Guidance

Trichloroethylene: toxicological overview

Updated 10 June 2021

Main points

Kinetics and metabolism

Trichloroethylene (TCE) is readily absorbed following exposure by inhalation or ingestion, and to some extent following skin contact.

Following absorption, trichloroethylene is rapidly distributed throughout the body.

Trichloroethylene undergoes metabolism via an oxidative pathway.

The main metabolites are trichloroethanol, trichloroethanol-glucuronide and trichloroacetic acid.

Trichloroethylene is excreted unchanged via the lungs and as metabolites in the urine.

Health effects of acute exposure

Acute inhalation or ingestion of trichloroethylene can cause systemic effects such as excitement, headache, dizziness, nausea and vomiting followed by loss of co-ordination, drowsiness and difficulty speaking. Coma, cardiac arrhythmias and death may occur following substantial exposures.

Local effects following ingestion of trichloroethylene include ‘burning’ in the mouth and throat, gastritis and diarrhoea.

Dermal exposure to trichloroethylene will cause irritation with erythema. Prolonged contact may cause severe irritation with blisters and burns.

Health effects of chronic exposure

Chronic exposure to trichloroethylene can cause neurological, liver and kidney damage.

Adverse effects on fertility have been reported in men occupationally exposed.

Trichloroethylene is classified as carcinogenic to humans.

Kinetics and metabolism

Absorption

Trichloroethylene is a low molecular weight lipophilic volatile solvent, and hence it is rapidly and extensively absorbed following all routes of exposure. [1]

Available reports of human exposure to trichloroethylene suggest significant absorption from the gastrointestinal tract. Clinical symptoms of trichloroethylene or its metabolites have been observed within few hours of ingestion, indicating absorption. [1]

In humans, trichloroethylene is rapidly and extensively absorbed into the alveolar capillaries by the lungs following inhalation exposure. Pulmonary uptake has been shown to be rapid during the first 30 to 60 minutes of exposure under non-steady state conditions; this uptake decreases significantly as concentrations of trichloroethylene in tissues achieve a steady state. [2] Studies have reported that approximately 25 to 55% of inhaled trichloroethylene is absorbed from the lungs. [3]

Both liquid and vapour TCE have been shown to be rapidly absorbed through the skin. [1]

Distribution

Following absorption, trichloroethylene is widely distributed to tissues around the body via systemic circulation, regardless of the route of exposure. Due to its high level of solubility in lipids, trichloroethylene is primarily found in adipose tissue. [4] It has also been detected in the brain, muscle, heart, kidney and liver. [1] Trichloroethylene can cross the placenta, the blood brain barrier and has also been measured in breast milk. [1, 4]

Metabolism

The metabolites of trichlorethylene are thought to be responsible for much of its toxicity. [1] Trichloroethylene metabolism has been extensively characterised in humans and laboratory animals. There are 2 main metabolic pathways of trichloroethylene metabolism. The first pathway involves oxidation by cytochrome P450 enzymes. This mainly occurs in the liver and can also take place in other tissues including the kidney, lungs and male reproductive organs. Subsequent processing of oxidative metabolites can involve alcohol and aldehyde dehydrogenase enzymes and glucuronidation. The main urinary oxidative metabolites are trichloroethanol, trichloroethanol-glucuronide and trichloroacetic acid. [1, 4, 5]

The second pathway involves conjugation of trichloroethylene with glutathione (GSH), resulting in the formation of reactive metabolites. [4] Initial conjugation occurs primarily in the liver to form isoforms of S-(1,2-dichlorovinyl) glutathione (DCVG), which can undergo subsequent processing to S-dichlorovinylcysteine (DCVC). Conversion of DCVG to DCVC occurs primarily in the kidney, but it can also occur in the bile or gut. DCVC is considered to be a major branching point in this pathway as it can undergo several pathways for further metabolism. [5]

Excretion

Trichloroethylene can be excreted unchanged via exhalation from lungs, with a half-life of between 6 to 44 hours. It is also excreted as metabolites of the parent compound in the urine. [4 to 6] The half-life for renal elimination of trichloroethanol and trichloroethanol glucuronide is reported to be approximately 10 hours. The excretion of trichloroacetic acid is slower as it binds tightly to plasma proteins, its elimination half-life is reported to be approximately 52 hours. [4] Minor routes of elimination include excretion of metabolites in saliva, sweat and faeces. [1]

Sources of exposure

Trichloroethylene is released into the environment as a result of its use, with the majority entering the atmosphere as the unchanged parent compound. [7] Once in the atmosphere, degradation by photo-oxidation occurs rapidly, with a half-life of approximately 1 day to 2.5 weeks. Concentrations of trichloroethylene in ambient outdoor air may widely fluctuate over relatively short periods of time; this depends on the strength of the emission source, variations in wind direction and velocity, scavenging and photo-oxidation. In Europe, outdoor air concentrations of trichloroethylene are generally below 1µg/m³. [3]

Wide ranging surveys have shown typical trichloroethylene groundwater concentrations to be low, at around < 0.2 to 2μg/L. Levels may be much higher in contaminated areas, with maximum levels in the UK found to be at 950mg/L. Due to its high volatility surface water levels of trichloroethylene are generally < 1μg/L. [3, 8]

The general public may be exposed to very low levels of trichloroethylene through contaminated air, water, food or soil; these are usually much lower than the levels which would be expected to cause significant adverse health effects. [4]

Exposure to trichloroethylene is more likely to occur in an occupational setting. Workplace exposure limits (WEL) for trichloroethylene have been set in the UK to protect workers from the harmful effects of trichloroethylene. The long-term WEL is 550mg/m³ (100ppm) for an 8 hour time weighted average exposure (TWA) reference period, whilst the short-term WEL is 820mg/m³ (150ppm) for a 15 minute reference period. [9]

Health effects of acute or single exposure

Human data

General toxicity

Central nervous system (CNS) toxicity is the main effect following acute exposure to trichloroethylene. There are 2 main stages of trichloroethylene-induced central nervous system toxicity: the excitation phase and the depression phase. Symptoms of the early excitation phase include euphoria, restlessness, irritability, confusion, headache, nausea, vomiting and dizziness. The subsequent central nervous system depression phase is characterised by loss of co-ordination, drowsiness, coma, respiratory depression and in severe cases, death. [3, 6]

Trichloroethylene is thought to sensitise the myocardium to endogenous catecholamines. [10] Cardiac effects reported include atrial and ventricular extrasystole, tachycardia and ventricular fibrillation. Sudden death due to cardiac arrest has been reported in subjects exposed to high levels of trichloroethylene. [3, 6]

Renal and hepatic damage can occur following large exposures. [10]

Inhalation

Trichloroethylene can cause severe acute toxicity, as described in the general toxicity section (table 1).

Table 1: Acute effects following inhalation exposure to trichloroethylene at various concentrations and durations

[6, 8, 11, 12]

Concentration	Time period	Effect
145 to 435mg/m3 (27 to 81ppm)	2 or 4 hours	Drowsiness and headache
270 to 540mg/m3 (50 to 100ppm)	6 hours	CNS depression (fatigue, decreased ability to concentrate)
485 to 700mg/m3 (90 to 130ppm)	Twice for 4 hours	Slight dizziness and eye irritation, bad performance in psycho-physiological tests
810 to 3,510mg/m3 (150 to 650ppm)	-	Irritation to mucous membranes, including the respiratory tract
1,075mg/m3 (200ppm)	7 hours	Nose and throat irritation, as well as mild depression of the CNS
5,400mg/m3 (1,000ppm)	2 hours	Depression of the CNS and effects on neurobehavioural and visual-motor functions. Dizziness, light-headedness and lethargy were also noted.
27,000mg/m3 (5,000ppm)	-	Light anaesthesia
108,000mg/m3 (20,000ppm)	-	Deeper anaesthesia

Neurological damage has also occasionally been reported, particularly involving the trigeminal and optic nerves. However, there is some evidence to show that this may have been caused by the decomposition products of trichloroethylene, such as dichloroacetylene, as opposed to the substance itself. [8, 10]

Ingestion

Ingestion of trichloroethylene can cause severe acute toxicity, as described in the general toxicity section. Ingestion may cause a burning sensation in the mouth and throat, epigastric pain, nausea and vomiting. [13] Ingestion of large amounts may cause diarrhoea, haemorrhagic gastritis and abdominal perforation and necrosis. [4]

In 2 case studies, men who ingested 350 and 500ml of trichloroethylene developed ventricular arrhythmias which continued for 3 days. In another study, a woman who accidentally ingested 20ml of trichloroethylene suffered a myocardial infarction 2 hours post ingestion. [4]

The lethal dose of trichloroethylene for adults is approximately 7g/kg body weight (bw), however, death has been reported following ingestion of 50ml (75g). [6] Some human studies have reported death due hepatorenal failure following accidental or intentional ingestion of trichloroethylene. The doses in these cases have not been determined. Pulmonary congestion and oedema have also been noted in some cases where ingestion of trichloroethylene has led to death. [4]

Alcohol intolerance has also been shown to occur when ingested simultaneously with exposure to trichloroethylene vapour. Greater performance changes in visual-motor function tests were observed. These same tests were also taken after ingestion of ethanol without exposure to trichloroethylene, and the same effects were not seen. [6, 8]

Dermal or ocular exposure

Dermal contact with trichloroethylene has been shown to cause skin irritation with erythema and defatting dermatitis. If kept in continuous contact with the skin, for example by clothing or footwear, trichloroethylene may cause severe irritation with blisters and burns. Following exposure to concentrated trichloroethylene vapour, chemical burns have also been reported. [4, 6, 8]

Humans who were experimentally exposed to trichloroethylene vapour at a concentration of 200ppm (1,075mg/m³) experienced eye irritation after 30 minutes of exposure. Irritation, lacrimation, and inflammation have also been observed following ocular exposure to the vapour. [4, 6, 8]

Liquid trichloroethylene splashes in the eye can cause irritation, pain and superficial damage to the cornea; however, individuals generally make a complete recovery. In severe cases, exposure to high concentration of trichloroethylene vapour or liquid can result in solvent-type burns of the eyelids, conjunctiva and cornea. [8]

Delayed effects following acute exposure

Following exposure to trichloroethylene, it may take up to 12 to 24 hours for cardiac dysrhythmias to develop. [14]

Animal data

General toxicity

Trichloroethylene causes low acute toxicity by inhalation, ingestion or dermal contact. The main signs of acute trichloroethylene toxicity in laboratory animals include central nervous system toxicity and adverse effects on the liver. Trichloroethylene is also a respiratory, skin and eye irritant. [6, 8] It is thought that humans may be more sensitive than animals to trichloroethylene, particularly to its neurological effects. [3]

Inhalation

In the rat, an LC50 value of approximately 26,000ppm (140,000mg/m³) was determined for one hour of exposure to trichloroethylene via inhalation, whilst a 4 hour exposure showed an LC50 of 12,500ppm (67,000mg/m³). After 4 hours of exposure in the mouse, an LC50 of 8,450ppm (45,500mg/m³) was determined. Another study showed that, following exposure at 6,400ppm (35,000mg/m³) for 4 hours, one-fifth of exposed mice died. [4, 6]

Haematological, renal, hepatic, immunological and neurological effects have been reported in laboratory animals following acute inhalation exposure to trichloroethylene. [4]

The morphology of the lung cells and the activity of cytochrome P450 enzymes have been studied in rodents. Vacuole formation and endoplasmic reticulum dilation, particularly to the Clara cells of the bronchial tree were observed in mice exposed to 500ppm (2,700mg/m³) of trichloroethylene for 30 minutes. Similar effects were observed in mice following 6 hours of exposure to trichloroethylene at 100ppm (550mg/m³). A reduction in the activity of pulmonary cytochrome P450 was also noted in both cases. [4]

Rats exposed to high levels of trichloroethylene (≥ 1,000ppm or 5,400mg/m³) for less than 24 hours showed dysfunction of the tubular and glomerular regions of the nephron. This was exhibited in the form of increases in urinary glucose, proteins, glucosaminidase, gamma glutamyl transpeptidase, and serum urea nitrogen. [4]

Rats exposed to 54mg/m³ (10ppm) and 540mg/m³ (100ppm) trichloroethylene for 6 hours showed moderate increases in aspartate aminotransferase levels at 24, 48 and 72 hours following the exposure. [6] Inhalation for acute periods has also been linked with enlargement of the liver within laboratory animals, although this effect was shown to usually be reversible following cessation of exposure. [4]

Cardiac sensitisation has been reported in rats, mice and dogs. In rats, a slight effect was observed at 25,000ppm (135,000mg/m³), whilst a lowest observed adverse effect level (LOAEL) and no observed adverse effect level (NOAEL) for rabbits was determined as 3,000ppm (exposure for 15 minutes) and 2,000ppm (exposure for 1 hour) (16,000mg/m³ and 11,000mg/m³ respectively). In dogs, a LOAEL was determined at 5,000ppm (27,000mg/m³) for cardiac sensitisation. [11, 15]

Minor haematological effects have also been observed in animal inhalation studies. Time and dose-related depression of activity of delta-aminolevulinate dehydratase within the liver, bone marrow, and erythrocytes was observed in rats exposed to between 50 to 800ppm (270 to 4,300mg/m³) of trichloroethylene continuously for 48 or 240 hours. [4]

Ingestion

Oral LD50 values have been reported for mice (2,402mg/kg) and rats (7,208mg/kg) administered trichloroethylene by gavage. [4]

Other acute studies involving rats showed increased rearing activity following administration of trichloroethylene in corn oil via gavage at 500mg/kg bw per day for 14 days. Adult male rats exposed to trichloroethylene in drinking water (312mg/L, approximately 23.3mg/kg a day) for 4 weeks, followed by 2 weeks of non-exposure before a further 2 more weeks of exposure, showed decreased brain myelination and an increased performance in the Morris Swim Test. [4]

Increased liver weights and hepatocellular hypertrophy were observed in rats administered 1,500mg/kg a day trichloroethylene in corn oil via gavage for 14 days. [4]

Dermal or ocular exposure

Trichloroethylene (0.5ml for 24 hours) applied to the shaven skin of rabbits, under an occlusive dressing, caused severe skin irritation. In guinea pigs, degenerative skin changes were noted 15 minutes after clipped skin was exposed to 1ml trichloroethylene. Degenerative changes were observed in the epidermis of the skin after just 15 minutes, progressing to cause pyknosis, karyolysis and junctional separation of the epidermis after 16 hours of contact with the skin. [6]

Instillation of 0.1ml of trichloroethylene into rabbit eyes caused conjunctivitis and keratitis, with complete recovery within 2 weeks. [6]

Ocular irritation was observed in rats which were exposed to vapours at 376ppm (2,000mg/m³). [4, 8]

Health effects following chronic or repeated exposure

Human data

Inhalation

Chronic inhalation exposure to trichloroethylene has been shown to primarily affect the central nervous system. Humans exposed occupationally have shown effects including dizziness, headache, sleepiness, nausea, confusion, blurred vision, facial numbness, and weakness. [1] Other neurological effects reported include mood swings, trigeminal neuropathy, cranial nerve VII damage, impaired acoustic-motor function and psychotic behaviour with impaired cognitive function. [4]

Human environmental and occupational studies have also found a link with exposure to trichloroethylene and a decrease in cognitive function. Memory deficits have been observed, with significant impairments found in both visual and verbal recall. Immediate memory and learning have also been shown to be decreased. [1]

Occupational studies have shown that exposure to trichloroethylene may be linked to the impairment of trigeminal nerve function, which was assessed using the blink reflex test or the trigeminal somatosensory evoked potential (TSEP). Other human studies have indicated that exposure can lead to decreases in the ability to discriminate between colours, visual depth perception and contrast sensitivity, with these effects mainly being observed in those living in areas with groundwater contamination with trichloroethylene. Inhalation exposure may also cause auditory impairments. [1]

Hepatic effects have been observed in workers exposed to trichloroethylene. However, there are limitations with these studies including lack of exposure level data and exposure to multiple chemicals. Some occupational studies have reported changes in liver function tests in workers, including glutamyl transpeptidase or γ-transpeptidase (GGT) and aspartate aminotransferase (AST). [1, 4]

Studies in workers exposed to high levels of TCE 100 to 500ppm (540 to 2700mg/m³) have reported elevated excretion of urinary proteins (α1-microglobulin, albumin and N-acetyl-β-D-glucosaminidase) which are indicative of renal tubule damage. [1]

Scleroderma (a chronic autoimmune disease that mainly affects the skin), exfoliative dermatitis and eosinophilic fasciitis have been reported in individuals occupationally exposed to trichloroethylene. [4]

Ingestion

There are limited studies available regarding the health effects of chronic oral exposure to trichloroethylene. A number of studies have attempted to assess the adverse health effects associated with the consumption of drinking water contaminated with trichloroethylene. Studies typically focused on concentrations of trichloroethylene between 0 and 1,000ppm (approximately 1000mg/L). Adverse effects reported include changes to cardiac, gastrointestinal, liver, kidney, immunological and endocrine function. [1, 4, 8] However, many studies involving consumption of water contaminated with trichloroethylene include exposure to other chemicals, therefore rendering the results inconclusive.

Dermal or ocular exposure

Repeated contact with trichloroethylene may lead to the development of erythematous, exudative, vesicular, eczematous or exfoliative dermatitis, due to a defatting action on the skin. [6]

Genotoxicity

The limited data available provides inconclusive evidence of genotoxic effects in humans following exposure to TCE. [8]

Whilst one occupational study did not show a significantly increased frequency of sister chromatid exchange (SCE) in workers when compared to non-exposed controls, another study reported that the frequency of structural aberrations and hyperdiploid cells in cultured lymphocytes was significantly increased in exposed metal workers, when compared to controls. [4, 5]

Several studies have also evaluated the possible association between exposure to trichloroethylene and mutation of the von Hippel-Lindau (VHL) tumour suppressor gene, which has been reported in a relatively large percentage of cases of renal cell carcinoma, however, the results of these studies have overall been inconclusive. [5]

Carcinogenicity

The International Agency for Research on Cancer (IARC) considered that the available human epidemiological data has shown positive associations between trichloroethylene and cancer of the liver and non-Hodgkin lymphoma. The IARC also concluded that there is sufficient evidence in humans for the carcinogenicity of trichloroethylene in terms of cancer of the kidney. [5]

Reproductive and developmental toxicity

Decreases in sex drive, sperm quality, and reproductive hormone levels have been observed in some men occupationally exposed to trichloroethylene. [4] Other studies have reported decreased potency and sexual disturbances following occupational exposure. It has been suggested that this effect could be due to the effects of trichloroethylene on the CNS. [1]

Women exposed to trichloroethylene in the workplace have shown menstrual cycle disturbances, with a trend observed for increasing concentrations of trichloroethylene and prolonged exposure. [1]

Several studies have reported an association between exposure to trichloroethylene (both occupationally and non-occupationally) and an increased risk of spontaneous abortion. However, other studies have not shown evidence of an association. [4]

Some developmental studies have reported an increased risk of congenital malformations in the offspring of women exposed to trichloroethylene. A threefold increase of congenital heart defects was reported for women who lived within 1.32 miles of a trichloroethylene emitting site compared with women who lived outside the 1.32 radius. However, the risk was only increased in women who were 38 years old or over at the time of delivery. Cardiac defects have been observed in the children of parents exposed to trichloroethylene in drinking water. Neural tube defects have also been reported with exposure to trichloroethylene in the workplace or from contaminated drinking water. However, it is not possible to draw any definitive conclusions from these studies, as most involved unknown levels of exposure and exposure to multiple chemicals. [4]

Animal data

General toxicity

The effects of long-term exposure (inhalation and oral exposure) to trichloroethylene have been extensively studied in laboratory animals. The main effects observed include neurotoxicity, nephrotoxicity and hepatic toxicity. [1, 4, 5]

Neurotoxic effects reported include impairment of auditory function, visual disturbances, changes in psychomotor effects, morphological changes in the trigeminal nerve and structural or functional changes in the hippocampus. [1, 11]

Renal tubule damage including cytomegaly and karyomegaly have been reported in rodents exposed to trichloroethylene via inhalation or gavage. Available evidence suggests that the metabolites of trichloroethylene, in particular DCVC, are responsible for the nephrotoxic effects. [5, 11]

Hepatotoxic effects observed in experimental animals include increased liver weight, transient increases in DNA synthesis, enlarged hepatocytes and peroxisome proliferation. The increase in liver weight is proportional to the trichloroethylene dose and appears to be accompanied by periportal hepatocellular hypertrophy. [1, 5]

Genotoxicity

The majority of evidence suggests that trichloroethylene itself does not act directly as a mutagenic agent, instead the observed mutagenicity is likely due to the production of reactive metabolites. In addition, stabilisers including epichlorhydrin and 1,2-epoxybutane used in commercial preparations of trichloroethylene are known to be mutagenic. [4, 5]

The Ames assay has been conducted with trichloroethylene (pure and unspecified purity) in various strains of Salmonella typhimurium. Both positive and negative results have been recorded. Several studies have reported positive results in strain TA100 in the presence of metabolic activation. However, pure trichloroethylene did not produce positive results in other strains. [4, 5]

In in vitro mammalian tests, trichloroethylene did not induce chromosomal aberrations in Chinese hamster cells. [5] Inconsistent results have been reported in sister chromatid exchange and unscheduled DNA synthesis assays. [5, 8] Increased micronucleus formation has been observed in Chinese hamster ovary cells, rat kidney cells and human hepatoma cells. [5]

Inconsistent results have been reported in in-vivo micronucleus assays. [4, 5] Trichloroethylene did not increase the incidence of sister chromatid exchange in the peripheral lymphocytes of rats or splenocytes of mice exposed via inhalation. [5] Negative results were obtained in liver unscheduled DNA synthesis assays in mice and rats exposed to pure or unspecified purity trichloroethylene. [4]

The genotoxicity of certain metabolites of trichloroethylene have also been reviewed. There is strong evidence that chloral or chloral hydrate is genotoxic and there is some data that suggests that metabolites such as dichloroacetic acid, dichlorovinyl cysteine, and dichlorovinyl glutathione may be genotoxic. [4, 5]

Carcinogenicity

Trichloroethylene is carcinogenic in rodents following oral and inhalation exposure. [3, 5, 8]

An increased incidence of hepatocellular tumours has been observed in mice following exposure via gavage or inhalation. Lung tumours have also been observed in mice exposed to trichloroethylene by inhalation. [3, 5, 8] Renal tumours and Leydig cell tumours in the testis have been reported in rats exposed to trichloroethylene via inhalation or gavage. [3, 5, 8]

Reproductive and developmental toxicity

Male reproductive toxicity has been reported in experimental animals exposed to trichloroethylene. Epididymal epithelium degeneration, increased sperm abnormalities and decreased reproductive success have been reported in male rats repeatedly exposed for 1 to 24 weeks to 376 to 1000ppm (2,030 to 5,400mg/m³ trichloroethylene). Exposure of male rats to 376ppm (2,030mg/m³) of trichloroethylene for 4 hours a day 5 days a week for up to 24 weeks resulted in testicular atrophy, decreased sperm count and motility and reductions in serum testosterone. [1, 4] Sloughing of the epithelium of the epididymal tissues has been observed in mice exposed to 1,000ppm (5,400mg/m³) trichloroethylene 6 hours a day 5 days a week for 4 weeks. [1]

In male rats, following oral exposure to 1,000mg/kg bw per day of trichloroethylene by gavage in corn oil 5 days a week for 6 weeks, effects on copulatory behaviour were observed, including ejaculation latency, number of mounts, and number of intromissions, although these effects were no longer seen 1 to 4 weeks post-treatment. A dose-dependent decrease in ability of sperm to in vitro fertilise oocytes from non-exposed females was observed in male rats exposed to trichloroethylene (0, 143 or 270mg/kg per day) in drinking water for 14 days. [1, 4]

There is some evidence of female reproductive toxicity in female animals. Exposure of female rats to 1,000mg/kg a day trichloroethylene in corn oil via gavage resulted in the death of 5 of the animals and decreased maternal body weight gain, but did not affect oestrous cycle length or female fertility. There were also no evident developmental abnormalities observed in the offspring at this treatment level, however, there was a significant increase in the number of pups born dead. [1, 4] A significant decrease in ability to bind to sperm in vitro was observed in the oocytes of female rats exposed to trichloroethylene via drinking water (666mg/kg per day) during the 2 week period preceding ovulation. [1]

Studies investigating the developmental effects of trichloroethylene have produced conflicting data. Increases in full litter absorptions, reduced postnatal and post weaning survival and decreased birth weight and postnatal growth have been observed in the offspring of rodents exposed to trichloroethylene. The effects are often seen at doses that caused maternal toxicity. However, other studies have not reported such effects. [1, 4]

Several rodent developmental toxicity studies have observed cardiac malformations in the offspring of mothers exposed to trichloroethylene via gavage or drinking water during gestation. Other studies including inhalation and oral studies have not reported cardiac malformations. [1, 4] These differences may be due to the study design including the strain of animal used, stage of gestation when exposure occurred, route of exposure and the procedures used to evaluate the fetal cardiac morphology. [1] Cardiac malformations have also been reported in chick embryos exposed to trichloroethylene. [1, 4]

Ocular defects and developmental neurological and immunotoxicity have also been reported in some rodents studies. [1, 4]

Studies in animals have linked developmental effects to exposure to trichloroethylene metabolites, including trichloroacetic acid and dichloroacetic acid. [1]

References

1. US Environmental Protection Agency (EPA), Toxicological Review of Trichloroethylene. 2011, PA: Washington D.C., US.

2. Health Canada, Trichloroethylene. Guidelines for Canadian Drinking Water Quality: Supporting Documentation. 2005, Health Canada: Ottawa, Ontario.

3. World Health Organization (WHO), WHO Guidelines for Indoor Air Quality: Selected Pollutants. 2010, WHO: Geneva, Switzerland.

4. Agency for Toxic Substances Disease Registry (ATSDR), Toxicological Profile for Trichloroethylene. 2019, US Department of Health and Human Services: Atlanta, US.

5. International Agency for Research on Cancer (IARC), Trichloroethylene. 2014, IARC: Lyon, France.

6. International Programme on Chemical Safety (IPCS), Trichloroethylene. Environmental Health Criteria 50. 1985, WHO: Geneva, Switzerland.

7. World Health Organization (WHO), Air quality guidelines for Europe. WHO Regional Publications, European Series, No. 91. 2nd edition. 2000, WHO Regional Office for Europe: Copenhagen, Denmark.

8. European Chemicals Agency (ECHA), European Union Risk Assessment Report: Trichloroethylene. 2004, ECHA: UK.

9. Health and Safety Executive (HSE), EH40/2005 Workplace exposure limits. Fourth Edition. 2020.

10. UK National Poisons Information Service (NPIS). TOXBASE: Trichloroethylene. 2020.

11. US Environmental Protection Agency (US EPA), Trichloroethylene: Degreasing, Spot Cleaning and Arts and Crafts Uses. 2014, US EPA: Washington, D.C., US.

12. Scientific Committee on Occupational Exposure Limits (SCOEL), Recommendation from the Scientific Committee on Occupational Exposure Limits for Trichloroethylene. 2009, European Commission: Brussels, Belgium.

13. UK National Poisons Information Service (NPIS), TOXBASE: Chlorinated hydrocarbons - features and management. 2020.

14. Agency for Toxic Substances and Disease Registry (ATSDR), Medical Management Guidelines for Trichloroethylene. 2014, ATSDR: Atlanta, US.

15. US Environmental Protection Agency (EPA), Interim Acute Exposure Guideline Levels (AEGLs): Trichloroethylene. 2009, NAS/COT Subcommittee for AEGLS Washington D.C., US.

Email chemcompendium@phe.gov.uk if you have any questions about this guidance or phe.enquiries@phe.gov.uk if you have any other questions.