Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Triisooctylamine
EC Number:
247-092-0
EC Name:
Triisooctylamine
Cas Number:
25549-16-0
Molecular formula:
C24H51N
IUPAC Name:
tris(6-methylheptyl)amine
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.: 0008924462

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: animals of comparable size and weight
- Fasting period before study: N/A
- Housing: Single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

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

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk)
- % coverage: About 40 cm² (corresponds to at least 10% of the body surface)
- Type of wrap if used: The test item was covered with an air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.47 mL/kg
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg
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: Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter. Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation. Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times (see results) until the last day of observation. A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.
Statistics:
N/A

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred
Mortality:
No mortality occurred
Clinical signs:
other: No systemic clinical signs were observed during clinical examination. Local effects see below.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Any other information on results incl. tables

Local effects males:

In all animals of the male group well-defined erythema (grade 2) was observed on study day 1 and persisted in four of these animals until study day 2, while in one animal severe erythema (grade 4) was noticed on the same day. On study day 3, one male showed moderate erythema (grade 3), while in the other animals severe erythema (grade 4) was noted. Severe erythema (grade 4) was noted persisted in three animals until study day 8, and in one male each until day 10 or day 13. Thereafter, moderate erythema (grade 3) was observed in two males from study day 9 until study day 10 or day 14. In another animal this grade was observed from study day 13 until study day 14, while in a further male animal grade 3 was observed only on study day 14. The fifth animal revealed well-defined erythema (grade 2) from study day 9 until study day 14.

Slight edema (grade 2) was noted in all male animals on study day 1 and persisted in four animals until study day 2. In one animal moderate edema (grade 3) was observed from study day 2 until day 3 and in the other four animals on study day 3. On study day 6, all animals showed severe edema (grade 4) which persisted in one animal up to study day 7. In this animal the finding decreased to moderate edema (grade 3) on day 8. In the other animals moderate edema (grade 3) was observed on study day 7 and persisted in one animal until day 8 and in two other animals until study day 10. Slight edema (grade 2) was seen in two male animals from study day 8 or 9 until study day 10 and in a third animal from day 9 until day 14. The two other animals revealed slight edema from study day 13 up to study day 14. In two animals edema decreased to very slight edema (grade 1) and was seen from study day 13 until study day 14. Dermal blisters were noted in 4 male animals on study day 1. From study day 2 until study day 14, incrustations were noted in all animals. In addition, scaling was seen in all males from study day 6 until study day 10 and persisted in one male until day 14.. Erythema and edema beyond the application area were noted in three animals from study day 6 until study day 10 or 13. Descriptions of any dermal finding were recorded in the table of results as raw data.

Local effects females:

In all animals of the female group well-defined erythema (grade 2) was noted from study day 1 until study day 2 and persisted in two of these animals up to study day 3, while in the other three females moderate erythema (grade 3) was noted on the same day. Thereafter, severe erythema (grade 4) was observed in all animals until study day 10 and persisted in four females up to study day 14, while in the fifth female moderate erythema (grade 3) was seen from study day 13 until study day 14. In all females slight edema (grade 2) was observed from study day 1 until study day 2 and persisted in four females up to study day 3, while in one animal moderate edema (grade 3) was observed on study day 3. On study day 6, severe edema (grade 4) was seen in all female animals and persisted in four of these females up to study day 7. In one female moderate edema (grade 3) was seen on study day 7, which decreased to slight edema (grade 2) from study day 8 until day 14. Moderate edema (grade 3) was noticed in four females on study day 8 and persisted in two of these females up to study day 10. Slight edema (grade 2) was noticed in two of these females on study day 9 and persisted in these animals up to study day 10 or 14.

In three females very slight edema (grade 1) was noted from study day 13 until study day 14. Dermal blisters with partly destroyed uppermost layer of the skin were noted in one female animal on study day 1. Eczema like skin lesion was seen in two females from study day 9 until day 14. From study day 2 or 3 until study day 14 incrustations were noted in all animals. In addition, scaling was seen from study day 6 until study day 14 in these animals. Erythema and edema beyond the application area were noted from study day 6 until study day 13 or 14 in three animals. In the two remaining animals findings beyond the application area were noted on study day 13 only. Descriptions of any dermal finding were recorded in the table of results as raw data.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met