Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 - 20 Nov 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Principles of method if other than guideline:
The dermal acute toxicity (LD50) was assess by exposing rabbits to the undiluted test substance. The animals' abdomens were shaved free of hair, and the skins in all the animals were further prepared by making abrasions. The test substance was spread over the prepared abdominal skin area, which was then covered with an occlusive dressing. After 24 hours, the skin area was cleaned and the animals were observed for 14 days following administration.
GLP compliance:
not specified
Remarks:
The protocol mentions that the study would be performed according to GLP, however, no statement was included
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-amino-2-ethylpropanediol
EC Number:
204-101-2
EC Name:
2-amino-2-ethylpropanediol
Cas Number:
115-70-8
Molecular formula:
C5H13NO2
IUPAC Name:
2-amino-2-ethylpropanediol
Details on test material:
- Name of test material (as cited in study report): 2-Amino-2-ethyl-1, 3-propanediol; AEPD; P-1050
- Physical state: Viscous, yellow liquid
- Analytical purity: 85.34%
- Impurities (identity and concentrations): 10.92% monomethyl amino butanol, 1.89% water, 1.48% methanol
- Lot/batch No.: NPP-41344
- Other: pH at 1% solution was 11.18; pH at 100% was 11.78

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kuiper Rabbit Ranch, Gary, Indiana, USA
- Age at study initiation: At least 9 weeks
- Weight at study initiation: 2.3 ± 0.2 kg
- Housing: Animals were caged individually during and after exposure
- Diet: Purina Certified Rabbit Chow No. 5532, ad libitum
- Water: ad libitum. Every quarter the animals' drinking water was analyzed to ensure that the levels of contaminants were equal to or less than the recommended levels as per the Primary Drinking water Regulations (40 CFR 141.11, 141.12, 141.14).
- Acclimation period: At least 7 days

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
The skin was examined for damage 24 hours before administration of the test substance to ensure the skin was healthy and uninjured before the exposure started, as any existing injuries may influence the results. The intentional abrasions were made after the examination.

- Area of exposure: an area of unknown size on the abdomen of all animals was shaved and the skin was abraded. The abrasions were minor incisions, deep enough to penetrate the epidermis but not the dermis.
- Type of wrap if used: The applied material was covered with a gauze patch and held in place with a rubberized cloth

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the exposed skin areas were cleaned; no further detailes were provided
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: No
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
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 and weighing: The animals were observed for any overt toxicity or pharmacological effect during the test and daily thereafter for 14 days. The body weights were measured on day 0, 7 and 14.
- Necropsy of survivors performed: Yes. On day 14, the surviving animals were sacrificed and examined for gross pathology. The animals that died during the observation period were necropsied the same day. The treated skin sites, all the major organs, and the abdominal cavities were examined for gross abnormalities. Any unusual observations were recorded and reported.
Statistics:
In the case of mortality, the dermal LD50 value, slope, and 95% percentile confidence limits would be estimated by the method of Finney (Probit Analysis. Cambridge Press 1979), adapted to BASIC computer program.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the study.
Clinical signs:
No clinical signs were noted during the observation period.
Body weight:
The animals in the treatment groups gained body weight during the observation period.
Gross pathology:
There were no unusual findings during the gross necropsy.
Other findings:
After 24 hours, the treated, abraded skin areas of all the rabbits were necrotic and edematous. After the 14 day observation period, the treated skin sites were necrotic. Due to the abrasions, the skin is much more vulnerable to irritation and damage by a topically applied substance.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified