Update of residential tetrachloroethylene exposure and decreases in visual contrast sensitivity.

In "Apartment Residents' and Day Care Workers' Exposures to Tetrachloroethylene and Deficits in Visual Contrast Sensitivity," Schreiber et al. (2002) reported significantly lower visual contrast sensitivity (VCS) in apartment residents exposed to tetrachloroethylene (perchloroethylene, or perc) compared to unexposed "matched" control subjects. The authors stated that the VCS deficit may "represent a long-lasting, adverse alteration in neurobehavioral function" caused by chronic, environmental perc exposures, although they cautioned that methodologic limitations preclude definitive attribution of causation.

Residential data reported by Schreiber et al. (2002) were originally collected by the New York State Department of Health (NYSDOH) as a pilot project to support development of a larger study (NYSDOH, unpublished data). Residents exposed to perc included in the study were 13 adults from six households (20-72 years of age) and 4 children from three households (6-13 years of age) located in two buildings. Continued research by the NYSDOH and others (Farrar et al. 2001; NYSDOH 2004) suggests that confounding factors may influence VCS test performance of children in this and other studies, Consequently, we would like to update the findings of the residential study described by Schreiber et al. (2002).

In the analyses described by Schreiber et al. (2002), VCS of all perc-exposed adult and child residents and unexposed matched controls were compared using analysis of variance and SAS software (version 8.2; SAS Institute, Cary, NC). Matched pair, exposure (perc exposed, unexposed), and spatial frequency (cycles per degree) were independent variables; VCS was the dependent variable. The authors reported a significant effect of exposure on VCS (F = 19.38; df = 1,144; p < 0.001). Sample sizes were not sufficient to support statistical analysis of VCS stratified by age (i.e., child, adult); VCS data were available for only four children. However, review of individual VCS functions suggested that the significant VCS deficit was likely to be attributable to the four children in the exposed group. VCS functions of the exposed children were therefore carefully examined with respect to VCS functions for their matched controls and with respect to information about the children available from parental questionnaires.

Individual VCS functions for each exposed child were lower than his/her marched control (Figure 1A). Although perc exposure may have influenced VCS of these children, other factors could have contributed to their poor performance. For example, conditions such as developmental delay (DD) and attention deficit disorder (ADD) are known to be associated with decreased VCS (Farrar et al. 2001; Hudnell et al. 1996). One of the exposed children was characterized as having psychologist-diagnosed DD, and another exposed child was characterized as having physician-diagnosed ADD (Table 1). These two children performed poorly on the VCS but similar to unexposed children with similar diagnoses examined in a recently completed NYSDOH study (Figure 1B) (NYSDOH 2004). Also, another perc-exposed child was characterized as being forgetful at school, although not specifically as developmentally or learning disabled. (Questionnaires administered to residents of dry-cleaner buildings are part of NYSDOH records for the residential study; questionnaires were not completed for controls.) It is therefore possible that the perc exposure--VCS association reported by Schreiber et al. (2002) may have been confounded by the presence of these conditions.

[FIGURE 1 OMITTED]

In studies now being conducted by the NYSDOH and as reported by Scharre et al. (1990), 5- and 6-year-old children perform variably on the VCS test; sometimes they perform well, and sometimes they are inattentive and unable to perform. Two exposed children included in the residential study were 6 years of age. The matched control for one of these was 8 years of age, and the matched control for the other was the average of a 5-year-old and 7-year-old. Thus, although VCS was poor in perc-exposed child residents compared to others not exposed to perc, this may have been partly due to differences between groups in factors other than perc exposure (e.g., age).

In an exploratory analysis, VCS was evaluated only among adult participants in the residential study. When VCS of perc-exposed adult residents and unexposed adult control subjects were analyzed alone, excluding the four child pairs, a significant effect of perc exposure was not observed (F = 2.04; df = 1,108; p = 0.16). The sample size was small (n = 13) and consequently the statistical power was limited; however, the results suggest that VCS was not significantly decreased in perc-exposed adult residents.

Clearly, the possible effect of perc on VCS in adults, and especially in children, should continue to be explored. However, as illustrated here and discussed by Swinker and Burke (2002) and Hudnell and Shoemaker (2002), the possible influence of factors other than perc exposure on VCS should also be considered. These factors include age and the presence of learning disabilities or developmental delay in children, as illustrated here, as well as conditions such as diabetes, high blood pressure, glaucoma, and cataracts, in adults (Bodis-Wollner and Camisa 1980).

Table 1. Child residents and matched controls in
the VCS studies.

         Exposed             Matched control

                     DD or               DD or
ID             Age    ADD    ID    Age   ADD

Children (a)
  E9            8      -     C9     9     -
  E10           6      X     C10    8     -
  E14          12      X     C14   12     -
  E17           6      -     C17   5,7    -
Children (b)
  P1            8      X
  P2           10      X

(a) Children shown in Figure 1A (NYSDOH, unpublished
data; Schreiber et al. 2002). (b) Children shown in Figure 1B;
E10 and E14 from Schreiber et al. (2002) and P1 and P2
examined in the NYSDOH study (NYSDOH 2004).

The authors declare they have no competing financial interests.

Jan E. Storm

Kimberly A. Mazor

New York State Department of Health

Center for Environmental Health

Troy, New York

E-mail: [e-mail]

REFERENCES

Bodis-Wollner I, Camisa JM. 1980. Contrast sensitivity measurement in clinical diagnosis. In: Neuro-ophthalmology, Vol 1 (Lessell S, Van Dalen JTW, eds). Amsterdam, the Netherlands:Excerpta Medica, 373-401.

Farrar R, Call M, Maples WC. 2001. A comparison of the visual symptoms between ADD/ADHD and normal children. Optometry 72:441-451.

Hudnell HK, Shoemaker RC. 2002. Visual contrast sensitivity: response [Letter]. Environ Health Perspect 110:A121-A123.

Hudnell HK, Skalik D, Otto D, House D, Subri P, Sram R. 1996. Visual contrast sensitivity deficits in Bohemian children. Neurotoxicology 17:615-628.

NYSDOH (New York State Department of Health). 2004. Pumpkin Patch Day Care Center Follow-up Evaluation. Troy NY:Center for Environmental Health, Bureau of Toxic Substance Assessment.

Scharre JE, Cotter SA, Block SS, Kelley SA. 1990. Normative contrast sensitivity data for young children. Opt Vis Sci 67:826-832.

Schreiber JS, Hudnell HK, Geller AM, House DE, Aldous KM. Forse ME, et al. 2002. Apartment residents' and day care workers' exposures to tetrachloroethylene and deficits in visual contrast sensitivity. Environ Health Perspect 110:655-664.

Swinker M, Burke WA. 2002. Visual contrast sensitivity as a diagnostic tool [Letter]. Environ Health Perspect 110:A120-A121.

Residential Tetrachloroethylene Exposure: Response

We are grateful for the opportunity to respond to Storm and Mazor's comments about our study "Apartment Residents' and Day Care Workers' Exposures to Tetrachloroethylene and Deficits in Visual Contrast Sensitivity" (Schreiber et al. 2002). We investigated potential relationships between environmental exposure to the dry-cleaning solvent perchloroethylene (perc, or tetrachloroethylene) and effects on visual function in two exposed populations (17 residents, including 4 children, in two apartment buildings and 9 adults working at a day care center) and age- and sex-matched control groups (n = 25 and n = 9, respectively). Mean airborne perc concentrations were 778 and 2,150 [micro]g/[m.sup.3] in the apartments and the day care center, respectively, levels well above the background range of < 1.6-22 [micro]g/[m.sup.3] [New York State Department of Health (NYSDOH) 1997]. Perc concentrations in biological samples were also elevated (Schreiber et al. 2002). We assessed visual function using tests of near acuity, near visual contrast sensitivity (VCS; a sensitive indicator of neurologic function), and color discrimination. Visual acuity did not differ between groups, but VCS scores from both the apartment residents and the day care workers were depressed across the spatial frequency spectrum, similar to results obtained in other solvent exposure studies (Broadwell et al, 1995; Campagna et al, 1995; Castillo et al. 2001; Donoghue et al. 1995; Frenette et al. 1991; Hudnell et al. 1996a; Mergler 1995; Mergler et al. 1991), We concluded that

Although the similar VCS deficits in both the residential study and day care investigation were apparently associated with chronic low-level environmental perc exposures, methodologic limitations preclude a definitive attribution of causation.

It is unlikely that age differences caused the group differences in VCS, as Storm and Mazor suggested. The exposed and control participants in the residential study were matched for age within 2 years, and the group means were within 1 year of each other. The mean age of the four exposed children was about 6 months greater than that of the six controls. The day care workers and controls were matched within 1 year of age, and the group means were within 6 months of each other. Such small age differences were highly unlikely to account for the VCS deficit.

Storm and Mazor reported that one exposed child was developmentally delayed and one had an attention deficit disorder, and they suggested that this may have caused the group difference in VCS. However, they did not provide comparable data for the control children, who were family members of NYSDOH employees. The same assessment of potentially confounding factors should have been applied to both groups. Furthermore, they cited a previously published article (Hudnell et al. 1996b) when suggesting that the VCS deficits in the exposed children may have been due to developmental delays. That article actually reported an association between perinatal exposure to airborne neurotoxicants and developmental delay in VCS (Hudnell et al. 1996b). We felt that it was inappropriate to exclude children from study participation because of conditions that may have been caused by perc exposure.

As noted by Storm and Mazor, "sample sizes were not sufficient to support statistical analysis of VCS stratified by age (i.e., child, adult)" in the residential study. It is not surprising that when they reduced the sample size to 13 pairs by excluding all children, the p-value increased from < 0.001 to 0.16, even though 7 of the 13 exposed adults had VCS scores in the lower 12th percentile of control scores.

We took several steps to minimize the influence of potentially confounding factors on VCS. A standard operating procedure and luminance control ensured test consistency. The exclusion criteria--failing to attentively complete the VCS test (one control resident excluded), having Snellen acuity worse than 20:70 (two eyes from exposed residents excluded, perhaps due to cataracts), and observing strabismus or other ocular anomalies (one control resident excluded)--were applied to both groups. None of the participants reported having an illness that might affect neurologic function. In the day care investigation, all participants were healthy females, and eight of nine were 21-29 years of age, thereby further reducing the potential for confounding. The observation of similar reductions in the VCS spatial-frequency profiles of the residential and day care exposed cohorts supported our conclusion that the effects may have been due to perc exposure.

Storm and colleagues recently conducted a study of apartment residents potentially exposed to perc and reported normal VCS in the exposed cohort (NYSDOH 1999, 2003). However, two factors limited comparability to our study (Schreiber et al. 2002). First, they measured far, rather than near, VCS. Near and far VCS do not provide comparable data due to differences in illumination, near and far visual acuity, and the visual field size of the test stimuli. Second, the mean airborne perc concentration was 34 [micro]g/[m.sup.3] in their study (NYSDOH 2003), 1-2 orders of magnitude lower than in our studies. These differences precluded an attempt to verify the VCS effects reported in our article (Schreiber et al. 2002). We stand by our methodologic procedures, results, and conclusions.

This letter was reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the agency.

The authors declare they have no competing financial interests.

H. Kenneth Hudnell

U.S. Environmental Protection Agency

Office of Research and Development

National Health and Effects

Research Laboratory

Neurotoxicology Division

E-mail: [e-mail]

Judith S. Schreiber

State of New York

Office of the Attorney General

Division of Public Advocacy

Environmental Protection Bureau

E-mail: [e-mail]

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Hudnell HK, Skalik I, Otto D, House D, Subrt P, Sram R. 1996b. Visual contrast sensitivity deficits in Bohemian children. Neurotoxicology 17(3-4):615-628.

Mergler D, Huel G, Bowler R, Frenette B, Cone J. 1991. Visual dysfunction among former microelectronics assembly workers. Arch Environ Health 46:326-334.

Mergler D. 1995. Behavioral neurophysiology: quantitative measures of sensory toxicity, Neurotoxicology: Approaches and Methods (Chang LW, Slikker W, eds). San Diego:Academic Press, 727-736.

NYSDOH. 1997. Tetrachloroethene Ambient Air Criteria Document. Final Report. Albany, NY:New York State Department of Health.

NYSDOH. 1999. Improving Human Health Risk Assessment for Tetrachloroethene by Using Biomarkers and Neurobehavioral Testing in Diverse Residential Populations. Albany, NY:New York State Department of Health. Available: http://cfpub2.epa.gov/ncer_abstracts/index.cfm/ fuseaction/display.abstractDetail/abstract/977/report/0 [accessed 24 August 2004].

NYSDOH. 2003. Progress Report: Improving Human Health Risk Assessment for Tetrachloroethene by Using Biomarkers and Neurobehavioral Testing in Diverse Residential Populations. Albany, NY:New York State Department of Health. Available: http://cfpub2.epa.gov/ncer_abstracts/ index.cfm/fuseaction/display.abstractDetail/abstract/ 977/report/2003 [accessed 24 August 2004].

Schreiber JS, Hudnell HK, Geller AM, House DE, Aldous KM, Force MS et al. 2002. Apartment residents' and day care workers' exposures to tetrachloroethylene and deficits in visual contrast sensitivity. Environ Health Perspect 110:655-664.