2-(2,4-diaminophenoxy)ethanol dihydrochloride

Endpoint summary

Description of key information

The test substance 2,4-diaminophenoxyethanol dihydrochloride was administered daily by gavage to Sprague-Dawley rats at the dose level of 4, 20 or 100 mg/kg bw/day for 13 weeks. At 4 and 20 mg/kg bw/day the test item was well tolerated. A 100 mg/kg bw/day, ptyalism was observed in both males and females and lower body weight gains were noted for males. Presence of urinary bilirubin, nitrites, glucose and coloured urine in both males and females was observed at the end of the treatment period. After a 4 week treatment-free period, all the above-mentioned changes were no longer noted. Deposition of brownish pigment in the thyroids and an augmented degree of spleen hemosiderosis were also observed for most animals given 100 mg/kg bw/day on completion of treatment and treatment-free periods. Under the experimental conditions of the study, the NOEL is established to be 20 mg/kg bw/day.  

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

20 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

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

The objective of this study was to evaluate the potential toxicity of the test item 2,4 -diaminophenoxyethanol dihydrochloride following daily oral administration (gavage) to rats for 13 weeks. On completion of the treatment period, designated animals were held for a 4 -week treatment free period in order to evaluate the reversibility of any findings.

A total of 140 Sprague-Dawley rats (70 males/70 females) were allocated to three treatment groups and one control group. Each group was composed of 10 males and 10 females. Recover animals (6 males and six females) were added to the control and high dose groups for a 4 -week treatment free period. The test item was administered daily by gavage as a solution in the vehicle (purified water) at the dose level of 4, 20 or 100 mg/kg bw/day for 13 weeks. Control animals received the vehicle alone under the same experimental conditions. The animals were checked daily for mortality and clinical signs. detailed clinical observations were carried out weekly and a functional observation battery was conducted at the end of the treatment period. Body weight and food consumption were recorded once a week throughout the study. Ophthalmological examinations were performed before and at the end of the treatment period. Haematological and blood biochemical investigations and urinalysis were performed at the end of the treatment period. On completion of the treatment or treatment-free periods, the animals were sacrificed and submitted to a full macroscopic examination. Designated organs were weighed and specified tissues preserved. A microscopic examination was performed on selected tissues from animals in the control and high dose groups and on macroscopic lesions from all animals killed on completion of the treatment period. The thyroids and spleen were submitted to microscopic examination for all low and intermediate dose animals at the end of the dosing period as well as for high dose animals at the end of the treatment free period.

No unscheduled deaths occurred during the study. Ptyalism, noted among almost all the animals given 100 mg/kg bw/day, was not considered as an adverse effect as it is commonly encountered when a test item is administered by gavage. There were no perturbations of the autonomic or physiological functions in any treated group. A slightly lower mean body weight gain was noted in males given 100 mg/kg bw/day during the whole dosing period and was most of the time statistically significant. Mean male body weight returned to control values during the treatment free period. No treatment related effect was noted on female body weight gain. No treatment related effects were noted on food consumption for either males or females and there were no ophthalmological treatment related findings at the end of the treatment period. No treatment related changes were noted for any haematological or blood biochemical parameters. At the end of the treatment period, the following treatment related differences from controls were observed in urinary parameters at 100 mg/kg bw/day : presence of low to high bilirubin levels in all males and in 7/10 females, traces of nitrite in 8/10 males and 6/10 females, traces of glucose in 6/10 males and 6/10 females, marked colouration of urine (from yellow to yellow-brown) in both males and females. All these changes were attributed to treatment and were no longer present on completion of the treatment free period. No treatment related effects on organ weights were noted. Brownish colouration of the thyroids was observed in all males and females given 100 mg/kg bw/day and was associated at microscopic examination with brownish pigment deposits in the thyroids. Spleen hemosiderosis was also observed for all animals given 100 mg/kg bw/day. Both these microscopic changes on thyroids and spleen were still observed at the end of the recovery period.

The test substance 2,4-diaminophenoxyethanol dihydrochloride was administered daily by gavage to Sprague-Dawley rats at the dose level of 4, 20 or 100 mg/kg bw/day for 13 weeks. At 4 and 20 mg/kg bw/day the test item was well tolerated. A 100 mg/kg bw/day, ptyalism was observed in both males and females and lower body weight gains were noted for males. Presence of urinary bilirubin, nitrites, glucose and coloured urine in both males and females was observed at the end of the treatment period. After a 4 week treatment-free period, all the above-mentioned changes were no longer noted. Deposition of brownish pigment in the thyroids and an augmented degree of spleen hemosiderosis were also observed for most animals given 100 mg/kg bw/day on completion of treatment and treatment-free periods. Under the experimental conditions of the study, the NOEL is established to be 20 mg/kg bw/day.