O,O-tert-butyl isopropyl monoperoxycarbonate

Endpoint summary

Description of key information

TERT-BUTYLPEROXIDE ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL

SPIRIT was administered to Wistar rats of each sex at 2000 mg/kg body weight. Since no mortality occurred, the oral LD50 value of TERT-BUTYLPEROXIDE ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT in Wistar rats was established as exceeding 2000 mg/kg body weight.

In the acute dermal toxicity sudy in rats, no mortality occurred. The LD50 of the substance was established as exceeding

2000 mg/kg body weight.

Assessment of acute oral toxicity was carried out based on OECD No.423, 'Acute Oral Toxicity - Acute Toxic Class Method'. For the dermal toxicity, testing was based on the guideline OECD No.402, “Acute Dermal Toxicity”. Based on these conclusions in oral and dermal toxicity testing, the substance does not have to be classified and has no obligatory labelling requirement for oral and dermal toxicity.

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:

Experimental start date: 14 October 1998 Experimental end date: 8 December 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Identification: Tert- butylperoxy isopropyl carbonate, 75% solution in
aromatic free mineral spirit
Description: Clear colourless liquid
Akzo Nobel Trade Name: Trigonox BPIC-C75
Chemical Name: Tert - butylperoxy isopropyl carbonate, 75% solution in
aromatic free mineral spirit
Cas-No: 2372-21 - 6
Batch: 0419804130350
Test substance storage: storage In refrigerator in the dark
Expiry date: 01 October 1999 (allocated by NOTOX, 1 year after receipt
of the test substance)
Density: 900 - 910 kg/m' {20'C)

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST SYSTEM
Species
Rat, Wistar strain Crl: (WI} BR (outbred, SPF- Quality}.
Recognised by international guidelines as the recommended
test system (e.g. OECD, EC}.
Source: Charles River, Sulzfeld, Germany.

Number of animals
6 Animals. Each dose group consisted of 3 animals of one
sex (females were nulliparous and non- pregnant).

Identification
Earmark

ANIMAL HUSBANDRY
Conditions
Air-conditioned room with approximately 15 air changes per hour and the
environment controlled with optimal,conditions considered as being a temperature
of 21°C and a relative humidity of 50%. Lighting was 12 hours artificial
fluorescent light and 12 hours dark per day. Deviations from these optimal
conditions were noted, but were considered not to have affected study integrity.

Accommodation
Group housing of 3 animals per sex per cage in labelled polycarbonate cages
containing purified sawdust as bedding material (Woody SPF, supplied by B. M. I. ,
Helmond, The Netherlands). Certificates of analysis were examined and then
retained in the NOTOX archives.
Acclimatisation period was at least 5 days before start of treatment under
laboratory conditions.

Diet
Free access to standard pelleted laboratory animal diet (from Carfil Quality
BVBA, Oud-Turnhout, Belgium). Certificates of analysis were examined and then
retained in the NOTOX archives.

Water
Free access to tap-water. Certificates of quarterly analysis were examined and
then retained in the NOTOX archives.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Method
Oral gavage, using a stainless steel stomach tube.
Fasting
Food was withheld overnight prior to dosing until
approximately 3 - 4 hours after administration of the test
substance.

Doses:

2000 mg/kg

No. of animals per sex per dose:

The test substance was tested at a dose level of 2000 mg/kg body weight performed with 3 males and 3 females.

Control animals:

no

Details on study design:

Study Design
TREATMENT
Frequency
Females: Single dosage, on day 1 .
Males: Unintentionally, two dosages were given on t=O and
t=0. 5 hours (see also dose volume). This event was
evaluated by the study director and considered not to
have affected the study integrity. These two dosages were
regarded as a single dose.

Dose level (volume)
Females: 2000 mg/kg (2. 2 ml/kg) body weight.
Males: 2000 mg/kg. This dose level was reached by
administration of 818 mg/kg (0. 9 ml/kg) b. w. and 1182
mg/kg (1.3 ml/kg) body weight.
Dose volumes calculated as follows:
dose level : density (905 kg/m3).

OBSERVATIONS
Mortality/Viability
Twice daily

Body weights
Days 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. The time of onset,
degree and duration were recorded and the symptoms graded
according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).

Necropsy
At the end of the observation period, all animals were
sacrificed by asphyxiation using an oxygen/carbon dioxide
procedure and subjected to necropsy. Descriptions of all
internal macroscopic abnormalities were recorded.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured

Clinical signs:

other: Males lethargy in one male on day 1. Females lethargy, hunched posture and uncoordinated movements on day 1 and red staining of the head and neck on days 2 and 3. Salivation was observed in one female immediately after treatment. This finding is commonly

Gross pathology:

An irregular surface of the forestomach or thickening of the glandular mucosa
and the limiting ridge was found in all animals at macroscopic post mortem
examination. No further abnormalities were found.

Interpretation of results:

GHS criteria not met

Conclusions:

Local toxicity was produced by the test substance in the stomach, which was
considered to be caused by the irritating properties of the test substance.
Since no mortality occurred, the oral LD50 value of TERT-BUTYLPEROXIDE ISOPROPYL
CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT in Wistar rats was
established as exceeding 2000 mg/kg body weight.
Based on these results and according to the EC criteria for classification and
labelling requirements for dangerous substances and preparations (Guidelines in
Commission Directive 93/21/EEC), TERT-BUTYLPEROXIDE ISOPROPYL CARBONATE, 75%
SOLUTION IN AROMATIC FREE MINERAL SPIRIT does not have to be classified and has
no obligatory labelling requirement for oral toxicity.

Executive summary:

Assessment of acute oral toxicity with TERT - BUTYLPEROXIDE ISOPROPYL CARBONATE,

75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT in the rat (Acute Toxic Class

Method).

The study was carried out based on the guidelines described in: EC Commission

Directive 96/54/EC, Part B.1 tris 'Acute Toxicity-Oral, Acute Toxic Class

Method' and OECD No.423, 'Acute Oral Toxicity - Acute Toxic Class Method'.

TERT-BUTYLPEROXIDE ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL

SPIRIT was administered by oral gavage to three 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.

Clinical signs observed during the study period were as follows:

Males: lethargy in one male on day 1.

Females: lethargy, hunched posture and uncoordinated movements on day 1 and red

staining of the head and neck on days 2 and 3.

The mean body weight gain shown by the animals over the study period was

considered to be normal.

An irregular surface of the forestomach or thickening of the glandular mucosa

and the limiting ridge was found in all animals at macroscopic post mortem

examination. No further abnormalities were found.

Local toxicity was produced by the test substance in the stomach, which was

considered to be caused by the irritating properties of the test substance.

Since no mortality occurred, the oral LD50 value of TERT-BUTYLPEROXIDE ISOPROPYL

CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT in Wistar rats was

established as exceeding 2000 mg/kg body weight.

Based on this conclusion and according to the EC criteria for classification and

labelling requirements for dangerous substances and preparations (Guidelines in

Commission Directive 93/21/EEC), TERT-BUTYLPEROXIDE ISOPROPYL CARBONATE, 75%

SOLUTION IN AROMATIC FREE MINERAL SPIRIT does not have to be classified and has

no obligatory labelling requirement for oral toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Good; GLP study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

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:

Experimental start date: 21 March 2001 Experimental end date: 21 March 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Temporary deviations from the maximum level for temperature (with a maximum of I’C) occurred. Based on laboratory historical data these deviations were considered not to have affected the study integrity.

Qualifier:

according to guideline

Guideline:

other: EU Method 8.3: “Acute Toxicity-Dermal”.

Deviations:

yes

Remarks:

Temporary deviations from the maximum level for temperature (with a maximum of I’C) occurred. Based on laboratory historical data these deviations were considered not to have affected the study integrity.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Identification Triaonox BPIC-C75
Chemical name Tert Butylperoxy isopropyl carbonate
CAS-Number 2372-21-6
Description Colourless liquid
Test substance storage At room temperature in the dark
Expiry date 11 January 2002
Density 0.89 (determined at NOTOX)

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST SYSTEM
Species
Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised
by international guidelines as the recommended test system (e.g.
OECD, EC).
Source: Charles River Deutschland, Sub&Id, Germany.

Number of animals
5 males and 5 females (females were nulliparous and nonpregnant).

Age and body weight
Young adult animals (approx. 9 weeks old) were selected. Body
weight variation did not exceed +I- 20% of the sex mean,

Identification
Earmark

ANIMAL HUSBANDRY
Conditions
A controlled environment was maintained in the room with optimal conditions considered as
being approximately 15 air changes per hour, a temperature of 21+3’C, a relative humidity of
30-70% and 12 hours artificial fluorescent light and 12 hours dark per day.
Temporary deviations from the maximum level for temperature (with a maximum of I’C)
occurred. Based on laboratory historical data these deviations were considered not to have
affected the study integrity.

Accommodation
Individually housed in labelled polycarbonate cages (type Ill, height 15 cm.) containing purified
sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis
were examined and then retained in the NOTOX archives.
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet
Free access to standard pelleted laboratory animal diet (from Altromin (code VRF I), Lage,
Germany). Certificates of analysis were examined and then retained in the NOTOX archives.

Water
Free access to tap-water. Certificates of quarterly analysis were examined and then retained in
the NOTOX archives.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Method: Dermal application.
Clipping: One day before exposure (day -1) an area of approximately 5x7
cm on the back of the animal was clipped.
Application: The test substance was applied in an area of approx. 10% of the
total body surface, i.e. approx. 25 cm2 for males and 18 cm for
females. The test substance was held in contact with the skin with
a dressing, consisting of a surgical gauze patch (Surgy 1 D) ,
successiyely covered with aluminium. foil and Coban flexible
bandage. A piece of Micropore tape was additionally used for
fixation of the bandages in females only.

Duration of exposure:

24 hours

Doses:

2000 mg/kg (2.25 ml/kg) body weight.

No. of animals per sex per dose:

5 males at 2000 mg/kg (2.25 ml/kg)
5 females at 2000 mg/kg (2.25 ml/kg)

Control animals:

no

Details on study design:

OBSERVATIONS
MortalityAliability: Twice daily
Body weights: Days 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. The time of onset, degree and duration
were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by
asphyxiation using an oxygen/carbon dioxide procedure and
subjected to necropsy. Descriptions of all internal macroscopic
abnormalities were recorded.

Statistics:

No statistical analysis was performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Lethargy, ptosis, hunched posture, chromodacryorrhoea, piloerection, hypothermia and/or quick breathing were noted among the animals. The animals had recovered from the symptoms by day between days 1 and 9. Scales, general erythema and/or scabs were seen

Gross pathology:

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

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LDso value of TRIGONOX BPIC-C75 in Wistar rats was established to exceed 2000 mg/kg body weight.
Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TRIGONOX BPIC-C75 does not have to be classified and has no obligatory labelling requirement for dermal toxicity.

Executive summary:

Assessment of acute dermal toxicity with TRIGONOX BPIC-C75 in the rat. The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, Part 8.3, “Acute Toxicity-Dermal” and OECD No.402, “Acute Dermal Toxicity”. TRIGONOX BPIC-C75 was administered to five Wistar rats of each sex 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 occurred.

Lethargy, ptosis, hunched posture, chromodacryorrhoea, piloerection, hypothermia and/or quick breathing were noted among the animals. The animals had recovered from the symptoms by day between days 1 and 9. Scales, general erythema and/or scabs were seen in the treated skin-area of the animals during the observation period. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and ware therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post modem examination of the animals.

The dermal LD50 value of TRIGONOX BPIC-C75 in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TRIGONOX BPIC-C75 does not have to be classified and has no obligatory labelling requirement for dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Good; GLP study

Justification for classification or non-classification

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), the test substance does not have to be classified and has no obligatory labelling requirement for acute toxicity. Data are conclusive, but not sufficient for classification.