Fatty acids, C16-18, reaction products with diethanolamine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-08-23 to 2012-11-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C16-18, reaction products with diethanolamine

EC Number:

293-014-3

EC Name:

Fatty acids, C16-18, reaction products with diethanolamine

Cas Number:

91032-08-5

Molecular formula:

C22H45NO3 to C52H101NO5

IUPAC Name:

Fatty acids, C16-18, reaction products with diethanolamine

Details on test material:

Name: Fatty acids, C16-18-, reaction products with diethanolamine
Product: Cepreton AT liq. conc.
Specification: Amide Intermediate of Cepreton AT (REACH)
CAS No.: 91032-08-5
Batch No.: ITA0058330
Physical State: solid
Colour: yellow
Molecular Weight: ca. 610-872
pH: 7-8
Active Components: > 99%
Storage Conditions: at room temperature, protected from light
Date of Analysis: 01.02.2012
Expiry Date: 11.01.2013
Safety Precautions: The routine hygienic procedures were sufficient to assure personnel health and safety.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Full barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. XX)
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. XX)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Vehicle:

water

Details on dermal exposure:

Preparation of the Animals:

The animals were marked for individual identification by tail painting.
Approximately 24 hours before the test, the fur was removed from the dorsal area of the trunk using an electric clipper. Care was taken to avoid abrading the skin, and only animals with healthy intact skin were used.
No less than 10% of the body surface was cleared for the application.
Prior to the application a detailed clinical observation was made of all animals.

Application:

The test item was applied at a single dose, uniformly over an area which was approximately 10% of the total body surface.
The test item was held in contact with the skin by a dressing throughout a 24-hour period. The dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.

Duration of exposure:

The test item was held in contact with the skin throughout a 24-hour period. At the end of the exposure period the residual test item was removed using aqua ad injectionem.

Doses:

The test item was applied at a single dose of 2000 mg/kg body weight to each animal.

No. of animals per sex per dose:

5 male and 5 female

Control animals:

not required

Details on study design:

Observation period:

All animals were observed for 14 days after dosing

Weight Assessment:

The animals were weighed on day 1 (prior to the application) and on days 8 and 15.

Clinical Examination:

careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Pathology:

At the end of the observation period the surviving animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally (Narcoren®, Merial) at the dosage of approximately 8 mL/kg bw. All animals were subjected to gross necropsy. All gross pathological changes were recorded.

Evaluation of Results:

Individual reactions of each animal were recorded at each time of observation.
Toxic response data were recorded by sex and dose level.
Nature, severity and duration of clinical observations were described.
The body weight changes were summarised in a tabular form.
Necropsy findings were described.

Statistics:

According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation of the results is not regarded as necessary.

Results and discussion

Effect levels

Dose descriptor:

approximate LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: No treatment-related effects were observed.

Gross pathology:

No treatment-related effects were observed.

Other findings:

No erythema or oedema was observed. Scratches were observed in 1 of 5 male and female animals.
All findings were reversible within the observation period.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Conclusions:

Under the conditions of the present study, single dermal application of the test item Fatty acids, C16-18-, reaction products with diethanolamine to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity but slight signs of irritation.
The dermal LD50 was determined to be > 2000 mg Fatty acids, C16-18-, reaction products with diethanolamine / kg body weight.

Executive summary:

Summary Results:

LD₅₀:                                                        > 2000 mg /kg bw

Species/strain:                                         WISTAR Crl: WI(Han) rats

Vehicle (moistening):                               aqua ad injectionem

Number of animals:                                  5 male and 5 female

Duration of exposure:                             24 hours

Method:                                                  OECD 402[3]
EC 440/2008, Method B.3[4]
OPPTS 870.1200[5]

Table:  Results per Step

Sex	Dose (mg/kg bw)	Number of Animals	Number of Intercurrent Deaths
male	2000	5	0
female	2000	5	0

Signs of toxicity related to dose level used, time of onset and duration:

No treatment-related effects were observed.

Effect on organs (related to dose level):

No treatment-related effects were observed.

Signs of irritation:

No erythema or oedema was observed. Scratches were observed in 1 of 5 male and female animals.

All signs of irritation were reversible within the observation period.

Conclusion:

Under the conditions of the present study, single dermal application of the test item Fatty acids, C16-18-, reaction products with diethanolamine to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity but slight signs of irritation.

The dermal LD50 was determined to be > 2000 mg Fatty acids, C16-18-, reaction products with diethanolamine / kg body weight.