Registration Dossier

Administrative data

Description of key information

The information on toxicity of this substance leads to conclusion that in overall this substance is of low toxicity.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The information of this endpoint has been provided by ECHA as a result of an inquiry, thus the full access to data in the report is not accessible to the registrant. However the reliability is estimated to be at level 1: Study conducted in accordance with generally accepted scientific principles. Possible deficiencies do not affect the quality of relevant results.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
GLP compliance:
yes
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
Method of administration was dietary admixture.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
Dosing regime: 7days/week
No. of animals per sex per dose:
Male: 30 animals at 0 mg/kg bw/day
Male: 20 animals at 123.1 mg/kg bw/day
Male: 20 animals at 406.4 mg/kg bw/day
Male: 20 animals at 1261.3 mg/kg bw/day

Female: 30 animals at 0 mg/kg bw/day
Female: 20 animals at 135.7 mg/kg bw/day
Female: 20 animals at 478.5 mg/kg bw/day
Female: 20 animals at 1479.2 mg/kg bw/day
Control animals:
yes
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
A decreased body weight gain was noted for group 3 males (not significant) and group 4 males and females (statistically significant)
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
A very slight increase of blood urea nitrogen was noted in group 4 (not significant when compared to controls). This effect was reversible after 4 weeks without treatment.
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
Considering weakness of the reactions noted during the study, the histopathological results (to be provided by end of November 1993) should not modify the classification of the substance. Only some kidney lesions may be noted at the highest does level group.
Dose descriptor:
NOAEL
Effect level:
406.4 mg/kg bw/day (nominal)
Based on:
not specified
Sex:
male/female
Dose descriptor:
NOEL
Effect level:
123.1 mg/kg bw/day (nominal)
Based on:
not specified
Sex:
male/female
Critical effects observed:
not specified
Conclusions:
Not classified as hazardous.
Executive summary:

In the study done according to OECD Guideline 408, the animals (rats) were feeded during 90 days, 7 days a week.

The 6 groups of 20 animals each (3 groups of males and 3 groups of females) ingested different doses of the substance: Male groups intake was 123.1 mg/kg bw/day (group 2) , 406.4 mg/kg bw/day (group 3) and 1261.3 mg/kg bw/day (group 4); Female groups intake was 135.7 mg/kg bw/day (group 2) , 478.5 mg/kg bw/day (group 3), 1479.2 mg/kg bw/day (group 4) The control groups (group 1) were from 30 animals each, male and female. During the feeding period a decreased body weight gain was noted for group 3 males (not significant) and group 4 males and females (statistically significant). No notice of deaths were observed in the control group or in the testing groups. A very slight increase of blood urea nitrogen was noted in group 4 (not significant when compared to controls). This effect was reversible after 4 weeks without treatment.

According to the information available the reactions observed during the study is considered weak, and lead to the conclusion that the substance is not hzardous. At the time that this study was submitted to the authorities, the histopathological results were not available but considering this weakness of the reactions noted during the study it was not expected that they should modify the classification of the substance. Only some kidney lesions may be noted at the highest does level group.

The result of this study allowed to obtian a NOEL of 123.1 mg/kg bw/day and a NOAEL of 406.4 mg/kg bw/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
406.4 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The key study is GLP compliant and scored Klimisch 1 for reliability.

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

Mode of Action Analysis / Human Relevance Framework

Additional information

There are two available repeated dose studies for oral route. For inhalation route and dermal route there isn't any data on repeated exposure. This substance is considered of an overall low toxicity and this fact is supported by all available toxicity tests.

The study done according to EU Test Method B.7 the animals (rats) were feeded with the substance during 28 days, 7 days a week. The controls after exposure showed a few effects on the kidney but there were not considered significant because this fact was observed too in the control groups and was atributed to the rats strain.

The result of the study allowed to obtain a NOEL of 200 mg/kg bw/day and a NOAEL of 1000 mg/kg bw/day.

In the study done according to OECD Guideline 408, the animals (rats) were feeded during 90 days, 7 days a week.

During the feeding period a decreased body weight gain was noted for group 3 males (not significant) and group 4 males and females (statistically significant). No notice of deaths were observed in the control group or in the testing groups. A very slight increase of blood urea nitrogen was noted in group 4 (not significant when compared to controls). This effect was reversible after 4 weeks without treatment.

According to the information available the reactions observed during the study is considered weak, and lead to the conclusion that the substance is not hazardous. At the time that this study was submitted to the authorities, the histopathological results were not available but considering this weakness of the reactions noted during the study it was not expected that they should modify the classification of the substance. Only some kidney lesions may be noted at the highest does level group.

The result of this study allowed to obtain a NOEL of 123.1 mg/kg bw/day and a NOAEL of 406.4 mg/kg bw/day.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The repeated dose study selected is 90-days repeated dosed instead of 28-days which allows a to a better definition of long-term effects.

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The values obtained have been compared to criteria set up in the Annex I of the Regulation (section 3.9).

As a result the substance is not considered to be classified for repeated dose toxicity under Regulation (EC) No. 1272/2008.