O,O-tert-butyl isopropyl monoperoxycarbonate

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

O,O-tert-butyl isopropyl monoperoxycarbonate

EC Number:

219-143-7

EC Name:

O,O-tert-butyl isopropyl monoperoxycarbonate

Cas Number:

2372-21-6

Molecular formula:

C8H16O4

IUPAC Name:

tert-butoxy propan-2-yl carbonate

additive 1

Reference substance name:

Hydrocarbons, C4, 1,3-butadiene-free, polymd., triisobutylene fraction, hydrogenated

EC Number:

297-629-8

EC Name:

Hydrocarbons, C4, 1,3-butadiene-free, polymd., triisobutylene fraction, hydrogenated

Cas Number:

93685-81-5

Molecular formula:

not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)

IUPAC Name:

isododecane

Test material form:

liquid

Details on test material:

Trigonox BPIC-C75

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)

Test animals

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.

Administration / exposure

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.

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.