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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was well documented and meets generally accepted scientific principles but was not conducted in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method: other: contract laboratory protocol
GLP compliance:
not specified
Test type:
other: LD50
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Alfol 8 Alcohol

- Lot/batch No.: 81031

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 2.3 to 2.9 kg

- Housing: During the exposure the animals were placed in a multiple animal holder in an immobilized position. After the 24 hour exposure period the animals were placed in their respective metal cages elevated above the droppings for the duration of the 14 day observation period.

- Diet: Purina Rabbit Chow (ad libitum)

- Water: tap water (ad libitum)


IN-LIFE DATES: No data available.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: undiluted test substance
Details on dermal exposure:
TEST SITE

- Area of exposure: Skin of the trunk. One half of the animals in each group were prepared by making epidermal abrasions every two or three centimeters longitudinally over the area of exposure.

- Type of wrap if used: plastic binder.


REMOVAL OF TEST SUBSTANCE

- Washing (if done): At the end of the period of exposure the plastic binders were removed, and the remaining test compound washed from the animals' bodies. The animals were then blotted dry with absorbent paper hand towels.

- Time after start of exposure: 24 hours.


TEST MATERIAL

- Amount(s) applied (volume or weight with unit): maximum dose 3-4 ml/kg

- Concentration (if solution): Doses 1, 2 and 4g/kg of body weight.

- Constant volume or concentration used: Not specified.



VEHICLE

- Applied undiluted

Duration of exposure:
24 hours.
Doses:
1, 2 and 4 g/kg
No. of animals per sex per dose:
For 1g/kg dose: 2M, 2F, for 2g/kg dose: 4M, 4F, for 4g/kg dose 2M, 2F.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were observed for gross effects at regular intervals on the day of dosing and daily thereafter for 14 days.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Mortality, clinical signs of systemic toxicity and skin reactions at the application site were recorded on the day of dosing and  throughout the 14 day observation period. Body weights were recorded  prior to dosing and on observation day 14. All decedents and survivors were subject to gross necropsy.
Statistics:
No statistical analysis was carried out in this study.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 - 4 000 mg/kg bw
Mortality:
Time of death: All deaths occurred within 4 days of exposure.  Number of deaths at each dose: Intact skin 0/2, 1/4 and 2/2, abraded skin 0/2, 3/4 and 2/2. LD50(s): Intact skin: 2-4 g/kg; Abraded skin: 1-2 g/kg; combined intact and abraded 2 g/kg. A visual assessment of test site suggested that >75% of  the dose was observed at each dose level.
Clinical signs:
At the end of the exposure period all animals showed slight to severe erythema and oedema particulary of the ventral skin and 
particularly in animals with abraded skin. In all survivors wrinkling and coreaceousness gradually developed forming an inelastic sheath around the trunk of the animal. The healing process continued throughout the 14 day observation period. Generalised weakness and inactivity was evident in most animals following exposure. Survivors appeared normal at 72 hours post exposure. 
These signs persisted and/or intensified in animals which eventually died. Final body weights of surviving animals showed moderate to severe 
loss in 2 animals, constant weight in 3 animals, and slight to moderate  gain in 3 animals. 
Body weight:
Final body weight of surviving animals at termination (14 days) showed moderate to severe loss (2 animals), a constant weight (3 animals) and slight to moderate gain (3 animals).
Gross pathology:
In animals which succumbed there was severe skin damage with maceration and erosion of the ventral skin and  musculature. Blanching and multiple focal haemorrhages of the gastric mucosa, friability of the liver, moderate heamaturia and a slight  accumulation of  amber, watery peritoneal fluid were observed internally. Rabbits surviving to 14 days showed moderate to marked desquamation, severe erosion and multiple focal haemorrhages of the gastric mucosa  and slight accumulation of clear or amber viscous fluid in the peritoneal cavity.
Other findings:
The experimental data was reported in combined form with no mention of sex differences.

Any other information on results incl. tables

Table 1: Number of animals with abraded skin dead and the time range within which mortality occurred.

 Dose
(g/kg
bw)

Mortality (# dead/total)

Time range of deaths (day)

Male

Female

Combined

1.00

 

 

 0/2

 

2.00

 

 

 3/4

 2 and 3

4.00

 

 

 2/2

 1 and 2

 Table 2: Number of animals with intact skin dead and the time range within which mortality occurred.

 Dose
(g/kg
bw)

Mortality (# dead/total)

Time range of deaths (day)

Male

Female

Combined

1.00

 

 

 0/2

 

2.00

 

 

 1/4

 4

4.00

 

 

 2/2

2 and 4

 

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: other: Federal Hazardous Substances Act
Conclusions:
The rabbit dermal LD50 for Alfol 8 following 24 hour occlusive exposure was 2000-4000 mg/kg. There was significant evidence of skin irritation at the application site persisting in some animals throughout the observation period. Clinical signs were indicative of a general toxic effect coupled with anorexia. The most common gross pathogical finding was erosion of the gastric mucosa. Not classified according to EU criteria.