Dexpanthenol

Endpoint summary

Description of key information

The acute oral LD50 was determined to be > 10000 mg/kg bw. The acute dermal LD50 was determined to be > 2000 mg/kg bw. No signs of inhalation toxicity could be detected during a 7 h inhalation study with an atmosphere saturated with the test item.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data are given, equivalent or similar to OECD guideline.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

BASF-Test.
In principle, the methods described in OCED guideline 401 were used.

GLP compliance:

no

Remarks:

pre-GLP study

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
male and female rats
- Age at study initiation: young adult, no further data

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
distilled water
- Concentration in vehicle: 46.4 - 50% (w/v)
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

up to 10000 mg/kg bw; no further details

No. of animals per sex per dose:

5-10/sex/group; no further data

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: before the start of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred.

Clinical signs:

other: In the highest dose group (10000 mg/kg bw), impaired general state with unspecific symptoms was noted at the first day of the study. No other findings were observed.

Gross pathology:

No pathological findings were observed.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item revealed an acute oral LD50 greater than 10000 mg/kg bw in rats.

Executive summary:

The LD50 was > 10000 mg/kg bw.

Groups of male and female rats were administered the test substance by gavage as an aqueous solution at doses of up to 10000 mg/kg bw and were observed for 14 days. No deaths were observed. Clinical signs of toxicity were limited to impaired general state with unspecific symptoms observed at the highest dose level at the day after dosing only. Pathology revealed no abnormal findings.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

10 000 mg/kg bw

Quality of whole database:

Basic data are given, equivalent or similar to OECD guideline.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data are given. Equivalent or similar to OECD guideline.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

The study was carried out in accordance with Smyth HF et al (1962). Am Ind Hyg Ass J 23: 95-107.
In principle, the methods described in OCED guideline 403 were used.

GLP compliance:

no

Remarks:

pre-GLP study

Test type:

other: Inhalation Risk Test

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
male and female rats
- Age at study initiation: young adult, no further data

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

7 h

Concentrations:

atmosphere saturated with vapours of the test substance, no further data

No. of animals per sex per dose:

totally 6 males and 6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: before the start of the study and at the end of the observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

no data

Sex:

male/female

Dose descriptor:

LC50

Based on:

test mat.

Exp. duration:

7 h

Remarks on result:

other: No death were observed during a 7 h-inhalation period of the test animals in a saturated atmosphere at room temperature. As the saturation vapour pressure is very low (less than 0.001 Pa at 20 °C), no exact concentration estimation could be performed..

Mortality:

No mortality was observed when 12 rats were exposed for 7 hours to an atmosphere that had been saturated at 20°C with the volatile parts of the compound.

Clinical signs:

other: No clinical signs of toxicity were observed.

Body weight:

no data

Gross pathology:

No abnormal findings were reported.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No death were observed during a 7 h-inhalation exposure of rats to a saturated atmosphere of the test item at room temperature.

Executive summary:

In an acute inhalation toxicity study, one group of 12 rats (6/sex) was exposed for 7 h to a saturated atmosphere of D-Panthenol at 20°C. Animals then were observed for 14 days. No mortality occurred. No clinical signs of toxicity. were observed. No gross pathological findings were reported.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Basic data are given. Equivalent or similar to OECD guideline.

Acute toxicity: via dermal route

Link to relevant study records

Reference

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.

Reason / purpose for cross-reference:

reference to other study

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

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.

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

Preliminary study:

NA

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.

no remarks

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP-Guideline study.

Additional information

Acute toxicity: oral

The LD50 was > 10000 mg/kg bw. Groups of male and female rats were administered the test substance by gavage as an aqueous solution at doses of up to 10000 mg/kg bw and were observed for 14 days. No deaths were observed. Clinical signs of toxicity were limited to impaired general state with unspecific symptoms observed at the highest dose level at the day after dosing only. Pathology revealed no abnormal findings.

 

Acute toxicity: inhalation

No mortality was observed when 12 rats were exposed for 7 hours to an atmosphere that had been saturated at 20°C with the volatile parts of the compound. No clinical signs of toxicity and no gross pathological findings were reported.  

Acute toxicity: dermal

Based on results obtained from read across on data in section 7.2.3 the dermal LD50 value for D-Panthenol was determined to be > 2000 mg/kg bw. The close structural similarity between the read-across substance and Panthenol strongly suggest that the LD50 for D-Panthenol is also > 2,000 mg/kg bw. For justification of read across please refer to the attachment in IUCLID5 section 13. Based on experience obtained from wide spread human use of the substance as pharmaceutical salve, no acute dermal toxicity is expected. Further, information on acute oral and inhalation toxicty is available. No acute oral toxicity was observed up to the limit dose. Furthermore, no acute inhalation toxicty was observed up to the maximal achievable concentration of test item in air. The substance is practically non-toxic after acute exposure and thus, no further information can be expected from acute dermal toxicty testing. Based on the available information acute dermal toxicity can be excluded and further testing would not be in line with animal welfare.

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – inhalation endpoint
Only one study available. No death were observed during a 7 h-inhalation exposure of rats to a saturated atmosphere of the test item at room temperature.

Justification for selection of acute toxicity – dermal endpoint
The close structural similarity between DL-Ethyl Panthenol and Panthenol strongly suggest that the LD50 for D-Panthenol is also > 2,000 mg/kg bw. For justification of read across please refer to the attachment in IUCLID5 section 13.

Justification for classification or non-classification

Based on the results obtained from testing the substance was not classified and labeled according to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD).