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Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw (OECD 401; GLP; male and female rats)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-04-13 to 1994-05-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987-02-24
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 1994-03-16
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan U.K. Ltd., Blackthorn, Bicester, Oxon, U.K.
- Age at study initiation: approx. 5 to 8 weeks old
- Weight at study initiation: males: 134 - 146 g, females: 127 - 135 g
- Fasting period: overnight fast immediately before dosing and for approx. tow hours after dosing
- Housing: housed in groups up to 5 by sex in solid floor polypropylene cages furnished with woodflakes
- Diet (ad libitum; except fasting period): Rat and Mouse Expanded Diet No. 1
- Water (ad libitum; except fasting period): mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 23 °C
- Relative humidity: 46 - 56 %
- Air changes: approx. 15/hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
arachis oil
Remarks:
B. P.
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL / kg

The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

DOSAGE PREPARATION:
The test material was freshly prepared as a suspension at the appropriate concentration in arachis oil B.P. Homogeneity was assured by the use of a Silverson homogeniser.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- death and overt signs of toxicity: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- body weights: prior to dosing on day 0 as well as on days 7 and 14
- Necropsy of survivors performed: yes, gross pathological examination
Statistics:
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.
Preliminary study:
A range-finding study was conducted in rats (1 male / 1 female) at each dose level of 1000 and 2000 mg/kg. Death and overt signs of toxicity were recorded 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 5 days. Individual body weights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.
There were no deaths. Signs of systemic toxicity noted were hunched posture and decreased respiratory rate, which were observed in the females of the 1000 and 2000 mg/kg dose levels..
Based on this results, a dose level of 2000 mg/kg bw was selected for the main study.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Incidents of systemic toxicity noted were hunched posture (3/5 males), lethargy (1/5 males) and ptosis (1/5 males). The males had recovered one day after dosing.
Body weight:
All animals showed expected body weight gain during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 (male and female rats) > 2000 mg/kg bw.
According to the Regulation (EC) 1272/2008 and subsequent adaptions, the substance is not acutely toxic via the oral route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP complaint guideline study reliable for risk assessment

Additional information

Acute oral toxicity study

The substance was not observed to be acutely toxic orally to rats in a reliable study according to OECD 401. The LD50 was determined to be greater than 2000 mg/kg bw

Justification for classification or non-classification

Acute oral toxicity

The substance is not acutely toxic via the oral route based on an acute oral toxicity test (OECD 401) and does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.

Specific target organ toxicant (STOT) - single exposure: oral

Reversible or irreversible adverse health effects were not observed immediately or after exposure in an acute oral toxicity test (OECD 401). Thus, the classification criteria as specific target organ toxicant (STOT) – single exposure, oral are not met and the substance does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.