Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C11-17 and C17 unsatd. alkyl) derivs. and sodium hydroxide and 2-propenoic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2007-05-09 to 2007-05-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(2-hydroxyethyl)-N-[2-[(1-oxooctyl)amino]ethyl]-β-alanine

EC Number:

264-761-2

EC Name:

N-(2-hydroxyethyl)-N-[2-[(1-oxooctyl)amino]ethyl]-β-alanine

Cas Number:

64265-45-8

IUPAC Name:

N-(2-hydroxyethyl)-N-[2-[(1-oxooctyl)amino]ethyl]-β-alanine

Test material form:

liquid

Details on test material:

- Physical state: liquid
- Analytical purity: 97.0%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: none
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage­enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiaten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Macrolon cages (MIV type).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.8 - 23.0°C
- Humidity (%): 39 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09 May 2007 To: 23 May 2007

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 5x7 cm
- % coverage: 10%
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1 D), successively covered with aluminum foil and Caban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only

REMOVAL OF TEST SUBSTANCE
24 hours after application the dressings were removed and the skin cleaned of residual test substance using tap water

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3738 mL/kg; 2024 mg a.i./kg bw
- Concentration (if solution): 50.6%
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2024 mg a.i./kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality: Twice daily; Body weights: Days 1 (pre-administration), 8 and 15; clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No mortality occurred.

Clinical signs:

other: Lethargy, flat posture, piloerection (head), chromodacryorrhoea (snout) and/or ptosis was noted among the animals. The animals had recovered from the symptoms between Days 2 and 3. Focal erythema, scars, scales and/or scabs were seen in the treated skin-

Gross pathology:

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

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of Amphopropionate C8 in Wistar rats was established to exceed 2000 mg a.i./kg body weight.

Executive summary:

In an acute dermal toxicity study according to OECD guideline 402 (1987) and EU Method B.3 (1992), groups of young adult Wistar rats (5 males and 5 females) were dermally exposed to Amphopropionate C8 (50.6% a.i.) for 24 hours to the limit dose of  2024 mg a.i./kg bw.  Animals then were observed for 14 days.

No mortality occurred. Lethargy, flat posture, piloerection (head), chromodacryorrhoea (snout) and/or ptosis was noted among the animals. The animals had recovered from the symptoms between Days 2 and 3. Focal erythema, scars, scales and/or scabs were seen in the treated skin-area of the females during the observation period.

 

Dermal LD50 Males    > 2000 mg/kg bw

                    Females > 2000 mg/kg bw

         

Based on these results, Amphopropionate C8 does not have to be classified and has no obligatory labelling requirement for dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).