2-ethylhexanoyl chloride

Endpoint summary

Description of key information

2-Ethylhexanoyl chloride is very toxic after inhalation, of moderate toxicity after swallowing and of low toxicyty after dermal contact.
- LD50 (oral; rat): 1410 mg/kg-bw.
- LD50 (demal; rabbit): >2010 mg/kg.
- LC50 (inhal.; rat): 1.26 mg/L/1h.

Additional information

oral
Sprague-Dawley rats (5/sex/dose) were exposed to 2-ethylhexanoyl chloride (EhCl) via gavage at doses of 1000, 1500 or 2000 mg/kg-bw (males) or 1000, 1250, or 1500 mg/kg-bw (females) and observed for 14 days (Stillmeadow, 1986). The number of deaths (and time of death) in the 1000, 1250 (females only), 1500, and 2000 (males only) mg/kg groups were as follows: at 1000, 1 female and 1 male (the page containing time of death was missing), at 1250 (females only), 1 female (Day 1); at 1500 mg/kg, 1 male (Day 1) and 4 females (from Days 1-3), and at 2000 (males only), all 5 males (from 6 hours to Day 2). Toxicological effects included decreased activity, ataxia, bradypnea, chromodacryorrhea, constricted pupils, diarrhea, dilated pupils, exophthalmos, gasping, lacrimation, nasal discharge, piloerection, polyuria, ptosis, respiratory gurgle, salivation and/or swollen tongue. At 1250 mg/kg-bw, one female had a stomach wall that was thickened and adhered to the liver. At 1500 mg/kg, three of 4 males and one female had a thickened fundus wall which adhered to the rib cage, diaphragm, spleen and adjacent lobes of the liver. Necropsy findings observed in animals that died included signs of GI tract distended with gas, discolouration of the contents of the GI tract, serosal blood vessels pronounced along the GI tract, discolouration of the stomach mucosa, thick stomach wall, stomach adhered to other tissues, oedematous lungs, discolouration of the pancreas, liver and adrenal glands, discoloration of the contents of the urinary bladder and/or testes drawn into abdominal cavity. The LD50is 1410 mg/kg-bw.

Similar results (LD50 = 1900 mg/kg) were found in another acute oral toxicity study equivalent to OECD 401but non-GLP (BASF 1968).

Toxicity of 2-ethylhexanoylchloride is lower when applied in olive oil. In two independent studies equivalent to OECD 401 an oral LD50 value of 2400-2500 mg/kg was found (BASF, 1980; BASF 1980).

dermal
In a study similar to OECD TG 402, New Zealand white rabbits (5/sex) were exposed to EhCl by the dermal route, under a semi-occlusive cover, to 2010 mg/kg bw for 24 hours (Stillmeadow, 1987). Animals were observed for mortality and signs of toxicity for 14 days post exposure. No animals died during the study. Toxicological effects included decreased activity, ataxia, decreased defecation and urination, haemorrhaging (at exposure area), and small feces. The maximum dermal irritation score was 6.8 (Days 2, 3 and 14). This corresponds to a rating of "severe irritant". Erythema and edema averaged 2.8 (well-defined to moderate) and 4.0 (severe) on Day 14, respectively. Since necrosis and ulceration occurred in all animals, the test material was given a descriptive rating of corrosive. The dermal LD50 value is greater than 2010 mg/kg bw.

inhalation
Sprague-Dawley rats (5/sex/concentration) were exposed to EhCl as an aerosol for one hour at 0.834, 1.16, 1.23 (females only) or 1.47 mg/L and observed for 14 days (Stillmeadow, 1986). The test material was generated as an aerosol. However, the atmosphere the animals were exposed to may have been vapor indicated by the volatility of the material. Particle sizing was not attempted. The number of deaths (and time of death) was as follows: no deaths at 0.834 mg/L; at 1.16 mg/L: 3/5 males (2 hr to Day 1), 0/5 females; at 1.23 mg/L: 5/5 females (from 2 hr to Day 1); and at 1.47 mg/L all animals died (from 2 hr to Day 1). Treatment-related effects were weight gain, decreased activity, constricted and/or dilated pupils, emaciation, bleeding from the nose, gasping, lacrimation, nasal discharge, piloerection, polyuria, ptosis, respiratory gurgle and/or salivation. Discolouration of the lungs and lung oedema were observed at necropsy in 9/10 surviving animals exposed to 0.834 mg/L. Gross necropsy findings in animals that died before and at study termination included emaciation, lacrimation, nasal discharge, polyuria, salivation, discoloration of lungs and contents of the GI tract, oedema in the lungs and/or GI tract distended with gas. The 1-hr LC50was 1.26 mg/L (combined sexes). According to GHS regulation Annex I, 3.1.2.1.b), extrapolation to 4h exposure for vapours is calculated with factor 2, resulting in an LC50 = 0.63 mg/L (4h). EhCl is regarded as vapour due to saturation concentration of 6.37 mg/L; 0.0412 * MW (162.7 g/mol) * 0.95 hPa (Vapour pressure).

A low LC50 is confirmed by another study.The 1-hr LC50was < 2.26 mg/L (BASF, 1979). Only one concentration was used, because study was designed to check for very toxic by inhalation.

Justification for classification or non-classification

According to the study results the substance is classified as toxic by inhalation (acute inhal. cat 2, H330) and harmful after swallowing (acute oral cat.4, H302). No classification suggested for acute dermal toxicity as criteria of regulations 1272/2008/EC are not met.