Registration Dossier

Diss Factsheets

Toxicological information

Repeated dose toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.
Cross-reference
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
sub-chronic toxicity: dermal
Type of information:
other: review publication
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Principles of method if other than guideline:
The dermal toxicity of a face cream containing 0.25% of 85% aq. Lactic Acid was evaluated using two groups of 15 female Sprague-Dawley rats (Avon Products, Inc., 1995b). The test group received daily applications of 886 mg/kg applied 5 days/week for 13 weeks to a shaved dorsal area of the back; the control group was untreated (The dose was determined by applying a factor of 100 x to the average daily human use determined using 1 g/day.) Animals were observed daily, and blood and urine samples were collected during weeks 7 and 13 from randomly selected animals.
Specific details on test material used for the study:
- Purity: 85%
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Type of coverage:
not specified
Vehicle:
other: cosmetic cream
Details on exposure:
The test group received daily applications of 886 mg/kg bw applied 5 days/week for 13 weeks to a shaved dorsal area of the back. The control group was untreated.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily, 5 days/week
Dose / conc.:
886 mg/kg bw/day (nominal)
Remarks:
dose group
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
untreated control group
No. of animals per sex per dose:
15 (female only)
Control animals:
yes, concurrent no treatment
Details on study design:
Animals were observed daily, and blood and urine samples were collected during weeks 7 and 13 from randomly selected animals.
Observations and examinations performed and frequency:
Animals were observed daily, and blood and urine samples were collected during weeks 7 and 13 from randomly selected animals.
Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
All animals survived to study termination. No significant gross observations, with the exception of minimal skin irritation throughout the study, could be attributed to dosing. During week 7, the blood urea nitrogen value was significantly increased for test animals as compared to controls; no other hematological effects were seen, and urinary parameters were normal. Absolute brain weight and kidney-to-body weight ratios were statistically significantly increased for the test animals. No lesions were observed at necropsy or at microscopic examination. The investigators concluded this formulation is "safe in terms of cumulative toxicity" and that "based upon the exaggerated dose level used in this study for skin care products, dermal application is not likely to produce adverse effects under conditions of consumer use."
Dose descriptor:
LOAEL
Effect level:
886 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
haematology
organ weights and organ / body weight ratios
Critical effects observed:
no

No significant gross observations, with the exception of minimal skin irritation. Absolute brain weight and kidney-to-body weight ratios were increased for test animals.No lesions were observed at necropsy or at microscopic examination.

Conclusions:
Formulation (face cream containing 0.25% lactic acid) is safe in terms of cumulative toxicity. Based upon the exaggerated dose levels used in this study for skin care products, dermal application is not likely to produce adverse effects under conditions of consumer use.
Executive summary:

A sub-chronic dermal toxicity study with a face cream containing 0.25% lactic acid (equals 886 mg/kg bw/day) was conducted on female rats. All animals survived to study termination. No significant gross observations, with the exception of minimal skin irritation throughout the study, could be attributed to dosing. During week 7, the blood urea nitrogen value was significantly increased for test ammals as compared to controls; no other hematological effects were seen, and urinary parameters were normal. Absolute brain weight and kidney-to-body weight ratios were statistically significantly increased for the test animals. No lesions were observed at necropsy or at microscopic exammation. The investigators concluded this formulation is "safe in terms of cumulative toxicity" and that "based upon the exaggerated dose level used in this study for skin care products, dermal application is not likely to produce adverse effects under conditions of consumer use."

Data source

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
(R)-lactic acid
EC Number:
233-713-2
EC Name:
(R)-lactic acid
Cas Number:
10326-41-7
Molecular formula:
C3H6O3
IUPAC Name:
(2R)-2-hydroxypropanoic acid

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
All animals survived to study termination. No significant gross observations, with the exception of minimal skin irritation throughout the study, could be attributed to dosing. During week 7, the blood urea nitrogen value was significantly increased for test animals as compared to controls; no other hematological effects were seen, and urinary parameters were normal. Absolute brain weight and kidney-to-body weight ratios were statistically significantly increased for the test animals. No lesions were observed at necropsy or at microscopic examination. The investigators concluded this formulation is "safe in terms of cumulative toxicity" and that "based upon the exaggerated dose level used in this study for skin care products, dermal application is not likely to produce adverse effects under conditions of consumer use."

Effect levels

Dose descriptor:
LOAEL
Effect level:
886 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
haematology
organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:
no

Any other information on results incl. tables

No significant gross observations, with the exception of minimal skin irritation. Absolute brain weight and kidney-to-body weight ratios were increased for test animals.No lesions were observed at necropsy or at microscopic examination.

Applicant's summary and conclusion

Conclusions:
Formulation (face cream containing 0.25% lactic acid) is safe in terms of cumulative toxicity. Based upon the exaggerated dose levels used in this study for skin care products, dermal application is not likely to produce adverse effects under conditions of consumer use.
Executive summary:

A sub-chronic dermal toxicity study with a face cream containing 0.25% lactic acid (equals 886 mg/kg bw/day) was conducted on female rats. All animals survived to study termination. No significant gross observations, with the exception of minimal skin irritation throughout the study, could be attributed to dosing. During week 7, the blood urea nitrogen value was significantly increased for test ammals as compared to controls; no other hematological effects were seen, and urinary parameters were normal. Absolute brain weight and kidney-to-body weight ratios were statistically significantly increased for the test animals. No lesions were observed at necropsy or at microscopic exammation. The investigators concluded this formulation is "safe in terms of cumulative toxicity" and that "based upon the exaggerated dose level used in this study for skin care products, dermal application is not likely to produce adverse effects under conditions of consumer use."

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Categories Display