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Description of key information

In a subacute oral (gavage) repeated dose toxicity study (28 days) in rats a NOAEL of 1000 mg/kg bw/day for males and females was observed. 
In a combined repeated gavage dose toxicity study with the reproduction/developmental toxicity screening test in rats a NOAEL of 1000 mg/kg bw/day for parental males and females was observed.
In both studies, no adverse effects were observed at the dose levels tested.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day

Additional information

In the key study, the repeated toxicity of the substance was assed in a combined repeated gavage dose toxicity study with the reproduction/developmental toxicity screening test (according to OECD guideline 422 and under GLP) in rats (Rohm and Haas, 2002)

1-(2-hydroxyethyl) imidazolidin-2-one was administered daily to rats by gavage at doses of 0, 100, 300 or 1000 mg/kg bw/day. Exposure of parental animals (12/sex/dose) began when the animals were approximately eleven weeks of age. Parental animals were mated after two weeks of exposure. Treatment continued throughout gestation, lactation, and until terminal necropsy.

Body weight, feed consumption, and clinical signs were monitored in parental animals

throughout treatment. Animals were examined weekly using Detailed Clinical Observations (DCO). During Week 5 (males) and Week 7 (females), animals were assessed using a Functional Observational Battery (FOB) and monitored for motor activity (MA). Parental animals were euthanized and necropsied after weaning of their litters. Blood samples were collected for hematology and clinical chemistry analysis from all adult rats at terminal necropsy. Selected organs were weighed, and tissues were collected for histopathologic evaluation. Histopathologic evaluation was performed on five randomly selected animals/sex in the control and high dose group, and in a female (Group 3, 300 mgkg bw/day) euthanized for humane reasons during the course of the study.

There were no treatment-related deaths or clinical signs of systemic toxicity in females during premating, females during gestation, females and pups during lactation, or in males throughout the study at any dose level. There were no treatment-related effects on body weight or feed consumption in females during the premating, gestation or lactation periods or in males throughout the study.

No treatment-related effects were seen in the Detailed Clinical Observations or Functional Observational Battery parameters. There were no treatment-related effects noted in motor activity in either sex at doses up to and including 1000 mg/kg bw/day. There were no treatment-related changes in any hematology or clinical chemistry parameters in either sex at any dose level. No treatment-related changes in organ weights were noted in either sex at any dose level. No treatment-related gross or microscopic pathological findings were observed in either sex at any dose level.

The NOAEL for parental animal toxicity was 1000 mg/kg bw/day.

In a second study, the repeated oral toxicity of the substance was assessed in a 28-day repeated-dose oral (gavage) toxicity study according to OECD guideline 407 and under GLP, using 5-week-old male and female Crj:CO (SO) rats (6 rats to a group) (Rohm and Haas, 1995). The highest dose used was 1000 mg/kg bw/day; the other doses were 200 mg/kg bw/day and 40 mg/kg bw/day.

No deaths due to the administration of the test substance were seen in this study.

No effects of the test substance administration were seen in the general conditions or food consumption during the administration period or in the hematological, blood chemistry, urinalysis, organ weight, autopsies, or histopathological tests performed after the administration period. No effects of the test substance administration were seen in the repeated-dose trial.

Based on these results, the NOEL of was inferred to be 1000 mg/kg bw/day.

Justification for classification or non-classification

Based on the available oral repeated dose toxicity studies, 1-(2-hydroxyethyl) imidazolidin-2-one does not need to be classified for repeated dose toxicity according to Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

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