Acetic acid, chloro-, sodium salt, reaction products with 4,5-dihydro-2-undecyl-1H-imidazole-1-ethanol and sodium hydroxide

Acute Toxicity: dermal

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Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 2009 - March 8, 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Group of constituents (alkyl derivatives) in Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7-C17 odd-numbered, C17-unsatd. alkyl) derivs. and sodium hydroxide and chloroacetic acid

Molecular formula:

For two representative potential structures: C20H36N2O6Na2 : 446 and C18H35N2O4Na: 367

IUPAC Name:

Group of constituents (alkyl derivatives) in Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7-C17 odd-numbered, C17-unsatd. alkyl) derivs. and sodium hydroxide and chloroacetic acid

Constituent 2

Reference substance name:

Sodium chloride

EC Number:

231-598-3

EC Name:

Sodium chloride

Cas Number:

7647-14-5

Molecular formula:

ClNa

IUPAC Name:

Sodium chloride

Constituent 3

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

Test material form:

liquid: viscous

Details on test material:

- Physical state: Aqueous solution (clear yellow viscous liquid)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Species: Rat, Wistar strain, Crl:WI (Han) (outbred, SPF-Quality)
- Source: Charles River Deutschland, Sulzfeld, Germany
- Number of animals: 5 males and 5 females (females were nulliparous and non-pregnant)
- Age and body weight: Young adult animals (approx. 11 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean
- Health inspection: A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality
- Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0ºC (actual range: 18.4 – 21.7ºC), a relative humidity of 40-70% (actual range: 31 - 88%) and 12 hours artificial fluorescent light and 12 hours darkness per day
- Accommodation: 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 cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom)
- 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)
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to tap water

IN-LIFE DATES: From: 15 December 2009 To: 29 December 2009

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure and % coverage: The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- 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 1D)*, successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24 hours (using tap water)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (4.47 mL/kg) body weight,
expressed as surfactant content and 2612 mg/kg, expressed as solid content
Dose volume calculated as: Dose level corrected for content (g/kg) / specific gravity (g/mL).
- Concentration (if solution): N/A; the aqueous solution is tested as such

VEHICLE
Not applicable, the aqueous solution is tested as such

Duration of exposure:

24 hours

Doses:

2000 mg/kg (expressed as surfactant content);
2612 mg/kg (expressed as solid content);
5236 mg/kg (expressed as test material, the aqueous solution)

No. of animals per sex per dose:

Single dosage, on Day 1: 5 males and 5 females (females were nulliparous and non-pregnant)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:

Mortality/Viability: Twice daily. The time of death was recorded as precisely as possible.
Body weights: Days 1 (pre-administration), 8 and 15 and at death.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: The animals surviving to the end of the observation period were sacrificed by an oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.

Statistics:

Not applicable

Results and discussion

Preliminary study:

Not applicable

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 236 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 612 mg/kg bw

Based on:

other: expressed as solid content

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

other: expressed as surfactant content

Mortality:

One female was found dead on day 2. No further mortality occurred.

Clinical signs:

other: The majority of surviving animals showed one or more of the following clinical signs between days 1 and 2: Chromodacryorrhoea, laboured respiration, rales, gasping, salivation, piloerection, hypothermia. Scales (grade 1) were seen in the treated skin-area

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the surviving animals.
Beginning autolysis was observed for the female that was found dead on day 2.

Other findings:

Not applicable

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 dermal ( rat): > 2612 mg/kg bw (expressed as solid content)

Executive summary:

An acute dermal toxicity study (limit test) was conducted with Alkylamidoamine glycinate maj. C12-14 (amphoacetate) (C8-C18 alkyl derivatives) in accordance with OECD 402 and according to GLP principles. A total of 10 rats (5 males and 5 females) were occlusive exposed to 4.47 mL/kg of an aqueous solution of the substance for 24 hours. The dose level was based on the surfactant content of the substance. One female was found dead on day 2. The majority of surviving animals showed chromodacryorrhoea, laboured respiration, rales, gasping, salivation, piloerection and hypothermia between days 1 and 2. No abnormalities were found at macroscopic post mortem examination of the surviving animals. Beginning autolysis was observed for the female that was found dead on day 2.

Based on the results of this study the substance does not need to be classified for acute dermal toxicity in accordance with the CLP Regulation as the acute dermal toxicity of the substance was determined to be above 2612 mg/kg.