Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Qualifier:
according to
Guideline:
other: JMAFF, 12 Nousan, No. 8147
Version / remarks:
November 2000, including the most recent partial revisions
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Wistar strain Crl:Wl (Han) (outbred, SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.

Details on test animals:
Young adult animals (approx. 8-9 weeks).
Body weight variation <20% of the sex mean.
Identificatin by earmark

Conditions:
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 +- 3.0°C (actual range: 19.8 —21.3°C), a relative humidity of 30-70% (actual range: 33 - 65%) and 12 hours artificial fluorescent light and 12 hours darkness per day.

Accommodation
Group housing of 3 animals per sex per cage in labelled Macrolon cages (type MIV; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argentueil, France) and paper as cage-enrichement (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet
Free access to pelleted rodent diet (SM R/M-Z from SSNIF Spezialdiäten GmbH, Soest, Germany)

Water
Free access to tap-water.

Results of analysis for each batch of diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the
study integrity. All certificates and results of analysis are retained in the NOTOX archives.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Remarks:
e vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
Doses:
single dosage of 2000 mg/kg (10 ml/kg) body weight on day 1
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality
of animals closed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account
for determination of the time interval between the dose groups.
Statistics:
No statistical analysis was performed (the method used is not intented to allow the calculation of a precise LD50 value)

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
Piloerection was noted among the animals on Day 1 and hunched posture was noted in all animals on Days 1 and/or 2.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic postmortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of SULFOBUTYL TMBI in Vlfistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results SULFOBUTYL TMBI does not have to be classified and has no obligatory labeling requirement for oral toxicity according to the:
- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures,
- EC criteria for classification and labeling of dangerous substances and preparations (Council Directive 67/548/EEC and all adaptations to technical progress and amendments of this Directive published in the Official Journal of the European Communities).