Toluene

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: observational study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: UK regulatory review of human population data on solvent/colour vision interactions, published in peer reviewed literature, adequately documented and contributing to a weight of evidence assessment.

Data source

Reference

Reference Type:

publication

Title:

Does occupational exposure to organic solvents affect colour discrimination?

Author:

Lomax RB, Ridgway P and Meldrum M

Year:

2004

Bibliographic source:

Toxicol Rev 23,91-121

Materials and methods

Study type:

other: review of epidemiological evidence

Endpoint addressed:

other: effects on colour vision

Principles of method if other than guideline:

This review assesses nine cross-sectional or longitudinal studies investigating colour discrimination in print workers and other workers exposed mainly to toluene. Exposure-response relationships and reversibility of effect were also addressed. It also considers the current state of knowledge of the possible mechanisms underlying changes in colour vision, and the human health significance of any reported changes.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Toluene

EC Number:

203-625-9

EC Name:

Toluene

Cas Number:

108-88-3

Molecular formula:

C7H8

IUPAC Name:

toluene

Method

Type of population:

occupational

Ethical approval:

not applicable

Details on study design:

Papers were reviewed which investigated colour discrimination in print workers and other workers exposed mainly to toluene. The review separately assessed the evidence of acute effects of contemporary toluene exposure versus evidence of persistent effects of past exposures.

Exposure assessment:

estimated

Details on exposure:

Workers who used rotary printing equipment in the different study groups were typically exposed to high ambient air levels of toluene of over 100 ppm. Other groups such as rubber production workers, workers who glued soles on shoes and those exposed to 'background' concentrations in printing plants were exposed to levels of toluene below 50 ppm. Exposure assessment was usually based on eight-hour air sampling in the breathing zone with stationary sampling locations performed on at most two occasions, but one study measured urinary excretion of toluene on one occasion during the second half of the workshift.

Statistical methods:

The authors did not use any statistical procedures such as meta-analysis to combine results from different studies.

Results and discussion

Results:

The review concluded that there is good evidence that toluene has no acute effects on colour discrimination for exposures in the region of 300-350 ppm for 30 minutes and 50-150 ppm 8h TWA. Evidence from studies investigating whether or not long-term repeated exposure to toluene can cause a persistent impairment of colour discrimination was considered to be inconclusive.

Confounding factors:

Confounding factors include age, gender, alcohol consumption, cigarette smoking habits, lighting conditions when tests were performed and exposure to other solvents. Bias can also result from the inclusion of subjects with congenital colour vision deficiency or conditions that can cause colour vision deficiency (e.g. diabetes mellitus, hypertension, cataracts, glaucoma), or low visual acuity. Most investigators made attempts to control confounding by making exclusions from the study or certain analyses, selecting matched exposed and comparison subjects or calculating adjusted scores, but some imbalances remained such as those for gender (Zavalic et al, 1998b,c) or alcohol consumption (Cavalleri et al, 2000).

Strengths and weaknesses:

Evidence of persistent effects is largely based on studies which have tested colour discrimination pre-shift only, often at the start of a working week, because the concentration of toluene in the bloodstream of exposed workers may undergo rapid changes during the working day. Such studies specifically exclude the ability to detect possible acute effects due to contemporary exposure to toluene. The authors note that these pre-shift studies typically provide no historical exposure data, which limits their usefulness with respect to the identification of exposure-response relationships.

Any other information on results incl. tables

The authors considered that all the studies that they reviewed which provided evidence on whether or not long-term repeated exposure to toluene can cause a persistent impairment of colour discrimination had limitations that resulted in them being inconclusive.

The authors had reservations about the exposure assessment in the study by Cavalleri et al (2000) noting that urinary toluene is not recognised as an index of toluene exposure and the cumulative exposure indices, which were based on a single sample, may not have accurately reflected past exposures. They concluded that the evidence from this study for a causal relationship between toluene exposure and chronic impairment of colour discrimination is not entirely definitive, but also concluded that the results pointed to poorer colour discrimination in the toluene-exposed group compared with controls.

The authors questioned whether five of the toluene exposed workers studied by Campagna et al (2001) had undiagnosed congenital colour deficiency and concluded that the study provided only weak evidence in support of there being a relationship between toluene exposure and colour vision impairment.

The authors raised a number of questions about the studies by Zavalic et al (1998a, b, c) including the validity of the age- and alcohol adjusted CCI parameter in one study and the differences in the female : male ratios in the study and comparison groups in the other study. They also noted discrepancies between the two reports of one study which made it unclear which of the two groups of workers was more heavily exposed to toluene: median blood toluene in the shoe-workers group was reported as being 0.01 mg/L and 0.01 mg/g, respectively, while in the printers median blood toluene was reported to be 0.042 mg/L and 0.0042 mg/g, respectively. They also noted that colour discrimination testing was not carried out under standardised lighting conditions and concluded that no reliable conclusions can be drawn from the two studies.

The study by Nakasuta et al (1985) showed no association between toluene exposure and colour discrimination but the investigators used only the first phase of the Lanthony New Colour Test which the reviewers considered to be relatively insensitive.

Muttray et al (1999) reported no evidence for a chronic impairment of colour discrimination in this subset of toluene-exposed printers with prior long-term exposure to toluene, but the reviewers concluded that the power to detect a long-term exposure-related effect will have been relatively low because of the small group sizes (8).

The authors concluded the weight of evidence tends to suggest that toluene does not cause a persistent impairment, but since all of these studies are subject to limitations, reassurance of the absence of an effect is lacking.

Applicant's summary and conclusion

Conclusions:

All of the studies investigating whether or not long-term repeated exposure to toluene can cause a persistent impairment of colour discrimination were subject to limitations such that the evidence from the studies was inconclusive.

Executive summary:

This review assesses the evidence regarding the effects of occupational exposure to toluene on colour discrimination. Nine studies were reviewed which investigated colour discrimination in print workers and other workers exposed mainly to toluene. The review separately assessed the evidence of acute effects of contemporary toluene exposure versus evidence of persistent effects of past exposures. It was concluded that there is good evidence that toluene has no acute effects on colour discrimination for exposures in the region of 300-350 ppm for 30 minutes and 50-150 ppm 8h TWA. It was also concluded that all of the studies investigating whether or not long-term repeated exposure to toluene can cause a persistent impairment of colour discrimination were subject to limitations such that the evidence from the studies was inconclusive. The authors considered that the weight of evidence from the studies tends to suggest that toluene does not cause a persistent impairment, but reassurance of the absence of an effect is lacking.