Naphtha (petroleum), steam-cracked middle arom.

Endpoint summary

Description of key information

Toluene is of low acute toxicity by the oral (LD50 > 5000 mg/kg), dermal (LD50> 5000 mg/kg) and inhalation (4 hour LC50 >20 mg/L) routes.  In humans a number of subjective sensations such as headache, dizziness, feeling of intoxication, irritation and sleepiness and decreases in acute neurobehavioural performance are seen following acute exposure ≥ 75 ppm.  The NOAEC of 50 ppm (192 mg/m3) for acute neurobehavioural effects in humans is taken into account in the risk characterisation of acute neurotoxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The available data provide information that is adequate for the purpose of hazard assessment

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

192 mg/m³ air

Quality of whole database:

The available data provide information that is adequate for the purpose of hazard assessment

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The available data provide information that is adequate for the purpose of hazard assessment

Additional information

The acute toxicity of toluene was reviewed and reported in the EU RAR (2003). No additional relevant animal data has been sourced in the updated literature review.

Non-human information

Acute toxicity: oral

The acute oral toxicity of toluene is considered to be low (LD₅₀> 5000 mg/kg). Withey and Hall (1975) performed what is considered to be the key study using a method which resembles that of EU guideline B1 (Acute toxicity (oral)). Groups of 20 male rats, were fasted overnight, dosed with 4000, 4560, 5200, 5930, or 6760 mg/kg of toluene and observed three times daily for at least 7 days after dosing. Rats dosed at high levels with toluene exhibited hind-limb paralysis and petechial bleeding, especially from the urinary tract, eyes and nose. The LD₅₀ was calculated to be 5580 mg/kg. Similar oral LD₅₀values (approximately 5600 mg/kg and 6400 mg/kg for younger and older adult rats, respectively) were reported by Kimura et al (1971).

Acute toxicity: inhalation

Acute 4 hour inhalation toxicity was investigated in groups of 10 male and female rats (BASF, 1980). Exposure concentrations were 6.08, 20.00, 23.98, 38.87 and 61.80 mg/L. The LC50 was calculated to be > 20 mg/L (28.1 mg/L in males and females; 25.7 mg/L in males and 30 mg/L in females). According to the EU RAR (2003), animals showed watery discharge from eyes and nose, unrest, increased respiration, rocking gait, narcosis, startling movements and hyperaemia of the ears and extremities. In the highest exposure group, salivation was observed. In the group exposed to 6.08 mg/L of toluene, no adverse clinical signs were observed. All surviving rats appeared normal after 3 days following the exposure.

Acute toxicity: dermal

A single acute dermal toxicity study on toluene in the rabbit has been found (Smyth et al, 1969). Fur was removed from the entire trunk by clipping and the dose held in contact with the skin for 24 hours (retained by impervious plastic film). The 4 animals per group were immobilised during the contact period, after which the film was removed and the rabbits caged for a 14 day observation period. The LD₅₀ value was reported to be 14.1 mL/kg, corresponding to 12267 mg/kg (using a density of 0.87). No information on clinical signs or mortality pattern was provided.

Human information

The acute effects of toluene inhalation exposure have been investigated in a number of human experimental studies in volunteers. These studies indicate that toluene produces a number of subjective sensations such as headache, dizziness, feeling of intoxication, irritation and sleepiness and decreases in acute neurobehavioural performance at concentrations ≥ 75 ppm (EU RAR, 2003). Muttray et al (2005) exposed twenty healthy men to a constant level of 50 ppm toluene. The Pupillographic Sleepiness Test (PST) was performed before and after 4.5 hours of exposure. Acute symptoms were assessed with the Swedish Performance Evaluation System (SPES) self-assessment questionnaire, once before and 3 times during exposure. There was no effect of toluene exposure on PST or tiredness but scores for unpleasant smell and irritation to the throat were increased.

When reviewing critical health effects underpinning an indicative occupational exposure limit (IOELV) for toluene, SCOEL noted that while human neurological changes were reported at high exposures the data supported a NOAEC of 80 ppm (300 mg/m3) for 4.5 hr. Since toxicokinetic information indicated that steady-state levels of toluene in blood were achieved after exposures of around 25 min of exposure, SCOEL concluded that a 15 min exposure to 100 ppm (384 mg/m3) would not lead to acute neurological effects. Furthermore, the IOELV-STEL was likely to protect against other short-term (subjective, irritative) effects.

Justification for selection of acute toxicity – oral endpoint
The available key and supporting studies indicate that the acute oral toxicity of toluene is low (LD50 >5000 mg/kg)

Justification for selection of acute toxicity – inhalation endpoint
The available animal data indicate that the acute inhalation toxicity of toluene is low (LC50 >20000 mg/m3). Information supporting the IOELV indicates that no adverse neurological effects are expected following short-term (15 min) exposure to 100 ppm (384 mg/m3) toluene. CNS depression is apparent at higher exposures.

Justification for selection of acute toxicity – dermal endpoint
The available data indicate that the acute dermal toxicity of toluene is low (LD50 >12000 mg/kg)

Justification for classification or non-classification

Toluene is of low acute toxicity by the oral, dermal, and inhalation routes with LD50/LC50 values exceeding the doses which would warrant classification under GHS / CLP.

Since data from experimental exposure of human volunteers show that dizziness and sleepiness are experienced at air levels < 20 mg/L for 4h and rocking gait and narcosis were observed in rats in the BASF study at this same concentration then toluene justifies classification as STOT-SE 3 (H336) under GHS / CLP.

The low viscosity of toluene (dynamic viscosity of 0.56 mPa s at 25°C and a surface tension of 27.93 nM at 25°C) justifies classification under GHS / CLP, Aspiration toxicity Category 1 assigned H304.