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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 October 1999- 14 March 2002
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
body weights were not recorded on day 15
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Alcohols, C12-14 (even numbered), propoxylated, aminated
Molecular formula:
C12H27N (C3H6O)n n=1-5, C14H31N (C3H6O)n n=1-4
IUPAC Name:
Alcohols, C12-14 (even numbered), propoxylated, aminated
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: test item provided by sponsor

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable) : the rabbit is a standar specied for acute dermal toxicity studies
- Source: Hare Marland
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 14 weeks
- Weight at study initiation: 2.512 -3.055 kg
- Fasting period before study:
- Housing: individually housed
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days
- Method of randomisation in assigning animals to test and control groups : by weight

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16- 21
- Humidity (%): 30- 70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 December 1999 To: 28 December 1999

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal trunk, clipped intact skin
- Type of wrap if used: gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washing was done with water and gauze
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg bw calculated based on body weight on day 1
Duration of exposure:
24h +/-0.5h
Doses:
2000mg/ kg bw
No. of animals per sex per dose:
5/ sex/ dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were done daily from prior to dosing to day 15, body weight was recorder on day 1 and 8
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: all surviving rats were sacrificen on day 15 and necropsis were perfomed including examination of the extermal body surface, all orifices and the thoracic, pelvic and the abdominal cavities and their contents

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal was found dead on day 8.
Clinical signs:
Abnormal gait and abnormal stance were observed on days 2- 15. Decreased activity and decreased body tone were observed on days 6-13 and 7-15 respectively with poor grooming observed on days 8-15. Erythema, edema, necrosis, fissuring and sloughing of the skin at the application site was also observed.
Body weight:
Body wight losses were observed through day 8 in a large percentage of surviving animals.
Gross pathology:
No visible lesions were observed in any of the animals at terminal necropsy. The animal found dead on day 8 exhibited mottled kidneys and bright red lungs.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 of the test item was estimated to be greater than 2000 mg/kg bw
Executive summary:

The purpose of the study was to evaluate the acute dermal toxicity of the test item in New Zeland White rabbits. One groupd of ten rabbits (5 males and 5 females) was dermally administed the test article at 2000mg/ kg bw. Clinical observations were recorded after unwrapping and daily from day 2 -15.

One animal was found dead on day 8. Clinical signs included abnormal gait and abnormal stance were observed on days 2- 15. Decreased activity and decreased body tone were observed on days 6-13 and 7-15 respectively with poor grooming observed on days 8-15. Erythema, edema, necrosis, fissuring and sloughing of the skin at the application site was also observed.

No visible lesions were observed in any of the animals at terminal necropsy. The animal found dead on day 8 exhibited mottled kidneys and bright red lungs.

The dermal LD50 of the test item was estimated to be greater than 2000 mg/kg bw