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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 May 2010 to 10 August 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary guideline study, compliant with GLP.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Deviations from maximum and minimum relative occurred. The second group was treated at too high a dose level due to a calculation error. One animal was not weighed prior to necropsy. These deviations did not affect the validity of the study.
Principles of method if other than guideline:
Not relevant
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Thioanisole
IUPAC Name:
Thioanisole
Constituent 2
Chemical structure
Reference substance name:
Methyl phenyl sulphide
EC Number:
202-878-2
EC Name:
Methyl phenyl sulphide
Cas Number:
100-68-5
Molecular formula:
C7H8S
IUPAC Name:
(methylsulfanyl)benzene
Details on test material:
- Name of test material (as cited in study report): Thioanisole
- Molecular formula (if other than submission substance): C7H8S
- Molecular weight (if other than submission substance): 124.19
- Smiles notation (if other than submission substance): Not documented
- InChl (if other than submission substance): Not documented
- Structural formula attached as image file (if other than submission substance): see Fig. Not documented
- Substance type: Not documented
- Physical state: Colourless to slightly yellowish liquid
- Analytical purity: 99% minimum
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Not documented
- Lot/batch No.: 100310
- Expiration date of the lot/batch: March 23rd 2011
- Radiochemical purity (if radiolabelling): Not documented
- Specific activity (if radiolabelling): Not documented
- Locations of the label (if radiolabelling): Not documented
- Expiration date of radiochemical substance (if radiolabelling): Not documented
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature protected from light under nitrogen
- Other: For test substance handling, use amber coloured glassware or wrap container in tin-foil.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 9 weeks old.
- Weight at study initiation: 164-225g. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours post administration of the test substance. Water was available throughout.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18cm), containing sterilized sawdust as bedding material and paper as cage enrichment.
- Diet (e.g. ad libitum): Pelleted SM R/M-Z rodent diet, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum.
- Acclimation period: At least 5 days before the start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3°C (actual range: 19.6 - 21.5°C)
- Humidity (%): 40 - 70% (actual range: 38-75%)
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 18 May 2010 to 22 June 2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not relevant as substance was undiluted

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg body weight, second group treated at 300 mg/kg bw. Both doses adjusted to take account of specific graviy of 1.053 g/mL to reach final dose volume

DOSAGE PREPARATION (if unusual): No information provided - administered as supplied

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The toxicity of the test substance was assessed by stepwise treatment of groups of three females. The 1st group was treated at a dose level of 2000mg/kg bw/day. The absence or presence of mortality of animals dosed at one step determined the next step. The onset, duration and severity of the toxic signs were taken into account for determination of the time interval between the dose groups.
Doses:
300 and 2000 mg/kg body weight
No. of animals per sex per dose:
12 females in total, 3 per group.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were made twice daily for mortality/viability and at periodic intervals on the day of dosing (day 1) and once daily until Day 15. Body weights were recorded on Days 1, 8 and 15 and at death (if dead or sacrificed after day 1).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology.
Statistics:
No statistical analysis was performed.

Results and discussion

Preliminary study:
Not relevant
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - <= 2 000 mg/kg bw
Based on:
test mat.
Remarks:
administered as supplied, adjusted for specific gravity
Remarks on result:
other: All three femalesdosed at 2000 mg/kg bw died within 24 hours. One of the six rats in the low dose group also died within 24 hours of dosing
Mortality:
All three females at 2000mg/kg bw were found dead or sacrificed in moribund condition on Day 2.
One female at 300mg/kg bw was found dead or sacrificed in moribund condition on Day 2.
Clinical signs:
other: 2000mg/kg bw: All three rats showed signs including lethargy, hunched posture, piloerection and/or ptosis on Day 1 and were dead by Day 2. 300mg/kg bw: Lethargy; abnormal, hunched and/or flat posture, uncoordinated movements, piloerection, watery disch
Gross pathology:
2000mg/kg bw: One animal showed dark red discolouration of the lungs and one showed pale discolouration of the liver.
300mg/kg bw: No macroscopic findings observed in the surviving animals. One animal sacrificed for ethical reasons showed pale discolouration and accentuated lobular pattern in the liver.
Other findings:
- Organ weights: No information provided
- Histopathology: No information provided
- Potential target organs: No information provided
- Other observations: No information provided

Any other information on results incl. tables

One groups of test animals (Females 4, 5 and 6) received a dose at too high a level due to a calculation error and as a result, the data for these animals are not reported.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the LD50 was determined to be in the range of 300 to 2000 mg/kg bw. Based on this result, the test substance should be classified as a Category 4 toxicant and have the signal word "Warning" and the risk phrase H302: Harmful if swallowed associated with it, in accordance with Regulation EC No. 1272/2008. According to Directive 67/548/EEC, the test substance should be have the risk phrase, R22: Harmful if swallowed.
Executive summary:

In a study conducted by Beerens-Heijnen (2010), the test substance was, Thioanisole, was administered to female Wistar rats by oral gavage in a single exposure to assess its ability to cause toxicity. The test was conducted according to the Acute Toxic Class Method, with doses of 300 and 2000 mg/kg bw used. Three female rats per dose group were used. All animals were subjected to daily observations, up to Day 15 of testing, and weekly determination of body weight, measured on Days 1, 8 and 15. Macroscopic examination was also performed on all animals. All three females at 2000mg/kg bw were found dead or sacrificed in moribund condition on Day 2. One female at 300mg/kg bw was found dead or sacrificed in moribund condition on Day 2. Body weight loss was noted in 2 females at 300mg/kg bw between Days 1 and 8. Body weight gain shown by the other surviving animals at this dose group was considered to be similar to that expected for normal untreated animals of the same age and strain. One animal showed dark red discolouration of the lungs and one showed pale discolouration of the liver at 2000mg/kg bw. At 300 mg/kg bw, no macroscopic findings observed in the surviving animals. One animal sacrificed for ethical reasons showed pale discolouration and accentuated lobular pattern in the liver.

Under the conditions of this study, the LD50 was determined to be in the range of 300 to 2000 mg/kg bw. Based on this result, the test substance should be classified as a Category 4 toxicant and have the signal word "Warning" and the risk phrase H302: Harmful if swallowed associated with it, in accordance with Regulation EC No. 1272/2008. According to Directive 67/548/EEC, the test substance should be have the risk phrase, R22: Harmful if swallowed.