National Industrial Chemicals Notification and Assessment Scheme

11.4Repeated dose toxicity

Subjective symptoms of CNS disturbances have been reported in most of these studies. Most common symptoms include fatigue, dizziness, vertigo, headaches and memory loss and impaired ability to concentrate. Skin and eye irritation have also been reported. A high incidence of CNS effects and hearing defects were noted in some workers.

Some studies have mainly investigated the liver effects of trichloroethylene. Evidence of liver damage has been reported in some studies while liver changes were not seen in other studies Workers exposed to trichloroethylene developed hepatomegaly, changes in serum hepatic enzyme levels (ALT, AST and aldolase) and abnormalities in liver function tests such as thymol turbidity and cephalin-cholesterol tests. Raised serum bilirubin levels and gamma globulins were noted in one study. Increased serum beta- and gamma- globulins and some abnormalities in the cephalin flocculation test were reported in workers regularly exposed to trichloroethylene (Guyotjeannin & Van Steenkiste, 1958). The hepatic effects seen in all these studies could not be definitively attributed to trichloroethylene as trichloroethylene exposure levels were not noted and similar changes are associated with alcohol ingestion.

In a recent correspondence to the editors of a journal, Bruning et al (1996b) has reported renal tubular damage in patients who had been diagnosed with renal cell carcinoma and had undergone nephrectomy. Seventeen patients had been exposed to high concentrations of trichloroethylene over many years and were later diagnosed with renal cell cancer. All these patients reported that prenarcotic symptoms such as feeling of drunkenness, dizziness, headache and drowsiness had occurred frequently during occupational exposure to trichloroethylene. Duration of exposure was 15 years with a mean latency period of 30.4 years. The frequency of pathologic protein excretion patterns in these patients were compared with 35 renal cell cancer patients (controls) from a large urological clinic. SDS PAGE (SDS polyacrylamide gradient electrophoresis) was used to separate and differentiate between different pathological protein patterns in the excreted urine. This method allows a high-resolution separation between 20 different urinary proteins according to molecular size and thus helps to differentiate between different pathological protein patterns excreted in urine indicating tubular, glomerular or mixed renal damage. Protein excretion patterns indicating tubular damage in the remaining kidney was identified in all the 17 exposed patients (6 severe tubular damage, 6 moderate damage, 2 minor and 3 mixed glomerular/tubular damage). Of the control patients 18 of the 35 showed normal protein excretion patterns with 12 controls showing tubular damage, 4 mixed glomerular/tubular damage and 1 with glomerular damage. One of these controls had been occupationally exposed to tetrachloroethylene. The others had no history of being occupationally exposed to potentially nephrotoxic substances. A lower prevalence of tubular damage was found among the non-exposed group of renal cell cancer patients than patients who had been occupationally exposed to trichloroethylene. This data, though limited, cannot be dismissed especially in the light of renal toxicity findings in rodents.

Alcohol intolerance has been reported in some workers who consumed alcohol during exposure to trichloroethylene and in single and repeated dose volunteer studies. This presented as transient flushing of the face, shoulders and neck due to vasodilatation of the superficial vessels. This condition is commonly known as “degreasers’ flush”. Competitive inhibition of acetaldehyde dehydrogenase resulting in accumulation of acetaldehyde in blood is thought to be the underlying mechanism.

Effects of trichloroethylene on the cardiovascular system have been investigated in a number of studies. Abnormalities in cardiac rhythm such as ventricular extra-systoles and tachycardia, have been reported.

The UK SIAR has described reports of other effects of trichloroethylene. Stevens-Johnson syndrome, an autoimmune disease, has been reported in some workers exposed to trichloroethylene by inhalation and also the dermal route (Phoon et al., 1984). Scleroderma has also been observed in some workers exposed to trichloroethylene (Flindt-Hansen & Isager, 1987). Stevens-Johnson syndrome and scleroderma may be idiosyncratic reactions to trichloroethylene, however more evidence is needed before any conclusions can be drawn.

11.4.1Oral

In the second study the residual neurological effects following past exposure to trichloroethylene in drinking water (up to 256 ppb) have been studied (Feldman et al., 1994). Blink reflex latency and neurological assessments were carried out in a group of 28 people. A significant difference in conduction latency was seen between control and exposed groups indicating subclinical changes in the 5th cranial nerve. However, other chlorinated solvents were also detected in the contaminated water indicating simultaneous exposure to other chemicals.