Reaction mass of N-(2-hydroxyethyl)alkyl] alkylamide and glycerol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

2017

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

liquid

Details on test material:

Reaction mass of N-[2-(2hydroxyethoxy) ethylacetamide and Glycerol
CAS number: 118974-46-2/56-81-5
Clear liquid, pale yellow to yellow
pH: 7.5-9.5 at 10% solution
Specific gravity / density: 1.15
Storage: RT in dark
Production date: 03/02/2018
Expiration date: 03/02/2019

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species: Rat
Strain: Crl: WI(Han)
Condition: Outbred, SPF-Quality
Source: Charles River Deutschland, Sulzfeld, Germany
Number of Animals: 3 females (nulliparous and non-pregnant).
Age at the Initiation of Dosing: Young adult animals (approximately 10-12 weeks old) were selected.
Weight at the Initiation of Dosing: 194 to 230 g.

following assignment to the study, animals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.

Target temperatures of 18 to 24°C with a relative target humidity of 40 to 70% were maintained. The actual daily mean temperature during the study period was 21°C with an actual daily mean relative humidity of 37 to 59% (see deviations in Appendix 3). A 12-hour light/12-hour dark cycle was maintained. Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- One day before dosing, an area of approximately 5x7 cm on the back of the animals was clipped.
- Area of exposure: 10% of the total body surface, i.e. approximately 18 cm² for females
- Type of wrap if used: The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the dressing was removed and the skin cleaned of residual test item using water.
- Time after start of exposure: 24 hours after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg. The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg) / spec.gravity or density (g/mL).
- Concentration (if solution): pure, no vehicle
- Constant volume or concentration used: Only one dose group of 2000 mg/kg bw

No vehicle; test item administered as received.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality: twice daily; Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. Body weight on Day 1 (predose), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: local effects and irritation, clinical signs, body weight, and examination for internal macroscopic abnormalities.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LDLo

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

No toxicity, and no irritation; Only observed effects include chromodacryorrhoea (snout) noted for two animals on Day 1 only.

Mortality:

No mortality

Clinical signs:

Chromodacryorrhoea (snout) was noted for two animals on Day 1.

Body weight:

No effects

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

No irritation was noted for any of the animals at any time point.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value in Wistar Han rats was established to exceed 2000 mg/kg body weight.

Executive summary:

The objective of this study was to determine the potential toxicity of Reaction mass of N-[2 -(2hydroxyethoxy) ethylacetamide and Glycerol, when given by a single dermal dose.  

The study was carried out based on the guidelines described in OECD No. 402 (2017) "Acute Dermal Toxicity"

Initially, Reaction mass of N-[2-(2hydroxyethoxy) ethylacetamide and Glycerol was administered to a single female Wistar Han rat by a single dermal application at 2000 mg/kg body weight for 24 hours in a range finder study.  Based on the results, the main study was performed by dosing two additional females at 2000 mg/kg.  All animals were subjected to daily observations and weekly determination of body weight.  Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15). Results for the main study include the results for the animal dosed at 2000 mg/kg in the range finder study.  

Results: No mortality occurred. No irritation was noted for any of the animals at any time point. Chromodacryorrhoea (snout) was noted for two animals on Day 1. The body weight gain shown by the animals during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of Reaction mass of N-[2-(2hydroxyethoxy) ethylacetamide and Glycerol in Wistar Han rats was established to exceed 2000 mg/kg body weight.  

Based on these results, Reaction mass of N-[2-(2hydroxyethoxy) ethylacetamide and Glycerol does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).