Does occupational exposure to organic solvents affect colour discrimination?

This review assesses the evidence regarding the effects of occupational exposure to organic solvents on colour discrimination and investigates exposure-response relationships and reversibility. This review 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. Among the commonly used organic solvents, styrene has been investigated the most thoroughly. Studies of styrene-exposed workers in Germany, Italy and Japan provide a sufficiently consistent body of evidence to support a robust conclusion that styrene does cause an impairment of colour discrimination relative to age-matched controls. Generally, the impairment of colour discrimination observed in styrene-exposed workers tends to be of the tritan (blue-yellow) type, although some cases of red-green impairment have also been found. The limited information available on exposure-response relationships indicates that the effects on colour discrimination would not be expected at 8-hour time weighted average (8 h TWA) exposures <20 ppm, although a precise threshold cannot be determined. The data on reversibility are limited and inconclusive. The results from the most rigorous study in which this aspect was investigated point to a reversibility of effects after a 4-week exposure-free period, whereas results from a study with limitations suggest a persistence of effect. The effects of toluene, tetrachloroethylene or mixed solvent exposure have also been investigated, although the information available is generally less reliable than for styrene. For toluene, it can be confidently concluded that this solvent does not have an acute effect on colour discrimination, even when exposures are relatively high (50-150 ppm 8 h TWA, and 290-360 ppm 30 minutes TWA). However, studies are inconclusive on whether long-term or repeated exposure to toluene can cause a persistent impairment of colour discrimination. There are few studies that have specifically investigated the effects of tetrachloroethylene on colour discrimination. Among these studies, none has examined the potential for any acute effects of this solvent vapour. A large-scale study in Japanese workers showed no effects of long-term exposure to tetrachloroethylene concentrations in the region of 12-13 ppm. However, the test methodology used was relatively insensitive to changes in colour discrimination, hence the results do not provide reassurance for an absence of subtle effects. A study in Italian dry-cleaners suggested a slight impairment of colour discrimination relative to controls, associated with relatively low exposures to tetrachloroethylene (mean 8 h TWA exposure approximately 6 ppm). The studies concerning the effects of mixed solvent exposure on colour discrimination are based on workers exposed to solvents in paints and lacquers, workers from the printing and petrochemical industries, people working in or living near to microelectronics factories and children exposed to solvents prenatally. However, these studies are subject to design limitations or methodological irregularities, such that no conclusions regarding the effects of mixed solvent exposure on colour discrimination can be drawn. Overall, the only credible evidence for an effect of solvents on colour discrimination derives from the studies on styrene. Because of limitations in the data for other solvents it is not possible to determine whether the evidence for styrene reflects a generic property of solvents. The mechanisms of styrene-induced effects on colour discrimination have not been properly investigated and can only be the subject of speculation. One conclusion that can be drawn is that pathological changes to the ocular system, such as changes to the lens, are unlikely to be involved. This is because there is an absence of convincing evidence for such changes from medical examinations conducted in epidemiological studies of solvent-exposed workers. Also, it seems unlikely that effects on colour discrimination are a nonspecific consequence of more generalised CNS depression, given that styrene-induced effects on colour discrimination appear to occur below the threshold for narcotic effects. The effects of styrene on colour discrimination are subtle and involve an impairment of the ability to discriminate accurately between closely related shades of the same colour rather than 'colour blindness'. There is no valid basis for using colour discrimination as a marker for other forms of solvent-induced neurotoxicity.

Basal and physiological Ca(2+) leak from the endoplasmic reticulum of pancreatic acinar cells. Second messenger-activated channels and translocons.

We have studied the Ca(2+) leak pathways in the endoplasmic reticulum of pancreatic acinar cells by directly measuring Ca(2+) in the endoplasmic reticulum ([Ca(2+)](ER)). Cytosolic Ca(2+) ([Ca(2+)](C)) was clamped to the resting level by a BAPTA-Ca(2+) mixture. Administration of cholecystokinin within the physiological concentration range caused a graded decrease of [Ca(2+)](ER), and the rate of Ca(2+) release generated by 10 pm cholecystokinin is at least 3x as fast as the basal Ca(2+) leak revealed by inhibition of the endoplasmic reticulum Ca(2+)-ATPase. Acetylcholine also evokes a dose-dependent decrease of [Ca(2+)](ER), with an EC(50) of 0.98 +/- 0.06 microm. Inhibition of receptors for inositol 1,4,5-trisphosphate (IP(3)) by heparin or flunarizine blocks the effect of acetylcholine but only partly blocks the effect of cholecystokinin. 8-NH(2) cyclic ADP-ribose (20 microm) inhibits the action of cholecystokinin, but not of acetylcholine(.) The basal Ca(2+) leak from the endoplasmic reticulum is not blocked by antagonists of the IP(3) receptor, the ryanodine receptor, or the receptor for nicotinic acid adenine dinucleotide phosphate. However, treatment with puromycin (0.1-1 mm) to remove nascent polypeptides from ribosomes increases Ca(2+) leak from the endoplasmic reticulum by a mechanism independent of the endoplasmic reticulum Ca(2+) pumps and of the receptors for IP(3) or ryanodine.