Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7 June 1977 - 12 August 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and OECD guidelines, but was according to acceptable procedures at that time.

Data source

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

Materials and methods

Principles of method if other than guideline:
Sprague-Dawley rats were administered AHTN in absolute ethanol (or undiluted) by dermal application to the shaved skin, and were observed for mortality and clinical effects immediately after the dosing at 1, 4, and 24 hours, and also once daily thereafter for a total of 7 days.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Fixolide

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Initial body weight ranged from 108 to 197 grams, and the animals were fasted overnight prior to dosing.

Administration / exposure

Type of coverage:
not specified
Vehicle:
ethanol
Details on dermal exposure:
AHTN was administered by gentle inunction to the shaved skin of 5 groups of five female rats
Duration of exposure:
single administration of dose
Doses:
0.5 to 10 g/kg
No. of animals per sex per dose:
5 (5 groups of 5 animals)
Control animals:
no
Statistics:
Mortality data was analyzed statistically, utilising the tables of Horn, H.J., Biometrics 12, 311, 1956.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
7 940 mg/kg bw
95% CL:
4 890 - 12 900
Remarks on result:
other: Assuming all dead at 21500 mg/kg.

Any other information on results incl. tables

Major necropsy findings: animals found dead exhibited the effects expected at their respecive stages of autolysis; all other animals exhibited no remarkable necroscopy findings.

Table 1: Mortality data and toxic effects of Fixolide tested on acute dermal toxicity on rats.

Dose Concentration  Time of death
g/kg bw % in ethanol Immediate 1-24 h. 24-48h.
0.464 10 0/5 0/5 0/5
1.000 10 0/5 0/5 1/5
2.150 10 0/5 0/5 0/5
4.640 20 0/5 0/5 1/5
10.000 40 0/5 0/5 3/5

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
LD 50 AHTN = 7940 mg/kg, which is larger than the upper limit for classification dermal toxicity (i.e. 2000 mg/kg).
Executive summary:

Groups of 5 female rats were fasted overnight prior to the experiment, and the test material in absolute ethanol was applied to the shaved skin of the animals. Observations for mortality and clinical effects were conducted immediately after the dosing at 1, 4, and 24 hours, and also once daily thereafter for a total of 7 days. Gross necropsy was conducted on all animals (those that died or were sacrificed at the end of the study). The LD50 value was 7.94 g/kg. Animals found dead exhibited the effects expected at their respective stages of autolysis; all other animals exhibited no remarkable necropsy findings.