Dihexyl ether

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Results from a developmental toxicity study and a subchronic toxicity study did not reveal any reason of concern for offspring and for parent animals with respect to developmental toxicity or fertility. Since significant scientific evidence for a lack of reprotoxic effects of the substance is drawn from these results and an additional extended one-generation study is not expected to add any further relevant knowledge on this endpoint. Due to animal welfare aspects and/or laws, an additional study is therefore not warranted.

Short description of key information:
no study is available; no effects are expected from results obtained in a 90 day study and in a developmental study

Effects on developmental toxicity

Description of key information

developmental toxicity (rat): NOAEL = 1000 mg/kg bw

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

439.9 mg/kg bw/day

Study duration:

subacute

Species:

rat

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

A developmental dietary toxicity study was performed to assess the effects of the test item dihexyl ether on the embryonic and foetal development (including the organogenesis period) of Wistar rats in their first pregnancy. Three groups of Wistar rats received Di-n-hexyl ether administered in diet, from gestation day 6 (GD 6) up to and including gestation day 20 (GD 20). Based on the results of a dose range finding, the following doses were selected: 1500, 5000 and 15000 ppm.

No test item related mortality was observed in the study. Piloerection was observed in 9 out of 24 Mid dose group animals, and 15 out of 25 High dose animals. Considering the general, transient, and mild nature of these findings, they are considered to be treatment-related changes, not sufficient to indicate a clear adverse effect. Test item related effect was observed on the body weight parameters and calculated body weight parameters in the High dose group. This was considered to be a test item related effect. No test item related effect on the body weight was observed in the test item treated Low and Mid dose groups when compared to the Control. At necropsy of the dams, no remarkable external observations related to test item treatment were recorded for any pregnant animals. No remarkable abnormalities were observed on the placentas in any group. Due to the observed body weight changes in the dams, a slight maternal toxicity at the dose level of 1210 mg/kg bw/day is indicated.

There was no test item related effect on the intrauterine mortality parameters. The mean number of viable foetuses was comparable with the control mean in all test item treated groups. There was no toxicologically significant difference in the sex distribution of fetuses between the control and treatment groups. The mean foetal weight per litter was significantly lower in the High dose group when compared to the control. Similarly, the number of foetuses with retarded body weight, and the number of affected litters were higher in this group. This body weight reduction is considered to be a secondary effect due to the body weight changes observed in the dams. The pattern of foetal weight and retarded weights seen in this study is consistent with other studies where maternal body weight was lower than controls; there was no evidence of a direct effect of test item on the foetuses. The mean foetal weight per litter values and the number of retarded foetuses (runts) in the Low and Mid dose groups were comparable with the control. There was no test item related effects on external, visceral, or skeletal development of foetuses in the study. Foetal malformations observed in the study were considered to be incidental. The malformations showed no dose dependency, and were not regarded as a test item related effect.

In conclusion, Di-n-hexyl ether, when administered daily through diet to pregnant rats from gestation days GD6 to GD20 at dose levels up to 1210 mg/kg bw/day did not induce embryotoxicity, foetotoxicity, or teratogenicity. The observed body weight changes in the dams indicates a slight maternal toxicity at the dose level of 1210 mg/kg bw/day, with consequent foetal body weight differences. There were no malformations or developmental effects attributed to the test item at any dose level.

The following no-observed-adverse-effect (NOAEL) levels were derived:

NOAELmaternal toxicity: 439 mg/kg bw/day

Based on the lower body weight indicating maternal toxicity effect in the High dose group.

NOELembryotoxicity: 1210 mg/kg bw/day

Based on the lack of any test-item related intrauterine effect in any treatment group.

NOAELfoetotoxicity: 439 mg/kg bw/day

Based on the lack of any test-item related foetotoxicity effect in any treatment group other than reduced weight secondary to maternal body weight in the High dose group.

NOELteratogenecity: 1210 mg/kg bw/day

Based on the lack of any developmental effects in any treatment group.

Justification for classification or non-classification

Based on results of the key study the substance does not need to be classified according to GHS (Regulation (EU) 1272/2008) and also does not need to be classified according to DPD (67/548/EEC).