2-ethylhexylamine

Endpoint summary

Description of key information

Acute Toxicity:

- oral: LD50 = 316 mg/kg bw (male/female rat) equivalent to OECD 401;

- inhalation: LC50 < 1.548 mg/L air (male/female rat) according to OECD 403;

- dermal: study using 'rabbit' as test species - disregarded

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

316 mg/kg bw

Quality of whole database:

Well documented study which is similar to Guideline and sufficient for assessment.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

1 548 mg/m³

Quality of whole database:

Guideline study with acceptable restrictions performed under GLP conditions.

Acute toxicity: via dermal route

Endpoint conclusion

Quality of whole database:

Only data from secondary sources are available.

Additional information

Oral:

In a study which was in large parts equivalent to methods described in OECD guideline 401, the LD50 for oral acute toxicity in rats was calculated as ca. 316 mg/kg body weight. Doses of 158, 316, 632 and 1264 mg/kg bw of an aqueous solution were applied by gavage followed by a post dose observation period of 7 days. Main clinical signs observed were strongly elevated respiration, anancasm to chew, salivation, strong twitches, dyspnoea, salivation, salaam convulsions, tremor, extension convulsions. At necropsy, kidney obstructions, red-pink coloring of the stomach were noted (BASF AG, 1968; reliability score: 2). Another study is reporting an LD50 of 446 mg/kg bodyweight with occurring lung hemorrhage and severe congestion of visceral organs (Smyth 1949; reliability score: 2).

 

Inhalation:

Acute inhalation toxicity was analyzed according to OECD guideline 403 but with only 1 concentration tested (Hoechst AG 1988, reliability score: 2). At a concentration of 1.548 mg/L air all rats died within 40 - 177 minutes after the start of exposure. Exposed animals showed impairment of respiration, salivation, nasal discharge and periodically arising tonic spasms. At necropsy, macroscopic dark red spots were found on the lungs, and when the lungs were opened small quantities of white foam were detected.

 

Additional data were available from an inhalation risk test (IRT) which meets generally accepted scientific principles (BASF AG, 1968; reliability score 2). The inhalation of a saturated vapor-air mixture for 30 min caused mortality. Clinical signs were escape attempts, mucosal irritation of the upper tract, elevated respiration, blood crusted snouts and eyes, tremor, unsteady gait, abdominal-lateral position, chemical burns of the corneal. At necropsy, chronic bronchitis, questionable coloring of blood and lungs were observed (BASF AG, 1968; reliability score: 2). In a further IRT with limited data provided, substantially saturated vapors produced at room temperature were lethal to rats in 2 hours but 6 of 6 survived a 1-hour exposure (Smyth 1949; reliability score: 2).

 

Dermal:

An acute dermal toxicity study does not need to be conducted as the test item is considered to be highly corrosive to skin (Skin Corrosion Category 1A, H314).

From a secondary source publication a dermal LD50 of 600 mg/kg bw was reported (RTECS entry 1978; reliability score: 4). A more recent specification in RTECS says 600 µL/kg bw = 474 mg/kg bw. However, this study was conducted using 'rabbit' as test species. The rabbit is the preferable laboratory animal for testing dermal corrosivity (highly sensitive in terms of corrosive effects). But the highly sensitive rabbit is not the appropriate species for acute dermal toxicity testing using corrosive substances. In the RTECS entry no details on methodology, study design, exposure duration etc. are given. In the dermal corrosivity study necrosis was observed within 30 min post exposure (exposure duration 3 min). Thus, it is unclear if death of rabbits was due to systemic toxicity of the test substance following dermal administration, or due to a stress response to the severe local effects (destroyed skin tissue as corrosion response), and in addition, if damage of the skin facilitated increased systemic absorption/exposure to the substance. Further, 2-Ethylhexylamine is classified as acute toxic via the oral route category 4. A retrospective analysis of data from acute oral and dermal toxicity testing, performed on pesticide active substances and new chemical entities submitted for the Notification of New Substances Regulations (a total of 240 substances), has demonstrated that there is a relationship between dermal acute toxicity and oral acute toxicity, and there are no significant numbers of compounds that are classified as a potential hazard only via the dermal route (Creton et al. 2010: Acute toxicity testing of chemicals - Opportunities to avoid redundant testing and use alternative approaches. Critical Reviews in Toxicology; 40(1), 50-83).

In conclusion, because the existing piece of information is not assignable and the available data a derived from an inappropriate test species 2-Ethylhexylamine will not be classified for acute dermal toxicity.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The substance is considered to be classified as Cat. 4 for acute oral toxicity (H302) and as Cat. 2 (H330) for acute inhalative toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.