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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
24 May to 7 June 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD 404 and GLP principles. It should be noted that a 2.38% solution of TMAH was tested.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Adopted 17 July 1992
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
August 1998
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2.38% TMAH
- Physical state: Clear colourless liquid
- Composition of test material, percentage of components: Tetramethylammonium hydroxide 2.38%
- Expiration date of the lot/batch: Not advised but assumed to be stable for six months from date of receipt (25 April 2000)
- Storage condition of test material: Room temperature under nitrogen until 17 May 2000 and from thereafter room temperature in the dark under nitrogen

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd., Bicester, Oxon, England
- Age at study initiation: at least 12 weeks
- Weight at study initiation: 2.5-3 kg
- Housing: individually
- Diet: ad libitum, standard laboratory rabbit diet (special diet services STANRAB (P) SQC pellet), additionally hay, on arrival and three times a week
- Water: potable water, ad libitum
- Acclimation period: ≥ 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-20.5
- Humidity (%): 46-73.5
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 24 May To: 7 June 2000

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: removed with electric clippers, 24 hours prior to application
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration (if solution): 2.38%; aqueous
Duration of treatment / exposure:
4 hours; one animal was dosed on three different spots with different exposure times (3 minutes, 1 hour and 4 hours resp.) .
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 25 mm * 25 mm
- Type of wrap if used: substance applied under 2-ply porous gauze pad, covered with "Elastoplast" elastic adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with warm water (34 to 36°C) and blotted dry with absorbent paper
- Time after start of exposure: 4 hours

SCORING SYSTEM: According to OECD guideline 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hours
Score:
2.43
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Effect not reversed in one animal
Irritation parameter:
edema score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hours
Score:
1.33
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
No dermal irritation was observed following a single semi-occlusive application of 2.38% TMAH to intact rabbit skin for three minutes.
Well-defined erythema was seen following application for one hour, which resolved completely on Day 6.
Severe erythema with moderate oedema was observed in one animal accompanied by a necrotic patch following the four hour exposure. Well-defined erythema with very slight oedema was seen in the remaining two animals. In addition desquamation (characterised by dryness and sloughing) was observed in all animals and thickening of the skin in one animal. Reactions had resolved in two animals by either Day 8 and 9, however very slight erythema was still evident in the remaining animal at study termination on Day 14.

Applicant's summary and conclusion

Interpretation of results:
Category 1C (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
An acute dermal irritation /corrosion test according to OECD 404 with 2.38% TMAH was performed under GLP circumstances. The 2.38% TMAH-solution was shown to be irritant to the skin, category 1C (according to EC regulation No 1272/2008).
Executive summary:

An acute dermal irritation /corrosion test according to OECD 404 with 2.38% TMAH was performed under GLP circumstances. No dermal irritation was observed following application for 3 minutes. Application for one hour elicited well-defined dermal irritation. Application for 4 hours resulted in well-defined to severe dermal irritation in all animals, with necrosis in one animal. Due to the severity in this animal and the irreversibility of the effect, the 2.38% TMAH-solution was shown to be corrosive to the skin, category 1C (according to EC regulation No 1272/2008).