Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 September 2009 - 13 October 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to EC and/or OECD guidelines and in compliance with GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Terate® 091 Residue
- Substance type: Dark brown solid with soft lumps
- Physical state: Solid
- Analytical purity: 100%
- Composition of test material, percentage of components: by-product from the manufacture of 1,4-Benzenedicarboxylic acid, dimethyl ester
- Lot/batch No.: NB8322-091
- Expiration date of the lot/batch: 14 July 2010
- Stability under test conditions: Not indicated
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Rat, Wistar strain, Crl:WI (Han)
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: mean: 262 gram formales and 204 gram for females
- Fasting period before study: not applicable
- Housing: Individually housed in labeled Macrolon cages containing sterilized sawdust as bedding material and paper as cage-enrichment
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before start of treatment under laboratory conditions and group housed.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 - 21.5ºC
- Humidity (%): 31 - 77%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 29 September 2009 To: 13 October 2009

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: Ethyl acetate (maximum 20% of total volume) and propylene glycol.
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 25 cm² for males and 18 cm² for females (ie approx. 10% of the total body surface).
- % coverage: 100%
- Type of wrap if used: a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): using tap water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): 200 mg/mL
- Constant volume or concentration used: yes, constant concentration


VEHICLE
- Amount(s) applied (volume or weight with unit): 10 mL/kg
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
Flat posture, chromodacryorrhoea, and/or ptosis were noted in the majority of animals, which had completely recovered from these symptoms by between Days 2 and 3.
Brown staining of the treated skin-area of all animals was observed during the observation period. Since the test substance is a dark brown solid, this finding was considered to be related to staining properties of the test substance and of no toxicological significance.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of Terate® 091 Residue in Wistar rats was established to exceed 2000 mg/kg body weight.
Based on these results, Terate® 091 Residue does not have to be classified and has no obligatory labeling requirement for acute dermal toxicity according to the:
-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 Union),
-Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007).
Executive summary:

Acute dermal toxicity of the test substance was determined in a guideline study (OECD TG 402) in rats. The dermal LD50 value exceeded 2000 mg/kg body weight.