Registration Dossier

Administrative data

Description of key information

From the read across with 1, (3) 4-bis(tert-butylperoxyisopropyl)benzene: 1,4-di-(2-t-butylperoxyisolpropyl)benzene is not irritating to skin and is very slightly irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
january 13, 1986 to january 16, 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study was conducted in accordance with a recognized scientific procedure for analyzing the primary dermal irritation of a test material in experimental animals. However, the test material was a solid and was not pre-moistened. The test was performed on a 40% formulation. Study details were sufficient to support the conclusions in the report regarding the dermal irritation toxicity of the formulated test material. However, they are not sufficient to identify the dermal irritation potential of the more pure form of Bis (t-butyl peroxyisopropyl) benzene.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
other: EEC Directive 79-831, Annex V, part B: Methods for the determination of toxicity, B.4. Acute toxicity, skin irritation, date December 1983
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ENKI-Konijnenfarm, Someren, the Netherlands
- Weight at study initiation: 2500-3500 g
- Housing: individually in galvanised cages
- Diet : ad libitum
- Acclimation period: six days

ENVIRONMENTAL CONDITIONS
- Temperature : 15-21 °C
- Humidity: 40-70 %
- Air changes : 10 per hour
- Photoperiod : 12 hrs dark /12 hrs light):
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded skin
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Amount applied: 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
76 hours
Number of animals:
6 rabbits per group (abraded and unabraded test groups); closed patch technique was used.
Details on study design:
TEST SITE
- Area of exposure: 1 inch diameter
- Type of wrap if used: impervious material

SCORING SYSTEM:
- The skin reaction were evaluated by the method of Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: at 4 hours, 28 hours, 52 hours, 76 hours
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: Only one animal had a score of 1 at 28 hours; all the other scores at all the time point and for all the animals were 0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 4 hours, 28 hours, 52 hours, 76 hours
Score:
0
Max. score:
0
Irritant / corrosive response data:
The undiluted test substance is not a primary skin irritant

MEASURED ENDPOINT/INDEX (i.e. LD50, PII): Test material
produced very slight erythema and was not considered a
primary dermal irritation.

There was not dermal irritation after 4 hours of contact.
After 28 hours there was very slight erythema (grade 1) on abraded sites, but cleared by 52 hours. There was no edema
and no irritation observed on intact skin sites.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU directive 67/548/EEC and EU Regulation (EC) N0. 1272/2008 (CLP):
Conclusions:
Test material is not considered as a primary dermal irritant.
Executive summary:

The acute dermal irritation of the peroxide was evaluated in rabbits according to OECD 404 guideline.

The substance was applied undiluted and not pre-moistened to the skin of 6 New-Zealand White albino rabbits and held in contact for 4 hours by means of an occlusive dressing.

No irritation was observed.

Under the experimental conditions,the substance was considered as non irritant when applied topically in rabits.

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
January 13 to january 17, 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study was conducted in accordance with a recognized scientific procedure for analyzing the primary eye irritation of a test material in experimental animals. The test was performed on a 40% formulation. Study details were sufficient to support the conclusions in the report regarding the eye irritation of the formulated test material.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
other: EEC Directive 79-831, Annex V, methods for the determination of toxicity, B.5., Acute toxicity, eye irritation, dated December 1983
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: ENKI-Konijnenfarm, Someren, the Netherlands
- Weight at study initiation: 2500-3000 g
- Housing: individually in galvanized cages
- Diet and water : ad libitum
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature: 15-21 °C
- Humidity: 40-70 %
- Air changes : 10 per hr
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: To:
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
Concentration: 0.1 g of test material was instilled into the everted lower eye lid of one eye of each rabbit.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
Comment: not rinsed
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: after one hour, 24 hours, 48 hours and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: after one hour, 24 hours, 48 hours and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: after 24, 48 and 72 hours
Score:
0.6
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: after 24, 48 and 72 hours
Score:
0.2
Max. score:
1
Reversibility:
fully reversible within: 72 hours

The scores recorded for cornea and iris were zero (0) in all
rabbits at all reading times. A maximum score of 2 (slight
to moderate) for redness and 2 (slight to moderate swelling)
for chemosis were observed in 2/3 rabbits after 1 hour. At
24 hours only 1/3 rabbits still had a score of 2 for
redness, all other scores were 1 or 0. 2/3animals had a
score of 1 for redness, and 1/3 had a score of 1 for
chemosis at 48 hours. At 72 hours all scores were zero (0).
The laboratory stated that the test material was not an eye
irritant based upon the EEC standards for evaluation.

  Rabbit Opacity Iris Redness Chemosis
After one hour 1 0 0 2 1
2 0 0 2 2
3 0 0 1 1
After 24 hours 1 0 0 1 0
2 0 0 2 1
3 0 0 1 0
After 48 hours 1 0 0 0 0
2 0 0 1 1
3 0 0 1 0
After 72 hours 1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: Directive 67/548/EEC and CLP
Conclusions:
The test material was not an eye irritant based upon the EEC standards for evaluation.
Executive summary:

The potential of the peroxide to induce ocular irritation was evaluated in rabbits according to OECD405 guideline.

The substance was administered to three male New Zealand White rabbits.

A single dose of 0.1 g of the substance was instilled into the left/right conjunctival sac. The right/left eye was 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 of the test substance. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal.

After one hour, the eyes effects observed in all rabbits consisted of slight or moderate redness and slight or moderate swelling of the consjunctivae. All these clinical signs were fully reversible within 72 hours.

Mean scores calculated for each animal over 24, 48 and 72 hours were (0) (0.6) and (0) for chemosis, (0.3) (1) and (0.6) for redness of the conjunctiva, (0) (0) and (0) for iris lesions and (0) (0) and (0) for corneal opacity.

Under these experimental conditions, the test item was considered as sligh irritant when administered by ocular route to rabbits.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is no data on 1,4-bis(tert-butylperoxyisopropyl)benzene. A read across approach is proposed with 1, (3 4-bis(tert-butylperoxyisopropyl)benzene.

Skin irritation:

The acute dermal irritation of 1, (3) 4-bis(tert-butylperoxyisopropyl)benzene was evaluated in rabbits according to OECD 404 guideline (TNO, 1986). The substance was applied undiluted (purity 40%) and not pre-moistened to the skin of New-Zealand White albino rabbits and held in contact for 4 hours by means of an occlusive dressing. No irritation was observed.

Even if the purity was only 40% and even if the substance was not pre-moistened, data available from an acute dermal toxicity study (CIT, 1999) where no dermal signs were observed at high doses (2000 mg/kg) strengthen that the pure substance is not irritant. In addition, an in vitro skin irritation test (performed according to the OECD 439 guideline) on the pure meta isomer (CAS 2212-81-9) is currently available (Warren, 2012). In this test, the relative mean viability of the test item was 99.5 % of the negative control item. Therefore there was no skin irritation potential for the pure meta isomer. It can be anticipated there is neither no skin irritation potential for the para isomer.

Eye irritation

The potential of 1,(3) 4-bis(tert-butylperoxyisopropyl)benzene to induce ocular irritation was evaluated in rabbits (TNO, 1986) according to OECD 405 guideline (Klimish 2 study). In this test, three male New Zealand White rabbits were used. A quantity of 0.1 g of the substance (purity: 40%) was instilled in the conjunctival sac, and the eyes were not rinsed. After one hour, the eyes effects observed in all rabbits consisted of slight or moderate redness and slight or moderate swelling of the conjunctivae. All these clinical signs were fully reversible within 72 hours. All the mean scores calculated for each animal over 24, 48 and 72 hours were less than 1 (for chemosis, redness of the conjunctiva, iris lesions and corneal opacity). The purity of the substance was only 40 %; nevertheless, as only minimal signs of eye irritation were observed ( all scores were between 0 and 1, and as all clinical signs were fully reversible within 3 days), it is foreseeable that the substance with a higher purity is neither an eye irritant.

Conclusion

The substance 1,(3) 4-bis(tert-butylperoxyisopropyl)benzene is considered as non-irritant for skin and slight irritant when administered by ocular route to rabbits.


Justification for selection of skin irritation / corrosion endpoint:
Key study, Klimisch 2.

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

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

According to the directive 67/548/EEC and according to EU Regulation (EC) N0. 1272/2008 (CLP): 1,4-bis(tert-butylperoxyisopropyl)benzene is not classified as an eye irritant (even slight eye irritation was observed, all mean scores < 1) or as a skin irritant (no skin irritation observed).