Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-08-17 to 1990-09-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
dibenzyltoluene
IUPAC Name:
dibenzyltoluene
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Marlotherm S
- Substance type: pure active substance
- Physical state: yellow liquid
- Lot/batch No.: 200 l barrel from August 21, 1991
- Stability under test conditions: unlimited
- Storage condition of test material: no data
Specific details on test material used for the study:
The purity of the material used for the test was lower than the purity of the actual material. It contained ca. 26% of isomers of dimethyl tribenzenes. However, based on comparable basic structure of the impurities and the assumption that any toxic effects would increase with higher molecular weight and lipophilicity, we regard that the studies conducted with the lower purity material being "worst case" and can be used for the evaluation of the actual product.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: not mentioned
- Weight at study initiation: 196 - 209 g (male); 187 - 194 g (female)
- Fasting period before study: not mentioned
- Housing: collective housing up to a maximum of 5 animals per cage (Macrolon type III)
- Diet (e.g. ad libitum): Ssniff-R complete feed ad libitum, Ssniff Spezialdiäten GmbH, Soest, Germany
- Water (e.g. ad libitum):drinking water ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 50 - 85
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 1990-08-08 To: 1990-09-03

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: roughly 5 x 10 cm on the back of each animal
- % coverage: not mentioned
- Type of wrap if used: porous gauze dressing and Elastoplast (Beiersdorf)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): not mentioned
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,38 - 0,42 mL

Duration of exposure:
24 hours
Doses:
2000 mg/kg
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: Clinical observations: 10 min, 1 h, 2 h, 6 h, 24 h after patch removal, and thereafter once daily up to day 14; skin reactions: once daily for 14 days after patch removal; weighing: before treatment (day 0) and surviving animals were reweighed on days 7 and 14 (termination)
- Necropsy of survivors performed: yes
- Other examinations performed:
Clinical observations: In each animal a number of clinical-toxicological signs were evaluated according to a modified Irwing-Screening procedure (Screening Methods in Pharmacology, R.A. Turner, 1965, p.26). Any changes from the normal condition was noted (increase or decrease) and the degree of severity of any clinical symptoms was assessed.
Skin reactions: After patch removal, dermal irritation was evaluated according to a scheme bazed on Draize
Statistics:
LD50 values were calculated according to Finney D.Y., Probit Analysis, 3rd edition, Cambridge, 1971

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no deaths occurred in the course of the study
Clinical signs:
no abnormal clinical signs were observed, no signs of erythema and oedema were observed
Body weight:
all animals showed normal weight gains
Gross pathology:
no test substance related findings were observed
Other findings:
- Potential target organs: not identified
- Other observations: no sex-specific differences were found

Any other information on results incl. tables

Table: Number of animals dead [and with evident toxicity]

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity (#/total)

Male

Female

Combined

Male

Female

Combined

2000

0/5 

0/5

0/10 

n.a. 

0/5 

 0/5

0/10 

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 after dermal application was found to be greater than 2000 mg/kg.
Executive summary:

The acute dermal toxicity of Dibenzylbenzene, ar-methyl derivative was tested in male and female Wistar rats at the limit dose of 2000 mg/kg. No mortality was observed during the exposure and 14 days following the exposure. Under the conditions of the study, the LD50 was considered to be > 2000 mg/kg.