Potassium (S)-lactate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

L-(+)-lactic acid

EC Number:

201-196-2

EC Name:

L-(+)-lactic acid

Cas Number:

79-33-4

Molecular formula:

C3H6O3

IUPAC Name:

(2S)-2-hydroxypropanoic acid

Details on test material:

SY-83

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Langshaw Farms, Route l, Box 256, Augusta, MI 49012
- Age at study initiation: Young adult
- Fasting period before study: No data
- Housing: Animals were housed individually in stainless steel, wire-bottomed cages that conformed to the size standards specified in DHEW Publication (NIH) 78.23. The cages on each rack were numbered in a Standard manner and a list of random numbers was generated by computer program* for each rack of cages. Upon receipt, each animal was removed from the shipping container and housed in the appropriate randomly selected cage. Each animal was then assigned a sequential animal number unique within ToxiGenics and identified with an ear tag bearing this animal number. The sequential animal number was listed on a cage card that was affixed to the front of the animal's cage.
- Diet (e.g. ad libitum): Ad libitum, food: Purina Certified Rabbit Chow 5322
- Water (e.g. ad libitum): Ad libitum, filtered tap water
- Acclimation period: The animals were quarantined for 2 weeks after receipt. During the quarantine period, Veterinary Sciences' personnel observed the animals at least once each day for mortality, morbidity, and abnormal signs. Animals were examined during quarantine and only those considered to be in good health were used in this study.

ENVIRONMENTAL CONDITIONS
- Rooms: The quarantine and study room (241) was cleaned daily and cages were cleaned and sanitized as specified in ToxiGenics' Standard Operating Procedures. Urine and feces feil through the wire mesh floor onto animal caging board. The cage boards were changed at least 3 times a week.
- Temperature (°C): 19–21 °C
- Humidity (%): 37–64 % (on one day, a relative humidity value of 72 % was recorded)
- Photoperiod (hrs dark/hrs light): 12-hour light/12-hour dark

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 2 application sites on each animal - % coverage: 10
- Type of wrap if used: The entire trunk of each animal was wrapped with an impervious binder consisting of a plastic wrap, adhesive tape, and masking tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Hourly on day 0, twice daily for all other days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None

Clinical signs:

other: No abnormal clinical signs were observed during the study.

Other findings:

Severe erythema and severe oedema were observed for all animals after test article removal on day 1. Erythema decreased in severity (to well defined or very slight) for 2 males on day 14 and for one female on day 12. Oedema decreased in severity (to moderate, slight, or very slight) for all males and 3 females as early as day 2. No erythema was observed on day 14, and no oedema was observed on days 12 to 14 for one female. Also, no oedema was observed on day 14 for one male. Other dermal reactions observed at test sites included:
- Blanching: All animals on day 1 and as late as days 2, 3, or 4 for 6 animals.
- Necrosis (brown-green discoloration): All animals on days 1 and 2, as late as days 3, 5, or 6 for 3 males, and to day 11 for 4 females.
- Eschar formation: All animals on days 2 to 11, and for 7 animals to day 14. Eschar was present along the abrasion lines only of one female on days 7 to 11.
- Eschar peeled off: One female on day 12, and 2 males on day 14.
- Atonia: All males and 3 females from days 3 or 4 to days 11 or 14.
- Desquamation: All animals from days 10 or 11 to day 14.
- Fissures: One male and 4 females as early as day 5 and as late as day 14.
- Denuded areas along abrasion lines: One female on day 14. No other dermal reactions were observed during the study. Brown, crusted, and raised discolorations of the treated skin were observed during necropsy of 3 males and 3 females. Multiple depressions in the treated skin were observed during necropsy of one of the same males, of 2 other males, and of one other female. A dark red focus was also observed on the lung of one male. No other abnormalities were observed during necropsy of all males and 4 females, and no abnormalities were observed during necropsy of one female.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Lactic acid is not dermally toxic up to 2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study according to EPA OPP 81-2, 6 young adult New Zealand White rabbits (3/sex) were dermally exposed to lactic acid for 24 hours to 10 % of the body surface area at a dose of 2000 mg/kg bw. Animals then were observed for 14 days.

A dermal LD50 > 2000 mg/kg bw was determined.

All animals survived the 14-day duration of the study and gained body weight. No abnormal clinical signs were observed during the study. Severe erythema and severe edema were observed at the test sites of all animals after removal on day 1. Other dermal reactions observed at test sites included: Banching, necrosis, eschar formation, eschar along abrasion lines, eschar peeled off, atonia, desquamation, fissures and denuded areas along abrasion lines. No other dermal reactions were observed during the study. Necropsy of 3 males and 3 females on day 14 revealed brown, crusted discolourations of the treated skin. Multiple depressions in the treated skin were observed during necropsy of one of the same males and of 3 other animals (2 males and one female), and a dark red focus was also observed during necropsy of one other male. No other abnormalities were observed during necropsy of all males and 4 females, and no abnormalities were observed during necropsy of one female.

According to GHS criteria, lactic acid does not need to be classified as acutely toxic by dermal route.