Hydrocarbons, C4, 1,3-butadiene-free, polymd., triisobutylene fraction

Endpoint summary

Description of key information

There is a 28 day repeat oral dosing study with triisobutylene with 14 day recovery. There are also repeat dose toxicity studies with other higher olefins spanning the range C8 to C20.  The data for these studies indicate that the location of the double bond or the addition of branching to the structure do not appear to affect the toxicity.  Higher olefins are of low  toxicity  in rats.  Male rat kidney effects indicative of alpha-2u-globulin nephropathy consistently occur with the C8 to C14 higher olefins.  Alpha-2u-globulin nephropathy is considered to be male rat-specific and is not relevant for humans.  Treatment-related liver effects (increased organ weights, hepatocyte cytoplasmic vacuolation, and centrilobular hepatocyte hypertrophy) are also observed in rats exposed to higher olefins, which may reflect adaptive changes as a result of the high liver burden of these substances.  There is no evidence of neurotoxicity.

Additional information

Non human data Isooctene (CAS 11071 -47 -9) has been tested in a combined subchronic inhalation study with a reproduction/developmental toxicity screening test at vapor concentrations of 0, 1000, 5000, and 15,000 mg/m3 (BASF, 2007). Male Wistar rats were exposed for approximately 13 weeks; females were exposed during premating (10 weeks), mating and gestation through day 4 after delivery (approximately 15 weeks). Absolute and relative liver and kidney weights were significantly increased in the mid- and high-exposure groups. The only histopathological effects were increased hyaline casts and basophilic cortical tubules, along with accumulation of alpha-2u-globulin in the cortical tubular cells of male rats at 5000 and 15,000 mg/3. These male rat-specific kidney effects are indicative of alpha-2u-globulin nephropathy and are not considered relevant to humans. The NOEC for this study is 1000 mg/m3.

The remaining higher olefins have been tested in oral gavage studies. In a 28-day oral study, male and female CD rats were given by gavage 0, 100, 300 or 1000 mg/kg 2,4,4-trimethylpentene (HLS, 1997 b). Compared to controls, kidney weights were increased in the 1000 mg/kg males and liver weights were increased in the 1000 mg/kg males and females. No adverse histopathological effects were noted. The NOAEL was 300 mg/kg-day. In an OECD 421 study, male and female CD rats were dosed by oral gavage with 0, 100, 300 or 1,000 mg/kg (HLS, 1997 c). Males received 44 to 46 doses and females received 40-45 doses. Liver and kidney weights were increased in both males (300 and 1,000 mg/kg) and females (1,000 mg/kg) compared to controls. Histopathological effects, however, were observed only in the kidneys of all treated male rats, and consisted of basophilic cortical tubules and proteinaceous casts and interstitial cells (300 and 1,000 mg/kg groups only). The kidney effects were further investigated in a special study (Shell, 2004) and concluded to bemale rat-specific kidney effects indicative of alpha-2u-globulin nephropathy which are considered not to be relevant to humans. The NOAEL for this study is 300 mg/kg.

In a 28 day study with triisobutylene (CAS 7756 -94 -7, Biosafety Research Centre Japan) there were no treatment related clinical signs and no effects on body weight or food consumption at doses up to 750 mg/kg/day. Small decreases inred blood cell counts were seen in females of the 150 and 750mg/kg bw/daygroups, and the prothrombin time was slightly shorter than control in females of the 750mg/kg bw/daygroup. Histopathological examination revealed swelling of liver cells in both sexes of the 150 and 750 mg/kg bw/day groups, and eosinophilic bodies in renal tubules in males of the 150 and 750 mg/kg groups. These changes were accompanied by increases in absolute and relative liver weights in both sexes at 750 mg/kg bw/day and in males at 150 mg/kg bw/ day. Absolute or relative kidney weights were increased in males of the 150 and 750 mg/kg groups but not in females. Absolute and relative spleen weights were decreased in females of the 750 mg/kg group. A systemic toxicity NOEL of 30 mg/kg/day was established based on, haematology, organ weight, and histopathology changes in the liver and kidneys at a dose level of 150 mg/kg bw/day. In animals dosed with for 28 days and then maintained for a 14 day recovery period the only finding was basophilic change in the kidneys of both sexes.

1-Tetradecene (CAS 1120 -36 -1, a C16 olefin) was administered by oral gavage to rats at doses of 0, 100, 500 or 1000 mg/kg/day in corn oil in an OECD 422 study (Springborn laboratories, 1995). The males and an unbred satellite group of females were dosed for 28 days prior to mating and until euthanasia (43-47 days of dosing). Breeding females were dosed for 14 days prior to mating, during mating, gestation, and lactation until euthanasia (42-51 days of dosing). Increased liver weights and minimal-to-moderate hepatocyte cytoplasmic vacuolation were observed in the 500 and 1000 mg/kg animals; and increased hyaline droplets in the proximal convoluted tubules only in male rats at all doses. The male rat hydrocarbon nephropathy was concluded to be unique to the male rat, and not suggestive of an adverse effect for human risk assessment.

In an OECD 421 study, male and female rats were dosed with 0, 100, 500 or 1000 mg/kg C18 branched and linear olefins (CAS 27070 -58 -2 and CAS 18236 -02 -8) for approximately 6 weeks (Springborn Laboratories, 2003). There were no treatment-related effects. The NOAEL was 1000 mg/kg-day. 

C20-24 branched and linear olefins were given by oral gavage to male and female rats for 13 weeks at doses of 0, 100, 500 or 1,000 mg/kg (HLS, 1999). An additional group of male and female rats were dosed with either 0 or 1000 mg/kg test material for 13 weeks followed by a 4-week recovery period. In treated females, liver weights were significantly increased, which was associated with centrilobular hepatocyte hypertrophy (statistically significant only in the 1000 mg/kg group. Adrenal weights were also significantly increased in all treated females, with a statistically significant increased incidence of minimal or slight adrenal cortical hypertrophy in the 1000 mg/kg females compared with controls.

Several of these repeat dose studies have neurotoxicity screening assessments in the repeat dose toxicity studies (isooctene, 2,4,4-trimethylpentene, C14 alpha olefin, and C20-24 linear/branched internal olefins). No treatment-related effects were observed.

Human data

No human information is available.

Justification for classification or non-classification

There are sufficient data available on olefins from C8 to C18 to conclude that the butylenes oligomers are of low repeat dose toxicity by the oral and inhalation routes with no indication of serious functional or morphological effects. Classification is not warranted for butylene oligomers under Dir 67/548/EEC or GHS/CLP.