Registration Dossier

Administrative data

Description of key information

The substance is not skin and eye irritating

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
Remarks:
read-across on structural analogue
Adequacy of study:
key study
Study period:
From 1984-03-26 To 1984-07-31
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed according to OECD guideline 404 and GLP, but is used in read across based on groupng of substances
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand White: Hy/Cr
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River France (76410 Saint Aubin les Elbeuf, France)
- Age at study initiation: no data
- Weight at study initiation: 2.35 kg +/- 0.05 kg
- Housing: individually in polystyrene cage (35 x 55 x 32 cm).
- Diet: rabbit diet SQC (Special diets Services Ltd, Witham, Essex, England), ad libitum
- Water: filtered water with 0.22 µm Millipore membrane (Millipore, 67120 Molsheim, France), ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 50 % +/- 20 %
- Air changes (per hr): no data (filtered Air)
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 1984-05-18 To: 1984-05-21
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated left flank
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.5 ml







Duration of treatment / exposure:
4 hours

Observation period:
3 days

Number of animals:
6

Details on study design:
TEST SITE
- Area of exposure: right flank (6 cm2)
- % coverage: no data
- Type of wrap if used: A gauze pad was applied on the tested area and was held in contact with the skin by means of an adhesive hypoallergenic
semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE: No

SCORING SYSTEM: according to the grading of skin reactions described in OECD guideline 404.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
> 0 - < 0.33
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Slight erythema was observed in all animals after one hour exposure and disappeared completely after 3 days. No edema was reported.
See table 1 in field "Remarks on results including tables and figures".
Other effects:
No other local or systemic effects were observed.

Table1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point/ Reversibility  Erythema
Max. score: 4
Edema
Max. score: 4

60 min

2/2/2/2/2/2 0/0/0/0/0/0

24 h

0/1/0/1/0/0 0/0/0/0/0/0

48 h

0/0/0/0/0/0 0/0/0/0/0/0

72 h

0/0/0/0/0/0 0/0/0/0/0/0

Average 24h, 48h, 72h

0.33/0/0 0

Reversibility*)

c. -

*) Reversibility: c.=completely reversible; n.c.= not completely reversible; n= not reversible

Grading of skin reactions:

Erythema and Eschar Formation

0 = No erythema

1 = Very slight erythema (barely perceptible)

2 = Well defined erythema

3 = Moderate to severe erythema

4 = Severe erythema (beef redness) to eschar formation preventing grading of erythema

Edema Formation

0 = No edema

1 = Very slight edema (barely perceptible)

2 = Slight edema (edges of area well defined by definite raising)

3 = Moderate edema (raised approximately 1 mm)

4 = Severe edema (raised more than 1 mm and extending beyond area of exposure)

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
Metiloil A was not considered to be a skin irritant.
Executive summary:

In a primary dermal irritation study (Kaysen A., 1984), young adult New Zealand White rabbits (6 males) were exposed by dermal contact to 0.5 ml of Metiloil A (batch No. 1169) onto one flank. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 3 days. Irritation was scored by the grading of skin reactions described in the OECD guideline 404. Slight erythema was observed in all animals after one hour exposure and disappeared completely after 3 days. No edema was observed. Mean scores over 1, 24, 48 and 72 hours were 2, 0.33, 0 and 0 for erythema and 0, 0, 0 and 0 for edema, respectivelly.

In this study, metiloil A is slightly irritating when applied topically to rabbit skin, but not classified according to the EU-GHS criteria.

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
Remarks:
read-across on structural analogue
Adequacy of study:
key study
Study period:
From 1984-03-26 To 1984-07-30
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed according to OECD guideline 405 and GLP but is used in read across based on grouping of substances.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand White: Hy/Cr
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River France (76410 Saint Aubin les Elbeuf, france)
- Age at study initiation: no data
- Weight at study initiation: 2.4 kg +/- 0.1 kg
- Housing: individually in polystyrene cage (35.0 x 55.0 x 32.0 cm)
- Diet: rabbit diet SQC (Special diets Services Ltd, Witham, Essex, England), ad libitum
- Water: filtered water with 0.22 µm Millipore membrane (Millipore, 67120 Molsheim, France), ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 50 % +/- 20 %
- Air changes (per hr): no data (filtered air)
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 1984-05-18 To: 1984-05-20
Vehicle:
unchanged (no vehicle)
Controls:
other: right eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:
not rinsed

Observation period (in vivo):
3 days

Number of animals or in vitro replicates:
6

Details on study design:
REMOVAL OF TEST SUBSTANCE: not rinsed

SCORING SYSTEM: similar to grading of ocular lesion described in 405 OECD guideline.


Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Remarks on result:
other: no effect
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
0.16
Max. score:
3
Reversibility:
fully reversible within: 1 day
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
2
Remarks on result:
other: no effect
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
4
Remarks on result:
other: no effect
Irritant / corrosive response data:
Conjunctivae effects were observed 1 hour after exposure. Slight chemosis and slight conjunctivae were observed in two animals and four animals, respectively. Two animals presented conjunctivae with diffuse, crimson colour and individual vessels not easily discernible. These effects were fully reversible within 1 day.
Other effects:
No data

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point/ Reversibility  Cornea
Max. score: 4
Iris
Max. score: 2
Conjunctivae
Max. score: 3
Chemosis
Max. score: 4
60 min 0/0/0/0/0/0 0/0/0/0/0/0 2/1/1/1/1/2 0/0/0/1/1/0
24 h 0/0/0/0/0/0 0/0/0/0/0/0 1/0/0/1/0/1 0/0/0/0/0/0
48 h 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0
72 h 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0

Average 24h, 48h, 72h

0 0 0.16 0
Reversibility*) - - c. c.

*) Reversibility: c.=completely reversible; n.c.= not completely reversible; n= not reversible

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
Metiloil A was not considered to be an eye irritant.
Executive summary:

In a primary eye irritation study (Kaysen A., 1984), 0.1 ml of Metiloil A (batch No. 1169) was instilled into the conjonctival sac of 6 New Zealand white male rabbits. Animals then were observed for 3 days. Slight irritation was observed one hour after treatment. Slight chemosis and slight conjunctivae were observed in two animals and four animals, respectively. Two animals presented conjunctivae with diffuse, crimson colour and individual vessels not easily discernible. Effects were reversible within one day. In this study, Metiloil A was not considered as an eye irritant based on EU-GHS.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

In general, esters of long-chain fatty acids are always negative with relation to irritation (from C18 onward), while esters of short-chain fatty acids are always (slightly) positive(up to C10). There are 2 relevant tests, for C16-C18and C18unsaturated me esters and fatty acids, rape oil, me esters , showing no irritation that support this conclusion. Eye irritation tests are negative too and it is unlikely that a substance would be less irritating to eyes than the skin.

However, as it is clear from literature that shorter chain fatty acid me esters can cause skin irritation, therefore this will need to be taken into account in the analysis. Directive 67/548/EEC (DSD) states for substances containing individual components then their classification should be taken into account when determining the classification of a substance. This does not mean automatically using the concentration limits set out in the DSD (for irritation it is 20%) but that would be a useful starting point. If any of the Biodiesel substances contained individual components causing irritation at a concentration>20% then this would be the starting point for any further analysis on irritation.

CONCLUSION

No classification for skin irritation is warranted under 67/548/EEC or Regulation 1272/2008.

No classification for eye irritation is warranted under 67/548/EEC or Regulation 1272/2008.