Styrene

Endpoint summary

Description of key information

- acute inhalation toxicity: study with 6 human volunteers exposed for 7 hours: NOAEC = 100 ppm; no effects on the central nervous system (CNS) function at this concentration (Stewart et al., 1968).
- acute inhalation toxicity: rat, 4 h inhalation: LC50 = 2770 ppm (11.8 mg/l) (Shugaev, 1969).

Additional information

EPS Acute Toxicity

In the UK RAR (June 2008) the data on acute toxicity were summarized as follows (the references are given in brackets):

In humans there is some acute inhalation toxicity information available indicating effects of styrene on the central nervous system (CNS) function. From the studies that have been reported there has been no convincing evidence of an effect on neurobehavioural test performance with exposures in the range 0.5 – 150 ppm (Stewart et al., 1968; Gamberale and Hultengren, 1974; Pierce et al., 1998; Ska et al., 2003). However, some impairment in test performance (reaction time, manual dexterity and coordination) appeared with exposures of 200, 350 and 376 ppm for periods of 30 – 90 minutes (Stewart et al., 1968; Gamberale and Hultengren, 1974; Oltramare et al., 1974). Higher concentrations (800 ppm in one study) have produced signs and symptoms of pronounced CNS depression (Carpenter et al., 1944). No other acute toxicity information is available from human studies.

In rats and guinea pigs styrene is of moderate-low acute toxicity via the inhalation and oral routes (Spencer et al., 1942; Fechter et al., 1993). Two inhalation studies in rats have reported a 4-hour LC₅₀of 2770 ppm (11.8 mg/l) (Shugaev, 1969) and death was observed at 9.3 mg/l (approx. 2000 ppm) for exposure durations >30 h (Spencer et al., 1942). An oral LD₅₀of approximately 5000 mg/kg has been reported in the rats (Wolf et al., 1956). In contrast, mice (at least some strains of mice) are much more sensitive to a single exposure to styrene, with cellular damage in the respiratory epithelium at 40 ppm (the lowest concentration tested) (Green, 2000b) and fatal hepatocellular damage at 250 ppm and above in acute inhalation studies (Morgan et al., 1993a; 1993b; Mahler et al., 1999). The most likely explanation for this species difference is the greater potential for build-up of the reactive styrene oxide metabolite in mouse, compared to rat or human (Filser, 2000; Csanady et al., 2003; Filser et al., 2002). An acute oral study in hamsters also indicates styrene-induced hepatoxicity at 6000 mg/kg (but not at 4500 mg/kg) (Parkki, 1978). No acute dermal toxicity studies have been performed in experimental animals, but one would predict low acute toxicity.

In view of the fact that humans (volunteers and workers) have been exposed without serious effects to acute exposure conditions that have proved toxic and even lethal to more sensitive mouse strains. Considering the known toxicokinetic difference between the mouse and the human in the activation/deactivation of styrene, the mouse is considered to be a poor and unreliable model for the acute toxicity of styrene in humans.

Therefore, for the purposes of risk characterization, information from the human volunteer studies will be used. The most useful reference point in relation to short-term single exposure is the observation that no CNS depression was seen in humans exposed to 100 ppm for 7 hours (Stewart et al., 1968) and that some minor impairment in neurobehavioural test performance was observed at about 200 ppm for 1.5 hour (Oltramare et al., 1974).

A literature search from 1998 to January 2010 overlapping the date of the UK RAR (June 2008) was conducted. A dermal toxicity study in rats and an investigation in human volunteers were identified in addition.

The Japan Styrene Industry Association (JSIA) submitted an acute dermal toxicity study in rats conducted at Hita Laboratories (Hita Laboratories, 2005). During the first 4 hours after dosing some unspecific clinical signs were recorded (decreased spontaneous locomotion, incomplete eyelid opening, decreased respiratory rate, writhing and vocalization just after dosing) that had disappeared on the next day. The LD50 was >2000 mg/kg.

Leitel et al. (2007) exposed human volunteers to 20 and 50 ppm styrene with and without concomitant noise exposure over 6 hours. Styrene did not affect hearing ability as determined by audiometry, high frequency audiometry, or transitory evoked otoacoustic emissions (TEOAE). Simultaneous exposure to noise and styrene led to the same transient hearing deficits as noise alone. As regards ototoxicity, due to the short exposure duration (only 4 exposures within two weeks), this study cannot be extrapolated to the workplace situation.

Ihrig et al. (2005) exposed 21 volunteers at 50 ppm over 6 h. In comparison to unexposed controls no significant differences were observed in neuropsychological tests (short term memory, reaction time, concentration, and attention) carried out 2 days before and during exposure. Subjective symptoms by standardized questionnaire showed an exposure related difference regarding smell and taste sensation.

Justification for classification or non-classification

The present data for the test substance identify styrene to cause acute toxicity via the inhalative route, as the LC50 in rats was 11.8 mg/l after a 4 hour inhalation period of the vapour.

Therefore, the test material fulfils the requirements to be classified as Category 4, H332 for acute inhalation toxicity according to GHS-CLP criteria (1272/2008/EC) and as Xn, R20 according to EU-DSD criteria (67/548/EEC).

Based on the physical-chemical properties of styrene, the substance fulfils the requirements to be classified as Category 1, H304 for aspiration hazard according to GHS-CLP criteria (1272/2008/EC) and as Xn, R65 according to EU-DSD criteria (67/548/EEC).

 

This classification augments the current legal classification laid down in Annex I of DSD-67/548/EEC (ATP 19) and Annex VI of CLP-1272/2008/EC, respectively.