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Description of key information

There were no repeated dose oral or inhalation studies identified.   However, OECD 422 studies by the oral dietary route are now planned on a number of substances within the category to fill this data gap and to act as range-finding for the EOGRTS (OECD 443) which is the subject of a testing proposal.

A key 90-day dermal toxicity study (OECD 411) examined RAE substances in male and female rats and determined a NOAEL of 500 mg/kg/day for Mobilsol 40; however, a NOAEL could not be clearly established for the BSE Australia, Ninian and Statjford since only a single dose level was evaluated for these three extracts.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

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:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

There were no repeated dose oral or inhalation studies identified. In a repeated dose dermal study, ten male and female [N(SD)fBR] rats were dosed dermally with four Bright Stock Extracts (BSEs) comprised of Mobilsol 40, BSE Australia, BSE Ninian, and BSE Statfjord 5 days/week for 13 weeks (Mobil, 1990). A group of ten male and female rats served as the control group. Prior to test material(s) application, each animal was clipped free of hair from the entire dorsal trunk area. Hair was re-clipped as required at least once per week. Mobilsol was applied at a dose of 500 and 2000 mg/kg-day, whereas, the other three BSE extracts were applied at a dose of 2000 mg/kg-day. The exposure sites were left uncovered. All treated and control rats were fitted with a cardboard Elizabethan-style collars lined with latex tubing to minimize ingestion of the test materials. Collars were fitted on the rats several days prior to dose administration and replaced as needed during the dosing period.

 

No signs of skin irritation were reported as a result of exposure to the four BSEs. No adverse clinical signs were attributed as a result of exposure to the test materials. Body weight gains were normal in all rats treated with the four BSEs. Urinalyses and sperm evaluations were not impacted as a result of exposure to the test materials. No histopathological changes were noted in the reproductive organs of male or female rats. Further, neither epididymal spermatozoa morphology and count nor testicular spermatid counts were affected by treatment with RAEs as shown in the table.

Table 1. Summaries of data on reproductive organs from subchronic studies with RAEs (CAS RN. 64742-10-5), derived from Mobil, 1990.

Test Material

Route, Species, Doses, Exposure Regimen

Endpoints

Results

Mobilsol 40

 

Dermal. Male and female rats.

0, 500, 2000 mg/kg on 5 d/wk for 13 wk.

Full necropsy. Weights of testes, prostate, epididymides, ovaries, and uterus. Histopathology of testes and ovaries. Weight of testicular parenchyma and cauda epididymis. Number of testicular sperm and number/g testis. Number and morphology of epididymal sperm, number/g cauda.

No treatment-related effect noted on reproductive organs.

BSE - Australia

Dermal. Male and female rats.

0, 2000 mg/kg on 5 d/wk for 13 wk.

Full necropsy. Weights of testes, prostate, epididymides, ovaries, and uterus. Histopathology of testes and ovaries. Weight of testicular parenchyma and cauda epididymis. Number of testicular sperm and number/g testis. Number and morphology of epididymal sperm, number/g cauda.

No treatment-related effect noted on reproductive organs.

BSE – Ninian

Dermal. Male rats.

2000 mg/kg on 5 d/wk for 13 wk.

Full necropsy. Weights of testes, prostate, and epididymides. Histopathology of testes.

No treatment-related effect noted on reproductive organs.

BSE-Statfjord

Dermal. Female rats.

2000 mg/kg on 5 d/wk for 13 wk.

Full necropsy. Weights of ovaries and uterus. Histopathology of ovaries.

No treatment-related effect noted on reproductive organs.

 

Changes in haematological parameters were noted in treated females, but not males. At 13 weeks, significant decreases in haematological parameters, compared to the control group, were noted in red blood cells (RBCs) and haematocrit in females treated with Mobilsol 40, RBCs, haemoglobin, and haematocrit in BSE Australia, and RBC, haemoglobin, and haematocrit in BSE Statjford (only females were exposed for this BSE).

 

Mobilsol 40, BSE Statjford, and BSE Ninian slightly affected the normal serum chemistry of treated rats. The serum chemistry of animals exposed to BSE Australia was more adverse compared to animals exposed to other BSEs. In Mobilsol 40, glucose, albumin, calcium (in males), glucose, and sorbitol dehydrogenase (SDH) (females) were significantly different from the control group. Animals treated with BSE Australia showed significant differences in urea nitrogen, creatinine, total protein, albumin, albumin/globulin ratio and SDH (males) levels compared to the concurrent controls. Alkaline phosphatase, calcium, and SDH levels were significantly different compared to the controls in animals treated with BSE Statjford (only females were treated with this BSE). Animals treated with BSE Ninian (only male rats were exposed to this BSE) exhibited significant changes in uric acid, albumin, calcium, inorganic phosphorus, chloride, and SDH compared to the concurrent controls.

 

Liver weights of male rats treated with Mobilsol 40 were increased in the 2000 mg/kg-day group and in male and female rats treated with 2000 mg/kg-day BSE Australia. The study authors reported that the increase in liver weight was more of an adaptive response rather than an adverse effect.

 

Based on these results, the study authors concluded that the No-Observed-Adverse-Level (NOAEL) for Mobilsol 40 is 500 mg/kg-day. A LOEL of 2000 mg/kg-day was established for the BSE Australia, Ninian and Statjford but a NOAEL could not be established for these materials since only a single dose level was evaluated for these three extracts.

Justification for classification or non-classification

There were no repeated dose toxicity studies for oral or inhalation exposure of RAEs. There was one repeated dose toxicity study identified for dermal exposure. Based on the 90 -day dermal results, RAEs are not classified under CLP Regulation, (EC)1272/2008, based on a NOAEL for Mobilsol 40 of

500 mg/kg-day. A NOAELs could not be clearly established for the BSE Australia, Ninian and Statjford since only a single dose level was evaluated for these three extracts.