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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

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.”

Dermal

Stream CAS 64741-68-0 was evaluated in a 28-Day dermal toxicity study in the rabbit conducted according to OECD Guideline 410 in groups of 5 male and 5 female rabbits. The neat test substance was applied to skin over a period of 28 days (3 times/week, total of 12 applications) at doses of 0, 200, 1000 or 2000 mg/kg/day. Animals were observed daily for clinical signs of toxicity and skin irritation, bodyweight was measured at intervals and at the end of the study blood samples were analysed for changes in haematology and clinical chemistry, a selection of organs were weighed and a full range of tissues examined histopathologically. The NOAEL CAS 64741-68-0 for systemic toxicity was 2000 mg/kg/day. A NOAEL was not established for local irritant effects - 200 mg/kg was a LOAEL reflecting slight to moderate irritation based on Draize scores.

Inhalation

The general systemic toxicity of Pyrolysis C5 (CAS 68476 -55 -1) to rats by inhalation administration was assessed. Groups of twelve male and twelve female rats were exposed for 6 h/day, 7 days/week for a period of 4 weeks to vapour at concentrations of 0, 98, 302 or 1012 ppm. Assessments of clinical condition, detailed functional observational battery, motor activity, bodyweight, food consumption, haematology, blood chemistry, organ weight and macroscopic and microscopic pathology investigations were undertaken.No general systemic effects were observed during the routine clinical examination or in the functional observational battery. Histopathological changes were seen in the liver (minimal centrilobular hepatocyte hypertrophy) at 1012 ppm in both sexes. In male rats only higher kidney weights and renal cortical tubules with hyaline droplets were apparent in all treatment groups.

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 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 as Xn, R48/20 according to Dir 67/548/EEC and Cat 2, H373 according to GHS/CLP.