Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 27 March 2013 to 10 April 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the OECD Guideline and EU Method in compliance with GLP.

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:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
other: Limit test
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): C12-14 alkylmorpholine
- Analytical purity: 98.3%:
- Lot/batch No.: S-001312
- Expiration date of the lot/batch: 05 December 2017
- Storage condition of test material: Room temperature in the dark

Test animals

Species:
rat
Strain:
other: Wistar (RccHan:WIST)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: 8-12 week
- Weight at study initiation: 200 g ±20%
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24 h exposure period and in groups of five, by sex, for the remainder of the study.
- Diet: 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK ( ad libitum)
- Water: Free access to mains drinking water
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature 19 to 25 °C
- Humidity: 30 to 70%
- Air changes: 15/h
- Photoperiod: 12 h dark/ 12 h light

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
On the day before treatment the back and flanks of each animal were clipped free of hair. The calculated volume of test substance, as received, using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage. The animals were caged individually for the 24 h exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place. After the 24-h contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test substance. The animals were returned to group housing for the remainder of the study period.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex
Control animals:
not required
Details on study design:
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 h after dosing and subsequently once daily for 14 d. After removal of the dressings and subsequently once daily for 14 d, the test sites were examined for evidence of primary irritation and scored according to the scale from Draize J H (1977). Individual body weights were recorded prior to application of the test substance on Day 0 and on Days 7 and 14. At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
Four males and four females showed bodyweight loss or no gain in bodyweight during the first week but expected gain in bodyweight during the second week. The remaining two animals showed expected gains in bodyweight over the study period
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Signs of dermal irritation noted were well-defined erythema, very slight edema, crust formation, small superficial scattered scabs and scab lifting at edges to reveal bleeding or dried blood.

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 substance in the Wistar strain rat was found to be greater than 2000 mg/kg bw.
Executive summary:

The study was performed to assess the acute dermal toxicity of C12-14 alkylmorpholine in the Wistar strain rat according to the OECD Guideline 402 and EU Method B3 in compliance with GLP.

A group of ten animals (five males and five females) was given a single, 24 h, semi-occluded dermal application of the undiluted test substance to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths or signs of systemic toxicity. Signs of dermal irritation noted were well-defined erythema, very slight edema, crust formation, small superficial scattered scabs and scab lifting at edges to reveal bleeding or dried blood. No abnormalities were noted at necropsy.

Under the study conditions, the acute dermal median lethal dose (LD50) of the test substance in the Wistar strain rat was found to be greater than 2000 mg/kg bw.