Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07 August 2013 - 21 August 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to OECD guidelines and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Name: PREPOLYMER D
Chemical Name: Reaction mass of Bis (2-chloroethoxy)methane and 1,15-dichloro-3,5,8,11,13-pentaoxa-pentadecane and 1-(2-chloroethoxy)-2-(2-chloroethoxymethoxy)ethane
Batch/Lot Number: 030613
Purity: 100% (multi constituent substance)
Appearance: slightly brownish liquid

Test animals

Species:
rat
Strain:
other: CRL:(WI)
Sex:
male/female
Details on test animals and environmental conditions:
Species and strain: CRL:(WI) Wistar rats
Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
Hygienic level at arrival: SPF
Hygienic level during
the study: Standard housing conditions
Justification of strain: The Wistar rat is one of the standard rodent species used in acute toxicity studies
Number of animals: 5 animals/sex
Sex: Male and female, female rats were nulliparous and non-pregnant.
Age of animals at study start: Young adult rats
Body weight range
at dosing: Between 217 g and 256 g
Acclimatization time: 6 days

Animal health: Only healthy animals were used for the study. The veterinarian certified the health status.
Room-Box: 242/7
Housing: Individual caging
Cage type: Type II. polypropylene/polycarbonate
Bedding: Laboratory bedding:
Lignocel Hygienic Animal Bedding produced by J. Rettenmaier & Söhne GmbH+Co.KG (Holzmühle 1, 73494 Rosenberg, Germany);
A copy of the relevant Certificate of Analysis is maintained in CiToxLAB Hungary Ltd.'s archive.
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 20.5 - 29.7 °C
Relative humidity: 30 - 70 %
Ventilation: 15-20 air exchanges/hour
Enrichment: Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities.
The temperature and relative humidity was recorded twice daily during the study.

Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany ad libitum, and tap water from the municipal supply, as for human consumption from 500 ml bottle ad libitum. The food is not considered to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
The batch of feed employed in the study was as follows:
 175 8935, expiry date: August 2013
The supplier provided an analytical certificate for the batch used. Copy of the certificate will be archived with the raw data.
Water quality control analysis is performed once every three months and microbiological assessment is performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A.u.36., Hungary). The quality control results are retained in the archives at CiToxLAB Hungary Ltd.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The back of each animal was shaved (approximately 10 % area of the total body surface) approximately 24 hours prior to treatment. The test item was applied as a single dose as supplied to the shaved skin and remained in contact with the skin for the 24- hour exposure period. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.
At the end of the exposure period, the area of skin treated with the test item was washed with water of body temperature.
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: Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14. Moreover, the body weight of the found dead animal was recorded at necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: None
Statistics:
None

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: 1 female died on day 1
Mortality:
Administration of the test item at a dose level of 2000 mg/kg body weight caused mortality in 1/10 animal on day 1.
Clinical signs:
No clinical signs were observed after treatment with the test item or during the 14-day observation period. There were no observed local dermal signs after treatment with the test item or during the 14 day observation period at a dose level of 2000 mg/kg bw.
Body weight:
The body weight and body weight gain of treated animals did not show any test item-related effect.
Gross pathology:
Dark/red discoloration/foci of the non-collapsed lungs, foamy red material in the trachea and thymus and red macule at the site of application were found in this female rat at necropsy.
There was no evidence of the any gross observations in surviving animals at a dose level of 2000 mg/kg bw and terminated on Day 14.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item PREPOLYMER D was found to be higher than 2000 mg/kg bw in male and female CRL:(WI) rats.
Executive summary:

An acute dermal toxicity study was performed with the test item in CRL:(WI) rats, in compliance with OECD Guideline No.: 402.

A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as supplied as a single dermal 24-hour exposure followed by a 14-day observation period.

Clinical observations were performed on all animals at 1 and 5 hours after dosing and on the surviving animals daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14 and of the animal found dead. Gross macroscopic examination was performed on the surviving animals at the end of the 2-week observation period (Day 14). Moreover, the animal found dead was examined macroscopically and body weight was recorded at necropsy.

The results of the study were summarized as follows:

Mortality

Administration of the test item at a dose level of 2000 mg/kg body weight caused mortality in 1/10 animal.

Systemic clinical signs

No clinical signs were observed after treatment with the test item or during the 14-day observation period.

Local dermal signs

There were no observed local dermal signs after treatment with the test item or during the 14 day observation period at a dose level of 2000 mg/kg bw.

Body weight

The body weight and body weight gain of treated animals did not show any test item-related effect.

Necropsy

Dark/red discoloration/foci of the non-collapsed lungs, foamy red material in the trachea and thymus and red macule at the site of application were found in this female rat at necropsy.

There was no evidence of the any gross observations in surviving animals at a dose level of 2000 mg/kg bw and terminated on Day 14.

Conclusions

The acute dermal median lethal dose (LD50) of the test item was found to be higher than 2000 mg/kg bw in male and female CRL:(WI) rats.