2-ethylhexylamine

Endpoint summary

Description of key information

Inhalation exposure of 5, 25 and 125 mg/m³ 2-Ethylhexylamine for 90 days (65 exposures) caused treatment-related adverse histological changes in the nasal cavity levels I and II. Moreover, slight but significantly lower body weight and body weight gain was observed in male animals of the high concentration group (125 mg/m³). No systemic effects were observed. The No Observed Adverse Effect Concentration (NOAEC) was 25 mg/m³ for local effects under the current study conditions.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

125 mg/m³

Study duration:

subchronic

Species:

rat

Quality of whole database:

GLP and Guideline conform study

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

25 mg/m³

Study duration:

subchronic

Species:

rat

Quality of whole database:

Guideline and GLP conform study

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

Inhalation repeated dose toxicity study

To evaluate the toxicity profile of 2-Ethylhexylamine after inhalation exposure, groups of ten male and ten female Wistar rats per test group were exposed nose-only to dynamic atmosphere of 2-Ethylhexylamine for 6 hours per day on 5 consecutive days per week for 3 months (90-day study) enabling vapor atmosphere generation. The target concentrations were 5, 25 and 125 mg/m³. A concurrent control group was exposed to conditioned air. For adaptation to the experimental conditions all animals were kept in glass restraining tubes identical to those used in the main study and were exposed nose-only to fresh air on two days before start of the exposure period. To detect reversibility of the effects, recovery group animals (5 male and 5 female animals per group) were exposed to high concentration. A concurrent control group was exposed to conditioned air. The recovery period was 4 weeks.

 

Clinical observation was performed at least three times on exposure days and once a day during the other days. Body weight and food consumptions were determined for all animals. Detailed clinical observation was performed three times (prior to start, at midterm and against the end of the exposure). Ophthalmological examinations were performed from the main group animals prior to exposure and towards the end of the exposure. Functional observation battery and motor activity test were performed on study day 90. Estrus cycle was determined in all female animals from study day 69.

After the last exposure, blood was sampled from main group animals, hematology and clinical chemistry parameters were determined. The animals were then subjected to gross necropsy (including macroscopic examination of the major internal organs and collection of organ weight data). Histological examinations were performed according to respective test guidelines. In addition, sperm parameters in testis and epididymidis were also examined. 

Lower mean body weight of the male animals on several days during exposure from day 51 onward were seen in male animals of the high concentration group (125 mg/m³).Lower body weight change and lower food consumption of the male animals were observed. Minimal to moderate degeneration/ regeneration of the transitional epithelium of level I of the nasal cavity in 9/10 male and 9/10 female animals were seen. Minimal degeneration/ regeneration of the transitional epithelium of level II of the nasal cavity in 5/10 male animals were observed. No treatment-related adverse effects were found in rats exposed to 25 mg/m³ and 5 mg/m³.

 

In conclusion, inhalation exposure of 5, 25 and 125 mg/m³ 2-Ethylhexylamine for 90 days (65 exposures) caused clearly treatment-related adverse histological changes in the nasal cavity levels I and II. Moreover, slight but significantly lower body weight and body weight gain was observed in male animals of the high concentration group (125 mg/m³). No systemic effects were observed. A No Observed Adverse Effect Concentration (NOAEC) was 25 mg/m³ for local effects under the current study conditions.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified with respect to repeated dose toxicity following inhalation exposure under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.