Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
02 July 2003- 16 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to OECD test guidance in compliance with GLP and reported with a valid GLP certificate. The study is read across to an analogous substance; refer to image and further information below.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

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
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
CAS Number: 144971-11-9
Description: Clear colourless liquid
Batch: D21287
Purity: >97.3%
Test substance storage: At room temperature in the dark
Stabilty under storage conditions: Not indicated
Expiry date: 01 September 2003

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species:Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g.OECD, EC)Source: Charles River Deutschland, Sulzfeld, Germany.Number of animals: 5 males and 5 females (females were nulliparous and nonpregnant).Age and bodyweight: Young adult animals (approx. 9-10 weeks old) were selected. Bodyweight variation did not exceed +/- 20% of the sex mean.Identification: EarmarkConditionsAnimals 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:i 3.0°C (actual range: 17.2 - 23.7°C), a relative humidity of 30-70% (actual range: 44 - 83%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relativehumidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.AccommodationIndividually housed in labelled Macrolon cages (type IIi, height 15 cm.) containing purified Sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives. Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.DietFree access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany). Cer!ifcates of analysis were examined and then retained in the NOTOX archives.WaterFree access to tap-water. Certifcates of quarterly analysis were examined and then retained in the NOTOX archives.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Method: Dermal application.Clipping: One day before exposure (day -1) an area of approximately 5x7cm on the back of the animal was clipped.Application: The test substance was applied in an area of approx. 10% of thetotal body surface, i.e. approx. 25 cm2 for males and 18 cm2 for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1 D), successively covered with aluminium foil and Coban flexible bandage'. A piece of Micropore tape was additionally used forfixation of the bandages in females only.Frequency: Single dosage, on day 1.Application period: 24 hours, after which dressings were removed and the skincleaned of residual test substance using water.
Duration of exposure:
24 h
Doses:
2000 mglkg (2.061 ml/kg) body weight. Dose volume calculated as follows: dose level : specific gravity.
No. of animals per sex per dose:
5 male, 5 female
Control animals:
no
Details on study design:
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 dailythereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:Maximum grade 4: grading slight (1) to very severe (4)Maximum grade 3: grading slight (1) to severe (3)Maximum grade 1: presence is scored (1).Necropsy: At the end of the observation period, all animals were sacrificed byasphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
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:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Hunched posture and/or chromodacryorrhoea were noted among all animals on day 2. In addition, maculate erythema or scales were seen on the treated skin site of one male and female between days 3 and 7.
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 mor!em examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Read across to structural analogue. Structural details are listed above. No mortality occurred.Hunched posture and/or chromodacryorrhoea were noted among all animals on day 2. In addition, maculate erythema or scales were seen on the treated skin site of one male and female between days 3 and 7.The body weight gain during the observation period was within the range expected for rats used in this type of study.No abnormalities were found at macroscopic post mortem examination of the animals.The dermal LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Read across to structural analogue. Structural details are listed above.

No mortality occurred.

Hunched posture and/or chromodacryorrhoea were noted among all animals on day 2. In addition, maculate erythema or scales were seen on the treated skin site of one male and female between days 3 and 7.

The body weight gain during the observation period was within the range expected for rats used in this type of study.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kg body weight.