Registration Dossier

Diss Factsheets

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Description of key information

There are data for repeat exposure to one low benzene naphtha streams representing the inhalation route of exposure and a related stream representing the dermal route.  These do not indicate any specific target organ toxicity which would warrant classification.  However, there are substantial data on the repeated dose toxicity of toluene which demonstrates significant target organ toxicity and, when present at concentrations greater than or equal to 10%, this component substance will influence classification due to mammalian toxicity effects.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
625 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Adequate information is available on the marker substance toluene to characterise the long-term hazards of these streams after ingestion.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
1 131 mg/m³
Study duration:
chronic
Species:
rat
Quality of whole database:
Adequate information is available on the marker substance toluene to characterise the long-term systemic hazards of these streams after inhalation.

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
1 131 mg/m³
Study duration:
chronic
Species:
rat
Quality of whole database:
Adequate information is available on the marker substance toluene to characterise the long-term local hazards of these streams after inhalation.

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Study duration:
subacute
Species:
rabbit
Quality of whole database:
Adequate information is available for a representative stream to characterise the long-term systemic hazards of these streams after skin contact.

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
200 mg/cm²
Study duration:
subacute
Species:
rabbit
Quality of whole database:
Adequate information is available for a representative stream to characterise the long-term local hazards of these streams after skin contact.

Additional information

Non human data

Repeat dose studies have been conducted for representative low benzene naphtha streams via the dermal and inhalation routes of exposure and indicate no significant target organ toxicity. It is noted that kidney effects in male rats in these studies are consistent with a well studied phenomenon known as light hydrocarbon nephropathy (Alden, 1986)." This phenomenon has been extensively evaluated and is a male rat-specific phenomenon and has no relevance for human risk assessment.”

Toluene (Classification: EU - Harmful Xn, R48/20; GHS/CLP - STOT-RE Category 2, H373): Toluene exposure can produce central nervous system pathology in animals after high oral doses. Repeated inhalation exposure can produce ototoxicity in the rat and high concentrations are associated with local toxicity (nasal erosion). In humans neuropsychological effects and disturbances of auditory function and colour vision have been reported, particularly when exposures are not well controlled and/or associated with noisy environments. The NOAEC for subchronic oral toxicity in rats is 625 mg/kg/day based on neuropathology (Huff, 1990). The NOAEC for inhalation toxicity in the rat is 300 ppm (1131 mg/m3) based on effects on body weight, mortality and adverse local effects (nasal erosion) (Gibson and Hardisty, 1983). The NOAEC for neuropsychological effects, auditory dysfunction and disturbances of colour vision in humans is 26 ppm (98 mg/m3) (Seeber et al, 2004; Schaper et al, 2003, 2004).

References

Alden CL (1986) A Review of Unique Male Rat Hydrocarbon Nephropathy. Toxicologic Pathology14 (1).

Schaper M, Demes P, Kiesswetter E, Zupanic M and Seeber A (2004). Colour vision and occupational toluene exposure: results of repeated examinations. Toxicology Letters 151, 193-202.

Schaper M, Demes P, Zupanic M, Blaszkewicz M and Seeber A (2003). Occupational toluene exposure and auditory function: results from a follow-up study. Ann. Occup. Hyg., Vol 47, No 6, pp493-502.

Seeber A, Schaper M, Zupanic M, Blaskewicz M, Demes P, Kiesswetter E and van Thriel C (2004). Toluene exposure below 50 ppm and cognitive function: a follow-up study with four repeated measurements in rotogravure printing plants. Int Arch Occup Environ Health, 77, 1-9.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
No repeat dose oral toxicity data are available for members of this category, however rats receiving high treatments of the key marker substance toluene for 13 wk showed signs of neuropathological changes with a NOAEL of 625 mg/kg bw/d.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Information available for the key component toluene indicates a potential auditory impairment and effects on the nervous system. The NOAEC for systemic inhalation toxicity in the rat is 300 ppm (1131 mg/m3) based on effects on body weight and mortality.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Information available for the key component toluene indicates a NOAEC for local inhalation toxicity in the rat of 300 ppm (1131 mg/m3) based on adverse local effects (nasal erosion).

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
Information available for a representative stream indicate a systemic NOAEL of 2000 mg/kg/day, the highest dose tested.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Information available for a representative stream indicate a local LOAEL of 200 mg/kg, reflecting slight to moderate skin irritation.

Repeated dose toxicity: via oral route - systemic effects (target organ) neurologic: central nervous system

Repeated dose toxicity: inhalation - systemic effects (target organ) other: all gross lesions and masses

Justification for classification or non-classification

There are sufficient data available to conclude that streams within this category which contain less than 10% toluene do not require a label for this endpoint.

After repeated dose exposure, toluene causes a number of adverse effects including impairment of auditory function and morphological evidence of cell loss in the rat cochlea, neuron loss in the central nervous system of animals and in humans neuropsychological effects, auditory dysfunction and effects on colour vision have been reported. Consequently low benzene naphtha streams containing ≥ 10% toluene should be classified Cat 2, H373 according to CLP.