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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
92/69/EEC
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
A mixture of: triphenylthiophosphate and tertiary butylated phenyl derivatives
EC Number:
421-820-9
EC Name:
A mixture of: triphenylthiophosphate and tertiary butylated phenyl derivatives
Cas Number:
192268-65-8
Molecular formula:
Unspecified
IUPAC Name:
A mixture of: triphenylthiophosphate and tertiary butylated phenyl derivatives
Details on test material:
- Storage condition of test material: In the original container at room temperature away from direct sunlight

Test animals

Species:
rat
Strain:
other: Hanlbm: WIST
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wolferstrasse 4, CH-4414 Fullinsdorf/ Switzerland.
- Age at study initiation: Males: 8 weeks; Females: 11 weeks.
- Weight at study initiation: Males: 227-242 g; Females: 194-217 g
- Housing: During acclimatization in groups of five in Makrolon type-4 cages with standard softwood bedding ("Lignocel", SchillAG, CH-4132 Muttenz). During treatment and observation individually in Makrolon type-3 cages with standard softwood bedding.
- Diet: Pelleted standard Kliba 343, batch no. 88/97 rat maintenance diet (Kliba Miihlen AG, CH-4303 Kaiseraugst) available ad libitum. Analysed for bacteriological, chemical and contaminant
- Water: ad libitum; tap water (analysed for bacteriological, chemical and contaminant)
- Acclimation period: One week under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3.
- Humidity (%): 40-70.
- Air changes (per hr): 10-15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Backs of the animals.
- % coverage: Approximately 10 % of the total body surface.
- Type of wrap if used: Covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Yes; with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hours.

TEST MATERIAL
Application volume/kg body weight: 2.0 mL.
Duration of exposure:
24 h.
Doses:
2000 mg/kg body weight.
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
Mortality / Viability: Four times during test Day 1 and once daily for surviving animals during Days 2-15.
Body weights: On test Day 1 (pre-administration), 8 and 15 for surviving animals.
Clinical signs: Each animal was examined for changes in appearance and behaviour (with special emphasis on the application area, except for the time when the semi-occlusive dressing was in place) four times during Day 1, and once daily for surviving animals during Days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: Yes.
Statistics:
No statistical analysis was used as no deaths occurred.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No death occurred
Mortality:
No deaths occurred during the study.
Clinical signs:
No signs of toxicity were observed.
Body weight:
The body weight of the animals was within the range of physiological variability known for rats of this strain and age. The slight loss of body weight in two female animals during the first observation week was considered to be a consequence of the semi-occlusive dressing used during treatment. Commonly, female animals prove to be more sensitive in relation to the effects on body weight caused by semi-occlusive dressing than male.
Gross pathology:
No treatment-related macroscopic findings were observed.
Other findings:
Signs of toxicity (local): No skin irritation was observed.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose of the test item after single dermal administration to rats of both sexes is greater than 2000 mg/kg.
Executive summary:

A group of five male and five female Hanlbm: WIST (SPF) rats was treated with the test item at 2000 mg/kg by dermal application. The undiluted test article was administered at a volume of 2 ml/kg. The animals were examined for clinical signs four times during day 1 and once daily during days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. Neither clinical signs of systemic toxicity nor local effects of the test article on the skin at the application site were observed during the observation period. The body weight of the animals was within the range of physiological variability known for rats of this strain and age. The slight loss of body weight in two female animals (nos. 6 and 8)

during the first observation week was considered to be a consequence of the semi-occlusive dressing used during treatment. Commonly female animals prove to be more sensitive in relation to the effects on body weight caused by semi-occlusive dressing than male. No macroscopic findings were observed at necropsy. The median lethal dose of the test item after single dermal administration to rats of both sexes is greater than 2000 mg/kg.