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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

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:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

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: The rabbits were individually housed in metal cages elevated above the droppings.

- Diet: Purina rabbit Chow (ad libitum)

- Water: Tap water (ad libitum)


IN-LIFE DATES: Not stated.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: 50% w/w dilution tetradecanol in 1 % w/w gum tragacanth
Details on dermal exposure:
TEST SITE

- Area of exposure: The skin of the trunk which was clipped free of hair.

- Type of wrap if used: plastic binder


REMOVAL OF TEST SUBSTANCE

- Washing (if done): The binder was removed and the amount of unabsorbed substance estimated. The animals were then washed and the carefully blotted dry with absorbent hand towels.

- Time after start of exposure: The test compound was removed after 24 hours of exposure.


TEST MATERIAL


- Amount(s) applied (volume or weight with unit): The animals were distributed evenly as to sex in each of three dosage groups as follows: 2M+2F (1M+1F each intact and abraded) and dosed 2.0, 4.0 and 8.0 g/kg of the test substance.


- Concentration (if solution): A 50% w/w dilution of ALFOL 14 alcohol in 1% w/w gum tragacanth.



VEHICLE

- Amount(s) applied (volume or weight with unit): 1% w/w gum tragacanth.



Duration of exposure:
24 hours
Doses:
2, 4 and 8 g/kg
No. of animals per sex per dose:
2
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 fourteen days.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Body weights were recorded prior to dosing and on observation day 14.
Statistics:
No statistical analysis was carried out.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
8 000 mg/kg bw
Based on:
test mat.
Mortality:
100% of the animals with abraded skin died between 8 and 10 days of the exposure period. The animals with intact skin survived.
Clinical signs:
At twenty-four hours following test application, all animals showed slight to moderate erythema, desquamation, wrinkling and dryness of the skin at the treatment site. In all surviving animals, desquamation and wrinkling of the skin occurred and persisted in varying degrees through determination (14 days). At the highest dosage level (8 g/kg body weight, two of the surviving animals showed signs of weakness, emaciation and pallor; however all appeared systematically normal within 96h following exposure. One animal showed signs of moribundity.
Body weight:
Final body weight records of the surviving animals at termination (fourteen days), showed a slight loss in one animal, a constant weight in one animal and gains within expected limits in the eight remaining animals.
Gross pathology:
Gross necropsy of animals which succumbed showed depletion of visceral fatty tissue (one animal), moderate dermal irritation and desquamation at the treatment site (two animals). Gross necropsy of the animals which survived the 14 day observation period and were sacrificed, showed one animal with slight accumulation of clear viscous fluid within the peritoneal cavity and crazing over cortex of both kidneys. Eight animals showed no signs of gross systemic abnormalities.

Any other information on results incl. tables

Table 1: Number of animals dead within the 14 day observation period.

Dose
(g/kg
bw)

Mortality (# dead/total)

Time range of deaths (day)

Male

Female

Combined

2.0

 0/2

0/2

0/4 

 -

4.0

 0/2

0/2

0/4 

 -

8.0

 1/2

1/2 

2/4 *

 9 and 11

*thedead animals were from the group with skin prepared with abrasion.

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The rabbit dermal LD50 (24 hour occluded) for Alfol 14 was approx. 8000 mg/kg. All survivors showed skin irritation at the application site throughout the observation period. Signs of intoxication included weakness, emaciation and pallor. The result is read across from tetradecan-1-ol (CAS 112-72-1).
Executive summary:

In the acute dermal toxicity study, 2, 4 and 8 g/kg of test material was applied to the flanks of 2 male and 2 female rabbits per dose, kept in contact to the skin under occlusive dressing for 24 hours. The experiement was performed on intact and abrated skin. Body weight changes and clinical signs of toxicity were noted regularly. Necropsy was performed at the end of the 14 -day study period.

100% of the animals with abraded skin died between 8 and 10 days of the exposure period. The animals with intact skin survived. At twenty-four hours following test application, all animals showed slight to moderate erythema, desquamation, wrinkling and dryness of the skin at the treatment site. In all surviving animals, desquamation and wrinkling of the skin occurred and persisted in varying degrees throughout the 14 -day study period. At the highest dosage level (8 g/kg body weight, two of the surviving animals showed signs of weakness, emaciation and pallor; however all appeared systematically normal within 96 hours following exposure. Final body weight records of the surviving animals at termination, showed a slight loss in one animal, a constant weight in one animal and gains within expected limits in the eight remaining animals. At necropsy, there was one animal with slight accumulation of clear viscous fluid within the peritoneal cavity and crazing over cortex of both kidneys. Eight animals showed no signs of gross systemic abnormalities.

An LD50 value of 8000 mg/kg bw was reported. The study was well documented and meets generally accepted scientific principles, but was not conducted in compliance with GLP.