Guidance

Styrene: toxicological overview

Updated 14 November 2024

Main points

Kinetics and metabolism

Styrene is readily absorbed and distributed throughout the body tissues following inhalation and dermal exposure.

Repeated exposure to styrene leads to a gradual accumulation in the adipose tissue.

Styrene is extensively metabolised by cytochrome P450 oxidation to yield styrene 7,8-oxide, which is the principal active metabolite.

Styrene 7,8-oxide is further metabolised and excreted in the urine as phenylglyoxycylic acid, mandelic acid and hippuric acid.

Health effects of acute exposure

Acute inhalation of styrene may cause irritation of the nose and throat, increased nasal secretion, wheezing, coughing, pulmonary oedema, cardiac arrhythmias, and coma.

Styrene inhalation may also lead to central nervous system (CNS) depression, termed “styrene sickness”, which includes headache, nausea, vomiting, weakness, fatigue, dizziness, and ataxia.

Ingestion of styrene may result in CNS depression effects.

Dermal exposure may result in irritation, itching and dermatitis. CNS depression may also occur following dermal absorption of styrene.

Health effects of chronic exposure

Chronic occupational exposure to styrene may cause signs and symptoms of CNS depression, including decreased coordination and concentration, impairment of short-term memory, altered liver function and abnormal electrocardiogram (ECG) patterns.

Repeated dermal exposure to styrene can result in persistent itching and the onset of dermatitis.

Styrene is considered to be a possible human carcinogen.

Kinetics and metabolism

Styrene is readily absorbed and extensively distributed throughout the body tissues following an inhalation exposure (1). No studies have been located in humans relating to the uptake of styrene following ingestion, although it is anticipated that the effects would be similar to those seen following inhalation (1, 2). After an acute oral exposure in rats, styrene was present in high concentrations in the adipose tissue, brain, kidney, liver, and pancreas. Repeated exposure resulted in a gradual accumulation of styrene in adipose tissue (1, 2).

Styrene is also absorbed following skin exposure in the form of a liquid or vapour, although animal studies have shown the amount absorbed from exposure to styrene vapour is much lower than is absorbed from skin contact with liquid styrene (1).

A significant amount (~90%) of the styrene absorbed by humans undergoes hepatic oxidation by cytochrome P450, to styrene 7,8-oxide, which is the active metabolite (1, 2). Styrene 7,8-oxide is further metabolised into phenyl glyoxylic acid, mandelic acid and hippuric acid which are excreted in the urine. Mandelic acid is the most prominent urinary metabolite and is responsible for between 60 to 80% of the excreted styrene metabolites. Approximately 30% of the excreted styrene is present as phenyl glyoxylic acid, with hippuric acid only being formed in small quantities (1). Styrene 7,8-oxide may also undergo conjugation with glutathione, to form hydroxy phenylethyl mercapturic acid, although this has been demonstrated to be only a minor metabolite (2, 3).

Sources and Route of Human Exposure

The major source of exposure to styrene is from occupational exposure, since it is principally produced and used industrially in the manufacture of many plastics, resins, and synthetic rubbers (2). The degree of occupational exposure to styrene varies widely depending upon the process involved (1, 2). The greatest exposures are encountered in the industries using unsaturated polyester resins dissolved in styrene (2). However, in all industrial processes involving the use of styrene, large exposures can occur during clean-up and maintenance procedures (1, 2). In all occupations where styrene is manufactured or used, suitable personal protective equipment is recommended, to reduce the potential for exposure (1, 10).

Styrene can be released into the environment in cigarette smoke, exhaust emissions from motor vehicles and during combustion or heating of styrene-containing polymers and some organic materials (2). However, the amounts of styrene present in the environment from such sources, are expected to be much smaller than may be found in an occupational setting (3). Polystyrene and styrene containing polymers, such as acrylonitrile-butadiene-styrene (ABS) are widely used as packaging materials for food products. Residues of styrene monomer present in such plastics can migrate into the food products contained within them, although in very small quantities in relation to the styrene content of the packaging material. The amount of styrene in food from such sources, is considered to represent only a minimal contribution to the total body burden of styrene and is unlikely to be of any concern (2, 11).

The major routes of occupational exposure to styrene are by inhalation of vapours or by dermal absorption (1 to 3). Styrene can also result in toxicity by ingestion. However, ingestion of styrene is not a significant occupational hazard (1).

Health effects of acute or single exposure

Human data

Inhalation

Harmful levels of styrene vapour form relatively slowly in the air following evaporation at room temperature (10).

Inhalation of styrene following a single exposure can lead to irritation of the mucous membranes of the nose and throat, increased nasal secretion, wheezing and coughing. Exposure to larger amounts of styrene can lead to the onset of “styrene sickness”, which relates to a series of health effects resulting from depression of the CNS. The features of “styrene sickness” include headache, nausea, vomiting, weakness, dizziness, fatigue, and ataxia. In some cases, inhalation of styrene can cause pulmonary oedema, cardiac arrhythmia, memory loss and a progressive loss of consciousness leading to coma (1 to 5).

Ingestion

Few data are available on the acute toxicity of styrene following ingestion by humans (1, 3, 4). However, the adverse health effects of styrene ingestion would be expected to be similar to those seen following inhalation, including CNS depression (1, 3 to 5).

Dermal or ocular exposure

Dermal exposure to styrene either from splashes of liquid or contact with vapours can result in skin irritation, burns and acute dermatitis (1). Styrene can be absorbed dermally following a prolonged single exposure, although the amounts absorbed are not considered to be sufficient to cause significant toxicity (1).

Ocular exposure to vapour or liquid splashes of styrene may cause conjunctival irritation with the severity of irritation related to the degree of exposure (1, 4). Splashes of styrene in the eyes may also result in hyperaemia of the conjunctiva and injury to the corneal epithelium (1).

Animal data and in-vitro data

General toxicity

The acute toxicity of styrene in experimental animals resembles that seen in man, with signs of respiratory tract irritation and CNS depression, although evidence of neurotoxic and neurobehavioral effects following acute exposure to styrene in experimental animals is limited (3).

Inhalation

The 4-hour LC₅₀ for styrene inhalation is 2700 mg m^-3 (634ppm) in rats (equating to an LCt₅₀ of 11.25 mg min^-1 m^-3), whilst in mice the 2-hour LC₅₀ is 2160 mg m^-3 (507ppm: equivalent to an LCt₅₀ of 18 mg min^-1 m^-3) (1, 12). Acute inhalation exposure of styrene vapour to mice resulted in irritation of the upper respiratory tract at 156ppm for 3 minutes (664 mg m^-3), and behavioural changes at 413ppm for 4 hours (1757 mg m^-3) (3).

Ingestion

The acute oral toxicity of styrene in rats is relatively low, with an LD₅₀ for oral administration of 5000 mg kg^-1 body weight. The oral toxicity of styrene is higher in mice compared to rats, with an LD₅₀ of 316 mg kg^-1 body weight (1).

Dermal or ocular exposure

Acute ocular administration of styrene (0.1ml) to rabbits resulted in the immediate production of moderate conjunctival irritation and transient corneal injury (3). No studies were located concerned with determining a lethal acute dose of styrene following dermal or ocular administration in experimental animals.

Health effects following chronic or repeated exposure

Human data

Inhalation

Long term occupational exposure to styrene by inhalation has resulted in some workers showing symptoms of CNS depression, including decreased coordination and concentration, impairment of short-term memory, alteration of liver function and abnormal ECG patterns (1, 2). Long term exposure to styrene vapour has also been reported to cause subtle changes in hearing, balance, colour vision and psychological performance (2, 4). There are some reports that long term styrene inhalation may cause occupational asthma, although it is not known whether this is due to styrene alone, or additional chemicals in the environment to which the workers may have been exposed (4 to 6).

Ingestion

There are currently no data on the effects of chronic styrene ingestion in humans.

Dermal or ocular exposure

Repeated or prolonged dermal exposure to styrene in liquid or vapour form can produce persisting itching and erythematous papular dermatitis (1, 4). Styrene may undergo dermal absorption, and therefore prolonged dermal contact may lead to the onset of CNS depression as can be observed following inhalation exposure (1, 4).

Genotoxicity

Some studies have shown an increased incidence in chromosomal aberrations of the peripheral lymphocytes in workers exposed to styrene in the reinforced plastics industry (1 to 4). However, it is not possible to show unequivocally that styrene was the cause of the somatic chromosome aberrations, due to simultaneous exposure of the workers to other chemicals in addition to styrene, the small sample sizes used and confounding factors such as age, sex, and smoking status of the workers (2 to 4). Reports from approximately 30 studies of workers exposed to styrene in various industries have demonstrated inconsistent results for chromosomal aberrations, micronuclei, and sister chromatid exchange. There was no indication of a dose response relationship for any of these effects in the studies which reported positive results (9). No conclusions can, therefore, be drawn regarding the genotoxicity of styrene in man.

Carcinogenicity

Studies of cancer incidence in humans following occupational exposure to styrene are inconclusive. The IARC has stated that there is limited evidence in humans for the carcinogenicity of styrene and has concluded overall that styrene is possibly carcinogenic to humans (group 2B) (9).

Reproductive and developmental toxicity

Information concerning the developmental effects of styrene in women exposed in the workplace during pregnancy is limited. In one study, the birth weights of infants whose mothers worked in areas with elevated levels of styrene during pregnancy were found to be 4% lower than those from unexposed mothers, but were not statistically significant (3, 4). In another study there was no increase in developmental effects for women who worked in the plastics industry during pregnancy (3, 4). In both cases the exposure was not solely to styrene, due to the presence of other chemicals. An additional study did not find any correlation between occupational exposure to styrene and the incidence of miscarriages (4). Exposure to styrene has shown no adverse effects upon the female reproductive system (4). Initial reports suggested that styrene exposure may give rise to effects on testicular sperm morphology. However, recent studies have shown no adverse effects of styrene upon the male reproductive system (4, 7). The studies suggest that reproductive and developmental effects in humans following exposure to styrene are not a major concern (3, 7, 8).

Animal data

Inhalation

A study of rats exposed to styrene vapour at 1000ppm (4260 mg m^-3) for 4 hr day^-1, 5 days week^-1 for 3 weeks, showed pathological changes in the respiratory mucosa and abnormal morphology and decreased ciliary activity of the upper nasal mucosa (3). Slight nasal and eye irritation was observed in rats and guineapigs exposed to styrene vapours at 5460 mg m^-3 (1300ppm) for 7 hr day^-1 for 216 to 360 days. However, no effects were observed in rabbits and rhesus monkeys exposed to styrene under the same conditions (2). Rats exposed to styrene vapour at 350, 700 and 1400ppm (1490, 2980 and 5960 mg m^-3) for 18 weeks initially showed signs of CNS depression and a reduction in activity and grip strength compared to those in the control groups. However, this effect diminished during the study period, suggesting that tolerance to the effects of styrene develops during continuous exposure. At the end of the study there was no significant difference in the performance of the rats treated with styrene compared to the control groups (3).

Ingestion

Rats orally administered with styrene for 6 months at 400 mg kg^-1 body weight^-1 for 5 days week^-1, were seen to have increased liver and kidney weights and a depression of growth (2, 3). Severe lung congestion was observed in mice orally administered with styrene at 1350 mg kg^-1 body weight^-1 on 1 day week^-1 for 16 weeks following weaning (3). Rats exposed to styrene at 100 and 200 mg kg^-1 body weight^-1 by oral administration for 14 days showed behavioural effects and significantly altered learning processes, although there was not an evident dose response relationship) (3). An additional study in rats given styrene by the oral route at 200 and 400 mg kg^-1 body weight^-1 for 90 days, suggested that styrene affects behaviour by altering the sensitivity of dopamine receptors in the brain (3).

Genotoxicity

Styrene has not been shown to induce reverse mutations in the Ames test for gene mutation in any of the Salmonella typhimurium strains used, in the absence of metabolic activation. In the presence of metabolic activation, styrene has been found to be positive for base-substitution mutations in the TA 100, TA 1530 and TA1535 strains. Other strains commonly used for detecting frame-shift mutations (TA 98, TA 1537 and TA 1538) have reported styrene to be negative (2). Styrene was not found to induce point mutations at the HPRT locus in Chinese hamster V79 cells with or without metabolic activation (mouse liver S-10 fraction). However, in the same system styrene was found to be weakly mutagenic following metabolic activation with rat liver S-9 fraction (2). Styrene was found to induce chromosomal aberrations, micronuclei, and sister chromatid exchange in human whole blood lymphocyte cultures in the absence of a metabolic activation system (2, 3). Styrene has also been found to induce chromosomal aberrations in Chinese hamster lung (CHL) cells and sister chromatid exchange in Chinese hamster ovary (CHO) cells in the presence of a metabolic activation system (2). Results from in-vitro studies on the genetic effects of styrene are not conclusive as to its mutagenicity. However, from these studies styrene does appear to have mutagenic potential but, in the presence of a metabolic activation system, presumably due to the epoxide metabolite (2, 9).

Results from in-vivo studies have also proved to be inconsistent. Most studies for assessing clastogenicity of styrene by the induction of chromosomal aberrations in the bone marrow cells of experimental animals reported negative data. A positive result for chromosomal aberrations was however, reported in rat bone marrow following inhalation exposure to styrene (2). A positive result for sister chromatid exchange was also described in mouse bone marrow, alveolar macrophages, and regenerating liver cells, following exposure to styrene by inhalation (2). Styrene also was reported to give positive results in the micronucleus test in mice but was found to be negative when tested in Chinese hamsters in vivo. The inconclusive nature of these studies may possibly be due to the differences in metabolic capacity among the species used (2). The fairly extensive data from animal bioassays do not suggest that styrene is a genotoxic carcinogen. It probably does not have any significant mutagenic effects in vivo.

Carcinogenicity

The carcinogenicity of styrene has been investigated in mice and rats, following inhalation and oral administration. An increase in the incidence of pulmonary adenomas was observed in both male and female mice exposed to styrene by inhalation. In addition, an increase in the incidence of carcinomas was also seen in female mice, but only in the high-dose group (2, 9). However, 2 oral studies in mice found no evidence for carcinogenicity of styrene, whilst 2 other oral studies were considered to be inadequate for an evaluation (9). In rats, overall, there was not found to be any reliable evidence for an increase in tumour incidence following exposure to styrene either by oral administration or inhalation (9). Overall, the IARC has concluded that there is limited evidence for the carcinogenicity of styrene in experimental animals (9).

Reproductive and developmental toxicity

Studies investigating the reproductive and developmental toxicity of styrene by inhalation exposure, conducted in rats, mice, rabbits, and Chinese hamsters have shown no significant effects upon the incidence of offspring malformations. However, an increased number of resorptions were observed in pregnant rats exposed to styrene at 0.35, 1.2 and 12ppm throughout gestation for 4 hr day^-1 (2). An increase in the incidence of resorptions was also observed in mice and Chinese hamsters exposed to 1000ppm styrene for 6 hr day^-1 from gestation days 6 to 16 and 6 to 18, respectively (2). Rabbits exposed to styrene by inhalation at 600ppm for 7 hr day^-1 from day 6 to 18 of gestation showed a delayed bone formation (2). The results from these studies suggest that styrene inhalation has some embryotoxic effects in animals (2). Adult male rats orally administered with styrene at 400 mg kg^-1 body weight^-1 for 60 days showed a reduction in testicular function and a decreased spermatozoa count. Degeneration of the seminiferous tubules and absence of sperm in the lumina was also identified by histopathological examination. This study suggests that the male reproductive system may be sensitive to effects following styrene exposure (3).

References 

1. International Programme on Chemical Safety (IPCS). Styrene. Poisons Information Monograph. PIM 509. 1996, WHO: Geneva.

2. International Programme on Chemical Safety (IPCS). Styrene. Environmental Health Criteria 26. 1983, WHO: Geneva.

3. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Styrene. 1992, US Department of Health and Human Services: Atlanta, US.

4. Canadian Centre for Occupational Health and Safety (CCOHS), Styrene, Cheminfo. 1994.

5. National Poisons Information Service (NPIS). Styrene. TOXBASE®. 2005.

6. Moscato G, Biscaldi G, Cottica D, Pugliese F, Candura S, and Candura F. ‘Occupational asthma due to styrene: two case reports* Journal of Occupational Medicine 1987. 29(12): p. 957-60.

7. Brown NA, Lamb JC, Brown SM, and Neal BH. ‘A review of the developmental and reproductive toxicity of styrene’ Regulatory Toxicology and Pharmacology, 2000. 32(3): p. 228-47.

8. National Toxicology Program (NTP). NTP-CERHR Expert Panel ‘Report on the reproductive and developmental toxicity of styrene’ 2005, Center for the Evaluation of Risks to Human Reproduction. US Department of Health and Human Services.

9. International Agency for Research on Cancer (IARC). ‘Styrene. Vol 82’ in IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 2002, IARC: Lyon.

10. International Programme on Chemical Safety (IPCS). Styrene. International Chemical Safety Card: 0073. 2006, WHO: Geneva.

11. Ministry of Agriculture Fisheries and Food (MAFF). ‘Survey of styrene levels in food contact materials and in food’ Food Surveillance Paper No. 11. 1983, Her Majesty’s Stationary Office.

12. US Environmental Protection Agency (US EPA). ‘Health and Environmental Effects Profile for Styrene’ 1984, Office of Research and Development. US EPA: Washington D.C.

The information contained in this document from the UKHSA Radiation, Chemicals, Climate and Environment Directorate is correct at the time of its publication. 

Email [email protected] if you have any questions about this guidance or [email protected] if you have any other questions.

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