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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:
18 March 1980 - 1 April 1980
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
yes
Remarks:
8 male and 8 female rats
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Labs (Wilmington, Mass., USA)
- Weight at study initiation: 180 to 280 grams
- Housing: singly in wire cages under standard laboratory conditions meeting the standards described in the 'Guide for the Care and Use of Laboratory Animals' (DHEW Publication No. (NIH) 78-23 Revised 1978).
- Diet: Purina Rodent Laboratory Chow 5001, ad libitum
- Water: ad libitum
- Acclimation period: 7 days

Administration / exposure

Type of coverage:
open
Vehicle:
other: SDA39C (alcoholic solution)
Details on dermal exposure:
TEST SITE
- Area of exposure: area bounded by the nape of the neck, the mid dorsum between pectoral and pelvic girdles and the lateral aspects of the scapulae
- % coverage: less than 30% of the body surface

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiping with a clean cloth
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml/100 g bw
- Concentration (if solution): 5000 mg/kg bw
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
8 males and 8 females
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and pharmacotoxic signs: at 1, 3, 5 and 24 hours following dosing and twice daily (once daily on weekends) for the remainder of the 14 day observation period. Weighing: pre-dose and on day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: necropsy-tissues examined: lungs, heart, liver, spleen, kidney, adrenals, bladder, stomach, intestines. Other tissues examined grossly: the external carcass (fur, skin and orifices), peritoneal and pleural mucosa, internal mesentery.

Results and discussion

Preliminary study:
In a preliminary range finding assay in which two rats (one of each sex) were treated at 5000 mg/kg bw., one animal died during the 72 hour observation period.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths in the eight males dosed with the test article during the 14 day observation period. One of the eight female rats died on Test Day 6.
Clinical signs:
There were no clinical signs of toxicity in any of the male animals dosed at 5000 mg/kg bw. One out of eight female rats died during the test period with all of the other female rats appearing normal in health and behavior.
Body weight:
The animals all gained weight in a normal pattern (10 g or more).
Gross pathology:
There were no signs indicative of toxicity in any of the eight male rats and seven female rats necropsied at term. The female rat that died during the experiment had red fluid in the intestines and congestion in the lungs at post-mortem examination.

Applicant's summary and conclusion

Interpretation of results:
other: Not acute harmful
Remarks:
according to EU CLP (EC No. 1272/2008 and its amendments)
Conclusions:
The dermal LD50 was greater than 5000 mg/kg bw (1/16 deaths at 5000 mg/kg). Therefore, the test substance does not need to be classified as acute dermal toxic.
Executive summary:

The dermal acute toxicity of the test substance, a colourless liquid, was examined (similar to OECD test guideline 402, 1987). In the preliminary assay in which two rats of each sex were dosed by application of a prepared alcoholic solution of the test substance to the skin at 5000 mg/kg bw, one animal died during the 72 hour observation period. In the main study eight male and eight female albino rats (Sprague-Dawley CD strain), weighing between 180 and 280 grams, were clipped on the day prior to dosing and the test substance, prepared in the diluent supplied, was applied onto the skin at 5000 mg/kg bw. The volume of solution administered was 0.5 ml/100 g bw. None of the male rats showed any clinical signs indicative of systemic toxicity. One of the eight female rats died on Test Day 6, but the others remained healthy throughout the study. All survivors gained weight in a normal manner. At necropsy performed on the survivors at term, none of the animals had any signs indicative of systemic toxicity. The female rat that died on Test Day 6 was examined post-mortem and there was red fluid in the intestines and congestion of the lungs. The dermal LD50 was greater than 5000 mg/kg bw, with only one death in the sixteen animals dosed.