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Description of key information

There are limited repeat dose toxicity data on any of the specific streams identified for this category. However, there are substantial data on the repeated dose toxicity of a number of specific components present in some streams i.e. benzene, toluene, ethylbenzene and styrene which demonstrate significant target organ toxicity. Classification will be required for streams that contain benzene or toluene at concentrations greater than or equal to 1%or 10% respectively.

Key value for chemical safety assessment

Additional information

There is limited repeated dose toxicity information on specific streams identified for this category. Further information is included in the Category Summary for Fuel Oils Category (ACC, 2005). EDS fuel oil was included in the ACC review and was considered to be of sufficiently similar composition to Fuel Oils streams to be used for read-across.

EDS Fuel Oil: In a 13 week oral gavage study in rats there was evidence of minor systemic toxicity at 500 mg/kg/day - slightly lower body weight gain, statistically significant lower erythrocyte counts, haemoglobin and haematocrit, and significantly increased liver weight in the absence of histopathological change. The NOAEC was 100 mg/kg/day (McKee et al, 1987). In a dermal toxicity study in New Zealand White rabbits animals were dosed 0, 50 or 200 mg/kg 5 days/week for 4 weeks. Dermal irritation and body weight loss were observed. A NOAEL for dermal irritation and systemic toxicity was not achieved. A LOAEL of 50 mg/kg/day was determined, based on body weight reduction, liver weight increase and serum cholesterol increase (McKee et al, 1985).

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

Other specific components which have been identified as present in some streams are benzene, toluene, ethylbenzene and styrene. 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 NOAEC 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).

Ethylbenzene (Not currently classified): No repeated dose toxicity studies in humans have been identified. The EU transitional RAR (EU, 2008b) concluded "Repeat-dose or prolonged exposure to ethylbenzene specifically affected the nervous system, but did not induce overt toxicity of any other organ system." The auditory system is the most sensitive to the toxic effects of ethylbenzene after inhalation exposure (Gagnaire et al, 2007) while the liver is the most sensitive following oral exposure (Mellert et al, 2006). The LOAEL for ototoxicity was 200 ppm (868 mg/m3) and the NOAEL for hepatotoxicity was 75 mg/kg/day in a 13 week oral gavage study in rats.

Styrene (Not currently classified): Inhalation studies in animals have reported damage to the nasal olfactory epithelium in rats and mice, liver damage in mice, eye irritation in rats and guinea pigs, ototoxicity in rats and impaired nerve conduction velocity. The EU transitional RAR (EU, 2008c) has identified a NOAEC of 50 ppm in humans based on colour vision discrimination effects in occupationally exposed workers.

References

ACC (2005). US High Production Chemical Program. Category summary for Fuel Oils Category. American Chemical Council.http://www.epa.gov/chemrtk/pubs/summaries/fueloils/c13435tc.htm

EU (2008b). Draft Risk Assessment Report for Ethylbenzene. http://echa.europa.eu/doc/trd_substances/ethylbenzene/rar/trd_rar_germany_ethylbenzene.pdf

EU (2008c). Annex XV Transitional Dossier: Styrene. echa. europa. eu/doc/trd_substances/styrene/RAR/trd_rar_uk_styrene. rtf

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, less than 10% ethylbenzene and less than 10% styrene do not require a label for this endpoint.

Streams which contain ≥1% benzene are expected to cause adverse effects and labelling will be required as follows: streams containing ≥1% but less than 10% benzene should be classified as Harmful Xn R48/20/21/22 according to Dir 1999/45/EC and Cat 2, H373 according to Reg (EC) 1272/2008.

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