the Federeral University of Bahia ethicalcommittee.

Occiptal hairsampling

GF‐AAS Analysis

Cleaning:0.5% Triton‐X100

6

Nitric AcidDigestion

Sociodemographic characteristics of the study population

7

Results Boys (n=34) Girls (n=36)

Mean SD Median Min. Max. Mean SD Median Min. Max.Children

Age (years) 9.5 1.6 10.0 7 12 9.4 1.6 10.0 7 12

Z-score HA -0.11 0.86 -0.18 -1.21 2.38 -0.17 1.31 0.00 -3.18 2.60Head circumference (cm) 52.9 1.3 53.0 49.5 56.1 52.6 2.0 53.0 48.2 58.5Blood Lead (µg/dL) 1.2 1.3 0.5 0.5 6.1 1.1 0.9 0.5 0.5 4.0Hair Mn (µg/g) 15.3 9.9 12.1 1.5 48.5 13.9 13.4 12.4 0.5 55.7

Externalizing BehaviorsDisruptive 3.5 3.4 3.0 0 14 2.9 2.8 2.0 0 12Aggressiveness 9.3 5.6 9.0 0 23 9.4 7.6 8.0 0 28

Internalizing BehaviorsAnxiety/depression 4.3 3.2 3.0 0 12 5.4 3.7 5.0 0 16Withdrawn 2.7 2.3 2.0 0 10 2.7 2.2 2.0 0 7

Inattention 6.1 3.5 6.0 0 13 4.9 3.9 5.0 0 13Main caregiver

Mothers 61 87%

Grandmothers 6 9%Others 3 4%Age (years) 35.9 2.1 112 16 62Estimated IQ 86.7 10.9 83 71 117

Results• No significant differences in any sociodemographic and

behavioral index according to children’s sex.

• Median and range of MnH and BLL were 11.48 (0.52 – 55.74) µg/g and 1.1 (0.5 – 6.1) µg/dL. 

• Externalizing behaviors were significantly correlated with MnH levels: 

– Disruptive: Spearman rho=0.347, p=0.004) 

– Aggressiveness: Sp rho=0.326, p=0.006 

– Total Externalizing behaviors: Sp rho= 0.359, p=0.002

9

Results• Non‐standardized coefficients of LogMnH levels of externalizing and inattention behaviors. 

10

BehaviorIndices

β 95% CI

Aggressiveness 5.69 (1.91-9.48)

Disruptive 2.07 (0.30-3.85)

Total

Externalizing

8.12 (2.94-13.39)

Inattention 3.35 (1.23-5.47Adjusted for age and sex. 

Discussion

• In the USA, Wright (2006) found conitive but no behavioralassociation with MnH on 32 children (11‐14 years) living neara waste disposal site.

• In Quebec, Bouchard (2007) using Conner’s Scale observedsignifcant association beteween MnH and oppositional andhyperactivity scores in 46 children exposed to Mn in the wellwater.

• In Bangladesh, Khan (2011) evaluated 201 children exposed to As and Mn in the well water. Significant associations foundbetween Internallizing (β=0.82) and externalizing (β =2.59) behaviors with logMnW.

11

Discunssion

• High exposure to Mn is associated to higher levels of prolactin, which may have an effect on early onset of puberty (Montes et al. 2011).

• Zhang et al. (1995) observed correlation of higher Mn levels with lower serotonin in exposed children compared to controls.

• It has been demonstrated increased impulsivity and violence in youngsters with lower levels of serotonin.

12

Conclusions

• Our results suggest that children’s high exposure to airborne Mn may be having detrimental effects on behavior, especially those related with externalizing anti‐social behaviors.

• We hypothesize that excessive Mn exposure may contribute to increased violence, especilay  in indiviaduals of vulnerable communities.

13

• Children, parents and teachers from Cotegipe and Santa Luzia Communities, Bahia, Brazil.

• Our Collaborators:– Dr. Neander Abreu, ISP/UFBA– Chrissie de Carvalho, ISP/UFBA– Júnia Dutra, FacFar/UFBA– Our team: Sério Prado, Gustavo Viana, Nathália Ribeiro, Juliana 

Rodrigues, Diego Andrade, Valu.

• Funding agencies:– FAPESB: research grant– CAPES: travel support

Acknowledgements

14

Thank you!