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Description of key information

NOAEL (90d, OECD 408) rat, oral = 300 mg/kg bw /day

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subchronic
Species:
rat
System:
gastrointestinal tract
Organ:
kidney

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 study OECD 408 was performed by adding in the examination, the evaluation of some reproductive parameters , such as:

-weight of male and female gonads and accessory sex organs

-stage of oestrous cycle and cycle duration for females

-histopathological examination of uterus and cervix

-histopathological examination, with special emphasis to stages of spermatogenesis, in males

-histopathology of interstitial testicular structure

No macro nor microscopic treatment related effects were observed in the reproductive organs, no change in the weights compared to the values of the vehicle control was recorded. Moreover the oestrus cycle was not affected by the tretment and the spermatogenesis was qualitatively assessed not affected

Justification for classification or non-classification

Regulation EC 1272/2008 regarding classification criteria for substances (Annex I, table 3.9.1) states that "Substances are classified in category 2 for target organ toxicity (repeated exposure) on the basis of observations from appropriate studies in experimental animals in which significant toxic effects, of relevance to human health, were produced at generally moderate exposure concentrations".

Moreover, at paragraph 3.9.2.9.2 it reads:" In order to help reach a decision about whether a substance shall be classified or not, and to what degree it shall be classified, dose/concentration ‘guidance values’ are provided for consideration of the dose/concentration which has been shown to produce significant health effects.

Repeated-dose studies conducted in experimental animals are designed to produce toxicity at the highest dose used in order to optimise the test objective and so most studies will reveal some toxic effect at least at this highest dose. What is therefore to be decided is not only what effects have been produced, but also at what dose/concentration they were produced and how relevant is that for humans".

 

These "guidance values" are provided in table 3.9.3, and refers to effects observed in a standard 90 day repeated dose study in which classification is not applicable when "significant toxic effects" are detected over a dose of 100 mg/kg/day.

Based on the reported NOAEL of 300 mg/kg bw /day the substance DiethyleneGlycolde Diformate is not classified for repeated dose toxicity under Regulation 1272/2008