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Table 2 Overview of endpoints conducted in OECD 408 studies for Oct-1-ene, Nonene, branched, Octadec-1-ene, Octadecene, and hydrocarbons, C12-30, olefin-rich, ethylene polymn. by-product

From: The subchronic toxicity of higher olefins in Han Wistar rats

Substances

Oct-1-ene

Nonene, branched

Octadec-1-ene

Octadecene

Hydrocarbons, C12-30, olefin-rich, ethylene polymn. by product

Dose level (mg/kg)

0, 100, 300 and 1000

0, 20, 100 and 500

0, 20, 100 and 500

0, 100, 300 and 1000

0, 100, 300 and 1000

Mortality

No unscheduled deaths

No unscheduled deaths

No unscheduled deaths

No unscheduled deaths

No unscheduled deaths

Clinical observations

Either sex treated with 1000 and 300 mg/kg bw/day showed episodes of increased salivation during the treatment period.

Either sex treated with 500 and 100 mg/kg bw/day showed episodes of increased salivation during the treatment period.

Either sex treated with 500 mg/kg bw/day showed episodes of increased salivation between Days 27 and 50 for males and between Days 27 and 90 for females.

Either sex treated with 1000 mg/kg bw/day showed episodes of increased salivation during the treatment period.

No clinical signs observed

Behavioral assessment

No treatment-related changes

No treatment-related changes

No treatment-related changes

No treatment-related changes

No treatment-related changes

Functional performance

No toxicologically significant changes

No toxicologically significant changes

No toxicologically significant changes

No toxicologically significant changes

No toxicologically significant changes

Sensory reactivity assessments

No treatment-related changes

No treatment-related changes

No treatment-related changes

No treatment-related changes

No treatment-related changes

Body weight

No effect on body weight performance

No effect on body weight performance

No effect on body weight performance

No effect on body weight performance

No effect on body weight performance

Food consumption

No treatment-related effects on food consumption or food conversion efficiency

No treatment-related effects on food consumption or food conversion efficiency

No treatment-related effects on food consumption or food conversion efficiency

No treatment-related effects on food consumption or food conversion efficiency

No treatment-related effects on food consumption or food conversion efficiency

Water consumption

No treatment-related effect

No treatment-related effect

No treatment-related effect

No treatment-related effect

No treatment-related effect

Ophthalmoscopy

No treatment-related ocular effects

No treatment-related ocular effects

No treatment-related ocular effects

No treatment-related ocular effects

No treatment-related ocular effects

Hematology

No toxicologically significant effects

No toxicologically significant effects

Males treated with 500 mg/kg bw/day showed a statistically significant reduction in prothrombin time and activated partial thromboplastin time

No toxicologically significant effects

No toxicologically significant effects

Blood chemistry

No toxicologically significant effects

No toxicologically significant effects

No toxicologically significant effects

No toxicologically significant effects

No toxicologically significant effects

Necropsy

No toxicologically significant macroscopic abnormalities

Three males treated with 500 mg/kg bw/day had enlarged kidneys. Two further males treated with 500 mg/kg bw/day had pale kidneys and one of these males also had mottled kidneys. All males treated with 500 mg/kg bw/day and three males treated with 100 mg/kg bw/day had an enlarged liver.

No toxicologically significant macroscopic abnormalities

Neither the type, incidence nor distribution of findings observed at terminal necropsy indicated any obvious effect of treatment

Neither the type, incidence nor distribution of findings observed at terminal necropsy indicated any obvious effect of treatment

Organ weights

Males treated 1000 mg/kg bw/day and females from all treatment groups showed a statistically

significant increase in liver weight both absolute and relative to terminal body weight Males treated with 1000 mg/kg bw/day showed a statistically

significant reduction in epididymides weight both absolute and relative to terminal body weight

Males treated with 500 and 100 mg/kg bw/day showed a statistically significant increase in kidney and liver weights both absolute and relative to terminal body weight. Females treated with 500 mg/kg bw/day also showed a statistically significant increase in absolute and relative liver weight. Females from all treatment groups showed a statistically significant increase in absolute and

relative kidney weight. Males treated with 100 and 20 mg/kg bw/day showed

a statistically significant reduction in spleen weight both absolute and relative to terminal body

weight

Males from all treatment groups showed a statistically significant reduction in spleen weight both absolute and relative to terminal body weight. Males treated with 500 mg/kg bw/day showed a statistically significant increase in absolute and relative thymus weight. Females treated with 500 mg/kg bw/day showed a statistically significant increase in absolute and relative liver weight.

No effects in the organ weights

No effects in the organ weights

Histopathology

Kidneys: increased incidence and severity of hyaline droplets and granular casts were evident in males from all treatment groups.

Stomach: Acanthosis, hyperkeratosis, ulceration and submucosal inflammation was evident in the forestomach of animals of either sex treated with 1000 and 300 mg/kg bw/day.

Lungs: increased incidence and severity of alveolar macrophages were evident in animals of either sex treated with 1000 mg/kg bw/day and in females treated with 100 mg/kg bw/day.

Kidneys: hyaline droplets and tubular basophilia was evident in males from all treatment groups. Granular casts were also evident in males treated with 500 and 100 mg/kg bw/day.

Liver: centrilobular hypertrophy was evident in animals of either sex treated with 500 and 100 mg/kg bw/day.

Thyroid: hypertrophy/hyperplasia of follicular cells was evident in animals of either sex treated with 500 and 100 mg/kg bw/day.

Stomach: acanthosis of the forestomach was evident at extremely low severity in males treated with 500 mg/kg bw/day.

Mesenteric Lymph nodes: A minimal or mild inflammatory cell infiltrate was present in the periglandular fat surrounding the mesenteric lymph nodes of eight males and nine females treated with 500 mg/kg bw/day.

Adrenals: Minimal diffuse hypertrophy of the adrenal cortex was present in two females treated with 500 mg/kg bw/day.

No abnormal findings observed during microscopic examination

No abnormal findings observed during microscopic examination

No Observed Effect Level (NOEL)

Male: Not established

Female: 100 mg/kg bw/day

Male: Not established

Female: 20 mg/kg bw/day

100 mg/kg bw/day for both sexes

1000 mg/kg bw/day for both sexes

1000 mg/kg bw/day for both sexes

No Observed Adverse Effect Level (NOAEL)

1000 mg/kg bw/day for both sexes

500 mg/kg bw/day for both sexes

500 mg/kg bw/day for both sexes

1000 mg/kg bw/day for both sexes

1000 mg/kg bw/day for both sexes