(R)-lactic acid

Repeated dose toxicity: dermal

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."

Materials and methods

Test material

Test material information

Constituent 1

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:

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.