Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Mode of Action Analysis / Human Relevance Framework

Additional information

Styrene is a volatile liquid substance for which vapour inhalation is the most likely route of exposure. It is extensively studied for its repeated-dose toxicity and the available for this substance experimental data is adequate, relevant and reliable to perform the safety assessment of styrene.

 

Available data on repeated dose toxicity of styrene report nervous system as the most sensitive target of styrene toxicity in humans following acute-duration inhalation exposure. Overall, no adverse effects were seen in humans at concentrations up to 100 mg/m3 (NOAEC).

 

The repeated exposure NOAELs/LOAELs observed in experimental animals are summarised as follows:

 

Human/ Occupational Data:

Inhalation exposure:

·       NOAEC =100 mg/m3

 

Experimental Animals Data:

Oral exposure:

·       LOEL (NOAEL) (rats, oral, 6-month) =400 mg/kg bw/day (effects on body weights, effects on liver & kidney weights) (NOEL =133 mg/kg bw/day)

·       LOEL (NOAEL) (rats, oral, 2-year) =500 mg/kg bw/day (effects on body weight, systemic toxicity).

·       NOAEL (mice, oral, 18-month) = 150 mg/kg bw/day (effects on body weight, systemic toxicity).

 

Inhalation exposure:

·       LOAEC (mice, inhalation, 2-week) =250 ppm [1065 mg/m3] (hepatotoxicity) (NOAEC =60 ppm [255 mg/m3])

·       LOAEC (rats, inhalation, 3-week) =800 ppm [3400 mg/m3] (ototoxicity)

·       LOAEC (rats, inhalation, 90-day) =500 ppm [2130 mg/m3] (nasal tract effects) (NOAEC =200 ppm [852 g/m3])

·       LOAEC (mice, inhalation, 90-day) =50 ppm [213 mg/m3] (nasal tract effects) (NOAEC: not identified for nasal tract effects)

·       LOAEC (mice, inhalation, 90-day) =150 ppm [639 mg/m3] (hepatotoxicity)

Available animal studies showed that mice are more sensitive to the toxic effects of styrene than rats.

Based on the data summarised in this section, styrene is self classified as  STOT Repeated Exposure Category 2 substance, H373: May cause damage to organs through prolonged or repeated exposure via inhalation.

Justification for classification or non-classification