Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05.11.2009 to 05.01.2010
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 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Test material form:
solid
Specific details on test material used for the study:
4-(Methacryloyloxy) bezophenone 97.26 %
Benzophenone acetate: 1.95 %

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Healthy rats, WISTAR rats Crl: WI(Han) (Full-Barrier)
Sex:
female
Details on test animals and environmental conditions:
Test System
Species/strain: Healthy rats, WIST AR rats Crl: WI(Han) (Full-Barrier)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: female, non-pregnant, nulliparous
Number of animals: 3 per step
Age at the beginning of the study: 8 - 9 weeks old
Body weight at the beginning of the study:
Animals no. 1- 3, step 1: 158-164 g;
Animals no. 4- 6, step 2: 163 - 170 g;

The animals were derived from a controlled full barrier maintained breeding system (SPF). According to Art. 9.2, No.7 of the German Act on Animal Welfare the animals were bred for experimental purposes.

Housing and Feeding Conditions
Full-barrier in an air-conditioned room Temperature: 22 ± 3 °C
Relative humidity: 55 ± 10%
Artificial light, sequence being 12 hours light, 12 hours dark
Air change: 10 x I hour
Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1452)
Free access to tap water, sulphur acidified to a pH value of approx. 2.8 ( drinking water, municipal residue control, microbiological control at regular intervals)
The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 06.06.09)
Certificates of food, water and bedding are filed at BSL BIOSERVICE Adequate acclimatisation period ( at least five days, for details see Schedule)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Remarks:
(Sigma, lot no. 038K0009, expiry date: 01.04.2010)
Details on oral exposure:
The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 10 mL/kg body weight.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
3 per step
Control animals:
no
Details on study design:
The starting dose was selected to be 2000 mg/kg body weight. No compound related mortality was recorded for any animal of step I or 2. Based on these results and according to the acute toxic class method regime no further testing was
required.
Weight Assessment:
All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.
Clinical Examination:
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded.
Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Pathology:
At the end of the observation period the animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally at a dosage of approx. 8 mL/kg bw.
All animals were subjected to gross necropsy. All gross pathological changes were recorded.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Remarks:
LD50 cut off
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Clinical signs:
None of the animals showed weight loss during the observation period
No special gross pathological changes were recorded for any animal
The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were apathy, prone position, reduced spontaneous activity, wasp waist, hypertonia, ataxia, half eyelid closure, kyphosis, prostation.
Body weight:
Animals no. 1-3, step 1: 158-164 g;
Animals no. 4-6, step 2: 163- 170 g;
Gross pathology:
No special gross pathological changes were recorded for any animal
Other findings:
At necropsy, no macroscopical findings were observed in any animal of any step.

Any other information on results incl. tables

LD50 cut off

Dose (unit)

Number of animals

investigated

Number of intercurrent

deaths

LD50cutoff

2000mg/kg

bodyweight

6

0

5000mg/kg

body weight

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, single oral application of the test item 4-(Methacryloyloxy)benzophenone to rats at a dose of 2000 mg/kg body weight was associated with slight to severe signs of toxicity but no mortality.
The median lethal dose of 4-(Methacryloyloxy)benzophenone after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut off (rat): 5000 mg/kg body weight.

In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the test item 4-(Methacryloyloxy)benzophenone has no obligatory labelling requirement for toxicity.

According to Annex I of Regulation (EC) 1272/2008 the test item 4-(Methacryloyloxy)benzophenone is unclassified

According to OECD-GHS (Globally Harmonized Classification System) the test item 4-(Methacryloyloxy)benzophenone requires no obligatory labelling for toxicity
Executive summary:

4-(Methacryloyloxy)benzophenone was tested in an acute oral toxicity study ( (Acute Toxic Class Method) acc. OECD 423. Two groups, each of three female WIST AR Cr!: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was suspended in a vehicle ( cottonseed oil) at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.

All animals survived until the end of the study. The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were apathy, prone position, reduced spontaneous activity, wasp

waist, hypertonia, ataxia, half eyelid closure, kyphosis, prostation. Throughout the 14-day observation period, the weight gain of the animals was within the expected range. At necropsy, no macroscopical findings were observed in any animal of any step.

Under the conditions of the present study, single oral application of the test item 4-(Methacryloyloxy)benzophenone to rats at a dose of 2000 mg/kg body weight was associated with slight to severe signs of toxicity but no mortality.

The median lethal dose of 4-(Methacryloyloxy)benzophenone after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut off (rat): 5000 mg/kg body weight.

In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the test item 4-(Methacryloyloxy)benzophenone has no obligatory labelling requirement for toxicity.

According to Annex I of Regulation (EC) 1272/2008 the test item 4-(Methacryloyloxy)benzophenone is unclassified:

According to OECD-GHS (Globally Harmonized Classification System) the test item 4-(Methacryloyloxy)benzophenone requires no obligatory labelling for toxicity