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Description of key information

The repeated oral dose toxicity study was performed according to OECD Guideline 407 and GLP principles.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 08 - October 12, 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD guidelines and according to GLP principles
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Deviations:
yes
Remarks:
The temperature of the freezer in which the samples for the clinical biochemistry parameters were stored, exceeded the maximum temperature on a few occasions. Evaluation: Deviation was considered not to have adversely affected the study outcome.
Qualifier:
according to guideline
Guideline:
EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
Deviations:
yes
Remarks:
The temperature of the freezer in which the samples for the clinical biochemistry parameters were stored, exceeded the maximum temperature on a few occasions. Evaluation: Deviation was considered not to have adversely affected the study outcome.
Principles of method if other than guideline:
United States Environmental Protection Agency (EPA). Health Effects Test Guidelines, OPPTS 870.3050, Repeated dose 28- day oral toxicity study in rodents. Office of Prevention, Pesticides and Toxic Substances (7101), EPA 712-C-00-366, July 2000.
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: The test substance was administered undiluted.
Details on oral exposure:
Method of administration:
Oral gavage, using a plastic feeding tube.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 450 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 450 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
Clinical observations:
No mortality occurred during the study period.

There were no clinical signs of toxicity noted during the
observation period.

Hearing ability, pupillary reflex, static righting reflex
and grip strength were normal in all animals.

The variation in motor activity did not indicate a relation
with treatment.

Laboratory findings:
Haematology:

Haematological parameters of treated rats were not affected.


Clinical biochemistry:

No toxicologically relevant changes occurred in clinical
biochemistry parameters of treated rats.


Any statistically significant changes occurring in clinical
biochemistry parameters were within the range considered
normal for rats of this age and strain and/or occurred in
the absence of a dose-related response. These changes
consisted of higher creatinine and glucose levels in males
at 1000 mg/kg/day and lower sodium levels in males at 450
mg/kg/day. No toxicological relevance was ascribed to these
findings.

Effects in organs:
Necropsy did not reveal any toxicologically relevant
alterations.

Organ weights and organ to body weight ratios of treated
animals were considered to be similar to those of control
animals.

There were no microscopic findings recorded which could be
attributed to treatment with the test substance.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects at highest dose tested.
Critical effects observed:
not specified

Comments:
No toxicologically significant changes in body weights and
body weight gain were noted.

Food consumption before or after allowance for body weight
was similar between treated and control animals.

Conclusions:
A NOAEL for Reaction products of Fatty acids, C16-18 and C18-unsatd. and reaction mass of 1,3-alkanediol, 2-(hydroxymethyl)-2-[(methoxymethoxy)methyl]- and 1,3-heteromonocycle-5,5-dimethanol of >=1000 mg/kg/day was established.
Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

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

In a 28 -day oral repeated dose toxicity study, performed according to OECD/EC/EPA test guidelines, rats in groups of 5/sexe/dose were exposed to 0, 150, 450 and 1000 mg/kg bw/day of Radia 7853 via gavage. These doses were based on a 5 -day range finding study. The following parameters were evaluated: mortality, clinical signs, fob, body weight, food consumpation, haematology, biochemical parameters, macroscopy, organ weights and microscopy. No toxicologically significant changes were noted in any of the parameters investigated in this study. Therefore, a NOAEL of >=1000 mg/kg bw/day was derived.

Justification for classification or non-classification

Based on the available data, the substance does not have to be classified for repeated dose toxicity according to the CLP Regulation (EC) No 1272/2008.