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Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
300 mg/kg bw/day

Additional information

Oral

90 -day subchronic oral dosing in rats to isooctanol (CAS number 68526 -83 -0; 100, 300, and 700mg/kg/d) resulted in nonadverse hepatic effects (hepatocellular hypertrophy correlated with increased liver weights) and non-human relevant changes to the kidneys in male rats. Exposure to isotridecanol (CAS number 68526 -86 -3; 100, 300, and 1000mg/kg/d) also resulted in nonadverse hepatic effects (hepatocellular hypertrophy correlated with increased liver weights) and non-human relevant changes to the kidneys in male rats with additional adaptive, non-adverse changes to lung, and adaptive, non-human relevant changes to thyroid. Exposure to isoundecanol (CAS number 68551 -08 -6; 100, 300, and 1000mg/kg/d) similarly resulted in nonadverse hepatic effects (hepatocellular hypertrophy correlated with increased liver weights) and non-human relevant changes to the kidneys in male rats with additional adaptive, non-human relevant changes to thyroid, and non-adverse changes to the adrenal gland in males only. A read-across justification for use of these test results for members of the Alcohol group will be used to fulfill relevant endpoints for the other Alcohols in the group (refer to the integrated testing strategy in the CSR and attachment in assessment reports).

Additionally, repeat oral dosing studies with related (C6, C8, C9, C10, and C13) linear alcohols indicate minimal effects (US HPV, 2006; OECD SIAR, 2006). In repeated oral dosing studies with related (C8, C9, C10, C13) linear alcohols there were minimal hepatic effects (i.e., elevated liver weight and hepatic peroxisomal enzyme levels along with changes in serum lipid levels), but testicular weight was unaffected. The NOAELs from these studies were set at the limit dose of 1mM/kg/day (130, 144, 168, and 184 mg/kg/day for C8, C9, C10, C13, respectively).

Dermal

Male and female rabbits were subjected to a repeated dose of either 0.5 or 2.5 ml/kg body weight isooctanol. Undiluted control and test material were applied to intact skin of the animals once daily for a total of 10 applications with a 1 day rest period between the first and second applications, and a 2 day rest period between the third and fourth and eighth and ninth applications. Repeated applications of isooctanol produced moderate or marked degree of dermal irritation. The irritation was characterized by slight or moderate erythema, slight or moderate edema, and slight to marked atonia and desquamation. In addition, two of the low level animals showed slight necrosis, and all of the high level animals showed fissuring and a coriaceous condition of the skin. There were no adverse systemic effects noted.

 

Inhalation

No data signs of toxicity were observed in rats inhaling 180 ppm isooctanol (maximal achievable concentration) 6 hours/day for 13 days (Gage, 1970). No maternal toxicity was seen after inhalation for 19 days of near saturated vapor concentrations of 840 ppm 1-hexanol, 200 ppm 2-EH, 65 ppm 1-octanol, 25 ppm 1-nonanol, or 15 ppm 1-decanol in a developmental toxicity study using pregnant rats (Nelson et al., 1990).

Justification for classification or non-classification

No classification for repeated dose toxicity is indicated according to the general classification and labeling requirements for dangerous substances and preparations (Directive 67-548-EEC) or the classification, labeling and packaging (CLP) regulation (EC) No 1272/2008.

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