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Administrative data

Description of key information

The test material  FAT 46014 is non-irritant to the skin and eye.  
  

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:
1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 1930-2270 g
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): ad libitum.
- Water (e.g. ad libitum): ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30-70
- Air changes (per hr): approximately 15 air changes/h.
- Photoperiod (hrs dark / hrs light): 12 hours light/day

Type of coverage:
semiocclusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
1,24, 48, 72 hours
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: at least 6 cm²

SCORING SYSTEM:
<0.5: non-irritant
0.6 - 3.0: slightly irritant
3.1 - 5.0: irritant
5.1 - 8.0: severely irritant
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 hrs
Score:
0.17
Max. score:
8
Reversibility:
no data
Irritant / corrosive response data:
None
Other effects:
None

None

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of the present experiment FAT 46'014/F was found to be slightly irritating when applied to the rabbit skin.
Executive summary:

A key study was performed to determine the skin irritation potential of FAT 46'014/F with purity of 35.7 % on

rabbits skin. This test was conducted in GLP compliance. The test was carried out on both intact and abraded skin areals under semi-occlusive conditions. The calculated dermal irritation index was 0.17. Under the conditions, the test substance FAT 46'014/F was found to be slightly irritating when applied to the rabbit 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:
weight of evidence
Study period:
1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 1890-2090 g
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30-70
- Air changes (per hr): approximately 15 air changes/h.
- Photoperiod (hrs dark / hrs light): 12 hours light/day

Vehicle:
unchanged (no vehicle)
Controls:
other: right eye remained untreated and served as a control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
one second
Observation period (in vivo):
1, 24, 48, and 72 hours
Number of animals or in vitro replicates:
3 males
Details on study design:
SCORING SYSTEM:
The ocular reactions were examined 1, 24, 48, and 72 hours after substance instillation and again during the following observation period by means of a slit-lamp. The ocular irritation scores were evaluated according to the scoring system presented in the following table.
The irritating and/or corrosive potential of the test article (theoretical range: non irritant - extremely irritant) was assessed on the basis of the maximum irritant effect observed
- in one or several of the ocular tissues (conjunctiva, iris, cornea), observed over the range of observation time
- in one or more animals and taking into account the reversibility of the effect.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 h , 24 h and 72 h
Score:
1 - 2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1 h , 24 h and 72 h
Score:
1 - 2
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 h , 24 h and 72 h
Score:
1 - 4
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 h , 24 h and 72 h
Score:
1 - 4
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
None
Other effects:
The animals showed a normal body weight development.

None

Interpretation of results:
irritating
Remarks:
Migrated information With fully reversible effects Criteria used for interpretation of results: OECD GHS
Conclusions:
It can be concluded, that FAT 46014/F is irritant and not corrosive when applied to the rabbit eye mucosa; the animals had recovered at the end of the observation period of 11 days.
Executive summary:

A study was performed to determine the eye irritation potential of FAT 46'014/F with purity of 35.7 % on rabbits. The test was performed in GLP compliance and done in accordance of the " OECD test Guideline 405. The substance was found to be severely irritant and not corrosive when applied to the rabbit eye mucosa, however the animals had recovered at the end of the observation period of 11 days. Based on fully reversible results the substance is considered to be mild irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The irritation capacity on the skin and eye of animals was intensivly tested in the past and numerous data with different test substance concentrations are available.

Skin irritation:

In total five different studies with different test material concentrations are available.

In the latest study FAT 46014/F with a purity of about 36 % was investigated according to OECD 404 in the rabbit. Three animals have been tested for 4 hours on the intact and abraded skin under semiocclusive conditions. Taking the 24h, 48h and 72h readings into account (mean value 0 for erythema and eschar formation and mean value 0 for edema formation) the test substance has to be judged as non-irritating.

A second study investigating FAT 46014/E with a purity of 35 % in a pre-guideline study on abraded and intact skin areas under occlusive testing conditions resulted a mean of 1 for erythema/eschar formation and a mean of 1 for edema formation taking the 24h, 48h and 72h readings of the intact skin areas into account. Interestingly abrasion does not lead to further elevation of scores compared with intact skin areas.

A third study on FAT 46014/C with a purity of 18 % was performed in a pre-guideline test on the intact and abraded skin under occlusive conditions. Results obtained in 6 animals on intact skin areas resulted in mean values of 0.16 for erythema/eschar formation and 0.16 for edema formation with full recovery after 48 hours. Based on these results the substance has to be judged as not irritating to the skin. Notably, even slightly enhanced effects observed on abraded skin areas returned to normal 3 days after test substance application.

In the fourth study FAT 46014/B with a purity of 45 % was investigated in a pre-guideline test in six rabbits. Again the test substance was applied to intact and abraded skin areas under occlusive conditions. Unfortunately only readings 24 h and 72 h after test substance application have been reported. Nevertheless, the test substance showed no signs of irritation at all (all readings in all animals are zero) and no other effects are reported. Therefore it is concluded that the test substance did not induce any signs of irritation to the animals.

Last but not least a study has been performed on FAT 46014/A with a purity of 45 %. The test material was investigated in a pre-guideline study in six rabbits on intact and abraded skin areas under occlusive conditions. Also in this test only results from the 24 hour and 72 hour reading have been reported. But since all reading on the intact skin have been zero for erythema/eschar formation and edema formation and no other signs of toxicity or irritation effects have been noted the substance is judged to be not-irritating in this test.

In summary it can be noted that in general all tests may be used for assessment of the irritation potential to the skin of rabbits since test substance application and terms of testing conditions are comparable or slightly elevated compared to today’s standards (occlusive vs. semiocclusive testing conditions; abrasive vs intact testing conditions). But since data are reported very detailed, some effects of elevated testing conditions might be judged separately. As an overall conclusion it can be noted that up the maximum substance concentration of 45 % the test substance has to be judged as non-irritant according to CLP.

 

Eye irritation:

In total five different studies with different test material concentrations are available.

In the latest study FAT 46014/F with a purity of about 36 % was investigated according to OECD 405 in the rabbit. Three animals have been tested by instillation of 0.1 g into one eye while the other eye has been left untreated to serve as internal control. Rinsing of the eye has not been performed (as recommended by the guideline) representing an elevated testing condition. As a result, mean value for the cornea (24, 48 and 72 hour readings) is 1.2, mean value for the iris and mean values for the conjunctiva (24, 48 and 72 hour readings) are 1.9 for redness and 0.66 for chemosis. Taking these results into account the test substance has to be judged as irritating to the eye.

A second study investigating FAT 46014/E with a purity of 35 % in a pre-guideline study in six rabbits. Instillation of 0.1 g of the test material into one eye was followed by a rinsing procedure after 30 seconds in 3 animals while in further 3 animals the test substance remained in the eye. Scoring of the animals after 24, 48 and 72 hours resulted in no scores neither for cornea, nor for iris nor for conjunctive (all scores reported, all scores zero). Based on these test results the substance was judged not-irritating to the eye.

A third study on FAT 46014/C with a purity of 18 % was performed in a pre-guideline test in six rabbits. Animals have been instilled with 0.1 ml of the test substance in one eye while the other one left untreated and served as internal control. 1 min after test substance instillation eyes have been rinsed with saline to flush remaining test material out of the eyes. While slight scores of conjunctival redness occurred in treated animals at the first reading after one hour all scores had returned to zero after 6 hours. Therefore for the 24, 48 and 72 hour readings all scored have been zero. Based on these test results the substance was judged not-irritating to the eye.

In the fourth study FAT 46014/B with a purity of 45 % was performed in a pre-guideline test in six rabbits. Animals have been instilled with 0.1 ml of the test substance in one eye while the other one left untreated and served as internal control. 30 seconds after test substance instillation eyes have been rinsed with saline to flush remaining test material out of the eyes. At the first reading after one day all scores reported have been zero as well as all scores at the 48 and 72 hour readings. No further signs of irritation or other effects on the eye have been reported. Based on these test results the substance was judged not-irritating to the eye.

Last but not least a study has been performed on FAT 46014/A with a purity of 45 %. Animals have been instilled with 0.1 mg of the test substance in one eye while the other one left untreated and served as internal control. 30 seconds after test substance instillation eyes have been rinsed with saline to flush remaining test material out of the eyes. At the first reading after one day all scores reported have been zero as well as all scores at the 48 and 72 hour readings. No further signs of irritation or other effects on the eye have been reported. Based on these test results the substance was judged not-irritating to the eye.

In summary it can be noted that in general all tests may be used for assessment of the irritation potential to the eye of rabbits (weight of evidence approach). In all cases tests have been conducted either according to OECD guideline 405 or according to the procedure described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO) representing a test standard being used as a guidance to develop OECD Guideline 405 in the late 1980ies.

Based on above mentioned results it remains unclear why clear irritating effects have been observed with FAT 46014/F having only a test substance purity of about 36 % while other test sample preparations having much higher test substance concentrations led to no irritation at all (FAT 46014/A and FAT 46014/B). And also results with a comparable purity demonstrated no irritating effects at all (FAT 46014/E). So the only difference is that in all other studies the treated eyes have been flushed with either lukewarm water or physiological saline to remove remaining test material after 30 sec or 1 minute to prevent mechanical damage to the eye which is known to also cause irritating effects. Another option could be that maybe other ingredients present in the coupage of the test material caused those effects, but this remains elusive.

 

In summary, the registrant proposes to judge the test material as non-irritant to the skin and irritant to the eye. Judgement is based on the key study selected for skin irritation and based on a worst case approach taking all available data for eye irritation into account. 

  


Justification for selection of skin irritation / corrosion endpoint:
GLP guideline study

Justification for selection of eye irritation endpoint:
Weight of evidence approach

Justification for classification or non-classification

In summary, the registrant proposes to judge the test material as non-irritant to the skin and irritant to the eye. Judgement is based on the key study selected for skin irritation and based on a worst case approach taking all data available for eye irritation into account.