Extracts (petroleum), heavy paraffinic distillates, solvent-deasphalted

Endpoint summary

Description of key information

After subacute dermal exposure to DAEs (equivalent to OECD 410), no signs of systemic toxicity were observed even at the high dose, 1000 mg/kg/day. After subchronic dermal exposure to DAEs (equivalent to OECD 411), a NOAEL could not be established since toxicity was observed at all dosing levels, including the lowest dose tested. The authors considered the NOAEL for dermal exposure to be less than 30 mg/kg/day.  The NOAEL for oral exposure after subchronic exposure to an DAE was less than 125 mg/kg (OECD 408).  
After subacute inhalation exposure to Other Lubricant Base Oils (equivalent to OECD 412), the overall NOAEL for systemic effects was determined to be > 980 mg/m3.  Animals were exposed to OLBOs in subacute (OECD 410), subchronic (OECD 411), and chronic (OECD 453) dermal toxicity tests, and the resulting NOAELs based on systemic toxicity were > 1000 mg/kg bw/day, > 2000 mg/kg bw/day, and > 75 μL/week, respectively.   

Additional information

Treated distillate aromatic extracts (TDAEs) are a further processing of distillate aromatic extracts (DAEs) in an attempt to reduce the amount of 3-7 ring PAC that is present. Since the treatment is mostly a selective reduction of PACs, the data from DAEs can serve as read across where treatment was insufficient and a significant amount of PACs still remain (≥ 3 wt% DMSO extractables as measured by IP-346). Where treatment was sufficient to reduce the 3-7 ring PACs (<3 wt% DMSO extractables as measured by IP-346), the material is most similar to a lubricating base oil and it is this data that should be used for read across. 

 

Oral Repeated Dose Toxicity Studies

There are no key repeated dose toxicity studies on OBLO (IP 346 < 3%) that could be used for read across to TDAEs (IP 346 < 3%). Two repeated dose toxicity studies on DAEs were used as read-across for TDAEs (IP 346 ≥ 3 wt%). Light paraffinic DAE(CAS number 64742-05-8) was tested dermally in a 28-day (subacute) toxicity study in rabbits (API, 1986). Heavy paraffinic DAE(CAS number 64742-04-7) was tested dermally and orally in a 13-week (subchronic) toxicity study in rats (Mobil, 1990). The NOAEL for oral exposure was less than 125 mg/kg.

 

In a key read-across subchronic oral toxicity study, heavy paraffinic distillate aromatic extract was administered to 10 male Sprague-Dawley rats/dose at dose levels 0, 125, or 500 mg/kg bw/day 5 days a week for 13 weeks (Mobil, 1990).  Four of ten mice in the 500 mg/kg/day group were sacrificed prior to scheduled termination. All animals in the 125 mg/kg/day survived to date of sacrifice. No details on clinical signs were provided. Body weight was significantly reduced in the 500-mg/kg/day group. A significant decrease (p<0.05) in red blood cell (RBC) parameters (including RBC count, haemoglobin, and haematocrit) and platelet in males dosed orally at 500 mg/kg/day. Males orally dosed at 125 mg/kg/day showed a significant decrease in RBC parameters; platelet counts were slightly decreased in these rats but did not achieve statistical significance. There were no significant differences in the RBC morphology or WBC differential data. The only statistically significant difference between the serum data from control and orally dosed rats was observed for SDH (0 mg/kg/day = 5±2 IU/l, 150 mg/kg/day = 8±2 IU/l, 500 mg/kg/day = 9±7 IU/l). Treatment-related dose-dependent changes in relative organ weights included increased liver weight in both groups, decreased prostate weight in both groups, decreased seminal vesicle weight in the high-dose group, and decreased thymus weight in both groups. Focal areas of red discoloration and or generalized reddening were also observed in the brain, spinal cord, stomach and testes of many of the rats dosed orally at 500 mg/kg/day. Treatment-related histopathology was generally dose-dependent and occurred in the following tissues: adrenals, bone marrow, liver, stomach and thymus. Atrophy occurred in the male sex organs (testes, seminal vesicle, and prostate). Sperm evaluations showed a significant increase in the frequency of sperm with abnormal heads in the rats dosed orally at 500 mg/kg/day (1.9% in controls and 3.2% in treated rats).  The NOAEL for heavy paraffinic distillate aromatic extract could not be identified and is less than 125 mg/kg/day when administered orally.

Inhalation Repeated Dose Toxicity Studies

Key read-across, subacute repeat-dose inhalation toxicity studies (Klimisch score = 2) have been conducted on three different other lubricant base oils with IP 346 < 3% (sufficiently refined) (Dalbey, et al., 1991). In the first study, Sprague-Dawley rats were exposed to an aerosol of a severely hydrotreated and hydrocracked heavy paraffinic oil (CAS No. 64742-54-7). Viscosity of the oil was 161 SUS at 40°C (approximately 34 mm²/s). Mean aerosol concentrations were 0, 47, 220, and 980 mg/m³; mass median aerodynamic diameter (MMAD) was ~1.2mm and GSD was ~1.8. Endpoints included a haematological profile (cell counts, differential, haemoglobin, haematocrit, cell volumes), 22 clinical chemistry measurements (e. g.,plasma enzymes, proteins, electrolytes,etc.), weights of 7 organs (lung, liver, kidney,etc.), and histopathology of major organs. A second, similar study was conducted with a solvent-extracted, catalytically dewaxed heavy paraffinic oil (CAS No. 64742-70-7), and a third study utilized a severely hydrotreated and acid-washed white oil (CAS No. 8042-47-5). Except for the lung and associated lymph nodes, no significant changes were observed following the last exposure for each of the three mineral base oils. The main changes in the lungs were concentration-related accumulations of foamy macrophages (FM) in alveoli, particularly those near alveolar ducts. A mild infiltrate of neutrophils and lymphocytes was sometimes observed with the FM, and the alveolar wall was slightly thickened near accumulations of FM at the higher aerosol concentrations. A mild accumulation of alveolar macrophages in the absence of other significant toxicity does not constitute an adverse effect. Thus, the NOEL for lung changes associated with oil deposition in the lungs was 220 mg/m³. As no systemic toxicity was observed, the overall NOAEL for systemic effects was > 980 mg/m³.

 

There are additional supporting studies on other lubricant base oils (IP 346 < 3 wt%) that support this read-across conclusion for TDAEs (Exxon Biomedical Sciences, Inc, 1991a; Exxon Biomedical Sciences, Inc, 1991b; Whitman, et al., 1989; Dalbey, 2001).

 

Dermal Repeated Dose Toxicity Studies

Based on the information presented below it was concluded that DAEs are harmful to health by prolonged exposure to skin, through read across, TDAEs (IP 346≥ 3 wt%) are also considered harmful to health by prolonged exposure to skin according to EU criteria. Other Lubricant Base Oils (IP 346 < 3 wt%) data did not show toxicity effects after prolonged exposure, so TDAEs (IP 346 < 3 wt%) are not classified according to EU criteria.

TDAEs (IP 346 ≥ 3 wt%)

In a key read-across dermal subacute toxicity study, light paraffinic DAE(CAS number 64742-05-8) was tested in rabbits at doses up to 1000 mg/kg/day (API, 1986c). The tested material was moderately irritating and caused proliferative changes to skin. No significant effects on body weight gain, haematology or gross and microscopic pathology were observed, and no significant systemic effects were noted.

 

In a key read-across dermal subchronic toxicity study, heavy paraffinic DAE(CAS number 64742-04-7) was tested in rats, at similar and lower doses than those tested in the 28-day test (Mobil, 1990). By contrast to the subacute test, lethality and a number of systemic effects were caused by exposure, while lesser skin irritation was observed. Histopathological changes were most prominent (and generally dose related) in the liver, thymus, adrenals, kidneys, lymph nodes, stomach, bone marrow and treated skin.

 

No NOAEL could be established for DAEs for dermal exposures since toxicity was observed at all dosing levels, including the lowest dose tested. The authors considered the NOAEL for dermal exposure to be less than 30 mg/kg/day.

 

Additional data support that DAEs are harmful to health by prolonged exposure to skin (Cruzan et al., 1986). This information is presented in the dossier.

 

TDAEs (IP 346 < 3 wt%)

In a key read-across subacute dermal toxicity study, dermal effects of hydrotreated heavy naphthenic oil (CAS 64742-52-5) were evaluated in rabbits (sufficiently refined, IP 346 < 3%, API, 1987). There was no mortality observed at any concentration tested. Statistically significant treatment-related decreases in mean body weight were observed in males and females at the 2000 mg/kg concentration. As well as irritation noted at various doses, topical administration of hydrotreated heavy naphthenic oil at 2000 mg/kg to both male and female rabbits was seen to induce changes in the liver characterized by multifocal to diffuse enlargement of hepatocytes (hepatocytomegaly) accompanied by multifocal areas of inflammation (subacute hepatitis). The systemic toxicity NOAEL is 1000 mg/kg, based on the lack of adverse systemic effects observed at this dose level. 

 

In a key read-across subchronic dermal toxicity key study (Mobil Environmental and Health Science Laboratory, 1983a), effects of Stock 141 (a lubricant base oil with IP 346 < 3%, sufficiently refined) on rat skin were assessed according to OECD Guideline 411. Treatment-related pathologies occurred in all groups, were never severe, and included liver enlargement and microscopic skin changes.  The absolute liver weight was 19% larger in males treated with Stock 141 than in control males.  The relative liver weight was 17% larger. The skin of the controls (sham-treated) showed epidermal thickening (hyperplasia), slight in males and trace in females.  The skin of most test-treated animals showed epidermal hyperplasia (trace to mild, in excess of that in the controls) and/or trace chronic inflammation of the superficial dermis. Both findings were very minimal in animals treated with Lubricant base oil Stock 141. The study authors conclude that these findings are not biologically significant. The NOAEL is greater than 2000 mg/kg/day based on lack of local or systemic toxic effects. 

 

In a key read-across chronic dermal carcinogenicity study, male C3H/HeNCrlBR mice (50/group) were dermally exposed to propane deasphalted mildly hydrorefined and dewaxed residuum from low cold test crude (IP 346 < 3%, sufficiently refined) and the appropriate controls at a frequency of twice per week for 24 months or until observation of carcinoma at which time the animal was sacrificed, at dose levels of 37.5 microlitres twice per week (ExxonMobil, 1991).  Treatment groups 011, 012, 014, 016 and the negative control group 721 were generally free of dermal irritation during most of the study and at histopathological examination. Forty-five of the fifty Group 951 animals (positive control) had confirmed squamous cell carcinomas at histopathology. All other groups were free of any skin neoplasms. With the exception of the positive control group, there were no statistical differences in time to tumour and tumour production between groups. Survivorship analysis indicated that the positive control displayed the lowest survivorship; however, this finding is related to the fact that animals were euthanized following the appearance of a carcinoma. The test materials did not cause local or systemic effects when applied neat. 

 

There are additional supporting studies on other lubricant base oils (IP 346 < 3 wt%) that support these read-across conclusions for TDAEs (Mobil Environmental and Health Science Laboratory, 1983b; API, 1982a; 1982b; 1982c; 1982d; 1982e; 1982f; 1982g; Trimmer, et al, 1989).

 

Justification for classification or non-classification

Based on read-across dermal subchronic repeat dose toxicity results and a NOAEL of < 30 mg/kg/day, Treated Distillate Aromatic Extracts (IP 346 ≥ 3 wt%) are classified under the EU CLP Regulation (EC No. 1272/2008) as STOT RE1 (H372) by prolonged exposure in contact with skin. 

Based on the lack of adverse effects in read-across studies, even with the highest doses administered, Treated Distillate Aromatic Extracts (IP 346< 3 wt%) are not classified under the EU CLP Regulation (EC No. 1272/2008).