O,O-tert-butyl isopropyl monoperoxycarbonate

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

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.

Test guideline 2

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

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 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)

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 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.

Administration / exposure

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.

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 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.

Applicant's summary and conclusion

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.