Dexpanthenol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

from 1994-08-11 to 1994-08-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study. For justification of read across please refer to the attachment in IUCLID5 section 13.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

directive 92/69/EEC

Deviations:

no

Principles of method if other than guideline:

NA

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethylbutanamide

Cas Number:

16485-10-2

IUPAC Name:

2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethylbutanamide

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: males: 207 g (mean; females: 175 g (mean)
- Fasting period before study: no
- Housing: individually in polycarbonate cages
- Diet: Kliba 343 rodent diet from Klingentalmühle AG, Kaiseraugst, Switzerland; ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: mean 21 °C
- Humidity: 50 % relative Humidity
- Air changes: approx. 15 air changes per hr
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The test substance was applied to an area of approximately 25 cm² (5x5 cm) for males and 18 cm² (3.5x5 cm) for females by application on a gauze patch fixed successively to aluminium foil and flexible bandage (Coban, 3M, St. Paul, U.S.A.), with drops of petrolatum.

Duration of exposure:

24 hours

Doses:

single dose: 2000 mg/kg b.w.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Shaving: One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
- Application: The test substance was applied to an area of approximately 25 cm² (5x5 cm) for males and 18 cm² (3.5x5 cm) for females by application on a gauze patch fixed successively to aluminium foil and flexible bandage (Coban, 3M, St. Paul, U.S.A.), with drops of petrolatum.
- Frequency: Once, on day 1.
- Dose level/volume: 2000 mg/kg (1.869 mL/kg) body weight. Dose volume calculated as follows: dose level : specific gravity
- Application period: 24 hours, thereafter dressings were removed and residual test substance removed using a tissue moistened with tap water.

Statistics:

NA

Results and discussion

Preliminary study:

NA

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of ill health or behavioural changes were observed during the study period. Abnormalites in the treated skin area included scabs in one male between days 5 and 9.

Gross pathology:

Macroscopic post mortem examination of the animals at termination revealed a yellowish hard nodule in the papillary process of the liver in one female and pelvic dilation of the kidney in one male. These findings are incidentally noted among the animals of this age and strain and are considered not related to treatment with the test substance.

Other findings:

Macroscopic post mortem examination of the animals at termination revealed a yellowish hard nodule in the papillary process of the liver in one female and pelvic dilation of the kidney in one male. These findings are incidentally noted among the animals of this age and strain and are considered not related to treatment with the test substance.

Any other information on results incl. tables

no remarks

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

rat: LD50 > 2000 mg/kg bw.

Executive summary:

Based on results obtained from read across substance the dermal LD50 value for D-Panthenol was determined to be > 2000 mg/kg bw.

The dermal LD50 value of the test item was determined in rats in a study according to OECD guideline 402 / EU method B.3. Five male and five female Wistar rats were exposed to a dose of 2000 mg/kg bw of the test item in a semi-occlusive exposure for a duration of 24 hours. The remaining test material was washed off with water, and the animals were observed for clinical signs for 14 days. No mortality occurred during the study period. No clinical signs of ill health or behavioural changes were observed during the study period. Abnormalities in the treated skin area included scabs in one male between days 5 and 9. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. However, three females showed low body weight gain over the second week of the study. Macroscopic post mortem examination of the animals at termination revealed a yellowish hard nodule in the papillary process of the liver in one female and pelvic dilation of the kidney in one male. These findings are incidentally noted among the animals of this age and strain and are considered not related to treatment with the test substance. The dermal LD50 value of the test item in rats was established as exceeding 2000 mg/kg body weight.