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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:
16 Sep - 14 Oct 2004 (experimental period)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
472-110-0
EC Name:
-
Cas Number:
71868-15-0
Molecular formula:
C20H22O5
IUPAC Name:
2-hydroxy-1-[4-[4-(2-hydroxy-2-methylpropanoyl)phenoxy]phenyl]-2-methylpropan-1-one
Test material form:
solid: particulate/powder
Details on test material:
- Appearance: white powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratoires, L'Arbresle Cedex, France.
- Females nulliparous and non-pregnant: yes .
- Age at study initiation: 8-12 weeks at the time of administration.
- Weight at study initiation: Within ± 20% of the mean weight of any previously dosed animals.
- Fasting period before study: yes, deprived of food since the previous day.
- Housing: Daily observations were performed at the time of delivery of the animals and during the period of acclimatization. Animals were housed in cages of standard dimensions with sawdust bedding (or equivalent). Cages were cleaned at least once per week. The animals were placed in an air-conditioned (19-23°C) animal house kept at relative humidity between 45% and 65% in which non-recycled filtered air was changed approximately 10 times per hour. The artificial day/night cycle involved 12 hours light and 12 hours darkness with light on at 7.30 a.m.
- Diet (e.g. ad libitum): RM1 (E)-SQC SDS/DIETEX feed (quality controlled/radiation sterilised) was available ad libitum (except during the fasting experimental period). The criteria for acceptable levels of contami­nants in the feed supply were within the limits of the analytical specifications established by the diet manufacturer.
- Water (e.g. ad libitum): Drinking water was available ad libitum in polycarbonate feeder bottles with a stainless steel nipple. A specimen of water is obtained every 6 months and sent to a laboratory for analysis. The criteria for acceptable levels of contaminants in the water supply were within the limits of the analytical specifications.
- Acclimation period: Minimum of five days before treatment in the laboratory animal house where the experiment took place.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- Vehicle: sterile water
- dose volume applied: 10mL/kg
Doses:
2000 mg/kg bw (limit test; at request of the sponsor)
No. of animals per sex per dose:
6 females
Control animals:
no

Results and discussion

Preliminary study:
-
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no 95% CL stated
Mortality:
There were no deaths.
Clinical signs:
No clinical signs were observed from D1 to D14 during the course of the first step of the study. On D1 (about 3 hours 30 minutes post-dosing), all females presented a piloerection during the second step of the study.
No clinical signs were observed from D2 to D14 during the course of the second step of the study.
Body weight:
Individual bodyweights and bodyweight changes: see 'Attached background material'.
Mean weight gain in treated animals was normal (when compared with the range of values usually found).
Gross pathology:
No organ or tissue gross findings were seen at necropsy
Other findings:
none

Applicant's summary and conclusion

Interpretation of results:
other: EU-GHS criteria not met
Conclusions:
LD50 > 2000 mg/kg bw
Executive summary:

The potential acute toxicity of the test substance 2-hydroxy-1-[4-(4-(2-hydroxy-2-methylpropionyl)phenoxy)phenyl]-2-methylpropan-1-one was evaluated after a single dose administration by the oral (gavage) route in female rat in accordance with OECD Guideline No. 423.

At the first step, a group of three females was treated with the starting dose of 2000 mg/kg body weight, followed by an additional group of three animals of the same sex at the same dose level.

The test substance was administered orally to animals, deprived of food since the previous day, in a volume of 10 mL/kg as a white homogeneous suspension in sterile water. Animals were monitored daily for 14 days after administration of the test substance. Animals were weighed on days D1, D7, D14 and D15.

Under the experimental conditions adopted, results obtained were as follows:

- Mortality: No mortality occurred during the study.

- Main clinical signs: No clinical signs were observed from D1 to D14 during the course of the first step of the study. On D1 (about 3 hours 30 minutes post-dosing), all females presented a piloerection during the second step of the study. No clinical signs were observed from D2 to D14 during the course of the second step of the study.

- Body weight: Mean weight gain in treated animals was normal when compared with the range of values usually found.

- Main necropsy finding: No organ or tissue gross findings were seen at necropsy.

Under the experimental conditions adopted, oral administration of 2-hydroxy-1-[4-(4-(2-hydroxy-2-methylpropionyl)phenoxy)phenyl]-2-methylpropan-1-one at 2000 mg/kg body weight, caused no mortality in female Sprague-Dawley rats. Under the experimental conditions adopted, the maximal non-lethal dose is higher than 2000 mg/kg body weight.