(R)-lactic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983-11-03 to 1984-01-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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:

- Test item: SY-83
- Appearance: liquid

Test animals

Species:

rat

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, MA, USA
- Age at study initiation: young
- Weight at study initiation: 200 g (m) and 219 g (f)
- Fasting period before study: overnight
- Housing: individually in stainless steel, wire-bottomed cages that conformed to the size standards specified in DHEW Publication (NIH) 78.23.
- Diet (e.g. ad libitum): Purina Certified Rodent Chow 5002 was fed to the animals ad libitum during the quarantine and study periods except for fasting prior to dosing.
- Water (e.g. ad libitum): Filtered tap water was provided ad libitum through an automatic watering system
- Acclimation period: The animals were quarantined for at least 7 days after receipt.

ENVIRONMENTAL CONDITIONS
The animal rooms were well ventilated and air-conditioned, and the temperature and humidity were monitored daily in these rooms during the quarantine and study periods. The temperature ranged from 68 to 74°F and the relative humidity to 68 percent in all 3 housing rooms with the following exceptions: relative humidity values were recorded as 29 percent on 3 days, 26 percent on one day, and 72 percent on one other day in room 247; and temperatures of 66°F or 67°F were recorded on 3 other days in room 247.
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.

IN-LIFE DATES: The study was performed at ToxiGenics, Inc., 1800 East Pershing Road, Decatur, IL 62526 from November 3, 1983 to December 12, 1983.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

In the morning of the days of dosing, body weights were recorded, doses were calculated, and a measured volume of the appropriate test article suspension was delivered to each animal by oral gavage in a single dose. Diet was returned to each surviving animal approximately 4 hours after test article administration.

Doses:

3162, 3548, 3981, 4467, 5012, 5623, 6310 mg/kg bw

No. of animals per sex per dose:

Males: 5 per dose: 6310, 5623, 5012 and 4467 mg/kg bw
Females: 5 per dose: 6310, 5623, 5012, 4467, 3981, 3548 and 3162 mg/kg bw

Control animals:

no

Details on study design:

The duration of testing was 14 days for range-finding and 14 days or less for each main study dose level.
Animals were observed for mortality and abnormal clinical signs once each hour after dosing on day 0 (to the 4 to 5 hour interval). Observations for mortality and abnormal clinical signs were done twice daily thereafter for the duration of range-finding or main study testing. These twice daily observations were done in the early morning and late afternoon of days 1 to 13 and in the morning of day 14. Body weights of all range-finding and main study animals were recorded prior to test article administration on the days of dosing (day 0). Body weights were also .recorded on days 7 and 14 for surviving range-finding and main study animals, and at the time found dead for other animals. All surviving range-finding animals were euthanized with carbon dioxide on day 14 and discarded. Range-finding animals found dead were also discarded. Range-finding animals were not examined at necropsy. All surviving main study animals were rendered unconscious with carbon dioxide and exsanguinated prior to necropsy on day 14. 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 main study animal (found dead or sacrificed on day 14) were examined at necropsy and all abnormal findings were recorded. Necropsies were conducted under the supervision of a qualified pathologist.

Statistics:

The oral LD50 value, the 95 percent confidence interval, the slope of the dose-response curve, and correction factors for 0 and 100 percent observed responses were calculated for each sex by computer program using a method adapted from Litchfield and Wilcoxon . Dose-response curves were prepared by computer program using the calculated LD50 data.
The mean, standard deviation, and Standard error were calculated for the main study body weight and test article administration data (millilitres of suspension administered and calculated milligram values).

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

3 543 mg/kg bw

Based on:

test mat.

95% CL:

9.7

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

4 936 mg/kg bw

Based on:

test mat.

95% CL:

10.8

Mortality:

All main study mortalities and range-finding mortalities (6,310 mg/kg bw) occurred after dosing on day 0 or in the morning of day 1 except for one main study female dosed at 3,162 mg/kg bw that was found dead in the morning of day 2. Range-finding animals dosed at 1,000, 1,585, 2,512, and 3,981 mg/kg bw and surviving main study animals were sacrificed after 14-day observation periods.
For individual results, see Table 1 in "Any other information on results incl. tables".

Clinical signs:

other: Lethargy, ataxia, prostration, irregular breathing, piloerection, squinting, lacrimation, salivation, crusty eyes and muzzle, loose stools, damp or yellow/brown stained fur, and moribund were abnormal clinical signs observed for main study animals as earl

Gross pathology:

Abnormal necropsy findings were observed for all found dead main study animals, and for the 4 surviving main study females dosed at 3,162 mg/kg bw. Abnormalities observed during necropsy of found dead animals included: discolored lungs; firm texture of lungs; green foci on one lung; erosion of stomachs; dark, black, brown, and/or fluid contents of stomachs; black and/or brown discolored stomachs; a distended stomach with white mucosa; mucosal sloughing, ulceration, and hemorrhage of stomachs; discolored livers; white foei on livers; pale capsular areas, superficial erosion, or mottled livers; a discolored diaphragm; green-black or brown-black discolored kidneys; and red-brown exudate in the nasal and/or oral regions. Mottled lungs were observed during necropsy of 3 surviving animals dosed at 3162 mg/kg bw, and thickened stomachs were also observed during necropsy of 2 surviving animals of the same group. No other abnormalities were observed during necropsy of all main study animals.

Any other information on results incl. tables

Table 1: Individual mortalities

	Main Study Dose Level (mg/kg bw) Number dead/number tested
	3162	3548	3981	4467	5012	5623	6310
Males	--	--	--	1/5	3/5	4/5	5/5
Females	1/5	2/5	5/5	5/5	5/5	5/5	5/5

-- = None tested

Applicant's summary and conclusion

Interpretation of results:

other: CLP criteria not met

Conclusions:

The oral LD50 value in rats after treatment with L(+)-lactic acid was determined to be 3543 mg/kg bw for females and 4936 mg/kg bw for males.

Executive summary:

In an acute oral toxicity study according to EPA OPP81-1, groups of young Albino rats (5/sex/dose) were given single oral doses of L(+)-lactic acid in water of 3162, 3548, 3981, 4467, 5012, 5623, 6310 mg/kg bw and were observed for 14 days. Mortality occured after dosing on day 0 or in the morning of day 1 except for one main study female dosed at 3162 mg/kg that was found dead in the morning of day 2. Mortality occured in a dose-dependent manner. At the highest dose, no animal survived. Abnormal clinical signs were observed 0 to 1 hour after dosing and day 2. Abnormal necropsy findings were observed for all found dead main study animals, and for the 4 surviving main study females dosed at 3162 mg/kg bw. Based on the results from this study, an oral LD50 in rats was determined to be 3543 mg/kg bw for females and 4936 mg/kg bw for males using the methodology described in the EPA/OPP Guidelines 1982.

L(+)-lactic acid does not need to be classified according to CLP Regulation 1272/2008.

This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study (EPA OPP 81-1) in the rats.