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Description of key information

The limited repeat dose toxicity data on specific streams identified for this category (dermal toxicity studies for API 83-04 [light catalytic reformed naphtha] and API 83-05 [catalytic reformed naphtha]) provided no evidence of systemic target organ toxicity. However, there are substantial data on the repeated dose toxicity of a number of specific components present in some streams i.e. benzene, toluene and hexane which demonstrate significant target organ toxicity and when present at concentrations greater than or equal to 1%, 10% or 10% respectively will drive the mammalian toxicity effects.

Key value for chemical safety assessment

Additional information

API 83-04 (CAS 64741-63-5) and API 83-05 (CAS 68955-35-1) are two petroleum based naphthas comprising up to 100% aromatics, including substituted mono and di-aromatics with approximately 2-5% benzene and are considered appropriate for read-across to high benzene naphthas.API 83-04 [ CAS 64741 -63 -5: light catalytic reformed naphtha] and API 83-05 [CAS 68955 -35 -1: catalytic reformed naphtha]: Repeated dose (6 hour dermal applications) toxicity was investigated 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. There were no effects on haematology, clinical chemistry, organ weights or histopathology indicative of systemic toxicity. Treatment-related effects of API 83-04 were confined to lower body weight and body weight gain at 2000 mg/kg/day in males and female, lower body weight gain in females at 1000 mg/kg/day and evidence (visual and histopathological) of moderate to severe skin irritation at all dose levels. Treatment-related effects of API 83-05 comprised mortality in males at 1000 and 2000 mg/kg/day, lower body weight at 2000 mg/kg/day in males and female, and evidence (visual and histopathological) of moderate to severe skin irritation at all dose levels.The NOAEL for systemic toxicity for API 83-04 [light catalytic reformed naphtha] was 1000 mg/kg/day for males and 200 mg/kg/day for females.The NOAEL for systemic toxicity for API 83-05 [catalytic reformed naphtha] was 200 mg/kg/day for males and 1000 mg/kg/day for females (API, 1986c, d).

The available data on the specific components xylene, 1,3–butadiene, naphthalene, isoprene and anthracene do not reveal any specific target organ toxicity of a severity that would warrant classification. Therefore, no classification or labelling is warranted for streams which only contain these components.

Other specific components which have been identified as present in some streams are benzene, toluene and hexane. These are all identified as producing serious target organ toxicity following repeated oral, dermal or inhalation exposures in animals and man:

Benzene (Classification: EU -Toxic T, R48/23/24/25; GHS/CLP - STOT-RE Category 1, H372): After repeated dose exposure via oral or inhalation routes, benzene causes adverse effects on the haematopoietic system of animals and man. The oral LOAEL was 25 mg/kg bw/day for male and female mice (NTP, 1986) and the inhalation LOAEC for haematotoxicity in mice is 10 ppm (32 mg/m3) (Ward et al, 1985). For human a NOAEC of 3.5 ppm (11.2 mg/m3) is obtained based on the 95% LCL for the threshold level of neutrophils, the most sensitive endpoint reported by Schnatter et al. (2010).

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 (NTP, 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).

n-Hexane (Classification: EU -Harmful Xn, R48/20; GHS/CLP - STOT-RE Category 2, H373): In animals following oral or inhalation exposure n-hexane can produce neurologic dysfunction of motor or sensorimotor nerves resulting in weight loss and paralysis (Spencer and Schaumberg, 1985). Epidemiological studies on n-hexane have shown an association between inhalation exposure to n-hexane and neurological symptoms in occupationally exposed individuals. However, the extent of exposure to n-hexane in many, if not all, of the occupational studies is imprecise, and subjects were likely exposed concurrently to other solvents. The NOAEC for peripheral neuropathy is reported to be 20 ppm (70 mg/m3).

References

Spencer PS and Schaumburg HH (1985). Organic solvent neurotoxicity - facts and research needs. Scand J Work Environ Health 11, 53 -60.

Justification for classification or non-classification

There are sufficient data available to conclude that streams within this class which contain less than 1% benzene, less than 10% toluene, and less than 10% hexane do not require classification for this endpoint.

Streams which contain ≥1% but less than 10% benzene will be required to be classified as follows: Harmful Xn R48/20/21/22 according to Dir 1999/45/EC and Cat 2, H373 according to Reg (EC) 1272/2008; streams containing ≥10% benzene should be classified as Toxic, R48/23/24/25 according to Dir 1999/45/EC and Cat 1, H372 according to Reg (EC) 1272/2008.

Streams which contain ≥10% toluene or hexane should be classified as Xn, labelled R48/20 according to Dir 1999/45/EC and Cat 2, H373 according to Reg (EC) 1272/2008.