Di-tert-butyl 1,1,4,4-tetramethylbut-2-yn-1,4-ylene diperoxide

Endpoint summary

Description of key information

In an acute oral toxicity study with the test substance (AKZO Nobel 2001, 317712), an LD50 >2000 mg/kg was observed.

In an acute dermal toxicity study with the test substance (AKZO Nobel 2003, 366301), an LD50 >2000 mg/kg was observed.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2001-02-20 to 2011-03-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(1996)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(1996)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

Wistar strain Crl:(WI) BR (outbred, SPF-Quality)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Weight at study initiation: Body weight variation did not exceed ± 20 % of the sex mean.
- Fasting period: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 15 cm) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany).
- Identification: Earmark
- Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany)
- Water: Free access to tap-water
- Acclimation period: at least 5 days before start of the treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 15 per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

Single dosage of 2000 mg/kg (1.55 mL/kg) bw

No. of animals per sex per dose:

3 animals per sex (females were nulliparous and non-pregnant)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations:
Body weights: Day 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured

Clinical signs:

other: Lethargy, hunched posture, piloerection, and/or ptosis were noted among the animals between days 1 and 3. Lethargy, rales and salivation were noted in one male on day 12. Two males showed alopecia (throat region) before commencement of the study and durin

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, an LD50 value of the test item in Wistar rats was established to exceed 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study according to OECD guideline 423, test item was administered by oral gavage to groups of 3 Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. Lethargy, hunched posture, piloerection, and/or ptosis were noted among the animals between days 1 and 3. Lethargy, rales and salivation were noted in one male on day 12. The mean body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of the test item in Wistar rats was established to exceed 2000 mg/kg bw. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2003-01-15 to 2003-01-29

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

(June 1996)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(July 2000)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

Wistar strain Crl:(WI) BR (outbred, SPE-Quality)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: Body weight variation did not exceed ± 20 % of the sex mean
- Housing: Animals were individually housed in labbelled Macrolon cages (type III, height 15 cm) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany).
- Identification: Earmark
- Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany)
- Water: Free access to tap-water.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 15 per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Method: dermal application
- Area of exposure: One day before exposure (day -1) an area of approximately 5x7 cm on the back of animal was clipped.
- % coverage: The test substance was applied in an area approx. 10 % of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- Type of wrap: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D, Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, minnesota, U.S.A. (Caban & Micropore)), successively covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape was additionaly used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing: the dressing were removed and the skin were cleaned of residual test substance using tap water
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

single dosis of 2000 mg/kg (2.27 mL/kg) body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations:
Mortality/Viability: Twice daily
Body weights: Day 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of sosing (day 1) and once daily therafter, until day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

No statistical analysis was performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture and chromodacryorrhoea were observed in the majority of animals. Lethargy and ptosis were observed in one male. The animals had recovered from the symptoms by day 3. Erythema and scales were seen in the treated skin-area among the females

Gross pathology:

No abnormalities were found at macroscopic post mortem examinations of the animals.

Protocol Deviations: Deviations from the maximum level for relative humidity (with a maximum of 20 %) occurred which might have been caused by cleaning procedures in the room. Since there were no indications that the animals were influenced by this deviation, this deviation was considered not to have affected the study integrity.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, a dermal LD50 of the test substance in Wistar rats was establiehed to exceed 2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study according to OECD guideline 402, the test substance was administered to five Wistar rats of each sex (females were nulliparous and non-pregnant) by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occured. Hunched posture and chromodacryorrhoea were observed in the majority of animals. Lethargy and ptosis were observed in one male. The animals had recovered from the symptoms by day 3. Erythema and scales were seen in the treated skin-area among the females from days 2 to 7. The body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of the test item in Wistar rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study.

Additional information

Acute toxicity: oral
In an acute oral toxicity study according to OECD guideline 423, the test item was administered by oral gavage to groups of 3 Wistar rats of each sex at 2000 mg/kg body weight (AKZO Nobel 2001, 317712). Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. Lethargy, hunched posture, piloerection, and/or ptosis were noted among the animals between days 1 and 3. Lethargy, rales and salivation were noted in one male on day 12. The mean body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of the test item in Wistar rats was established to exceed 2000 mg/kg bw. 

Acute toxicity: inhalation
Additional testing by inhalation route is not applicable as data for oral and dermal toxicity were available. According to the REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5.1 only information on two application routes needs to be provided, with test item administration via the most appropriate route. Additionally, the vapour pressure of the test item is low (0.1 Pa at 25 °C) and exposure via inhalation route is not expected.

Acute toxicity: dermal
In an acute dermal toxicity study according to OECD guideline 402, the test item was administered to five Wistar rats of each sex (females were nulliparous and non-pregnant) by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).
No mortality occured. Hunched posture and chromodacryorrhoea were observed in the majority of animals. Lethargy and ptosis were observed in one male. The animals had recovered from the symptoms by day 3. Erythema and scales were seen in the treated skin-area among the females from days 2 to 7. The body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of the test item in Wistar rats was established to exceed 2000 mg/kg body weight.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008.

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for acute oral and dermal toxicity under Regulation (EC) No 1272/2008, as amended for the fifteenth time in Regulation (EU) 2020/1182.