Extracts (petroleum), heavy naphthenic distillate solvent

Endpoint summary

Description of key information

NOAEL for heavy paraffinic distillate aromatic extract could not be identified in a 90-day oral study (equivalent to OECD 408) and is less than 125 mg/kg/day when administered orally to male rats.  Systemic toxicity was observed in a 90-day dermal study (equivalent to OECD 411) in rats exposed to heavy paraffinic DAE (CAS number 64742-04-7).  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.  In a 28-day dermal study (equivalent to OECD 410), no signs of systemic toxicity were observed in rabbits even at the high dose, 1000 mg/kg/day.  

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

125 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

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

Dose descriptor:

LOAEL

30 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

Heavy paraffinic DAE (CAS number 64742-04-7) was tested dermally and orally in a 13-week (subchronic) toxicity study in rats (Mobil, 1990). Light paraffinic DAE (CAS number 64742-05-8) also was tested dermally in a 28-day (subacute) toxicity study in rabbits (API, 1986b). There are no repeated dose toxicity studies identified for exposure via inhalation.

Repeated Dose Toxicity - Oral

In a 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. Four of ten rats 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 count occurred 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). 

A NOAEL for heavy paraffinic distillate aromatic extract could not be identified and is less than 125 mg/kg/day when administered orally.

Repeated Dose Toxicity - Dermal 

Heavy paraffinic DAE (CAS number 64742-04-7) was tested in a 13-week dermal toxicity study 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.

A NOAEL could be established for DAE 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.

Light paraffinic DAE (CAS number 64742-05-8) was tested by repeated dermal exposure for 28 days in rabbits at doses up to 1000 mg/kg/day (API, 1986b). 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.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

only one study available

Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: bone marrow; cardiovascular / hematological: thymus; digestive: liver; digestive: stomach; glandular: adrenal gland; urogenital: prostate; urogenital: seminal vesicle; urogenital: testes

Repeated dose toxicity: dermal - systemic effects (target organ) cardiovascular / hematological: bone marrow; cardiovascular / hematological: lymph nodes; cardiovascular / hematological: thymus; digestive: liver; glandular: adrenal gland; urogenital: kidneys; other: skin

Justification for classification or non-classification

Based on dermal subchronic repeat dose toxicity results and a NOAEL of < 30 mg/kg/day, distillate aromatic extracts are classified under the EU CLP Regulation (EC No. 1272/2008) as STOT RE1 (H372).