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Description of key information

Oral (feeding) 90-d repeated dose toxicity study (equivalent to OECD408): NOAEL 7.3 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
7.3 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

The effects of repeated exposure to 2EHDPP are investigated in two studies. Both studies report hypertrophy of the liver as key finding. In addition it seems that the palatability of the test substance influences feed intake to some extent. The authors attribute the effects on body weight and water intake to the effect on food intake. However, this cannot be fully excluded. The effect on liver weight and histopathological findings cannot be relate to reduced food intake only. Therefore, based on the full BIBRA study it is not possible to derive a NOAEL as the liver effects were also seen at the lowest dose level tested. This study leads to a LOAEL of 164-174 mg/kg bw. This LOAEL is in line with the LOAEL parental coming from the one generation study where similar liver effects were reported. In the one generation study, the effects on relative liver weight were supported by histopatological examination in the high dose group only. Absence of histopathological data for the other groups makes it impossible to derive a parental NOAEL. Therefore the LOAEL parental is set at 132-144 mg/kg bw which is the lowest dose level.

For the selected key study for repeated dose toxicity only an abstract is available. This study is a 90 -day study that addresses the liver effects in more detail (NB it is a full 90 -day study). In this study effects on liver and liver enzymes are reported at a dose level of 17-20 mg/kg bw in males. For females, effects are observed only at 20.8 mg/kg bw. The NOAEL is set at 7.3-8.4 mg/kg bw based on these effects in males.

In addition, a 12 -d repeated dose toxicity is available in which 12 female rats were given 10000 mg/kg bw/day for 12 days by oral gavage. 12 male rats received 5000 mg/kg bw/day. Under the conditions of this study, treatment with Santicizer 141 only induced weight loss and some minor clinical signs. No NOAEL could be identified.

Another supporting study is available, which was a long-term repeated dose toxicity study in dogs. Two doses were tested: 0.5 ml/kg bw/day and 1 ml/kg bw/day. Dogs of the high dose group were found to have a decreased body weight over the treatment period. No other adverse effects were identified (including gross necropsy/histopathology) after chronic exposure.


Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver

Justification for classification or non-classification

Based on the available data, no conclusion can be drawn considering the classification for repeated dose toxicity.