Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016-09-15 to 2016-10-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
1998
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3-[(3-{[(3-acetoxy-2,2-dimethylpropylidene)amino]methyl}-3,5,5-trimethylcyclohexyl)imino]-2,2-dimethylpropyl acetate
EC Number:
805-722-7
Cas Number:
1064082-81-0
Molecular formula:
C24H42N2O4
IUPAC Name:
3-[(3-{[(3-acetoxy-2,2-dimethylpropylidene)amino]methyl}-3,5,5-trimethylcyclohexyl)imino]-2,2-dimethylpropyl acetate
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system 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: males: 267-277 g; females: 225-249 g
- Housing: single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 - 20 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 30 - 70 %
- Air changes: > 10 per hr
- Photoperiod: 12 / 12 hrs dark / hrs light

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: at least 10 % of the body surface
- Type of wrap if used: sterile gaze pads, adhesive hypoallergenic plaster, semiocclusive wrap

REMOVAL OF TEST SUBSTANCE
- Washing: body temperature water
- Time after start of exposure 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Inspection was made twice daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Preliminary study:
There were no deaths in preliminary study, where doses of 5, 50, 300, and 2000 mg/kg bw were tested.
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 to the test item in Crl(WI) male and female rats during the study.
Clinical signs:
No behavioural changes or systemic toxic signs were noted during the study.
Dermal irritation symptoms as erythema, oedema and other signs as desquamation, wounds and crusting were observed on the treatment site. Very slight (score 1) and/or well defined erythema (score 2) occurred in all males. It was detectable between Day 1 and Day 10. Very slight redness (score 1) was observed in all females between Day 1 and Day 5. Very slight oedema (score 1) was found in two males (No.: 2979, 2983) on Day 4. Wounds, desquamation and crusting were detected in males between Day 4 and Day 9. Wounds and desquamation were recorded in all males and crusting was observed in four males (No.: 2980, 2981, 2982, 2983).
Body weight:
Mean body weight development was within the normal range for male animals of this strain and age. A body weight loss was observed in female No.: 2922 between Day 0 and Day 7. The body weight loss was very slight (approx. 2.4 %).
Gross pathology:
All animals survived until the scheduled necropsy on Day 15.
Internal macroscopic changes were observed. A seminal vesicle atrophy was detected in male animal No.: 2981 on the right side. Ovary cyst was seen in female No.: 2925 on the right side and severely wide section of uterus was detected in same female. These alterations could not be related to the test item toxic effect, but were regarded an individual variation. Most likely the observations are a congenital anomaly.
Moderate hydrometra was observed in female No.: 2926. Hydrometra is a physiological finding and connected to the cycle of the animal.
No macroscopic alterations due to the systemic toxic effects of the test item were found.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this acute dermal toxicity study with the test item, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in Crl(WI) male and female rats. According to Regulation (EC) No 1272/2008 and UN GHS, the test item has not been classified into any category.
On the other hand, it is to be noted that the test item caused dermal irritation response on the site of administration.
Executive summary:

An acute dermal toxicity study was performed with test item in Crl(WI) rats, in compliance with OECD Guideline No. 402 and OPPTS 870.1200.

A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to the test item at 2000 mg/kg bw by dermal route. The test item was applied in undiluted form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

No mortality occurred after the 24-hour dermal exposure to the test item in male and female rats during the study.

Neither male nor female animals treated with 2000 mg/kg bw of the test item showed behavioural changes and no systemic toxic signs were noted during the study. The test item caused dermal irritation symptoms in both sexes. Very slight and well defined erythema was observed in males between Day 1 and Day 10 and very slight erythema was found in females between Day 1 and Day 5. Erythema occurred in all animals. Very slight oedema was recorded in two males on Day 4. Other dermal irritation symptoms as desquamation, wounds and crusting occurred in four males between Day 4 and Day 9.

Mean body weight development was within the normal range for male animals of this strain and age. Slight body weight loss was observed in one female on first week. It was not evaluated as a toxic effect of the test item.

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

In this acute dermal toxicity study with the test item, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in Crl(WI) male and female rats. According to Regulation (EC) No 1272/2008 and UN GHS, the test item has not been classified into any category.

On the other hand, it is to be noted that the test item caused dermal irritation response on the site of administration.