Elsevier

NeuroToxicology

Volume 26, Issue 4, August 2005, Pages 599-613
NeuroToxicology

Vision abnormalities in young children exposed prenatally to organic solvents

https://doi.org/10.1016/j.neuro.2005.05.011Get rights and content

Abstract

Despite an accumulating body of evidence demonstrating that the visual system is an important target for organic solvent toxicity in adults, little attention has been paid to the visual functioning of children with prenatal exposure to organic solvents. The present study aimed to: (1) determine prospectively whether prenatal solvent exposure increases the risk of visual deficits in infants and (2) assess the relationship between estimates of exposure level and integrity of visual responses. A sample of 21 infants born to women who were occupationally exposed to solvents during pregnancy was compared with 27 non-exposed age-matched control infants. All mothers were recruited from Motherisk, an antenatal counseling service in Toronto, Canada. Contrast sensitivity and grating acuity were assessed using a sweep visual evoked potential (VEP) technique whereas chromatic- and achromatic mechanisms were assessed using a transient VEP technique. Exposure level was estimated from questionnaire data obtained during pregnancy. Testers were masked to exposure status. Results showed a significant reduction in contrast sensitivity in the low and intermediate spatial frequency range in solvent-exposed infants compared to controls (p < 0.001). With respect to grating acuity, there was a significant effect of exposure level, with children in the high exposed having reduced grating acuity compared with children in the low exposed group (p < 0.025) and controls (p = 0.02). Regarding color vision, 26.3% of infants in the exposed group versus 0% of the controls produced abnormal VEP responses to the red–green onset stimulus (p < 0.01), but not to either blue–yellow or achromatic stimuli. No differences were found with respect to latency or amplitude of chromatic and achromatic response. These findings suggest that prenatal solvent exposure is associated with selective visual deficits, including reduced contrast sensitivity and abnormal red–green vision. Increasing levels of exposure may lead to further visual deficits affecting grating acuity. These findings support the need for a re-evaluation of current occupational exposure standards for pregnant women.

Introduction

Organic solvents comprise a large and structurally diverse group of chemicals, which are used in a variety of workplace settings such as laboratories and dry cleaning, printing, and textile industries. Because women of child-bearing age are commonly employed in these settings, the potential for exposure to organic solvents during pregnancy is large. This is an important public health issue because studies of animals and humans have previously linked prenatal organic solvent exposure to adverse reproductive outcomes including increased risk of spontaneous abortion (Kyyronen et al., 1989, Lindbohm et al., 1990, McDonald et al., 1988, Taskinen et al., 1994) and congenital malformations in the offspring (Garcia and Fletcher, 1998, McDonald et al., 1987, Tikkanen and Heinonen, 1988). While a number of investigations have reported persistent central nervous system (CNS) effects in solvent-exposed workers and animals exposed postnatally, information regarding functional neurological outcomes in children with prenatal solvent exposure is surprisingly limited.

Previous research has shown that the visual system is an important target for organic solvent toxicity. Studies of adult workers who received continuous low-level exposure to styrene (Campagna et al., 1996, Chia et al., 1994, Fallas et al., 1992, Gobba et al., 1991), toluene (Zavalic et al., 1998a), n-hexane (Raitta et al., 1978), and various solvent mixtures (Mergler et al., 1988, Muttray et al., 1997) have shown acquired color vision loss as well as reduced contrast sensitivity in the intermediate spatial frequency range (Broadwell et al., 1995, Frenette et al., 1991, Mergler et al., 1991). These visual impairments have been detected at permissible occupational exposure levels, signifying that color discrimination and contrast sensitivity are particularly sensitive markers of neurological dysfunction.

Similar research involving macaque monkeys exposed postnatally to organic solvents has shown consequent effects on specific visual functions. For example, exposure to carbon disulfide has been found to lead to reduced contrast sensitivity and degeneration of central retinal ganglion cells (Eskin et al., 1988, Merigan et al., 1988) while acrylamide monomer was shown to cause a selective loss of parvocellular retinal ganglion cells (i.e., color opponent cells) with sparing of magnocellular pathways. Since the magnocellular pathway of the visual system is critical for contrast detection while the parvocellular pathway is critical for color vision and visual acuity, these findings suggest selective effects of different types of organic solvent compounds on different pathways of the visual system.

Regarding children, a preliminary study by our group (Till et al., 2001b) showed an increased incidence of visual deficits following gestational exposure to organic solvents. We used clinical instruments to compare color vision, visual acuity, and visuomotor abilities in 3- to 7-year-old children born to women who were either exposed occupationally to solvents during pregnancy or not exposed. Our results revealed that solvent-exposed children displayed mild to severe visual impairments in red–green and blue–yellow color discrimination and they had reduced visual acuity and poorer visuomotor skills compared to non-exposed controls. Also noted was a nonsignificant trend for clinical red–green color vision loss with approximately 10% of exposed group showing this loss compared with none of the non-exposed children. In light of similar visual disturbances following prenatal exposure to other neurotoxic agents, such as mercury or methylmercury (Burbacher et al., 1999, Grandjean et al., 2001, Rice and Gilbert, 1990), cocaine (Block et al., 1997), and alcohol (Hug et al., 2000, Katz and Fox, 1991, Stromland, 1987, Stromland and Hellstrom, 1996), we hypothesized that prenatal exposure to organic solvents may similarly affect the development of primary visual system structures such as the retina, lateral geniculate nucleus (LGN), and primary visual cortex (Banks and Salapatek, 1983, Meissirel et al., 1997).

The objective of the present study was to use objective and sensitive techniques to assess selective aspects of visual functioning (viz., contrast sensitivity, grating acuity, color vision) in infant offspring of women exposed occupationally to organic solvents during pregnancy. Two questions were asked: Do these infants have altered visual functioning and is there a relation between estimates of exposure level and severity and type of visual deficit? Because little is known about the physiological mechanisms of solvent-related visual toxicity, this study assessed multiple visual functions to help determine whether specific neural systems, such as the parvocellular and magnocellular system, are selectively compromised.

Section snippets

Participants

Participants were recruited during the period January 1999–March 2003 from the records of the Motherisk Program, a Toronto-based antenatal consulting service for teratogenic exposures. All mothers had telephoned this program to obtain information about potential risks in pregnancy. At the time of the initial Motherisk call, a trained counselor used a structured questionnaire to interview each pregnant woman about her age; medical, genetic, and obstetrical history; occupation; smoking, drug use,

Results

Table 3 provides information about the occupations and types of chemical exposures of the women in the original cohort who met criteria and whose children participated versus those who refused participation. In the study cohort, the most common occupations were factory workers (23.8%), laboratory workers (14.3%), and women in the dry cleaning industry (14.3%). Among those who refused to participate in the study, occupations were similarly represented. Regarding type of chemical exposures, the

Discussion

Present findings showed that prenatal exposure to organic solvents is associated with both a significant reduction in contrast sensitivity and an increased risk of red–green color vision anomalies in offspring at exposure levels encountered in the workplace. In addition, we also found reductions in grating acuity in the high compared with the low exposed group and controls, which is consistent with our previous findings on older children showing that decreased visual acuity was associated with

Acknowledgments

This research study, which was conducted in partial fulfillment of Christine Till's doctoral thesis, was presented at the 21st International Neurotoxicology Conference in Hawaii. Christine Till was the recipient of the Pre-Doctoral Student Poster Award. This study was funded by the Workers Safety Insurance Board (WSIB), Canadian Institute for Health Research (CIHR) and the Vision Science Research Program. Gideon Koren is a Senior Scientist of the CIHR and a holder of the Ivey Chair in Molecular

References (63)

  • A.M. Norcia et al.

    Spatial frequency sweep VEP: visual acuity during the first year of life

    Vis Res

    (1985)
  • A.M. Norcia et al.

    Development of contrast sensitivity in the human infant

    Vis Res

    (1990)
  • A.M. Norcia et al.

    Measurement of spatial contrast sensitivity with the swept contrast VEP

    Vis Res

    (1989)
  • D.R. Peeples et al.

    White-adapted photopic spectral sensitivity in human infants

    Vis Res

    (1978)
  • J. Rabin et al.

    Visual evoked potentials in three-dimensional color space: correlates of spatio-chromatic processing

    Vis Res

    (1994)
  • D.C. Rice et al.

    Effects of developmental exposure to methyl mercury on spatial and temporal visual function in monkeys

    Toxicol Appl Pharmacol

    (1990)
  • G.A. Rudduck et al.

    Visual electrophysiology to achromatic and chromatic stimuli in premature and full term infants

    Int J Psychophysiol

    (1994)
  • K. Stromland

    Ocular involvement in the fetal alcohol syndrome

    Surv Ophthalmol

    (1987)
  • C. Till et al.

    Prenatal exposure to organic solvents and child neurobehavioral performance

    Neurotoxicol Teratol

    (2001)
  • M.S. Banks et al.

    Infant visual perception

    (1983)
  • S.S. Block et al.

    Visual anomalies in young children exposed to cocaine

    Optom Vis Sc

    (1997)
  • D.K. Broadwell et al.

    Work-site clinical and neurobehavioral assessment of solvent-exposed microelectronics workers

    Am J Ind Med

    (1995)
  • T.M. Burbacher et al.

    The effects of methylmercury exposure on visual and auditory functions in nonhuman primates

    Toxicologist

    (1999)
  • D. Campagna et al.

    Color vision loss among styrene-exposed workers neurotoxicological threshold assessment

    Neurotoxicology

    (1996)
  • S.E. Chia et al.

    Impairment of color vision among workers exposed to low concentrations of styrene

    Am J Ind Med

    (1994)
  • G. Cole et al.

    Computation of cone contrasts for colour vision research

    Behav Res Meth Instr Comp

    (1992)
  • M.A. Crognale

    Development, maturation, and aging of chromatic visual pathways: VEP results

    J Vis

    (2002)
  • M.A. Crognale et al.

    Objective assessment of short wavelength sensitive (SWS) mechanisms with spatio-chromatic VEP: X-linked achromatoplasia and transient tritanopia

  • A.M. Donoghue et al.

    Contrast sensitivity in organic-solvent-induced chronic toxic encephalopathy

    J Occup Environ Med

    (1995)
  • B. Eskenazi et al.

    In utero exposure to organic solvents and human neurodevelopment

    Dev Med Child Neurol

    (1988)
  • T.A. Eskin et al.

    Carbon disulfide effects on the visual system. Part II. Retinogeniculate degeneration

    Invest Ophthalmol Vis Sci

    (1988)
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