Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary literature

Data source

Reference
Reference Type:
review article or handbook
Title:
SIDS INITIAL ASSESSMENT REPORT - Cyanoacetates
Author:
OECD
Year:
2006

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl cyanoacetate
EC Number:
203-309-0
EC Name:
Ethyl cyanoacetate
Cas Number:
105-56-6
Molecular formula:
C5H7NO2
IUPAC Name:
ethyl 2-cyanoacetate

Test animals

Species:
rat
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
90 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0; 100; 300; 1000 mg/kg bw/day
Basis:

No. of animals per sex per dose:
10

Examinations

Observations and examinations performed and frequency:
- clinical signs, eye affections, body weight food consumption, FOB
- clinical chemistry and hematological examinations were performed at the end of the treatmentand recovery periods respectively
- additional examinations: determination of estrus cycle length by vaginal smear of all surviving females 14 days prior to the completion of the treatment adn recovery periods, respectively; sperm motility and epididymal sperm counts were determined of all males at the terminal sacrifice.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
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
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
effects observed, treatment-related
Details on results:
CLINICAL SIGNS AND MORTALITY
No mortalities occured.

HAEMATOLOGY
1000 mg/kg bw: reduction of haemoglobin (female)
300 mg/kg bw: reduction of haemoglobin (female)

URINALYSIS
1000 mg/kg bw: increased urine volume

HISTOPATHOLOGY: NON-NEOPLASTIC
1000 mg/kg bw: reversible chronic peribiliary inflammation in the liver (male), reversible vacuolization in the zona fasciculata of the adrenals (males); decreased percentage of motile sperms and sperm count in the epididymides (males); these changes were not accompanied by significant reductions in testicular or epididymal weights, or any histopathological findings in these organs.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
100
Sex:
female
Dose descriptor:
NOAEL
Effect level:
300
Sex:
male

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No effects were observed on the estrus cycle of the female rats.

Sperm analysis in males revealed a statistically significant decrease in the percentage of motile sperms (ca. 18% decrease) and progressively motile sperms (ca. 20%) in the high dose group compared to concurrent controls, although the reduction was less pronounced than after the treatment period. The number of homogenization resistant, detergent resistant sperms per cauda epididymis or per gram epididymis was significantly reduced in the high dose group animals. In the recovery group animals the reduction was not accompanied by reductions in testicular or epididymal weights or any histopathological findings in testes or epididymis.

Applicant's summary and conclusion