Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 November 2012 to 19 December 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to relevant testing guidelines, with no significant deviations.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
The test site in the preliminary study was 5% of total body surface area instead of 10%; this was not considered to have affected the overall integrity of the study
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
The test site in the preliminary study was 5% of total body surface area instead of 10%; this was not considered to have affected the overall integrity of the study
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
The test material, OLEIC_DimerFA_TETA_PAA, was a brown/yellow viscous liquid, with batch number BB 100860 V1. The test material was stored in a sealed container at room temperature in the dark.

Test animals

Species:
rat
Strain:
other: HsdHan:WIST
Sex:
male/female
Details on test animals and environmental conditions:
The animals were 8-10 week old male and female HsdHan:WIST rats, obtained from Harlan UK Ltd., Bicester. Females were nulliparous and non-pregnant. The males weighed 246 to 344 g on Day 1 and females weighed 169 to 219 g. The acclimatisation period was 8 to 16 days.
Rats were housed in same sex groups of up to 5 during the acclimatisation period, and individually from the day prior to dosing. After the Day 3 observation the animals were returned to group housing. The rats were fed SQC(E) Rat and Mouse Maintenance Diet No. 1 (Special Diet Services Ltd., Witham, UK) ad libitum, and mains water was available ad libitum. The animal rooms were maintained at a temperature of 20 to 24°C, relative humidity of 45% to 65% and there were 15 to 20 air changes per hour. Fluorescent lighting was provided on a 12 hour light/dark cycle.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
All hair was removed from the dorsum of each rat on the day before dosing. The test site was an area of at least 10% of the total body surface area, calculated according to the largest animal in each group using the following formula: Surface area (cm²) = K x body weight (g)²/³ (where K = 9).
The test material was spread as uniformly as possible over the test site. The dose volume was 2.15 mL/kg bw, and was calculated from the body weights of the rats on the morning of dosing and the density of the test material. A dense gauze patch was placed over the treated skin and retained in place by an elasticated, open-weave, adhesive compression bandage. This was wrapped securely around the torso of the animal. At the end of the exposure period the dressings were removed and the test site was lightly brushed clean of any solid residues and swabbed with water-moistened cotton wool.
The test material was administered as supplied, and corrections for purity or active content were not made.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex (including preliminary study)
Control animals:
not required
Details on study design:
A preliminary study was conducted with one male and one female rat. Each rat received a single dermal dose of the test substance at 2000 mg/kg bw. Due to a calculation error, the body surface area used was 5% instead of 10%. This was not considered to have affected the overall integrity or outcome of the study as the responses seen in these animals were consistent with those seen in the main study animals. Since no mortalities were observed in the preliminary test, the test material was applied dermally to four male and four female rats at a dose of 2000 mg/kg bw. The rats were observed for 14 days after dosing. Treated rats were observed for clinical signs of toxicity immediately post-dose, at approximately 15 and 30 minutes post-dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to the last day of the observation period. Checks for mortality and general health were made at the beginning and end of each working day throughout the acclimatisation period and study period. The second observation on Day 3 for the female main study animals was not performed, but this was not considered to have affected the outcome of the study. Body weights were recorded the day prior to dosing, and on Days 1, 4, 8 and 15. The test site was evaluated for dermal reactions following removal of the dressings on Day 2 and daily therefore for the remainder of the observation period.
Rats were sacrificed on Day 15, and full necropsy was performed and all lesions were recorded. The necropsy procedure included inspection of external surfaces and orifices, the dermal test site, all viscera and tissue within the abdominal, thoracic and cranial cavities, free hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach and intestinal tract.
Statistics:
Not required.

Results and discussion

Preliminary study:
No mortalities occurred in the preliminary study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities occurred.
Clinical signs:
No clinical signs of toxicity were observed.
Body weight:
All rats gained weight during the first and second weeks of the study, except for one male and one female which showed no weight change during the first week.
Gross pathology:
No abnormalities were noted at necropsy, except sore appearance of the test site which was noted in one female.
Other findings:
Dermal reactions noted at the test sites of treated animals were confined to discolouration in one male on Day 2, in four males on Day 3 and in all males from Day 4 to Day 14, and scabbing in one female from Day 4 to Day 14. It could not be confirmed if the discolouration of the skin was a treatment-related effect. The test article was described as a brown/yellow liquid but the treatment sites were washed following removal of the bandages and in the majority of cases, the discolouration did not develop until Days 3 or 4.

Any other information on results incl. tables

One male rat incorrectly received a dose volume of 0.64 mL instead of 0.62 mL. The rat showed no signs of toxicity therefore the deviation was not considered to have affected the integrity or outcome of the study.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 was found to exceed 2000 mg/kg bw in rats.
Executive summary:

The acute dermal toxicity of OLEIC_DimerFA_TETA_PAA was investigated in male and female HsdHan:WIST rats, in a GLP study according to OECD Test Guideline 402. A preliminary study was conducted with one male and one female. Following the preliminary study an additional 4 rats per sex were treated. The test material was applied undiluted to the clipped dorsum of the rats at a dose of 2000 mg/kg bw. The test site was covered with a semi-occlusive dressing for 24 hours. Following dressing removal the animals were observed for dermal reactions at the test site, clinical signs of toxicity and mortality for 14 days. All animals were sacrificed at the end of the observation period and subject to full necropsy.

There were no mortalities and no clinical signs of toxicity. Discolouration and scabbing of the test site was noted in treated animals, lasting up to Day 14. There were no treatment-related effects on body weight, and no abnormalities were noted at necropsy except for sore appearance of the test site in one female. Under the conditions of the study, the acute dermal LD50 of OLEIC_DimerFA_TETA_PAA was found to exceed 2000 mg/kg bw in rats.