Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

No data are available for sodium tert butanolate. Sodium tert-butanolate is the salt of tert-butyl alcohol ion and the sodium metal cation. In the presence of water it reacts under formation of tert-butyl alcohol and sodium hydroxide (NaOH). For that reason, a weight of evidence approach with read-across to tert-butyl alcohol was performed. Additionally, isopropanol as a secondary alcohol was used for read-across. It contains a propyl group compared to the ethyl group of tert-butyl alcohol. Here, several reproductive toxicity studies are available.

A screening test according to OECD 421 and GLP was published by Huntingdon Life Sciences in 2004. Here, 12 Albino (Sprague-Dawley derived strain (outbred), Crl:CD(SD) IGS BR) rats were treated orally by gavage with tert. butyl alcohol with the following concentrations: 64, 160, 400, 1000 mg/kg body weight. Males were dosed from 4 weeks prior to mating until termination (approximately 63 doses). Females were treated from the beginning of the premating period through gestation until termination on PND 21. Selected weanlings (1/sex/litter) were dosed once daily on PND 21-27 at the same dose levels received by their parents, then terminated on PND 28. Mild to moderate parental toxicity, including CNS effects, decreased body weight gain, and decreased food consumption, was observed at 400 and 1000 mg/kg. No clear evidence of an adverse effect on reproductive parameters including mating index, fertility index, pregnancy index, or gestation index could be found. This leads to a NOAEL of 160 mg/kg. Fetotoxicity was evidenced by reductions in mean litter size, a decrease in number of live born pups, an increase in the number of stillborn pups, reduced pup body weights, and increased mortality in the offspring of dams receiving approximately 1000 mg/kg bw/day by oral gavage. All effects occurred in the presence of parental toxicity. The NOAEL was set at 400 mg/kg. A second study was published by Bevan et al., 1997. Based on metabolism studies which demonstrate that methyl tertiary butyl ether (MTBE) is rapidly metabolized to tertiary butyl alcohol in vivo, data from a two-generation study conducted with MTBE are also relevant for evaluation of the reproductive toxicity of tertiary butyl alcohol. There were no adverse effects on mating performance, fertility or reproductive organs in the two-generation study in which Sprague-Dawley rats were exposed to 400, 3000 or 8000 ppm MTBE. General signs of toxicity were observed in both parental generations at 3000 and 8000 ppm. The NOAEC for reproductive toxicity in the MTBE study was 8000 ppm while the NOAEC for parental toxicity was 400 ppm. In a study published by Daniel et al., 1982, Maus Swiss-Webster-mice were treated from GD 6 to GD 20 to tert butyl alcohol with the following doses: 0, 0.5, 0.75, and 1 % (according to MAK: ca. 3110, 4660, and 6220 mg/kg). At 0.75 and 1 % decreased food consumption occurred leading to increased maternal sedation. Authors discussed it as a result from difficulties in pair feeding. At the same doses, a decreased number of litters (control: 77 %; 0.5 % t-butanol: 80 %; 0.75 % t-butanol: 53 %; 1 % t-butanol: 47 %), decreased fetal weight (control: 1.78 g, 0.75 % t-butanol: 1.45 g; 1 % t-butanol 1.1 g) and increased number of total still borns (control: 3; 0.75 %: 14; 1 % t-butanol: 20) occurred. The righting reflex of 0.75% and 1 % t-butanol treatment groups was impaired developed compared to the control and between fostered and nonfostered pups, indicating an effect of postnatal maternal nutritional and behavioral effect. Similar results were obtained in the open field analysis. The NOAEL was set at 0.5 % (= 3110 mg/kg).

Effects on developmental toxicity

Additional information

No data are available for sodium tert butanolate. Sodium tert-butanolate is the salt of tert-butyl alcohol ion and the sodium metal cation. In the presence of water it reacts under formation of tert-butyl alcohol and sodium hydroxide (NaOH). For that reason, a weight of evidence approach with read-across to tert-butyl alcohol was performed. Here, two developmental toxicity studies are available.

Nelson et al., 1989 published a study where 13 -18 Sprague-Dawley rats were exposed for 7 h/day to tert-butyl alcohol vapor containing the following concentrations: 2000, 3500, and 5000 ppm (200, 350, and 500 mg/kg). Exposure to 5000 ppm induced narcosis of all animals, an unsteady gait, reduced body weight gain, reduced food consumption, and impaired locomotor activity. Exposure to 3500 and 2000 ppm also resulted in an unsteady state and impaired locomotor acitity. Body weight gain in the dams was reduced dose-dependently compared to the controls and was significant at 5000 ppm. All pubs of all treatment groups had also reduced body weight gain. The number of skeletal variations increased significantly in the 3500 and 5000 ppm groups. The majority of skeletal malformations were rudimentary cervical ribs and were correlated to increasing concentrations of t-butanol. The lowest concentration was not associated with any defects. Variations seen were typical of fetotoxicity, especially reduced ossification. The NOAEC for maternal toxicity is 3500 ppm and for fetotoxicity below 2000 ppm.

A second study was performed by Faulkner et al., 1989. Here, CBA/J and C57BL/6J mice were treated with ca. 780 mg tert-butyl alcohol/kg bodyweight every 12 hours per oral gavage from GD 6 through GD 18. A significant increase in the number of resorptions per litter, and a decrease in the number of live fetuses per litter was observed. 8 of the 21 litters in the tert-butyl alcohol treated groups had all of the fetuses resorbed compared to 0 in the control. Body weight was slightly decreased in the pubs but no teratogenic effects of t-butanol could be detected. Defects limited to the skull and sternum and minor variations such as misaligned or underossified sternebrae and underossified supraoccipital bones occurred. No data were given for clinical signs of maternal toxicity.

Justification for classification or non-classification

In the study published by Daniel et al, 1982 too high unrelevant doses were applied exceeding the maximum recommended dose of 1000 mg/kg body weight. In the study of Bevan et al., 1997, no significant changes were observed in the reproductive parameters and signs of developmental toxicity such as lowered body weight and body weight gains were observed only in the presence of maternal toxicity. In the study published by Huntingdon Life Sciences in 2004, no adverse effects on reproductive parameters could be detected. Decreased body weight gain correlated with decreased food consumption which might have been a result of drunkness. Fetotoxic effects were based on maternal toxicity. In the developmental study published by Faulkner et al., 1989 too high doses were applied exceeding the maximum recommended dose of 1000 mg/kg/day. In the publication from Nelson et al., 1989, doses higher than 3500 ppm (350 mg/kg/day) showed increasing developmental toxicity by increased skeletal variations. Doses of 350 to 500 mg/kg would be in accordance with doses of 455 to 650 mg/kg sodium tert-butanolate (based on the molecular weight). These doses would probably lead to high mortality due to the high corrosivity.

Based on the available data received from tert-butyl alcohol, no classification is proposed according to EU directive 67/548/EEC and EU regulation (EC) NO. 1272/2008 (CLP).

Additional information