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Toxicological information

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:
28. Dec. 2005 - 11. Jan. 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
480-680-7
EC Name:
-
Cas Number:
120128-90-7
Molecular formula:
Hill formula: C8H16N2O3 CAS formula: C8H16N2O3
IUPAC Name:
2-[(3-formamidopropyl)dimethylazaniumyl]acetate

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 (outbred, SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. OECD, EC).
Source : Charles River Deutschland, Sulzfeld, Germany.
Number of animals : 5 males and 5 females (females were nulliparous and nonpregnant).
Age and body weight : Young adult animals (approx. 9 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification : Earmark
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 ± 3.0°C (actual range: 20.5 - 22.4°C), a relative humidity of 30-70% (actual range: 45 - 70%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
Accommodation : Individually housed in labeled Macrolon cages (Mill type, height 18 cm.) containing sterilized sawdust as bedding material (Woody-Clean type 3/4; Tecnilab-BMI BV, Someren , The Netherlands) and paper as cage-enrichment (Enviro-dri, Tecnilab-BMI BV, Someren, The Netherlands ). 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 standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany).
Water : Free access to tap water.
Results of analysis for each batch of diet (nutrients) and results of quarterly analysis of diet (contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Method : Dermal application.
Clipping : One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application : 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. 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 Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).
Frequency : Single dosage, on day 1.
Dose level (volume) : 2000 mglkg (3.8 mllkg) body weight. Purity of the test substance was taken into account. Dose volume calculated as dose level: specific gravity.
Application period : 24 hours, after which dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Mortality/Viability : 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. 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 : At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

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:
Chromodacryorrhoea was noted among the animals on days 1 and 2. Scales were seen in the treated skin-area of some animals between days 3 and 12.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity,
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals,

Any other information on results incl. tables

BODY WEIGHTS (GRAM)

Sex/dose level

animal

Day 1

Day 8

Day 15

Males 2000 mg/kg

1

290

318

348

 

2

286

307

332

 

3

292

316

341

 

4

326

352

400

 

5

319

337

375

 

Mean

303

326

359

 

St Dev

18

18

28

 

N

5

5

5

Females 2000 mg/kg

6

211

229

243

 

7

195

206

209

 

8

206

228

244

 

9

217

233

241

 

10

220

241

251

 

Mean

210

227

238

 

St Dev

10

13

16

 

N

5

5

5

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The dermal LD50 value of FORMAMIDOPROPYLBETAINE in Wistar rats was established to exceed 2000 mg/kg body weight (corrected for purity of the test substance).
Executive summary:

Assessment of acute dermal toxicity with FORMAMIDOPROPYLBETAINE in the rat.

The study was carried out based on the guidelines described in: OECD No 402 (1987) "Acute Dermal Toxicity" EC, Council Directive 67/548/EEC, Annex V, B.3 (1992) "Acute Toxicity (Dermal)" EPA, OPPTS 870.1200 (1998), "Acute Dermal Toxicity" JMAFF Guidelines (2000), including the most recent revisions.

FORMAMIDOPROPYLBETAINE was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred, Chromodacryorrhoea was noted among the animals on days 1 and 2, Scales were seen in the treated skin-area of some animals between days 3 and 12. The body weight gain 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 FORMAMIDOPROPYLBETAINE in Wistar rats was established to exceed 2000 mg/kg body weight (corrected for purity of the test substance).

Based on these results FORMAMIDOPROPYLBETAINE 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) of the United Nations (New York and Geneva, 2003) and EC criteria for classification and labelling requirements for dangerous substance and preparations (Council Directive 67/548/EEC).