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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-08-01 to 2008-08-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2004
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Qualifier:
according to
Guideline:
other: JMAFF, Notification No. 8147, Nov. 2000
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: young adult animals (approx. 9-12 weeks old)
- Weight at study initiation: 165 - 200 g
- Fasting period before study: max 20 h, 3- 4 hours after administration
- Housing: group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.)
- Diet: ad libitum, pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: ad libitum, tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ±3.0°C (actual range: 19.7 - 21.5°C)
- Humidity (%):30-70% (actual range: 47 - 82%)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% aq. carboxymethyl cellulose and water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1 % aqueous carboxymethyl cellulose
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw


Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 300 mg/kg bw. In a stepwise procedure additional groups of females were dosed at 300 and 2000 mg/kg bw.
- Frequency of dosage: single dosage, on day 1
- Duration of observation period following administration: 15 days
- Frequency of observations (mortaliity/viability): twice daily
- Frequency of weighing: day 1 (pre-administration), 8 and 15
- Frequency of observation (clinical signs): at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15
- Necropsy of survivors performed: yes
- Clinical signs: The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Statistics:
- No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: no mortality
Mortality:
- No mortality occurred.
Clinical signs:
- Hunched posture and/or piloerection were noted in all animals on day 1 and in the first set of animals at 300 mg/kg bw on day 2.
Body weight:
- The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
- No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of test substance in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

In an acute oral toxicity study according to OECD TG 423, groups of fasted, young adult female Wistar rats were given a single oral dose of test substance Isostearic acid, esters with methyl α-D-glucoside in 1% aq. carboxymethyl cellulose and water. The substance was administered by oral gavage at 300 mg/kg bw. In a stepwise procedure additional groups of females were dosed at 300 and 2000 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice on day 15.

Oral LD50 Females > 2000 mg/kg bw

No mortality occurred. Hunched posture and/or piloerection were noted in all animals on day 1 and in the first set of animals at 300 mg/kg bw on day 2. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

In this study Isostearic acid, esters with methyl α-D-glucoside in 1% aq. carboxymethyl cellulose and water is practically non-toxic based on LD50 in female rats.