Di-tert-pentyl peroxide

Endpoint summary

Description of key information

Skin irritation:

For this endpoint, 2 studies are available (Doubs, 1995; Rees, 1992)

The study of Doubs (1995) was chosen as key study since it was performed with the highest substance purity. Both studies were performed according to OECD 404 guideline (or similarly) and the cutaneous reaction were observed until day 15. In both studies, erythema and edema were observed but disappeared before day 15.

In the study of Doubs (1995), the mean erythema and edema scores (over 24, 48 and 72 hours) were respectively 3.88 and 1.15. These scores were higher than those noted in the study of Rees (1992): 2.25 for the mean erythema score (3 animals), 1.11 for the mean edema score. These difference of scores could be partially explained by a lower purity.

In conclusion, di-tert-amyl peroxide is considered as a skin irritant.

 

Eye irritation:

For this endpoint, 2 studies are available (Doubs, 1995; Rees, 1992). Both were performed according to OECD 405 guideline (or similarly). The purity was close 100 % in the study of Doubs (1995) and 85 % in the study of Rees (1992). In both studies, mean scores calculated for animals over 24, 48 and 72 hours were less than 0.5. Therefore di-tert-amyl peroxide is considered as not irritating for rabbit’s eye.

.

Respiratory tract irritation

No sign of respiratory tract irritation was observed in the acute inhalation toxicity study performed with the analogue substance di-tert-butyl peroxide (Pothmann, 2010).

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:

1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: 1a: GLP, OECD Guideline 404

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Adult, New Zealand White rabbits were received at SLS from Myrtle's Rabbitry, Thompson Station, TN.
- Method of Identification: Upon receipt, plastic ear tags displaying unique identification numbers were used to individually identify the animals.
- Housing: The animals were housed individually in suspended stainless steel cages
-Food and water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature : 71 °F
- Humidity (%): 48-67
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied : 0.5mL on a clipped area
- Concentration: undiluted

Duration of treatment / exposure:

4H

Observation period:

72H
Examination time points: 1h, 24 h, 48 h and 72 hours after the patch removal.

Number of animals:

6 males

Details on study design:

Preliminary Procedures: On day -1, the animals chosen for use on the primary skin irritation study had the fur removed from the dorsal area of the trunk using an animal clipper. Care was taken to avoid abrading the skin during the clipping procedure.

TEST SITE
- Area of exposure: flank - Details:
- % coverage:
- Type of wrap if used:


REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with moistened cotton pad.
- Time after start of exposure: 4H


SCORING SYSTEM:
Irritation evaluated for each animal according to the grading scale originally proposed by Draize

Mortality checks were performed twice daily, in the morning and afternoon. lndividual body weights were obtained for each animal prior to dosing on study day O. Gross Necropsy: Each animal was euthanized (intravenous injection of sodium pentobarbital) following its final scoring interval. Gross necropsy examinations were not required for these animals

Irritation parameter:

erythema score

Basis:

animal: mean

Remarks:

see attached file

Time point:

24/48/72 h

Score:

3.88

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: mean for the 6 rabbits (5 rabbits with mean erythema score of 4)

Irritation parameter:

edema score

Basis:

animal: mean

Remarks:

see attached file

Time point:

24/48/72 h

Score:

1.15

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: mean for the 6 rabbits (4 rabbits with mean edema score of 1)

Irritant / corrosive response data:

Exposure to the test article produced very slight erythema on 1/6 test sites, mild to severe blanching on 5/6 test sites and very slight to slight edema on 6/6 test sites at the
1 hour scoring interval. The dermal irritation resolved completely in all animals by study
day 14. Additional dermal findings noted during the period included focal/pinpoint to moderate eschar, eschar exfoliation and desquamation, which were noted on 1/6, 1/6 and 6/6 test sites, respectively.

See individual results in the attached tables.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under these experimental conditions, di-tert-amyl peroxide is considered as a skin irritant.

Executive summary:

The acute dermal irritation of di-tert-amyl peroxide was evaluated in rabbits according to a method similar to OECD 404 guideline. 0.5 ml of the substance was applied undiluted during 4 hours in 6 rabbits on intact or scarified skin (occlusive dressing). The cutaneous reaction was observed 24, 48 and 72 hours after removal of the dressing, and at day 7, 10 and 14.

Exposure to the test article produced very slight erythema on 1/6 test sites, mild to severe blanching on 5/6 test sites and very slight to slight edema on 6/6 test sites at the 1 hour scoring interval. The mean erythema score (over 24, 48 and 72 hours) was 3.88 and the mean edema score was 1.75 (over 24, 48 and 72 hours).The dermal irritation resolved completely in all animals by study

day 14. Additional dermal findings noted during the period included focal/pinpoint to moderate eschar, eschar exfoliation and desquamation, which were noted on 1/6, 1/6 and 6/6 test sites, respectively.

The mena erythema and edema scores over 24, 48 and 72 hours were respectively 3.88 and 1.15.

Under these experimental conditions, di-tert-amyl peroxide is considered as a skin irritant.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: 1a, Eq to OECD Guideline 405, GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Adult, New Zealand White rabbits were received at SLS from Myrtle's Rabbitry, Thompson Station, TN.
- Upon receipt, plastic ear tags displaying unique identification numbers were used to individually identify the animais. Cage cards displaying at least the study number, animal number and sex were affixed to each cage.
- Age at study initiation: no data. Adults animals were used
- Weight at study initiation: 2.65-3.01kg
- Housing: The animals were housed individually in suspended stainless steel cages.
- Diet and water: ad libitum
- Quarantine period: 5days


ENVIRONMENTAL CONDITIONS
- Temperature: 71-73°F
- Humidity : 57-72%
- Air changes (per hr): approx. 12
- Photoperiod : 12 hrs dark / 12 hrs light

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye

Amount / concentration applied:

- Amount applied : 0.1mL

Duration of treatment / exposure:

24 h then rinced

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

6

Irritation parameter:

cornea opacity score

Basis:

animal: all

Remarks:

see attached file

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: all

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal: mean

Time point:

24/48/72 h

Score:

0.5

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal: mean

Time point:

24/48/72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Interpretation of results:

GHS criteria not met

Conclusions:

Under these experimental conditions, the test item di-tert-amyl peroxide was not irritant when administered by ocular route to rabbits.

Executive summary:

The potential of di-tert-amyl peroxide to induce ocular irritation was evaluated in rabbits according to a method similar to OECD 405 guideline.

A single dose of 0.1mL of the undiluted test item was instilled into the right conjunctival sac of 6 New Zealand White rabbits. The left eyes were not treated and served as control. The eyes were not rinsed after administration of the test item. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal. Mean scores calculated for animals over 24, 48 and 72 hours were 0.2 chemosis, 0.5 for redness of the conjunctiva, 0 for iris lesions and 0 for corneal opacity. Under these experimental conditions, the di-tert-amyl peroxide was slightly irritant when administered by ocular route to rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

According to EU Regulation (EC) N0. 1272/2008 (CLP), di-tert amyl peroxide is classified for skin irritation (Skin Irr cat 2/H315) but not for eye and respiratory tract irritation.