Registration Dossier

Administrative data

Description of key information

Oral

NOAEL (male) = 500 ppm

NOAEL (female) = 2500 ppm

Inhalation: NOEL for both males and females is 0.8 mg/m3

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
93.75 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
0.8 mg/m³
Study duration:
subacute
Species:
rat
Organ:
lungs

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
8 mg/m³
Study duration:
subacute
Species:
rat

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 toxicity of the substance after a repeated exposure via the oral and inhalation route were evaluated considering data on a similar substance.

 

The toxic potential of the similar substance after a repeated exposure via the oral route was evaluated. Ten male and ten female Wistar rats were exposed to four dose levels (0 -100 -500 -2500 ppm) for 5 weeks.

Food and water intake, general behaviour and mortality were not affected by treatment. Growth was reduced only in male rats administered 2500 ppm. Up to 2500 ppm, no damage to blood or organs have been observed.

No liver effects have been observed in clinic, anatomy, pathology and histopathology studies up to 2500 ppm. No kidney effects have been observed in blood and urine analysis, and histopathological studies.

Glucose and cholesterol concentrations in plasma and sodium, potassium, calcium, inorganic phosphate and chlorine products in serum were in the normal range in all dose groups.

Pathology and anatomy analysis revealed no other damage to other organs related to the test item.

NOAEL (male) = 500 ppm; NOAEL (female) = 2500 ppm

The NOAEL is subsequently determined as 93.75 mg/kg bw/day considering the purity of the test material and the terminal body weight of male rats in the relevant dose group.

The toxic potential of the similar substance after a repeated exposure via the inhalation route was evaluated according to the OECD Guideline 412. Five male and five female Wistar rats were exposed to four dose levels (0 -0.8 -8 -80 mg/m3) for 28 days. The rats were exposed to the substance 6 hours per day, 5 days per week.

Due to the effects observed in the organ weights ( increased absolute and relative lung weights)in the 8 mg/m3 group main group the NOEL for both males and females is 0.8 mg/m3

Justification for classification or non-classification

According to the CLP Regulation (EC) No 1272/2008 substances are classified as specific target organ toxicants following repeated exposure by the use of expert judgement, on the basis of the weight of all evidence available, including the use of recommended guidance values which take into account the duration of exposure and the dose/concentration which produced the effect(s), and are placed in one of two categories, depending upon the nature and severity of the effect(s) observed:

Category 1: substances that have produced significant toxicity in humans or that, on the basis of evidence from studies in experimental animals, can be presumed to have the potential to produce significant toxicity in humans following repeated exposure. Substances are classified in Category 1 for target organ toxicity (repeat exposure) on the basis of: reliable and good quality evidence from human cases or epidemiological studies; or observations from appropriate studies in experimental animals in which significant and/or severe toxic effects, of relevance to human health, were produced at generally low exposure concentrations. Guidance dose/concentration values are provided in 3.9.2.9, to be used as part of a weight-of- evidence evaluation.

Category 2: substances that, on the basis of evidence from studies in experimental animals can be presumed to have the potential to be harmful to human health following repeated exposure. Substances are classified in category 2 for target organ toxicity (repeat 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.

To evaluate whether the substance should be classified or not for specific target organ toxicity-repeated exposure, the available data from a sub-acute study via oral route on a similar substance is used. Based on the results of the study, a NOAEL of 93.75 mg/kg bw/day is determined. Therefore the LOAEL can be extrapolated from the study and is determined to be 2500 pmm which corresponds to 448 mg/kg bw/day (considering the purity of the substance and the terinal body weight of male rats in the specific dose level)

To evaluate whether the substance should be classified or not for specific target organ toxicity-repeated exposure, the available data from a sub-acute study via inhalation route on a similar substance is used. The NOEL was identified as

0.8 mg/m3 and thererefore a LOEL of 8.0 mg/m3 can be extrapolated.

Based on the available data (for both oral and inhalation route) and according to the CLP Regulation EC No.1272/2008, the substance is not classified for specific target organ toxicity after repeated exposure.