Sodium lactate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983-10-19 to 1983-11-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

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

Specific details on test material used for the study:

- Name of the test material: SY-83
- Appearance: liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Young adult, New Zealand White albino rabbits were obtained from Langshaw Farms, Route l, Box 256, Augusta, MI 49012. The albino rabbit is the species preferred in the EPA/OPP Guidelines for acute dermal toxicity testing.
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 the number of animals of each sex received. 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.
The animals were quarantined for approximately 3 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.
The quarantine and study room (252) was cleaned daily and the cages were cleaned and sanitized as specified in ToxiGenics1 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.
The animal room was well ventilated and air-conditioned, and the temperature and humidity were monitored daily in this room during the quarantine and study periods. The temperature ranged from 68 to 70°F and the relative humidity varied from 47 to 68 percent with the following exception: a relative humidity value of 72 percent was recorded on one day during quarantine. The animal room was lighted from approximately 6:00 a.m. to 6:00 p.m. (12-hour light/12-hour dark cycle) using automatic timers. The test article applications were completed at 1:45 p.m. on October 19, 1983.
Purina Certified Rabbit Chow 5322 was fed to the animals ad libitum during the quarantine and study periods. Filtered tap water was provided ad libitum through an automatic watering system and was analyzed periodically as specified in ToxiGenics1 Standard Operating Procedures.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: applied neat

Details on dermal exposure:

The dorsal trunk (approximately 10% of the body surface area) of each animal was clipped free of hair with Oster electric clippers equipped with a number 40 (surgical) blade. The areas were reclipped as needed during the study for evaluation of dermal reactions. On the day of dosing (day 0), body weights were recorded, and doses were calculated. Approximately 24 hours after the initial clipping, the prepared area of each animal was abraded. The longitudinal epidermal abrasions were spaced 2 to 3 cm. apart and were sufficiently deep to penetrate the stratum corneum but not the dermis. After abrading, a measured volume of the test article was introduced under an impervious binder, consisting of a plastic wrap and adhesive tape secured around the trunk of each manually restrained animal, and gently spread over the application site. After test article application, the trunk of each animal was wrapped with additional adhesive tape and masking tape. After a 24-hour exposure period, each binder was removed, and the test site of each animal was wiped (not washed) with gauze sponges moistened with water to remove remaining test article.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Hourly on day 0, twice daily for all other days.
- Body weight: Body weights were recorded prior to test article application on day 0, on day 7, and prior to sacrifice on day 14
- Necropsy of survivors performed: On day 14, all animals were rendered unconscious by administration of intraveneus injections of a barbiturate and were exsanguinated prior to gross necropsy. All external surfaces, orifices, and organs; cranial cavity; carcass; external and cut surfaces of the brain; abdominal, thoracic, and pelvic cavities and their viscera; and cervical tissues and organs of each animal were examined at necropsy. All abnormalities observed during these examinations were recorded.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived the 14-day duration of the study.

Clinical signs:

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

Gross pathology:

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.

Any other information on results incl. tables

Skin reactions:

Severe erythema and severe edema 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. Edema 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 edema was observed on days 12 to 14 for one female. Also, no edema was observed on day 14 for one male. Other dermal reactions observed at test sites included:

- Blanching: all animals on day l and as late as days 2, 3, or 4 for 6 animals.

- Necrosis (brown-green discoloration): all animals on days l 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.

Applicant's summary and conclusion

Interpretation of results:

other: CLP criteria not met

Conclusions:

L(+)-lactic acid is not dermally toxic and the LD50 is >2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study conducted according to EPA OPP 81-2, young adult New Zealand White rabbits (5/sex) were dermally exposed to L(+)-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.

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: Blanching, 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. Based on the results the dermal LD50 is > 2000 mg/kg bw.

This acute dermal study is classified as acceptable. It does satisfy the guideline requirement for an acute dermal study (EPA OPP 81 -2) in the rabbits.