Registration Dossier

Administrative data

Description of key information

Based on the available human and animal data, TAME is not irritating to the skin, eyes and respiratory tract.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, no restrictions, fully adequate for assessment.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK
- Age at study initiation: not indicated
- Weight at study initiation: 3.8 kg
- Housing: individually
- Diet: appr. 100-120 gram per animal/day
- Water: ad libitum
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/ artificial illumination from 6 to 18 hours
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral skin of each rabbit area acted as control.
Amount / concentration applied:
500 µl TAME
Duration of treatment / exposure:
4 hours
Observation period:
Draize scores were recorded for each animal at 1, 24, 48 and 72 hours and 7 days after the application of the substance.
Number of animals:
3
Details on study design:
A semiocclusive patch was used to cover a clipped patch on the dorso-lateral area of the trunk to which 500 μl of the test substance had been applied. The patch was left in place for 4 hours after which the exposed skin area was washed carefully. The contralateral skin area acted as control. Dermal irritation was scored and the degree of erythema and oedema, together with any other lesions, was recorded. Draize scores were recorded for each animal at 24, 48 and 72 hours after the application of the substance. The index was separately calculated for erythema/eschar and oedema formation.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours and 7 days
Score:
0
Max. score:
4
Reversibility:
other: no effects were seen at all
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours and 7 days
Score:
0
Max. score:
4
Reversibility:
other: no effects were seen at all
Irritant / corrosive response data:
All scores were zero at all time points. TAME was not irritating to albino rat skin.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, no restrictions, fully adequate for assessment.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK
- Age at study initiation: not indicated
- Weight at study initiation: 3.8 kg
- Housing: individually
- Diet: appr. 100-120 gram per animal/day
- Water: ad libitum
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / artificial illumination from 6 to 18 hours
Vehicle:
unchanged (no vehicle)
Controls:
other: the unexposed eye of each rabbit was the control
Amount / concentration applied:
100 µl TAME
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
Eye irritation was recorded 1, 24, 48, 72 hours, 7, 14 and 21 days after administration.
Number of animals or in vitro replicates:
3
Details on study design:
Three albino rabbits were administered 100 μl TAME to the conjunctival sac of one eye while the other remained as an untreated control. 24 hours after instillation, the test substance of the treated eye was rinsed with saline. Eye irritation was scored according to Draize and recorded 1, 24, 48, 72 hours, 7, 14 and 21 days after administration.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: maximal score (2) at 24 and 48 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: no effects were seen at all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects were seen at all
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1, 24 hours
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: maximal score (4) at 1 hour. The effects were observed in only one of the animals.
Irritant / corrosive response data:
The data do not imply classifying TAME as an eye irritating substance.
Other effects:
Discharge (grade 2-3) was observed after 1 hour in all three animals.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

TAME did not cause skin irritation in a study conducted on three albino rabbits under semi occlusive dressing following OECD Guideline 404 and performed under GLP (Bayer AG, 1991a). All scores for erythema and oedema formation were zero at all time points.

The eye irritation potentail of TAME has been studied in a study with three albino rabbits following OECD Guideline 405 and performed under GLP (Bayer AG, 1991b). Slight redness and swelling of the conjunctiva were recorded; however, the effects were reversible within 7 days of instillation of the test substance.

No animal studies regarding respiratory tract irritation are available. In the acute inhalation toxicity study (exposure to 5400 mg/m3 for 4 hours, ITT Research Institute, 1991) rales were seen in all rats immediately following the exposure. The rales were present in 7/10 animals about 2 hours after the exposure, but 3 ¼ hours later all rats appeared normal. Redness around the nose was noticed in 7/10 rats during the study at 5400 mg/m3.

The inhalation repeated dose toxicity studies with rats and mice do not trigger a concern for respiratory tract irritation.

In a volunteer study with six humans (Pekari et al, 1997b, see section on acute toxicity for study summary), TAME caused only minor acute effects (exposure concentrations: 15 (60 mg/m3) and 50 (212 mg/m3)). Slight irritation of the eyes, nose and throat and drying of the mouth were reported. The effects were considered marginal and do not give reason to classify TAME for eye and respiratory tract irritation.

Justification for classification or non-classification

Based on the available data and in accordance with the EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for skin, eye and respiratory tract irritation.