O-ethylhydroxylamine

Endpoint summary

Description of key information

- Acute oral toxicity: LD 50 = 177 mg/kg bw (GLP, equivalent to OECD 401)
- Acute dermal toxicity: LD 50 = 176.6 - 882.7 mg/kg bw
- Acute inhalation toxicity: LC 50 = 0.87 mg/l (GLP, equivalent to OECD 403)

Additional information

Acute Oral Toxicity:

In an acute oral toxicity study, with similarities to the guideline protocols OECD 401, groups of 5 (SPF) Wistar derived albino rats (A1pk :AP strain) rats per sex weighing 243-353g (males) or 180-220g (females) were given a single oral dose of the test sample containing Substance H109360 (50% (w/v) aqueous solution (approx. 45% ethoxyamine and approx. 5% ethanol by gavage at nominal doses of 100, 250 and 500 mg/kg bw. 10 ml/kg bw was administered per dose. The animals were then observed for a period of 14 days. The median lethal dose (LD 50) of the test sample based on observed mortality was calculated to be 354 mg/kg bw for both sexes (males: 95% confidence limits 83.5, 2686; and for the females: approx. confidence limits 250, 500). The acute oral median lethal dose (LD50) of the substance H109360 was calculated to be 177 mg/kg bw for both sexes. No mortality occurred at 100 mg/kg/bw. 1/10 animal died at 250 mg/kg bw and 9/10 animals died at 500 mg/kg bw. No symptoms were exhibited by the animals dosed with 100 mg/kg bw. In the intermediate and high dose groups, the most common signs observed were; decreased activity, tonic convulsions, cyanosis, piloerection, upward curvature of the spine, reduced righting reflex, decreased breathing rate and increased breathing depth. The signs were consistent with the test sample acting either as a CNS depressant at the CNS respiratory centre and/or that the compound may induce methemoglobinemia. The effects were short-lived. Most of the animals showed findings on day 1 persisting only in one animal up to day 4. No test sample-related effect on body weight, body weight gain were observed. No macroscopic abnormalities were detected at necropsy (Central Toxicology Laboratories, 1987).

Acute Inhalation Toxicity:

In a 4-hour acute inhalation toxicity study, groups of 8 weeks Alpk:AP rats (Wistar-derived) (5/sex/group) - males weighing 231-272 g and females weighing 198-222 g - were exposed whole-bodily to aerosols of 50 % (w/v) Substance H109360 (approx. 46.4% ethoxyamine and approx. 5% ethanol)) for a duration of 4 hours. GC- FID analytically determined aerosol concentrations indicated that the animals were exposed to 0, 52, 220, 347 and 517 ppm (0, 0.13, 0.56, 0.89 and 1.32 mg/l)) of Substance H109360. Animals were then observed for a period of 14 days. The median lethal concentration (LD 50) was calculated based on observed mortality using the Spearman-Karber method. No mortality occurred at the lowest two doses while 5/10 animals died at 347 ppm (all on day 1) and 10/10 animals died at 517 ppm (all on day 1). The LD 50 was 347 ppm (0.89 mg/l ≈ 890 mg/m3). Clinical signs of toxicity included hunched posture and piloerection, reduced refelxes, tonic convulsions occuring during and immediately after exposure. Up until day 14, only mild non-specific responses; hunched posture, piloerection together with slight respiratory irritation (abnormal respiratory noise) were evident in the survivors dosed with 52 and 220 ppm. These findings were not dose-related and all surviving animals were normal by day 5. Ophthalmoscopic examinations revealed unilateral retinal hemorrhage (1 animal; 220 ppm), corneal opacity (1 animal in each of the control, 50 and 220 ppm groups), slight corneal scarring/corneal erosion (2 animals; 347 ppm) which lasted till day 14 in the survivors. Body weight loss was experienced by animals of the 220 and 347 ppm dose groups on day 2, but thereafter their day-to-day body weight gain was similar to the control group. Gross pathology examinations of the survivors did not show any treatment-related findings. Animals that died or were killed in extremis had pale/dark patches on the lungs and/or dark livers. Some had froth in the trachea. Statistically significant reductions of the absolute and relative (to body weights) liver weights (52 ppm; males only) and statistically significant increases in relative (to body weights) heart weights (52 ppm and 350 ppm; males only) were noticed at necropsy. These findings however are considered as not being biologically/toxicologically relevant as their occurrence was not aligned in a dose dependent fashion. Moreover, only one sex was affected and the organ weight changes lacked assiociative correlations with clinical or gross pathological findings (Central Toxicology Laboratories, 1987).

Acute Dermal Toxicity:

In an acute dermal toxicity study, 50% (w/v) Substance H109360 (approx. 46.4% ethoxyamine and approx. 5% ethanol)) was occlusively applied to the shaved back of Alderly Park SPF albino rats (2 rats/ dose) at dose levels of 0.05; 0.4; 2 ml/kg bw. This corresponds to 44.1; 353.1; 1765.4 mg/kg bw (density 0.8827 g/ml). Normalised to the percentage (50%) of Substance H109360, this corresponds to 22.05, 176.6 and 882.7 mg Substance H109360 /kg bw. Animals were then observed for 14 days. Deaths occurred at the highest dose group only. All 4 animals subjected to treatment with 882.7 mg/kg bw perished within 24 hour post termination of treatment. LD 50 was determined to lie between 176.6 - 882.7 mg/kg bw. Clinical signs observed at the dose levels of 22.05 or 176.6 mg/kg bw included; tip-toe gait, stains around the nose, chromodacryorrhea, signs of urinary incontinence and upward curvature of the spine. These findings were reversible with 72 hours after termination of treatment. The only sign of skin irritation observed was small scattered scabs. Necropsy of survivals or dead animals revealed no gross pathological findings (Central Toxicology Laboratories, 1986).

Justification for classification or non-classification

Ethoxyamine is listed in Annex I of directive 67/548/EEC and carries the classification of "R23/24/25" with the label "Toxic" This classfication and labelling will be maintained.

According to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the criteria for classification as Cat 3 for the inhalative (H331), dermal (H311) and oral (H301) routes are met.