Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Mar 03 to May 12, 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Batch No. 6F11027000
- Expiration date of the lot/batch: 17. Nov. 2016
- Purity: 96%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: young adult rats
- Weight at study initiation: Range in preliminary study = 203 – 237 g. Range in main study = 203-211 g (males) and 230-251 g (females)
- Housing: Type II polypropylene/polycarbonate; rat type cages with a solid floor, stainless steel wire covers and self- feeding baskets. During acclimatization: 3 animals/sex/cage. During the study: animals were housed individually.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days in preliminary study. 19 days at females, 5 days at males in main study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 10-15 air exchanges/hour by central air-condition system
- Photoperiod (hrs dark / hrs light): Artificial light, from 6 a.m. to 6 p.m.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back, shaven
- % coverage: 10% of area of total body surface
- Type of wrap if used: sterile gauze pads and semi occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: residual test item was removed using body temperature water.
- Time after start of exposure: 24 hr
Duration of exposure:
24 hrs
Doses:
Preliminary Study: 2000 mg/kg, 300 mg/kg, 50 mg/kg, 5 mg/kg (all but 2000 mg/kg dose where in a vehicle of sunflower oil)
Main Study: 2000 mg/kg (no vehicle)
No. of animals per sex per dose:
Preliminary study: 2 females/dose
Main study: 5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days for main study; 7 days for preliminary study
- Frequency of observations and weighing: morbidity/mortality observations made twice daily at the beginning and end of the working day. Clinical observation was made at the following intervals: 1h, 5h after the treatment and once each day for 14 days thereafter. Body weight was recorded on day 0 (shortly before the treatment), on day 7 and on day 15 in main study.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Observations included the skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. All necropsied rats were examined for external appearance. The cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed, and any abnormality was recorded with details of its location, colour, shape and size.

Results and discussion

Preliminary study:
There were no deaths in preliminary study at 5, 50, 300 and 2000 mg/kg bw dose levels. Based on results of preliminary study, a limit test was performed on a dose of 2000 mg/kg bw.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred after the 24-hour dermal exposure in male and female rats during the study
Clinical signs:
No behavioural changes, symptoms of dermal irritation and corrosion or signs of systemic toxity were noted during the study
Body weight:
The mean body weight of the all animals corresponded to their species and age throughout the study
Gross pathology:
No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Internal necropsy finding as pale kidneys was detected in one male animal (No.: 4228) and in two female animals (No.: 3944, 3947). This alteration could not be related to the test item toxic effect, but was regarded an individual variation. Most likely the observation is a congenital anomaly.
Moderate hydrometra was found in female No.: 3931. The hydrometra is physiological finding and connected to the cycle of the animal.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
according to EC 1272/2008 as amended
Conclusions:
Under our experimental conditions, the acute dermal LD50 value of the test item 1,3,5-Triisopropylbenzene proved to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.
Executive summary:

The acute dermal toxicity of 1,3,5-triisopropylbenzen was tested according to the standard acute method with Wistar rats according to OECD TG 402. A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed at 2000 mg/kg bw by dermal route. The test item was applied in original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

Neither male nor female animals treated at 2000 mg/kg bw showed behavioural changes and no systemic toxic signs were noted during the study.

The test item did not cause dermal irritation symptoms as erythema or oedema during 14-day observation period.

The body weight development was undisturbed in all animals.

No macroscopic alterations of organs referred to the systemic toxic effect of the test item were seen during the necropsy.

Under our experimental conditions, the acute dermal LD50 value of the test item 1,3,5-Triisopropylbenzene proved to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.