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Key value for chemical safety assessment

Effects on fertility

Description of key information

No data identified.

Additional information

Data on reproductive endpoints were derived from subchronic toxicity studies on four bright stock extracts (BSEs, a synonym for RAEs). The undiluted test materials were applied to the skin of rats, 5 days per week for 13 weeks. A summary of the studies are provided in Table 1.  The study director assigned NOAELs based on altered organ weights. The NOAEL was judged to be 500 mg/kg/day for Mobilsol 40. NOAELs could not be established for the other BSEs since only one dose level was tested (Mobil, 1990).

Some indication of the likely effect of a test substance on reproductive organs can be gained from the results of these studies. As shown in Table 1, 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 (Mobil, 1990).

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.

In addition to the reproductive endpoints, other endpoints of toxicity that were evaluated included skin irritation, body weight, haematology, serum chemistry, urine analysis, gross pathology, microscopic histopathology of ~22 organs.

Short description of key information:

Effects on reproductive performance are not expected. Nevertheless, a testing proposal is included for an extended one-generation reproductive toxicity study with a representative Residual Aromatic Extract.

Effects on developmental toxicity

Description of key information

A developmental study (equivalent to OECD 414) was conducted in rats, in which the NOAEL for Mobilsol 40 for developmental toxicity was  2000 mg/kg-day when the test material was applied dermally.

Effect on developmental toxicity: via dermal route
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Additional information

In a developmental toxicity study via dermal application, groups of 15 pregnant Sprague-Dawley rats were clipped free of hair and collared on gestation day 0 prior to treatment with Mobilsol 40. Mobilsol 40 was applied once daily to the clipped and intact dorsal surface of the dams using a spatula at doses of 0, 500 or 2000 mg /kg-day until gestation day 19. The application sites were left uncovered. Animals were clipped once a week and collars were replaced as necessary. Dams were observed once daily for signs of pathosis, abortion, premature delivery, dystocia and or death throughout the gestation period until sacrifice on gestation day 20. On postpartum day 0, pups were examined for external malformations and variations and for the presence or absence of milk in their stomachs.

 

Pregnant rats treated with Mobilsol 40 exhibited slight skin irritation at the site of application at 500 and 2000 mg/kg-day dose levels. The study authors reported a significant lack in weight gain in animals dosed with 2000 mg/kg-day. However, they concluded that lack in weight gain was not treatment related since a similar lack in weight gain was also noted in a separate postpartum group treated with the same dose of Mobilsol 40. No evidence of developmental effects were observed during external, skeletal and visceral evaluation of rat fetuses from pregnant rats exposed to the test material. Mean fetal body weights were similar for the two dosed groups and the control group. Maternal serum chemistry of pregnant dams were marginally affected in the 2000 mg/kg-day dose. However, the study authors reported that since other indications of maternal toxicity were not present, the biological significance of serum chemistry findings were uncertain.

 

Based on these results, a NOAEL of 2000 mg/kg-day was identified for developmental toxicity.

Justification for classification or non-classification

There are no guideline data available for effects on reproductive performance.

A key developmental toxicity study was identified. Based on the study results, RAEs are not classified as a developmental toxicant according to the EU CLP Regulation (EC No.1272/2008).