2-(tert-butylamino)acetic acid hydrochloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 - 23 September 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines (2011)

Version / remarks:

Including the most recent partial revisions

Principles of method if other than guideline:

Protocol deviations:
1. Deviations from the maximum level of relative humidity occurred.
Evaluation: Laboratory historical data do not indicate an effect of the deviations. The study integrity was not adversely affected by the deviation.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-(tert-butylamino)acetic acid hydrochloride

EC Number:

614-959-3

Cas Number:

6939-23-7

Molecular formula:

C6H14ClNO2

IUPAC Name:

2-(tert-butylamino)acetic acid hydrochloride

Test material form:

solid: particulate/powder

Details on test material:

White powder
Test substance storage: In refrigerator (2-8°C) in the dark

Specific details on test material used for the study:

White powder
Test substance storage: In refrigerator (2-8°C) in the dark
Batch #: 11681004

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Albino rabbit, New Zealand White, from Charles River France, L’Arbresle Cedex, France . Recognized by international guidelines as the recommended test system. 3 males used within the study were 10-20 weeks old and body weights were 2-4 kg.
The 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: 18.7 – 20.2ºC), a relative humidity of 40-70% (actual range: 47 - 89%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
Animals were individually housed in labeled cages with perforated floors and shelters. Acclimatization period was at least 5 days before start of treatment under laboratory conditions.
Pelleted diet for rabbits approximately 100 grams per day. Hay and wooden sticks were available during the study period. Free access to tap water.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes

Amount / concentration applied:

Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was moistened with 0.2 mL of the vehicle and applied to the skin of one flank, using a metalline patch# of 2x3 cm.

Duration of treatment / exposure:

Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water

Observation period:

1 hr., 24 hrs., 48 hrs., and 72 hrs.

Number of animals:

3 males

Details on study design:

The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of skin irritation observed in the first animal.
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.
Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was moistened with 0.2 mL of the vehicle and applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.
After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20%
Observations:
Mortality/Viability - Twice daily.
Toxicity - At least once daily.
Body Weight - Day of treatment (prior to application) and after the final observation.
Necropsy - No necropsy was performed according to protocol.
Irritation - The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 149 (sentinel)

Time point:

other: 1 hr., 24 hrs., 48 hrs., and 72 hrs.

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal: 146

Time point:

other: 1 hr., 24 hrs., 48 hrs., and 72 hrs.

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal: 147

Time point:

other: 1 hr., 24 hrs., 48 hrs., and 72 hrs.

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal: 149 (sentinel)

Time point:

other: 1 hr., 24 hrs., 48 hrs., and 72 hrs.

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal: 146

Time point:

other: 1 hr., 24 hrs., 48 hrs., and 72 hrs.

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal: 147

Time point:

other: 1 hr., 24 hrs., 48 hrs., and 72 hrs.

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Irritation:
No skin irritation was caused by 4 hours exposure to N-butylglycine HCl.
Corrosion:
There was no evidence of a corrosive effect on the skin.

Other effects:

Coloration / Remnants:
No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
Toxicity / Mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

The irritation was assessed according to the following numerical scoring system. At each observation,

the highest scores given were recorded:

Erythema and eschar formation:

No erythema .......................................................................................................................... 0

Very slight erythema (barely perceptible) ............................................................................... 1

Well-defined erythema ........................................................................................................... 2

Moderate to severe erythema ................................................................................................. 3

Severe erythema (beet redness) * .......................................................................................... 4

*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.

Oedema formation:

No oedema ............................................................................................................................ 0

Very slight oedema (barely perceptible) ................................................................................. 1

Slight oedema (edges of area well-defined by definite raising) ............................................... 2

Moderate oedema (raised approximately 1 millimeter) ........................................................... 3

Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Three rabbits were exposed to 0.5 grams of N-butylglycine HCl, moistened with water, by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure. No skin irritation was caused by 4 hours exposure to N-butylglycine HCl.

Executive summary:

Based on these results, N-butylglycine HCl does not have to be classified and has no obligatory labelling requirement for skin irritation according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United

Nations (2011),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and

mixtures