Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
February 24, 1987
Deviations:
yes
Remarks:
dose volume of 20 ml/ bw
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Remarks:
albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
-Source: Charles River Wiga, Sulzfeld, West-Germany
-Age at start of treatment: approx. 7 weeks
-Body weight at start of treatment: males 230-260 g, females: 162-185 g
-Identification: earmark
-Acclimation period: at least 5 days under laboratory conditions
-Housing: groups of five per sex in polycarbonate cages containing purified sawdust as bedding material (Woody Clean supplied by Broekman Institute, Someren, The Netherlands).
-Diet: standard pelleted laboratory animal diet (RMH-B from Hope Farms, Woerden, The Netherlands), ad libitum
-Water: tap-water, ad libitum

ENVIRONMENTAL CONDITIONS
-Temperature: 21 ± 3 °C
-Humidity: 30-70 %
-Air changes: 7.5-15 per hr with air-conditioned
-Photoperiod: 12 hrs artificial fluorescent light / 12 hrs dark per day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
prepared by reverse osmosis
Details on oral exposure:
TREATMENT
-Fasting: feed was withheld overnight prior to dosing until approximately 3-4 hours after administration of the test substance.
-Frequency: once, on day 1
-Dose volume: 20 ml/kg bw.
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
-5 males at 5000 mg/kg
-5 females at 5000 mg/kg
Control animals:
no
Details on study design:
TEST SUBSTANCE PREPARATION
The formulations were prepared immediately prior to dosing. The test substance was weighed into a glass flask on an analytical balance and the vehicle (w/w) was added. Homogeneity was obtained by a homogeniser.

OBSERVATIONS
-Mortality / Viability: at periodic intervals on the day of dosing (day 1) and twice daily thereafter for at least 14 days
-Body Weights: test days 1 (pre-administration), 8 and 15
-Symptoms: at periodic intervals on the day 1, once daily thereafter. All signs of reaction to treatment were recorded with particular attention paid to changes in the skin, fur, eyes and mucous membranes, as well as to behaviour pattern, tremors, convulsion, salivations, diarrhoea, lethargy, sleep and coma.

NECROPSY FINDINGS
All animals were necropsied and descriptions of all macroscopic abnormalities were recorded. All animals surviving to the end of the observation period were sacrificed by carbon dioxide asphyxiation and subjected to necropsy.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Lethargy was noted among all the animals on days 1 and/or 2.
All animals appeared blue in colour (having blue discoloured skin) and all males had diarrhoea or blue discoloured diarrhoea on day 1.
No other clinical signs of toxicity or behavioural changes were seen during the study.
Body weight:
All animals showed body weight gain during the study period.
Gross pathology:
Macroscopic examination of all animals at termination revealed the stomach wall and testes of one male to be greyish in colour.
Two females were noted to have greyish coloured stomach walls and one of these females also had a greyish discolouration of the subcutis and most other organs, enlarged spleen and a black surface to the kidneys.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified according to CLP Regulation (EC 1272/2008)
Conclusions:
The acute oral LD50 of the substance in rats (both sexes) was estimated to exceed 5000 mg/kg bw.
Executive summary:

The oral acute toxicity of the substance was evaluated with a limit test to albino rat Wistar, according to the OECD Guideline 401 (1987). Two groups, each of 5 males and 5 females, were treated with a 5000 mg/kg bw single dose of the substance suspended in an aqueous solution and administered by oral gavage. Symptoms and mortality after administration were recorded during the observation period of 14 days. Thereafter all animals were submitted to necropsy and macroscopic examination. No mortality occurred during the study period.

The oral LD50 value of the substance in rats was estimated to exceed 5000 mg/kg bw.