Vision abnormalities in young children exposed prenatally to organic solvents
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
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