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Description of key information

For assessment of repeated dose toxicity, the test item 2,2'-Oxybisethanol, ethoxylated and propoxylated (>1 < 4.5 mol EO and >1 <4.5 mol PO) was administered to male and female Wistar rats via the diet at dose levels of 0, 1200, 4000 and 12000 ppm (977.5, 330.5, 96 mg/kg bw) for 28 days. The test was conducted according to the OECD 407 (2008) under GLP conditions (BASFSE30C0042/11C117, 2012). The NOAEL, was set at 12000 ppm for both male and female Wistar rats, corresponding respectively to 977.5 and 1014.6 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
977.5 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
OECD guideline study conducted under GLP conditions.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

For assessment of repeated dose toxicity, the test item 2,2'-Oxybisethanol, ethoxylated and propoxylated (>1 < 4.5 mol EO and >1 <4.5 mol PO) was administered to male and female Wistar rats via the diet at dose levels of 0, 1200, 4000 and 12000 ppm over a period of 4 weeks. Each group consisted of 5 animals per sex. The test was conducted according to the OECD 407 (2008) under GLP conditions.

The mean daily test item intake over the entire study period was as follows:

In the low dose group (1200 ppm): the mean daily intake was 96 and 104.5 mg/kg bw/day for males and females, respectively.

In the mid dose group (4000 ppm): the mean daily intake was 330.5 and 332.5 mg/kg bw/day for males and females, respectively.

In the high dose group (12000 ppm): the mean daily intake was 977.5 and 1014.6 mg/kg bw/day for males and females, respectively.

No mortality occurred. No adverse treatment-related effects could be reported referring to clinical symptoms, body weight and body weight gain, food and water consumption, FOB, motor activity, hematological and clinical-chemical parameters, organ weight, gross pathology and histopathology.

In males urinalysis revealed a statistically significant increase in the specific gravity and a decrease in of urinary volume which did not result in a statistical significance.

No crystals of calcium oxalates, pH shifts or other indications of renal toxicity were identified in any male dose group. The changes observed in male animals were therefore interpreted as adaptation of the renal function in response to a decreased water intake, and consequenttly as treatment related, but not adverse.

No effects were identified in the urinalysis of females.

Thus, under the conditions of the present study the no observed adverse effect level, NOAEL, was set at 12000 ppm for both male and female Wistar rats, corresponding respectively to 977.5 and 1014.6 mg/kg bw/day.

A subchronic oral toxicity study is available for the read-across substance EDA EO PO:

The purpose of this study was to evaluate the potential toxicity of Ethylenediamine, ethoxylated and propoxylated (>1 - <8.5 mol of EO and PO) in rats following oral administration for at least 90 days.

Ten male and ten female F344/DuCrl rats per group were administered 0, 100, 300, or 1000 milligrams Ethylenediamine, ethoxylated and propoxylated (>1 - <8.5 mol of EO and PO) per kilogram body weight per day (mg/kg/day) in ultrapure water via oral gavage for at least 90 days to evaluate the potential for systemic toxicity. Parameters evaluated were daily cage-side observations, daily clinical observations, weekly detailed clinical observations, ophthalmic examinations, body weights, feed consumption, hematology, coagulation parameters, urinalysis, clinical chemistry, selected organ weights, and gross and

histopathologic examinations.

There were no treatment-related effects in cage-side or clinical observations, weekly detailed clinical observations, body weights, feed consumption, ophthalmic examinations, clinical chemistry, prothrombin time or urinalysis parameters. There were no treatment related organ weight effects, and no treatment-related gross pathologic observations.

Males and females administered 1000 mg/kg/day had statistically significant lower red blood cell counts, hemoglobin concentrations and hematocrits, which were interpreted to be treatment-related. These lower erythrocytic parameters were accompanied by the

histopathologic observation of very slight increased erythrocytic extramedullary hematopoiesis of the spleen in 8/10 males administered 1000 mg/kg/day. The increased splenic extramedullary hematopoiesis in males administered 1000 mg/kg/day was

interpreted to be a treatment-related compensatory response to the minor decrements in erythrocytic parameters. Females did not have a corresponding increase in erythrocytic extramedullary hematopoiesis of the spleen at any dose level.

Other treatment-related histopathologic effects were interpreted to be point-of-contact irritative lesions, located in the nasal tissues, lungs and stomach. Numerous irritative lesions were present in the olfactory and/or respiratory epithelium of the nasal passages in some males and females from all treated dose levels. The nasal alterations were most prominent in the ethmoid turbinates, ventral wall, and/or ventral septum of the posterior aspect of the nasal passages. The most common nasal epithelial alteration was atrophy of the olfactory epithelium. Other irritative nasal effects, noted in lesser numbers of rats, consisted of atrophy of the respiratory epithelium, suppurative exudate, acute inflammation of the olfactory and/or respiratory epithelium, necrosis of the olfactory epithelium, and ulcers of the olfactory and/or respiratory epithelium. All of these nasal epithelial effects were consistent with entry of the test material into the posterior aspect of the nasal passages due to inadvertent reflux of the test material from the esophagus or oropharynx immediately following the oral gavage dosing procedure, and were not related to systemic toxicity of the test material. One male administered 1000 mg/kg/day had slight, multifocal bronchioloalveolar hyperplasia with inflammation, and slight, multifocal hyperplasia of peribronchial lymphoid tissue of the lungs. The lung lesions in this rat were interpreted to be caused by inadvertent reflux of the test material into the lungs immediately following the oral gavage dosing procedure, and were not related to systemic toxicity of the test material. The stomach of males and females administered 1000 mg/kg/day also had irritative lesions which were not related to systemic toxicity, but were due to direct contact with the test material following oral gavage administration. The most common stomach lesion was very slight or slight, focally extensive hyperplasia with inflammation of the epithelium lining the limiting ridge.

Most of the males and females administered 1000 mg/kg/day also had very slight, multifocal vacuolar degeneration of epithelial cells in the limiting ridge of the stomach, and very slight or slight, multifocal subacute to chronic inflammation of the glandular submucosa of the stomach.

Based on the treatment-related point-of-contact irritative lesions in the nasal tissues that were present in some males and females from all treated dose levels, the overall noobserved- effect level (NOEL) for F344/DuCrl rats of either sex was not determined. However, the only treatment-related effects indicative of systemic toxicity were lower red blood cell counts, hemoglobin concentrations and hematocrits in males and females administered 1000 mg/kg/day, with compensatory increased erythrocytic extramedullary hematopoiesis of the spleen in males administered 1000 mg/kg day. Therefore, the NOEL for systemic toxicity was 300 mg/kg/day Ethylenediamine, ethoxylated and propoxylated (>1 - <8.5 mol of EO and PO).


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
valid studies, suitable for assessment.

Justification for classification or non-classification

Based on the results of a valid OECD TG 407 study conducted with male and female Wistar rats, a NOAEL of 977.5 and 1014.6 mg/kg bw/day, for males and females, respectively, could be assessed for the oral route. Furthermore, a valid OECD TG 408 study with the read-across substance EDA EO PO showed a NOEL of 300 mg/kg bw/d in rats.

Thus,there is no indication for classification/labelling of the the test item according to either the EU Directive 67/548/EEC or the CLP Regulation (EC) No. 1272/2008.