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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003-12-15 to 2004-01-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 2001-12-17
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2003-06-04
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
480-070-0
EC Name:
-
Cas Number:
85-27-8
Molecular formula:
C14H14O2
IUPAC Name:
4-(1-phenylethyl)benzene-1,3-diol
Details on test material:
- Name of test material (as cited in study report): BIO 377
- Chemical name: 1,3-Benzenediol, 4-(1-phenylethyl)-
- Physical state: clear viscous to solid
- Storage condition of test material: cool, dry, dark
- Solubility: 50 % in Mygliol (nautral oil) = well soluble; 50 % in peanut oil (conditionally soluble); 20 % in peanut oil (well soluble)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS - SPF Wistar rats of the stock Shoe:WIST
- Source: DIMED Schönwalde GmbH, D-16352 Schönwalde
- Weight at study initiation: 129 g - 165 g
- Fasting period before study: rats were fasted overnight prior to dosing. After dosing diet was withheld for 4 more hours.
- Housing: the rats were kept in transparent polycarbonate cages (macrolone type III, floor area 810 cm^2) with two or three in each cage. The cages were cleaned and the bedding changed at least twice a week. Bedding was pinewood sawdust "Lignocel-Fasern" from Altromin, D-32791 Lage, Lippe.
- Diet (ad libitum): a pelleted complete rodent diet "Altromin 1314" from Altromin GmbH, D-32791 Lage, Lippe
- Water (ad libitum): domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS- the study took place ina room provided with filtered air.
- Temperature: 21 °C +/- 3 °C
- Relative humidity: 55 % +/- 15 %
- Air changes: 10 times/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: peanut oil was used as the vehicle for the preparation of the test item. For this the test item was initially liquefied by heavy warming up to approx. 80 - 90 °C and afterwards mixed with peanut oil to an applicable solution with a temperature of about 37 °C.
Doses:
2000 mg/kg bw and 300 mg/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 3 females
300 mg/kg bw: 6 females (divided in two groups of three)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: each rat was observed 30 min, 2, 4 and 6 hours after the administration and thereafter daily for a period of 14 consecutive days. Body weight (b.w.) was recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes, all rats were killed by inhalation of CO2 on day 14 and subjected to a gross necropsy examination.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Mortality:
All animals of the 2000 mg/kg bw dose level died. Death occurred by day 1.
None of the animals at the 300 mg/kg bw dose level died.
Clinical signs:
other: All animals of the 2000 mg/kg bw dose level showed a severe intoxication and died on account of the treatment. None of the animals at the 300 mg/kg bw dose level showed severe signs of toxicosis. 2000 mg/kg bw: All animals showed a hunched posture and pi
Gross pathology:
The necropsy revealed the following pathological abnormalities:
2000 mg/kg bw: the rigor mortis had already begun. Furthermore a distended gastrointestinal tract with bleeding of the stomach and intestinal mucosa as well as residues of feed in the stomach were revealed.
300 mg/kg bw: one animal showed a liquid stomach content and petechial bleeding of the stomach wall. No pathological abnormalities were observed in the remaining animals.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 in female rats was found to be below 2000 mg/kg bw and above 300 mg/kg bw (LD50 cut-off mg/kg bw: 500 mg/kg bw).
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is classified as harmful if swallowed.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is classified as Category 4.