Registration Dossier

Administrative data

Description of key information

Tert-amyl hydroperoxide is corrosive to skin after 4 hours exposure (Manciaux, 1998) and after 24 hours exposure (Lina, 1981a) and it is very severely irritating for eye (Lina, 1981b). No respiratory tract irritation was observed in inhalation toxicity studies.

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:
1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Animals:
Breeder: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
Number and identification: one animal was used. The animal was identified with a metal tag in the ear.
Weight: on the day of treatment, the animal had a body weight of 2.4 kg.
Acclimatization: at least 5 days before the beginning of the study.

Environmental conditions:
The animal was housed in a polystyrene cage (35 cm x 55 cm x 32 cm or 48.2 cm x 58 cm x 36.5 cm) equipped with a food container and a water bottle
. temperature: 18 ± 3°C
. relative humidity: 30 to 70%
. light/dark cycle: 12 h/12 h
. ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
. Food and water were provided at libitum
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
3 minutes and 4 hours
Observation period:
The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing, and then daily until day 9.
Number of animals:
1
Details on study design:
Doses of 0.5 ml of the test substance were placed on a 6 cm2 dry gauze pad, which was then applied to the right flank (application for 4 hours) or the left flank (application for 3 minutes) of the animal.
As possible irritant effects were anticipated, the test substance was evaluated in one animal in a first assay. The duration of exposure was 3 minutes on one flank and 4 hours on the other flank.
The animal was killed on day 9 for ethical reasons.
Irritation parameter:
other: mean erythema score after a 3-min exposure
Basis:
animal #1
Time point:
other: 24 h, 48 h, 72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 9 days
Remarks on result:
other: Black coloration and thickening of the skin from day 5.
Irritation parameter:
other: mean oedema score after a 3-min exposure
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
other: score masked by thickening of the skin from D5
Irritation parameter:
other: mean erythema scores after a 4 hour-exposure
Basis:
animal #1
Time point:
other: 24h, 48 h and 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
9 days (the animal was sacrified at day 9 for ethical reasons)
Remarks on result:
other: necrosis until day 9, then tissue destruction
Irritation parameter:
other: mean oedema scores after a 4 hour-exposure
Basis:
animal #1
Time point:
other: 24 h, 48 h, 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
scoring masked by necrosis from D5
Irritant / corrosive response data:
After a 3-minute exposure: A well-defined or moderate erythema (grade 2 or 3) was observed between day 1 and day 5 and
a slight oedema (grade 2) was noted between day 1 and day 4. A thickening and a black colouration of the skin were noted from day 5.

After a 4-hour exposure: A severe erythema (grade 4) and a slight or severe oedema (grade 2 or 4) were observed from day 1. Signs of necrosis were observed from day 2; they have masked the evaluation of cutaneous reactions from day 5. A tissular destruction was recorded on day 9.


Other effects:
No other effects.
The animal was killed on day 9 for ethical reasons.
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Under the experimental conditions, tert-amyl hydroperoxide is corrosive when applied topically to rabbits for 4 hours.
Executive summary:

The potential of the test substance LUPEROX TAH 85 to induce skin irritation was evaluated in rabbits according to OECD guideline no. 404 and GLP. The test substance was applied for periods of 3 minutes and 4 hours to one male New Zealand White rabbit. A single dose of 0.5 ml of the undiluted test substance was applied to the closely-clipped skin of each flank. The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until day 9. The mean values of the scores for erythema and oedema were calculated.

After a 3-minute exposure, a well-defined or moderate erythema was observed between day 1 and day 5 and a slight oedema was noted between day 1 and day 4. A thickening and a black colouration of the skin were noted from day 5. After a 4-hour exposure, a severe erythema and a slight or severe oedema were observed from day 1. Signs of necrosis were observed from day 2; they have masked the evaluation of cutaneous reactions from day 5. A tissular destruction was recorded on day 9.

The animal was killed on day 9 for ethical reasons. LUPEROX TAH 85 is corrosive when applied topically to rabbits for 4 hours.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Some data are missing (no certificat of analysis for example), nevertheless the sutdy is sufficiently detaile for eye irritation assessment
Qualifier:
no guideline available
Principles of method if other than guideline:
Techniques of tests as published by the F.DA of the United States (Fed. R.eg.28(119), 5582, 1963) and Draize and Kelley.
GLP compliance:
not specified
Species:
rabbit
Strain:
other: White albino
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
other: one eye served as control
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
The eye was examined at 24, 48, 72 hours and 7 days after instilla­
tion of the test material.
Number of animals or in vitro replicates:
1
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal 1
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Iris not discernable after 14 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal 1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Score of 3 after 7 and 14 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal 1
Time point:
other: 24, 48 and 72 hours
Score:
2.3
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritant / corrosive response data:
Immediately after the instillation of the test substance the animal expressed pain by squealing.
The ocular effects after 24 hours consisted of moderate corneal opacity, slight iritis, moderate discharge of eye fluid and moderate redness and severe swelling of the conjunctivae. After seven days severe corneal opacity and deformation of the eyeball (ulcus corneae) was observed.
In addition vascularisation of the cornea was noted after 4 days.

Eye irritative effects following instillation of tert.

amylhydroperoxid into the eye of one albino rabbit.

  cornea Iris Conjunctivae score
    redness chemosis
after 1 day 2 1 2 4
after 2 days 2 1 2 3
after 3 days 2 1 3 3
after 7 days 3 1 2 1
after 14 days 3 ? 1 1

? = iris not discernable

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Tert-amyl hydroperoxide is severely irritating for eyes.
Executive summary:

The potential of tert-amyl hydroperoxide to induce ocular irritation was evaluated in a rabbit after 24 hour exposure to 0.1 ml of the substance.

Immediately after the instillation of the test substance the animal expressed pain by squealing. Due to severity of the effects, no other animal was used.

The ocular effects after 24 hours consisted of moderate corneal opacity, slight iritis, moderate discharge of eye fluid and moderate redness and severe swelling of the conjunctivae. After seven days severe corneal opacity and deformation of the eyeball (ulcus corneae) was observed.

In addition vascularisation of the cornea was noted after 14 days. Iris was not discernable after 14 days.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

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

Additional information

Skin irritation/corrosion

Two reliable studies are available for this endpoint: Manciaux (1998) and Lina (1981a).

In a key study (Manciaux, 1998), the potential of LUPEROX TAH 85 (containing 86.7% t-amyl hydroperoxide) to induce skin irritation was evaluated in rabbits according to OECD guideline no. 404 and GLP. The test substance was applied for periods of 3 minutes and 4 hours to one male New Zealand White rabbit. A single dose of 0.5 ml of the undiluted test substance was applied to the closely-clipped skin of each flank. The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until day 9. The mean values of the scores for erythema and oedema were calculated.

After a 3-minute exposure, a well-defined or moderate erythema was observed between day 1 and day 5 and a slight oedema was noted between day 1 and day 4. A thickening and a black colouration of the skin were noted from day 5. After a 4-hour exposure, a severe erythema and a slight or severe oedema were observed from day 1. Signs of necrosis were observed from day 2; they have masked the evaluation of cutaneous reactions from day 5. A tissular destruction was recorded on day 9. The animal was killed on day 9 for ethical reasons. LUPEROX TAH 85 is corrosive when applied topically to rabbits for 4 hours.

This conclusion is supported by results of Lina study (1981a), which assessed in several rabbits skin irritation/corrosion potential after topical application of tert-amyl hydroperoxide on the intact or abraded skin of 12 rabbits for 24 hours. The skin reactions were observed at 24 and 72 hours. The test material caused very severe skin irritation. The dermal effects consisted of distinct ischemia and very severe oedema extending far beyond the area of exposure after 24 hours and very severe incrustation after 72 hours.

Eye irritation/corrosion

The potential of tert-amyl hydroperoxide to induce ocular irritation was evaluated in a rabbit after 24 hour exposure to 0.1 ml of the substance (Lina, 1981b). Immediately after the instillation of the test substance the animal expressed pain by squealing. Due to severity of the effects, no other animal was used. The ocular effects after 24 hours consisted of moderate corneal opacity, slight iritis, moderate discharge of eye fluid and moderate redness and severe swelling of the conjunctivae. After seven days severe corneal opacity and deformation ofthe eyeball (ulcus corneae) was observed. In addition vascularisation of the cornea was noted after 14 days. Iris was not discernable after 14 days. In conclusion, tert-amyl hydroperoxide causes severe eye damages in rabbits.

Respiratory irritation:

No clinical and/or histological sign of respiratory tract irritation was observed in acute, 5-day and 28-day inhalation toxicity studies.


Justification for selection of skin irritation / corrosion endpoint:
Key study, Klimisch 1.

Justification for selection of eye irritation endpoint:
Key study, Klimisch 2.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

According to Regulation (EC) N°1272/2008 (CLP), the substance is classified category 1B for skin corrosion (H314), since it is an hydroperoxide and since there is no data after 1 hour to justify a category 1C. In addition TAHP is classified category 1 for eye irritation (H318).