dimethyl 1,2-benzenedicarboxylate;reaction mass of: 1,2-dimethylpropylidene dihydroperoxide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 November 2001 - 06 December 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

442-480-8

EC Name:

-

Cas Number:

182893-11-4

Molecular formula:

Mixture of C5H12O4 and C10H22O6

IUPAC Name:

reaction mass of 1,2-dimethylpropylidene dihydroperoxide and dimethyl 1,2-benzenedicarboxylate

Details on test material:

Identification: Trigonox R-938
Chemical name: Methyl Isopropyl Ketone Peroxide
CASRN: Mixture of 13921-99-8, 33372-83-7, 131-11-3 and 563-80-4
Description: Clear colourless liquid
Batch: 1510-14
Test substance storage: In refrigerator in the dark
Stability under storage conditions: Stable
Expiry date: 01 January 2003

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Germany.
- Age at study initiation: ± 11 weeks old
- Weight at study initiation: males mean: 415g, females mean: 272g
- Fasting period before study: none
- Housing: Individually housed in labelled polycarbonate cages (type III, height 15 em.) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
- Water (e.g. ad libitum): Free access to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.
- Acclimation period: Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 22 November 2001 - 06 December 2001

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 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 cm2 for females.
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze (Surgy 1D), successively covered with aluminium foil and Coban flexible bandage·. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
24 hours, after which dressings were removed and residual test substance removed using a tissue moistened with water.

TEST MATERIAL
2000 mg/kg (1.72 ml/kg) body weight. Dose volume calculated as follows: dose level: density.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality: twice daily. Body weight: Days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: 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).

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred.

Clinical signs:

other: Chromodacryorrhoea was noted among the animals between days 2 and 6. One male and one female showed hunched posture on day 2. Maculate or general erythema, scales, fissures, scabs, necrosis and/or wounds were seen in the treated skin-area of the animals d

Gross pathology:

Most males showed isolated scab formation on the treated skin. No further abnomalities were found at macroscopic post mortem examination of the animals.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

The dermal LD50 value in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

Assessment of acute dermal toxicity in the rat.

The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, Part B.3, "Acute Toxicity-Dermal" and OECD No.402, "Acute Dermal Toxicity". The test substance was administered to five 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. Chromodacryorrhoea was noted among the animals between days 2 and 6. One male and one female showed hunched posture on day 2. Maculate or general erythema, scales, fissures, scabs, necrosis and/or wounds were seen in the treated skin-area of the animals during the observation period. One male showed brown staining of the head on day 1. 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 were therefore considered not indicative of toxicity. Most males showed isolated scab formation on the treated skin. No further abnomalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of MIKP in Wistar rats was established to exceed 2000 mg/kg body weight.