Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 Dec 2009 - 09 Feb 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
adopted Oct 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom, UK
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
other: Wistar (HsdRccHan:WIST)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Bicester, UK
- Age at study initiation: 8 - 12 weeks old
- Weight at study initiation: 156 - 205 g
- Fasting period before study: overnight until 3 - 4 hours after dosing
- Housing: animals were individually housed in suspended solid-floor polypropylene cages furnished with woodflakes and with enviromental enrichment items
- Diet: 2014 Teklad Global Rodent diet (Harlan Teklad, Bicester, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 17.5, 55 and 200 mg/mL
- Justification for choice of vehicle: arachis oil BP was used as the test substance did not dissolve in water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): the test material was formulated within 2 hours of administration. No analysis was conducted to determine the homogeneity, concentration or stability of the formulation.
Doses:
175, 550 and 2000 mg/kg bw
No. of animals per sex per dose:
5 females per dose group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for mortality and clinical signs 0.5, 1, 2 and 4 hours after dosing, and thereafter once daily for the rest of the observation period; the body weight was recorded on Day 0 (prior to dosing), 7 and 14
- Necropsy of survivors performed: yes
-Other: No information was available regarding the toxicity of the test substance. Therefore, the default values for LD50 and sigma were entered into AOT425 Statistical Program. The program gave a recommended dose progression of 2000, 550, 175, 55, 17.5, 5.5 and 1.75 mg/kg bw. The first animal was dosed with 175 mg/kg bw, the second with 550 mg/kg bw and animal 3 - 5 were dosed with 2000 mg/kg bw. The animals were treated sequentially, with at least 48 hours between each one to confirm the outcome of the previously dosed animal.
Statistics:
The mortality data was used by the statistical program to calculate an oral LD50 (the maximum likelihood method).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Hunched posture was observed from 2 hours after dosing on the day of dosing only in 2/3 rats administered 2000 mg/kg bw. No other clinical signs were observed during the 14-day observation period.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy did not reveal substance-related findings.

Any other information on results incl. tables

Table 1. Mortality and clinical signs

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Females

175

0/0/1

---

---

0

550

0/0/1

--

--

0

2000

0/2/3

2 h – Day 1

--

0

LD50 = 2000 mg/kg bw

* first number = number of dead animals

 second number = number of animals with clinical signs

 third number = number of animals used

 

Applicant's summary and conclusion

Interpretation of results:
other: not classified