Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating; similar to US FHSA Federal regulation: 16 CFR 1500.41; pre-GLP; RL=2; undiluted test material applied to intact and abraded skin sites for 24 h under occlusive dressing; very slight erythema in 2/6 animals, no dermal irritation in 4/6 animals
Eye irritation: not irritating; similar to FHSA Federal regulation: 16 CFR 1500.42; pre-GLP; RL=2; undiluted test material applied to left eye of 6 animals without washing; no effects on cornea and iris, transient conjunctival redness (grade 1-2) in 5/6 animals and chemosis (grade 1) in 2/6 animals, fully reversible within 4 days

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
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure according to national (US) standard. Pre-GLP.
Qualifier:
according to
Guideline:
other: Appraisal of the safety of chemicals in foods, druge and cosmetics, by the Staft of the Division of Pharmacology, US FDA, skin toxicity according to Draize (1959)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
other: US FHSA Federal regulation: 16 CFR 1500.41
Deviations:
no
GLP compliance:
no
Remarks:
study performed before implementation of GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
DETAILS ON TEST ANIMALS
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.4 to 2.6 kg
- Housing: individually
- Diet (e.g. ad libitum): standard diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±1°C
- Humidity (%): 45 to 55%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light):12/12
Type of coverage:
occlusive
Preparation of test site:
other: one site shaved/intact + one site shaved/abraded
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated control sites on the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): used as suppplied
Duration of treatment / exposure:
24 h
Observation period:
72 h
Number of animals:
6
Details on study design:
TEST SITE
- The test material was applied to two clipped areas on each of six animals, one abraded and one left intact.
- Area of exposure: 2.5 x 2.5 cm
- Coverage ad wrap: Test sites were covered with medical strips which were fixed by leucoplast stripes. Whole animal trunk was wrapped in rubberized impervious cloth to minimize evaporation of the test substance. The animals were immobilized for the 24 hour exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

SCORING SYSTEM: erythema/eschar and edema scoring similar to OECD guideline 404
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: timepoint
Remarks:
no scoring at 48 h
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: timepoint
Remarks:
no scoring at 48 h
Irritation parameter:
erythema score
Remarks:
inta ct skin
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: timepoint
Remarks:
no scoring at 48 h
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not specified
Remarks:
study termination at 72 h, thus, reversibility cannot be evaluated
Remarks on result:
other: timepoint
Remarks:
no scoring at 48 h,
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: timepoint
Remarks:
no scoring at 48 h
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: timepoint
Remarks:
no scoring at 48 h
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: timepoint
Remarks:
no scoring at 48 h
Irritant / corrosive response data:
1/6 animals showed very slight erythema (grade 1) after 24 h, which was fully reversible within 72 h. In 1/6 animals very slight erythema (grade 1) was observed after 24 and 72 h. 4/6 animals showed no skin reactions at all.

Abraded skin:
1/6 animals showed very slight erythema (grade 1) after 24 and 72 h.

The observation time did not extend beyond 72 hours, even though a slight skin response was still present at that time in one animal. Therefore, the full reversibility of the effects can not be proved. However skin effects showed clear tendency of reversibility. At study termination, reversibility was complete in 1/2 affected animals. Therefore, a full reversibility seems to be very likely if the observation period had been extended to the period stipulated in the international guidelines.
Other effects:
No other effects were reported.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
In this primary dermal irritation study in rabbit, THFMA is not a dermal irritant.
Executive summary:

In a primary dermal irritation study similar to US FHSA Federal regulation: 16 CFR 1500.41, 6 rabbits were dermally exposed to 0.5 mL of THFMA (according to sponsor's information: purity ca. 98%) to approximately 2.5 cm² skin area. Two application sites per animal were treated, one site was left intact, the other was abraded. Test sites were covered with an occlusive dressing for 24 hours. Animals were observed for 72 hours. Irritation was scored similar to FHSA Federal guideline 16 CFR 1500.41. This scoring system is similar to OECD guideline 404.

Very slight dermal irritation response was observed in 1/6 animals on intact and abraded skin after 24 and 27 h and in 1/6 animals on intact skin after 24 h. All other animals showed no dermal irritation response.

The observation time did not extend beyond 72 hours, even though a slight skin response was still present at that time in one animal. Therefore, the full reversibility of the effects can not be proved. However skin effects showed clear tendency of reversibility. At study termination, reversibility was complete in 1/2 affected animals. Therefore, a full reversibility seems to be very likely if the observation period had been extended to the period stipulated in the international guidelines.

In this study, THFMA is not a dermal irritant.

 

Study performance does not comply with requirements of the relevant recent EU and OECD guidelines, where a less vigorous application regime with semi-occlusive dressing, an exposure period of 4 hours, treatment of only intact skin is stipulated.

Thus, it can be assumed, that a substance which shows no irritating activity under the application regime of guideline US FHSA Federal regulation: 16 CFR 1500.41 will also be non irritating under the application regimes of the relevant recent EU and OECD guidelines. Therefore the study is adequate for C&L purposes.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

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
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure according to national (US) standards comparable to international guidelines. Pre-GLP.
Qualifier:
according to
Guideline:
other: Appraisal of the safety of chemicals in foods, druge and cosmetics, by the Staft of the Division of Pharmacology, US FDA, Bewertung von Augen-Läsionen nach Draize (1959)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
other: US FHSA Federal regulation: 16 CFR 1500.42
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Remarks:
study performed before implementation of GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.4 to 2.6 kg
- Housing: individually
- Diet (e.g. ad libitum): standard diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±1°C
- Humidity (%): 45 to 55%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light):12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated right eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted, as supplied
Duration of treatment / exposure:
eys were not rinsed after application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): eyes were not rinsed for substance removal after treatment

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: no data
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 4 d
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 4 d
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3, #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal: #4, #5
Time point:
24/48/72 h
Score:
0.67
Max. score:
7
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
Transient conjunctival redness grade 1 (some blood vessels hyperaemic (injected)) to 2 (diffuse, crimson colour; individual vessels not easily discernible) was seen up to 72 h after application in 5/6 animals. Chemosis grade 1 (some swelling above normal) was observed in 2/6 animals. All other animals showed no reactions. All effects were completely reversible within 4 days.
Other effects:
no other effects reported
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
In this study, THFMA is not an eye irritant.
Executive summary:

In a primary eye irritation study similar to US FHSA Federal regulation: 16 CFR 1500.42 (similar to OECD guideline 405),

0.1 mL of THFMA (according to sponsor's information purity ca. 98%) was instilled into the conjunctival sac of the left eye of 6 New Zealand White rabbits without removing the test substance. Animals then were observed for 7 days. Irritation was scored by the method of Draize.

 

Transient conjunctival redness grade 1 (some blood vessels hyperaemic (injected)) to 2 (diffuse, crimson colour; individual vessels not easily discernible) was seen up to 72 h after application in 5/6 animals. Chemosis grade 1 (some swelling above normal) was observed in 2/6 animals. All other animals showed no reactions. All effects were completely reversible within 4 days. No irritating effects to the cornea and iris have been observed.

 

In this study, THFMA is not an eye irritant.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Reliable (RL=2), relevant and adequate studies are available to assess the skin and eye irritation potential of THFMA.

 

Skin irritation

In a primary dermal irritation study similar to US FHSA Federal regulation: 16 CFR 1500.41, 6 rabbits were dermally exposed to 0.5 mL of THFMA (according to sponsor's information: purity ca. 98%) to approximately 2.5 cm² skin area. Two application sites per animal were treated, one site was left intact, the other was abraded. Test sites were covered with an occlusive dressing for 24 hours. Animals were observed for 72 hours. Irritation was scored similar to FHSA Federal guideline 16 CFR 1500.41. This scoring system is similar to OECD guideline 404.

Very slight dermal irritation response was observed in 1/6 animals on intact and abraded skin after 24 and 27 h and in 1/6 animals on intact skin after 24 h. All other animals showed no dermal irritation response.

The observation time did not extend beyond 72 hours, even though a slight skin response was still present at that time in one animal. Therefore, the full reversibility of the effects can not be proved. However, skin effects showed clear tendency of reversibility. At study termination, reversibility was complete in 1/2 affected animals. Therefore, a full reversibility seems to be very likely if the observation period had been extended to the period stipulated in the international guidelines.

In this study, THFMA is not a dermal irritant.

Study performance does not comply with requirements of the relevant recent EU and OECD guidelines, where a less vigorous application regime with semi-occlusive dressing, an exposure period of 4 hours, treatment of only intact skin is stipulated. Thus, it can be assumed, that a substance which shows no irritating activity under the application regime of guideline US FHSA Federal regulation: 16 CFR 1500.41 will also be not irritating under the application regimes of the relevant recent EU and OECD guidelines. Therefore, the study is adequate for C&L purposes.

 

Eye irritation

In a primary eye irritation study similar to US FHSA Federal regulation: 16 CFR 1500.42 (similar to OECD guideline 405),

0.1 mL of THFMA (according to sponsor's information purity ca. 98%) was instilled into the conjunctival sac of the left eye of 6 New Zealand White rabbits without removing the test substance. Animals then were observed for 7 days. Irritation was scored by the method of Draize.

Transient conjunctival redness grade 1 (some blood vessels hyperaemic (injected)) to 2 (diffuse, crimson colour; individual vessels not easily discernible) was seen up to 72 h after application in 5/6 animals. Chemosis grade 1 (some swelling above normal) was observed in 2/6 animals. All other animals showed no reactions. All effects were completely reversible within 4 days. No irritating effects to the cornea and iris have been observed.

In this study, THFMA is not an eye irritant.

 

Respiratory irritation

No data on the respiratory irritation of THFMA are available.

 

There are no data gaps for the endpoint irritation/corrosion. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.


Justification for classification or non-classification

Based on the available data, THFMA does not need to be classified for eye irritation or skin irritation according to regulation (EC) 1272/2008 or the former European directive on classification and labelling 67/548/EEC. Thus, no labelling is required.