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Endpoint summary

Description of key information

Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) was formerly a member of the LOA Category L (Resin Oils and Cyclic Dienes), and the following Category L streams, with which these studies were conducted, resemble Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) from a compositional standpoint, only containing much lower levels of benzene.

Other data included are for key constituents of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich), including benzene, toluene, DCPD and ethylbenzene.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

25 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Adequate information is available on the constituents to characterise the repeated oral hazards of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

11.2 mg/m³

Study duration:

chronic

Species:

other: human

Quality of whole database:

Adequate information is available on the constituents to characterise the repeated inhalation hazards of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich).

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

Adequate information is available on the constituents to characterise the repeated dermal hazards of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich).

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) is a UVCB in which the marker constituents benzene, DCPD and toluene drive the overall hazard assessment. Additionally, the constituent ethylbenzene can also be present, and is currently classified for repeated-dose effects on the auditory system.

3a,4,7,7a-tetrahydro-4,7-methanoindene (DCPD, dicyclopentadiene) is not classified for repeat dose toxicity under CLP. While some effects were seen in repeat dose studies, these are believed to be due to chronic irritation of the lungs and gastrointestinal tract with secondary stress-related effects rather specific target organ toxicity. DCPD is irritating; therefore it is biologically plausible that the mortality is mostly attributable to respiratory and gastric irritation effects rather than systemic effects. Liver effects seen in the rat oral study were not considered sufficient to warrant classification. Repeated exposure inhalation studies in rodents show mortality at levels that would be predicted by their LC50s, and appears related to respiratory irritation/portal-of-entry effects. The original Bushy Run 90-day study showed mortality in the mice at 276 mg/m3. The LC50 in mice is about half that of rats, which might be expected for a respiratory irritant (higher ventilation rate in the mouse).

Benzene (Classification: 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). In humans, a recent study of petroleum distribution workers exposed to relatively low levels of benzene (Schnatter et al., 2012) reported associations between myelodysplastic syndrome (MDS) and benzene exposure, however while the association appeared to be reasonably robust, it was difficult to ascribe a precise dose/response relationship

In a review by Schnatter et al. 2020, benzene repeat dose studies in workers (seventy-seven genotoxicity and thirty-six haematotoxicity) were scored for study quality. Genotoxicity and haematoxicity endpoints were selected as they are the most sensitive and relevant to the proposed mode of action (MOA) and protecting against these will protect against benzene carcinogenicity. Lowest and No- Adverse Effect Concentrations (LOAECs and NOAECs) were derived from the highest quality studies and further assessed as being “more certain” or “less certain”. The lowest haematotoxicity LOAECs showed effects near 2 ppm (8 h TWA), and no effects at 0.59 ppm. For genotoxicity, studies also showed effects near 2 ppm and showed no effects at about 0.69 ppm. Several sensitivity analyses supported these observations. These data define a benzene LOAEC of 2 ppm (8 h TWA) and a NOAEC of 0.5 ppm (8 h TWA). Allowing for possible subclinical effects in bone marrow not apparent in studies of peripheral blood endpoints, an OEL of 0.25 ppm (8 h TWA) is proposed.

Toluene (Classification: 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).

Ethylbenzene (Not currently classified): No repeated dose toxicity studies in humans have been identified. The EU transitional RAR (EU, 2008a) 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.

In addition to data presented above on constituents of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich), data are available for UVCBs with similar compositions – these are also produced via similar manufacturing processes and are rich in DCPD and other cyclic olefins, as well as aromatic compounds. These studies indicate that Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) does not produce adverse effects in target animals.

CAS 68477-54-3 [Low Dicyclopentadiene Resin Oil]: Oral doses of 0, 35, 125, or 375 mg/Kg/day were administered once daily for 29 or 30 days. At 375 mg/Kg/day clinical signs of toxicity, lower body weight and food consumption and histopathological changes were observed. In addition, effects on body weight, clinical signs and food consumption were observed in males at 125 mg/Kg/day. The NOAEL for systemic toxicity was 35 mg/Kg/day in male and 125 mg/Kg/day in female rats.

CAS 648478-10-4 [Dicyclopentadiene/Codimer Concentrate]: Oral gavage doses of 0, 5, 25, or 100 mg/Kg/day were administered once daily for 29 or 30 days. The only toxicologically significant treatment-related effects were histopathological changes in the thyroid (follicular cell hypertrophy) at 25 and 100 mg/Kg/day in both males and females. The NOAEL for systemic toxicity was 5 mg/Kg/day in male and female rats.

Reference

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

Justification for classification or non-classification

Since benzene is present >10%, Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) is classified as Cat 1, H372 according to Reg (EC) 1272/2008.

After repeated dose exposure via oral or inhalation routes, benzene causes adverse effects on the haematopoietic system of animals and in humans. Consequently, benzene is classified as STOT RE, Cat 1 (H372) according to Regulation (EC) No 1272/2008 of the European Parliament.