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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9-26 June 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD TG 402

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
2-[(2-hydroxyethyl)(octadecyl)amino]ethan-1-ol; 2-[(2-hydroxyethyl)(octadecyl)amino]ethyl hexadecanoate; 2-[(2-hydroxyethyl)(octadecyl)amino]ethyl octadecanoate; 2-{[2-(hexadecanoyloxy)ethyl](octadecyl)amino}ethyl hexadecanoate; 2-{[2-(hexadecanoyloxy)ethyl](octadecyl)amino}ethyl octadecanoate; 2-{[2-(octadecanoyloxy)ethyl](octadecyl)amino}ethyl octadecanoate
EC Number:
943-080-0
Molecular formula:
Not applicable, UVCB
IUPAC Name:
2-[(2-hydroxyethyl)(octadecyl)amino]ethan-1-ol; 2-[(2-hydroxyethyl)(octadecyl)amino]ethyl hexadecanoate; 2-[(2-hydroxyethyl)(octadecyl)amino]ethyl octadecanoate; 2-{[2-(hexadecanoyloxy)ethyl](octadecyl)amino}ethyl hexadecanoate; 2-{[2-(hexadecanoyloxy)ethyl](octadecyl)amino}ethyl octadecanoate; 2-{[2-(octadecanoyloxy)ethyl](octadecyl)amino}ethyl octadecanoate
Test material form:
other: pastilles
Details on test material:
Test Item SABOSTAT A 300
Lot Number 20085596
CAS No Not applicable
Certificate Test Item Specification Sheet of LAUS GmbH
Manufacturer SABO S.p.A.
Appearance Whitish pastilles
Composition
Reaction product of stearyl-diethanol-amine with C16-C18
saturated fatty acids
Expiry Date 10. April 2016
Storage Room temperature (20 ± 5 °C), keep away from light/humidity
Test Item Receipt According to SPPA-00147-BIO, Test and Reference Items

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Wistar rats
Source: Velaz Prague, Czech Republic
Number and Sex of Animals Received/Used: 10 females and 5 males / 5 males and 5 females
Age at First Dose: 8-12 weeks; female animals were non-pregnant and nulliparous
Animal Health: The health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation: The animals were acclimated to the condition identical to the conditions during the experiment 5 days prior to the start of treatment.
The acclimation was according to the standard operation procedure.
Housing Condition: The animals were housed in plastic cages suspended on stainless steel racks, up to 2-3 animals per cage, males and females separately in a room equipped with central air-conditioning. The room temperature was maintained within the range of 22 ± 2° C, relative humidity within
55 ± 10 %. The light regimen was set to a 12-hour light /12-hour dark cycle (deviation ± 30 minute). The sanitation was performed accordingto the standard operation procedures.
Diet: A laboratory food Altromin (Altromin Spezialfutter GmbH, Germany) was offered in recommended doses each day approximately at the same time after dosing. The certificate of analysis is included in the raw data. The food consumption was recorded.
Water: The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodical analysed (including microbiological control) and recorded; certificate of analysis is included in raw data.
Bedding: Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification: Each animal was marked with an ID number. Each cage was affixed with a cage card containing pertinent animal and study information. The animals in cages were marked by a line on the tail with an ink marker.
Justification for the Choice of Species: Normally females are used in the test according to OECD TG 402 because mostly females are the more sensitivegender, but there is still a possibility that this assumption will not be confirmed. For this reason, one dose in males was used to verify sensitivity of sexes after assessing acute toxicity in females.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
olive oil
Details on dermal exposure:
Approximately 24 hours before the test, fur was removed from the dorsal area of the trunk of the test animals by clipping and shaving. A precise amount of the test item was aspirated into an adjustable pipette and application directly on the shaved skin of back in a single dose uniformly on over an area approximately 10 % of the total body surface area. Test item was held in contact with the skin by using a Cosmopor E and a semi-occlusive dressing with non-irritating tape throughout the 24-hours exposure period. At the end of the exposure period, any residuals of the test item were removed by using lukewarm water without altering the existing response or integrity of the epidermis.
Duration of exposure:
24h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Sighting Study
The purpose of the sighting study was to allow selection of the appropriate starting dose for the main test. The starting dose for sighting study could be selected from the fixed dose levels of 50, 200, 1000, and 2000 mg/kg. Available information indicated that the test item was likely to be nontoxic regard to acute toxicity. Therefore, a limit dose of 2000 mg/kg was used as starting dose. One female rat was dosed. Test item-related mortality was not produced during 24-hours exposure period. The sighting study was finished; the main test was started with dose of 2000 mg/kg.

Main Study
A total of five female rats (one from the sighting study with an additional four animals) were dosed with a dose of 2000 mg/kg. Test item-related mortality was not produced during 24 hours. An additional group of 5 male rats were tested at the same dose.

Clinical Observation
Animals were observed individually immediately after the application of the test item and then ½, 1, 2, and 4 hours later. Then each animal was inspected daily for the next 14 days. Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Body Weight
Individual weights of animals were determined shortly before the test item was applicated and at weekly thereafter. Weight differences after first and second week after application were calculated and recorded.

Necropsy
All test animals were subjected to gross necropsy. Full, detailed gross necropsy included careful examination of external surface of the body, all orifices, and cranial, thoracic and abdominal cavities and their contents. All gross pathological changes were recorded for each animal.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
All 5/5 females and 5/5 males at the limit dose of 2000 mg/kg survived. No further dosing was necessary.
Clinical signs:
other: No mortality was observed during the study. No important symptoms were observed during the first 4 hours neither in females nor in males or in 14 days observation period.
Gross pathology:
All animals (5 females and 5 males) were necropsied. During necropsy, no macroscopical changes were noticed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on OECD TG 402 and OECD Draft TG 434 it can be concluded that for the substance LD50 is equal to 2000 mg/kg, after single dermal application to Wistar rats.
Executive summary:

The test item applicated to 5♀ and 5♂ in limit dose 2000 mg/kg did not cause

death. All 5/5 females and 5/5 males survived the limit dose 2000 mg/kg thereafter no further

dosing was necessary.

No body weight losses were observed one and two week after application of the test item. No

important symptoms were observed during first 4 hours neither in females nor in males or in 14

days observation period. During necropsy, no macroscopically changes were noticed.