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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:
end of study: 31 March 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Credo, 69210 L'Arbresle. France.
- Age at study initiation: 8 weeks old
- Weight at study initiation: 263 +/- 5g for the males, 212 +/- 7 g for the females
- Fasting period before study: no fasted
- Housing: The animals were housed in groups of 4 to 7 animals of the same sex per cage (sterilizable polycarbonate cages (48x27x20 cm)) during the acclimatization period and individually (sterilizable polycarbonate cages (35.5x23.5x19.3 cm)) during the study.
- Food consumption (e.g. ad libitum): ad libitum
- Water consumption (e.g. ad libitum): ad libitum
- Acclimation period: 5 days during which they were observed daily.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3°C
- Humidity: 50 +/- 20% relative humidity
- Air changes: the air was non-recycled and filtered by absolute filters.
- Photoperiod: 12hr of light / 12hr of dark

In-life dates: From 10 December 1991 to 11 February 1992

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: paraffin oil
Details on dermal exposure:
TEST SITE
- Area of exposure: 5x6 cm for the females and 5x7 cm for the males
- % coverage: 10
- Type of wrap if used: hydrophilic gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing: after removal of the dresses, any residual test item was wiped out with a gauze moistened with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied (volume): 5 mL/kg
- Doses: 500, 750, 1120, 1690 and 2000 mg/kg bw for the males and 750, 1120 and 2000 mg/kg bw for the females

VEHICLE:
A different vehicle (water for injections) was used for the preliminary assay.
preliminary assay: water for injections batch n° 1336
main assay: paraffin oil batch n° 6852

Duration of exposure:
24 hours
Doses:
preliminary assay: 2000 mg/kg bw
main assay: 500, 750, 1120 and 1690 mg/kg bw (males) and 750 and 1120 mg/kg bw (females)
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: the animals were observed frequently after administration of the test substance and then at least once a day.
- Frequency of weighing: animals were weighed just before administration of the test substance and then on days 5, 8 and 15.
- Necropsy of survivors performed: yes on day 15
- Other examinations performed: macroscopic examination at necropsy (digestive tract, herat, kidneys, liver, lungs, pancreas, spleen and any other organ with obvious abnormalities)
Statistics:
no

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
1 331 mg/kg bw
95% CL:
954 - 1 863
Mortality:
Mortality was observed within 48 hours of administration of the test substance. No sex-related differences were noted.
At the dose level of 2000 mg/kg, all animals found dead.
The mortality in males was 0%, 0%, 60% and 40% at the dose levels of 500, 750, 1120 and 1690 mg/kg respectively. The mortality in females was 40% and 60% at the dose levels of 750 and 1120 mg/kg respectively.
Clinical signs:
During the first few hours following application of the test substance, hypokinesia, sedation and dyspnea were noted in all treated animals. Clinical signs had reversed by day 3 at 500 mg/kg, by day 5 at 750 mg/kg and by day 7 at 1120 and 1690 mg/kg.
After the removal of the dressing and for at least one week, signs of severe cutaneous reactions were observed at all dose levels.
Body weight:
Between days 1 and 5, slight or severe loss of body weight was recorded in a few animals at 750 and 1120 mg/kg, respectively. Body weight gain was not influenced by the treatment in the other surviving animals.
Gross pathology:
At necropsy, signs of cutaneous necrosis were observed in all animals found dead during the study. The macroscopic examination revealed no abnormalities in the animals killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
TBC 100% ECAILLES is considered as harmful in contact with skin.
The toxicity of the test substance in the females was similar to that in the males. In order to comply with new ethic and scientific recommandations concerning the LD50, a more precise determination was not necessary in the females.

EU GHS classification:
Acute dermal toxicity Category 4 (H312)
Executive summary:

In an acute dermal toxicity study (CIT study 7675 TAR, 1992), groups of 8 weeks old non-fasted Sprague-Dawley rats (5/sex) were dermally exposed to 4 -tert-butylpyrocatechol (100% Ecailles) for 24 hours on approximately 10% of the body surface at doses of 500, 750, 1120, 1690 and 2000  mg/kg bw for males and at doses of 750, 1120 and 2000 mg/kg bw for females.  Animals then were observed for 14 days.

Dermal LD50 Males = 1331 mg/kg bw (95% C.I.: 954 - 1863 mg/kg bw)

4 -tert-butylpyrocatechol is harmful based on the LD50 in males. The toxicity of the test substance in the females was similar to that of the males.

The mortality in males was 0%, 0%, 60%, 40% and 100% at the dose levels of 500, 750, 1120, 1690 and 2000 mg/kg respectivley. The mortality in females was 40%, 60% and 100% at the dose levels of 750, 1120 and 2000 mg/kg respectively.

During the first few hours following application of the test substance, hypokinesia, sedation and dyspnea were noted in all treated animals. Clinical signs was reversed between day 3 and 7.

After the removal of the dressing and for at least one week, signs of severe cutaneous reactions were observed for all dose levels.

This acute dermal study is classified as acceptable. It does satisfy the guideline requirement for an acute dermal study (OECD 402) in the rat.