Registration Dossier

Administrative data

Description of key information

There are key in vivo skin and eye studies showing no adverse effects.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Remarks:
SPF-Quality
Details on test animals or test system and environmental conditions:
3 males, animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.

Conditions:
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 +/- 3.0 oC (actual range: 19.4-21.4 oC), a relative humidity of 30-70% (actual range: 25-63%) and 12 hours artificial fluorescent light and 12 hours darkness per day.

Accomodation:
Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet:
Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day. Hay (BMI, Helmond, The Netherlands) was provided at least three times a week.

Water:
Free access to tap water.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.5 ml applied onto clipped skin
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours and 7 days after exposure
Number of animals:
three
Details on study design:
Observations:
Mortality/Viability: Twice daily
Toxicity: At least once daily
Body weight: Day of treatment (prior to application) and at termination
Irritation: The skin reactions were assessed at approximately 1, 24, 48, and 72 hours and 7 days after the removal of dressings and test substance. One animal was inadvertendly observed at 69.5 instead of 72 hours after exposure. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.
Histopathology: none
Irritation parameter:
erythema score
Basis:
animal: 601, 603, 605
Time point:
other: 1/24 hrs
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal: 601, 603, 605
Time point:
other: 48/72 hrs
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal: 601
Time point:
other: 1 hr
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
edema score
Basis:
animal: 601
Time point:
24/48 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
edema score
Basis:
animal: 603, 605
Time point:
other: 1 hr
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
edema score
Basis:
animal: 603, 605
Time point:
24 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 48 hrs
Irritant / corrosive response data:
Irritation:
Four hours exposure to 0.5 ml of pentamethyl-trioxepane resulted in well defined erythema and slight or moderate oedema in the treated skin-areas of the three rabbits. At 69.5/72 hrs the erythema was only observed at the edges of the application area. The skin irritation had resolved within 7 days after exposure in all animals.

Corrosion:
There was no evidence of a corrosive effect on the skin.

Colouration/Remnants:
No staining of the treated skin by the test substance was observed. Dry remnants of the test substance were present at the edges of the application-area of all rabbits during the observation period.

Toxicity/mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on these results pentamethyl-trioxepane does not have to be classified and has no obligatory labelling requirement for skin irriation.
Executive summary:

Based on these results pentamethyl-trioxepane does not have to be classified and has no obligatory labelling requirement for skin irriation.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
The temporary deviations from the minimum level of relative humidity occurred. Evaluation: laboratory historical data do not indicate an effect of the deviations. The study integrity was not adversely affected by the deviations.
GLP compliance:
yes
Specific details on test material used for the study:
Clear colourless liquid, purity 96.5%.
Species:
rabbit
Strain:
New Zealand White
Remarks:
SPF-Quality
Details on test animals or tissues and environmental conditions:
3 males, animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg

Conditions:
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 +/- 3.0 oC (actual range: 19.1-21.8 oC), a relative humidity of 30-70% (actual range: 25-61%) and 12 hours artificial fluorescent light and 12 hours darkness per day.

Accomodation:
Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet:
Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day. Hay (BMI, Helmond, The Netherlands) was provided at least three times a week.

Water:
Free access to tap water.
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
Single samples of 0.1 ml were instilled into one eye
Observation period (in vivo):
Observations were made 1, 24, 48 and 72 hours and 7 days after instillation
Number of animals or in vitro replicates:
3
Details on study design:
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner two weeks later, after considering the degree of eye irritation observed in the first animal.

Observations:
Mortality/Viability: Twice daily
Toxicity: At least once daily
Body weight: Day of treatment (prior to application) and at termination
Irritation: The eyes of each animal were examined approximately 1, 24, 48, and 72 hours and 7 days installation of the test substance. The irritation scores and a description of all other (local) effects were recorded.
Irritation parameter:
cornea opacity score
Basis:
animal: 547, 609, 611
Time point:
other: 1, 24, 48, 72 hrs and 7 days
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal: 547, 609, 611
Time point:
other: 1, 24, 48, 72 hrs and 7 days
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 547
Time point:
other: 1 hr
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 547
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 609
Time point:
other: 1/24 hrs
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 609
Time point:
other: 48/72 hrs
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 611
Time point:
other: 1/24/48 hrs
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 611
Time point:
72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal: 547
Time point:
other: 1/24 hrs
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal: 547
Time point:
other: 48/72 hrs
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal: 609
Time point:
other: 1 hr
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
chemosis score
Basis:
animal: 609
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
chemosis score
Basis:
animal: 611
Time point:
other: 1 hr
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
chemosis score
Basis:
animal: 611
Time point:
24 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 48 hrs
Irritant / corrosive response data:
Irritation:
Instillation of 0.1 ml of pentamethyl-trioxepane into one eye of each of three rabbits resulted in irritation of the conjuntivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 7 days.

No iridial irriation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage.

Corrosion:
There was no evidence of ocular corrosion.

Colouration/Remnants:
No staining of (peri)ocular tissues by the test substance was observed and no test substance remnants were seen.

Toxicity/mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on these results pentamethyl-trioxepane does not have to be classified and has no obligatory labelling requirement for eye irritation
Executive summary:

Based on these results pentamethyl-trioxepane does not have to be classified and has no obligatory labelling requirement for eye irritation

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Justification for classification or non-classification

Both the skin and eye studies are non-irritating. The data are conclusive but not sufficient for classification.