2-ethylhexylamine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No valid reproductive toxicity studies for 2-ethylhexylamine are available. However, a read-across to a combined repeated dose toxicity study within the reproduction/developmental toxicity screening test according to OECD guideline 422 with octylamine hydrochloride was performed (ACC, Oxea Group). The NOAEL for reproductive and developmental toxicity was 100 mg/kg bw/day.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Guideline conform study performed under GLP conditions.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

The structural analogue substance, Octylamine-HCl, was examined for its potential for repeated toxicity, developmental and neurotoxicity in a combined OECD TG 422 study under GLP conditions. The dose levels used (0, 37.5, 75, an 100/150 mg/kg bw/day; oral gavage; 12 rats/sex/dose) were selected based on the results of two range finding studies, one in the range 100-1000 mg/kg bw/day, and one in the range 3-100 mg/kg bw/day. The high dose group was initially dosed at 150 mg/kg bw/day, but this was lowered 100 mg/kg bw/day by test day 14 because two mortalities were seen in this group. Therefore, this dose level is called “100/150 mg/kg bw/day”. It should however be mentioned that subsequent examinations revealed that these mortalities resulted from dosing errors and were not related to the test substance.

The parameters examined in parental animals (gestation length, reproductive function indices [mating index, fertility index, gestation index, implantation efficiency], and corpora lutea counts] and in the offspring (viability at birth and on post partum day 4, sex ratio, weight at birth and on post partum day 4, clinical signs) were comparable across all groups including the control group. Reproduction function indices (mating index, fertility index, number of implantation sites, duration of pregnancy, birth index, live birth index, pregnancy index, litter size, litter weight, pup weight; sex ratio, survival index, viability index) indicate absence of adverse effects. The NOAEL for reproductive and developmental toxicity was therefore 100 mg/kg bw/day under the conditions of this study. A definitive NOEL was not established for systemic toxicity in P1 males and females since reductions in body weights, weight gains, and food consumption, as compared with vehicle controls, were observed at all dose levels tested (≥ 37.5 mg/kg bw/day). There was no target organ identified.

Effects on developmental toxicity

Description of key information

Under the conditions of this prenatal developmental toxicity study, the oral administration of 2-Ethylhexylamine to pregnant Wistar rats from implantation to one day prior to the expected day of parturition (GD 6-19) at doses as high as 75 mg/kg bw/d provided no evidence of maternal or developmental toxicity.

In conclusion, the no observed adverse effect level (NOAEL) for maternal and prenatal developmental toxicity is 75 mg/kg bw/d.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Guideline conform study performed under test conditions.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

The test item was tested for its prenatal developmental toxicity in Wistar rats. The test substance was administered as an aqueous suspension to groups of 25 time-mated female Wistar rats by gavage at doses of 8, 25 and 75 mg/kg body weight/day (mg/kg bw/d) on gestation days (GD) 6 through 19. One control group, consisting of 25 females, was dosed with the vehicle (0.5% Carboxymethylcellulose suspension in drinking water (0.5% CMC)) in parallel.

A standard dose volume of 10 mL/kg body weight was used for each test group.

 

At terminal sacrifice on GD 20, 25 females per group had implantation sites.

 

Generally, clinical observations including food consumption and body weight gain revealed no toxicologically relevant difference between the animals receiving 8, 25 or 75 mg/kg bw/d of the test item and controls.

Most of the females (21 out of 25) of the high-dose group (75 mg/kg bw/d) showed transient salivation during the treatment period. Salivation occurred in the respective animals only within the 2-hour examination interval (i.e. < 2h after treatment). It is considered to be treatment-related, most likely as a local irritation of the upper digestive tract or as a result of the bad taste of the test substance/vehicle preparation. It is not considered to be a sign of systemic toxicity.

No differences of toxicological relevance between the control and the treated groups (8, 25 or 75 mg/kg bw/d) were determined for any reproductive parameters, such as conception rate, mean number of corpora lutea, mean number of implantations, as well as pre- and postimplantation loss. Similarly, no influence of the test substance on fetal weight and sex distribution of the fetuses was noted at any dose.

Overall, there was no evidence for toxicologically relevant adverse effects of the test substance on fetal morphology at any dose.

 

Under the conditions of this prenatal developmental toxicity study, the oral administration of the test item to pregnant Wistar rats from implantation to one day prior to the expected day of parturition (GD 6-19) at doses as high as 75 mg/kg bw/d provided no evidence of maternal or developmental toxicity.

In conclusion, the no observed adverse effect level (NOAEL) for maternal and prenatal developmental toxicity is 75 mg/kg bw/d.

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 reproduction/fertility toxicity and/or developmental toxicity via oral route under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.