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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:
from March to August 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Missing information on purity of test article.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: IFF Protocol No. DLD (9/7/79) supplied by International Flavors & Fragrances, Inc.
Deviations:
not specified
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Missing information on purity.
Principles of method if other than guideline:
In a preliminary assay in which two rats of each sex were dosed by application of a prepared alcoholic solution of (crystal dissolved in diluent IFF 80-007) of the test substance to the skin at 5.0 g/kg body weight, there were no deaths during the 72 hour observation period.
Main test: The same dose was used on eight male and eight female albino rats in which the reactions were observed over a period of 14 days.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
Name of the substance as cited in the report: IFF #: 80-007-03
Description: white crystalline material

Test animals

Species:
rat
Strain:
other: Sprague-Dawley CD strain
Sex:
male/female
Details on test animals or test system and environmental conditions:
Sixteen (8 male and 8 female) young adult albino rats were used. The animals obtained from Charles River Breeding Labs (Wilmington, Mass.) were within the body weight range of 180-280 grams when assigned to the study (18 hours prior to dosing). The animals were housed 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]. The rats were fed Purina Rodent Laboratory Chow 5001 and allowed water ad libitum. Animals were acclimatized to the study room for seven days and were assigned to this study using a system of random numbers. The animals were individually numbered and were marked by ear tags. The entire study was identified by a colour coded label bearing a notation of the dose on each cage.
The animals were examined by a veterinarian and all animals assigned to the study had to be in good health and condition prior to the start of the study.

Administration / exposure

Type of coverage:
open
Vehicle:
other: alcohol
Details on dermal exposure:
On the day prior to treatment, the backs of the rats were clipped from the scapular region to the hips.
The test substance was applied evenly over the back using a B-D disposable syringe. The site of application was approximately that area bounded by the nape of the neck, the mid dorsum between pectoral and pelvic girdles and the lateral aspects of the scapulae, judged to comprise less than 30% of the body surface. The test article was allowed to remain in contact with the skin and open to the air for 24 hours after which any excess material was removed by wiping with a clean cloth. The day of dosing was designed Day 0.
Duration of exposure:
24 hours
Doses:
Based on the result of the preliminary test, 8 male and 8 female rats were treated with a single dose of 5.0 grams of the test article, administered per kilogram body weight. The volume of the prepared test article given to the rats was 1.0 mL/100 g body weight.
No. of animals per sex per dose:
In the preliminary test: 2 males and 2 females
In the main study: 8 males and 8 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 1, 3, 5 and 24 hours following dosing and twice daily (once daily on weekend) for the remainder of the 14 day observation period.
- Frequency of weighing: the rats were weighted at day 0 and at day 14
- Necropsy: All the animals underwent a gross necropsy at the end of the experiment.
- Other examinations performed: mortality, clinical signs, body weight, macroscopic pathology (lungs, heart, liver, spleen, kidney, adrenals, bladder, stomach, intestines, skin, fur, orifices, peritoneal and pleural mucosa, and internal mesentery)
Statistics:
no data available

Results and discussion

Preliminary study:
No animals died during the 72 hours observation period.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: None
Mortality:
There were no deaths in the eight males and eight females dosed with the test article.
Clinical signs:
There were no clinical signs of toxicity in any animal dosed with #80-007-03 at 5.0 g/Kg body weight. All animals appeared normal in health and behaviour throughout the 14 day observation period.
Body weight:
The animals all gained weight in a normal pattern ( 10 g or more) except one female animal which lost 10 grams but appeared normal in health and behaviour.
Gross pathology:
There were no signs indicative of toxicity in any of the sixteen animals necropsied at term (no findings reported in the lungs, heart, liver, spleen, kidney, adrenals, bladder, stomach, intestines, skin, fur, orifices, peritoneal and pleural mucosa, or internal mesentery).
Other findings:
No data available

Any other information on results incl. tables

The dermal LD50was greater than 5000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information under CLP REGULATION (EC) No 1272/2008 Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
Conclusions:
The dermal LD50 was greater than 5000 mg/kg body weight.
Executive summary:

None of the animals showed any clinical signs indicative of systemic toxicity. There were no deaths and all animals remained healthy throughout the study and gained weight in a normal manner, except for one female which lost 10 grams over the course of the study. At necropsy, none of the animals had any signs indicative of systemic toxicity (no findings reported in the lungs, heart, liver, spleen, kidney, adrenals, bladder, stomach, intestines, skin, fur, orifices, peritoneal and pleural mucosa, or internal mesentery). Based on these findings, the dermal LD50 was reported to be > 5,000 mg/kg body weight.