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Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw (OECD 423; GLP compliant)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015-02-04 to 2015-03-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 2001-12-17
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 2008
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
, signed 2014-05-14
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 172 - 188 g
- Fasting period before study: feeding was discontinued approx. 16 hours before administration
- Housing: granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages; animals were kept in groups of 3 animals in MAKROLON cages (type III plus)
- Diet: commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C (maximum range)
- Humidity: 55% ± 15% (maximum range)
- Air changes: 12 to 18-fold air change/hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: 0.8% aqueous hydroxypropylmethylcellulose
Details on oral exposure:
VEHICLE
- Vehicle: 0.8% aqueous hydroxypropylmethylcellulose (Fagron GmbH & Co., 22885 Barsbüttel, Germany)
- Lot/batch no.: batch no. 13 D03-N03 (Methocel)

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg b.w.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed before and immediately, 5, 15, 30 and 60 minutes, as well as 3, 6 and 24 hours after administration
During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on prematurely deceased animals were made at least once daily to minimize loss of animals during the study. The time of death would have been recorded as precisely as possible. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.

- Necropsy of survivors performed: yes
Statistics:
No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).
The LD50 value was ranked exceeding 2000 mg/kg body weight
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
A single oral administration of 2000 mg 4,4’-Sulfonyldiphthalic acid dianhydride (DSDA)/kg b.w. did not reveal any signs of toxicity.
Body weight:
All animals gained the expected body weight at the end of the study.
Gross pathology:
No signs of abnormalities were noted at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (female rats) > 2000 mg/kg b.w..
According to the Regulation (EC) No 1272/2008 and subsequent regulations the test material does not require classification as acute toxic via oral route.
According to the Directive 67/548/EEC and its subsequent amendments, the test material does not require classification as acute toxic via oral route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

One reliable animal study according to OECD 423 (k_Haferkorn_2015) is considered to be reliable without restrictions. The LD50 was determined to be greater than 2000 mg/kg bw. The test item is not acutely toxic via the oral route.


Justification for selection of acute toxicity – oral endpoint
GLP guideline study conducted with the test item

Justification for classification or non-classification

Acute oral toxicity

The available guideline-conform study conducted under GLP indicate that test item is not acutely toxic via the oral route. Thus, according to Directive 67/548/EEC and its subsequent amendments and according to Regulation (EC) No 1272/2008 and subsequent regulations, no classification or labelling is required.

Specific target organ toxicant (STOT) - single exposure: oral

The classification criteria according to Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification (C ≤ 300 mg/kg bw) and at the guidance value, oral for a Category 2 classification (2000 mg/kg bw ≥ C > 300 mg/kg bw). Hence, no classification required.