Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-560-6 | CAS number: 108-20-3
In a key subchronic toxicity study in Sprague-Dawley rats, animals were exposed to vapourised di-isopropylether (DIPE) at concentrations of 0 (untreated), 0 (sham), 480 ppm, 3300 ppm, or 7100 ppm for 6 hours/day, 5 days/week for 13 weeks. This non-GLP study was equivalent to OECD Test Guideline 413. Although no effect levels were established by the study authors, based on a review of the data, a no-observed-adverse-effect concentration (NOAEC) of 3300 ppm for systemic effects was established due to minor changes in liver and kidney weights without discernable morphological effects and a no-observed-effect concentration (NOEC) of 480 ppm was established. No local effects were described in the study report.
Supportive studies for DIPE were not located. No oral or dermal studies were conducted for this compound.
Table 1. Mean parameters ( ±SD) of hematology and serum chemistry that had significant differences between exposed and control groups following subchronic exposures.
480 ppm DIPE
3300 ppm DIPE
7100 ppm DIPE
0.61 ± 0.06
0.64 ± 0.04
0.67 ± 0.06
0.69 ± 0.03b
71 ± 10
74 ± 13
77 ± 17
77 ± 9
95 ± 22d
11 ± 5
16 ± 7
13 ± 6
9 ± 3c
92 ± 3
92 ± 4
90 ± 6
90 ± 4
87 ± 6b
1 ± 2
2 ± 2
3 ± 2b
4.96 ± 0.35
4.68 ± 0.24
4.58 ± 0.41
4.51 ± 0.37b
4.45 ± 0.40b
88 ± 5
86 ± 6b
85 ± 7b
86 ± 3b
apercent of total white blood cells.
bSignificantly different from untreated controls.
cSignificantly different from sham-exposed controls.
dSignificantly different from both control groups.
Mild hypertrophy was observed at the high-dose in combination with 39% (male) and 18% (female) increased absolute liver weight. The high dose of 7100 ppm was considered to be the LOAEC effect level.
At the mid-dose, no histopathological changes were observed. Absolute liver weight gain was 26% in males only; 6% in females. Sorbitol dehydrogenase dropped from 11(5) or 16(7) IU/L in controls to 9(3) IU/L. The absolute liver weight gain seen only in males, and unaccompanied by other effects, is considered to be a suitable NOAEC.
Based on "adverse liver effects" criteria by TERA (Toxicology Excellence for Risk Assessment): presence of histopathology (moderate hypertrophy) in combination with statistically significant absolute or relative weight changes; or liver weight change >10%; or doubling of serum levels of liver enzyme activity.
In a key, subchronic, non-GLP, whole-body inhalation toxicity study, equivalent to OECD Test Guideline 413, Sprague-Dawley rats were exposed to DIPE at nominal concentrations of 0 (untreated), 0 (sham), 480, 3300, or 7100 ppm (0, 0, 2000, 13800, or 29700 mg/m3, respectively) for 6 hours/day and 5 days/week for 13 weeks (Dalbey and Feuston, 1996).
There were no DIPE-related mortalities, clinical signs, or gross pathology changes in exposed rats. Males exposed to DIPE had greater weight gain in the initial half of the study, compared to controls. This was statistically significant in weeks 6 to 14 at the 3300 ppm concentration. Statistically significant changes were noted in haematology (lymphocytes, monocytes) and clinical chemistry (creatinine, cholesterol, and sorbitol deyhdrogenase) parameters in the mid- or high-dose exposure groups in males and/or females and compared to only one control; however, these changes were not considered biologically significant. Significant liver weight increases were observed in males and females (39% and 18%, respectively) at the high-dose (7100 ppm). At the mid-dose (3300 ppm) a significant increase (26%) was observed in males compared to both controls and in females (6%) compared to sham controls. Significant kidney weight increases also were noted in males at both mid- and high-doses. Increases also were observed in females at the high-dose but were only significant compared to sham-exposed controls. Mild hypertrophy was observed in liver cells in males exposed to 7100 ppm DIPE, however not in the females exposed to this dose or in animals at the mid-dose. Mild increases of hyaline droplets in the proximal convoluted tubules of male kidneys were noted at the high-dose group. No other histopathological changes were noted.
Although the authors did not establish effect levels, based on a review of the data, a NOAEC of 3300 ppm was derived due to minor changes in liver and kidney weights without discernable morphological effects at 3300 ppm. A NOEC of 480 ppm also was derived as no changes were observed at this dose.
No supportive studies were located.
The submission substance did not exhibit significant toxic effects arising from a repeated exposure. As a result, the substance does not meet the criteria for classification for STOT RE (specific target organ toxicity, repeat exposure) according to Regulation (EC) No 1272/2008, Annex I section 3.9.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again