Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Jun. 1978 to Mar. 6, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Higher doses than OECD 402 limit dose, non GLP
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Wistar-AF/HAN-EMD-SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: 150 to 185 g (mean weight 165 g)
- Fasting period before study: Not reported
- Housing: Individually housed in model III wire cages
- Diet (e.g. ad libitum): Altromin Standard Diet TPF No. 1324, batch 1151 dated 01.06.78. ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 27 ± 7
- Humidity (%): 52 ± 20
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: shaved skin (back and stomach)
- % coverage: 6 x 6 cm area
- Type of wrap if used: The part of the skin that was treated was covered with tinfoil which was held in place and made snug with a rubber sleeve.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The rubber sleeve and tinfoil were removed, and any residue was washed off carefully with lukewarm water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.37, 0.46, 0.59, 0.74 and 0.926 mL/100 g body weight
- Concentration (if solution): Not reported
- Constant volume or concentration used: no


Duration of exposure:
24 hours
Doses:
0, 4000, 5000, 6400, 8000, and 10000 mg/kg body weight
No. of animals per sex per dose:
5/sex/dose group
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All of the animals were weighed at regular intervals. They were weighed prior to administration of the substance and also at 1, 5, 7, 12, and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
The behavior and general condition of all of the rats were observed closely during the 5-6 hours after the treatment and were then checked daily.
With the exception of animals which died within 24 hours of the treatment, rats that died after this period were dissected and examined pathologico-anatomically. In the cases where dead animals had been savagely mutilated by other rats, the dissection was not carried out. All of the animals which survived were sacrificed, dissected and examined pathologico-anatomically at the end of the trial.
Any local changes in the treated area in the case of topical application were assessed according to DRAIZE (1959).
Statistics:
All statistical calculations were made using a modified test according to DUNNETT, C.W. (1955, 1964), and significant differences between the dose groups and the control group were expressed as a + in the case of p ≤ 0.05 and as ++ in the case of p ≤ 0.01. The calculations were made in the Scientific Data Processing Department of E. Merck, Darmstadt.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
6 929 mg/kg bw
95% CL:
6 028 - 7 964
Mortality:
Mortality observations are provided in a table attached.
Clinical signs:
The general condition and mobility of the rats treated topically had to be restricted on the day of treatment due to reasons related to the method used. Because of this, it is possible that certain preparation-induced symptoms were masked, meaning that some of these symptoms were not observed or that it was not possible to distinguish them from reactions induced by the method of application. The symptoms observed after the removal of the sleeve are listed in tables according to type, intensity and duration.
Body weight:
Body weight measurements were not discussed by the authors but individual and mean body weight measurements were provided in tables.
Gross pathology:
Animals which died:
The dead rats to which a substance had been applied topically had fatty infiltration of the liver and dilation of the urinary bladder with hemorrhaging of the mucosa (starting at 6400 mg/kg).
Animals which were sacrificed:
The body organs were examined microscopically in all of the rats that were treated. There were no abnormal histopathological findings.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of the test item after single dermal administration to rats of both sexes, observed over a period of 14 days is:
LD50 (rat): 6929 mg/kg body weight.
Executive summary:

In this (OECD 402) study conducted to generally accepted scientific standards, the acute dermal LD50 of the test material (EC 231-272-0) to the rat was determined to be 6929 mg/kg bw (both sexes). The test material was administered at doses of 4000, 5000, 6400, 8000, and 10000 mg/kg body weight under occlusive conditions to males and females for 24 hours, with a post application observation period of 14 days. The result of the test does not trigger classification of the test material as acutely toxic according to the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).