L-(+)-lactic acid

Endpoint summary

Description of key information

Suitable data is available for the target substance L(+)-lactic acid to assess the acute toxicity via the standard routes of administration (oral, inhalation, dermal). In all studies the LD50 or LC50 values for the oral, dermal or inhalation route are above the limit values of the relevant OECD guidelines. Thus, no classification for acute toxicity is warranted.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

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

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

no

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

Specific details on test material used for the study:

- Test item: SY-83
- Appearance: liquid

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.

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).

Sex:

female

Dose descriptor:

LD50

Effect level:

3 543 mg/kg bw

Based on:

test mat.

95% CL:

9.7

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 3162 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.

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

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 GHS criteria.

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.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of the test material: SY-83

Species:

rat

Strain:

other: albino

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Material was administered neat

Doses:

5 g/kg bw

No. of animals per sex per dose:

5

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing at end of test or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 1 out of 5 males died

Sex:

female

Dose descriptor:

LD100

Effect level:

< 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All females died

Mortality:

Four males survived the 14-day duration of the study. One male and all 5 females were found dead at 1 to 2 or 3 to 4 hours after dosing (2 females), in the morning of day 1 (one male and 2 females), and in the morning of day 10 (one female).

Clinical signs:

other: All individuals showed signs of adverse effects.

Gross pathology:

Gross necropsy of one male and 5 females found dead on days 0, 1, or 10 revealed diffuse or multiple, focal, black or black- brown discolorations of the glandular stomach; and dark contents in the stomachs of 4 of these 6 animals. Also observed during necropsy of 2 females found dead on day 0 or day 10 were: a diffuse, grey-green discoloration of the lung and a diffuse, grey-black discoloration of the trachea for the female found dead
on day 0; and diffuse, tan adhesion of the liver to the stomach (serosa) and diffuse, severe dilation (with food material) of the stomach for the female found dead on day 10. Necropsy of 2 surviving males revealed: a solitary depression on one kidney and multiple, red discolorations on the lung of one male; and diffuse, moderate dilation of the stomach, mucosal sloughing of the non-glandular stomach, a solitary, yellow-white discoloration on the liver, and multiple adhesions between the liver and stomach of the second surviving male.
No other abnormalities were observed during necropsy of all animals.

Four males survived the 14-day duration of the study. One male and all females were found dead on the day of dosing, on  day 1 or on day 10. For male rats the LD50 was > 5000 mg/kg bw. For female rats the LD50 was < 5000 mg/kg bw.

Interpretation of results:

study cannot be used for classification

Conclusions:

Based on the results and in accordance with EPA OPP-81-1 guideline, the LD50 values of the test article were determined to be higher to 5000 mg/kg bw for males and lower to 5000 mg/kg bw for females.

Executive summary:

L(+)-lactic acid was administered by oral gavage to 5 male and 5 female albino rats at a dose level of 5 grams per kilogram of body weight to evaluate the acute oral toxic potential. This study was designed to comply with procedures described in the EPA/OPP Guidelines, 1982. Four males survived the 14-day duration of the study. One male and all females were found dead on the day of dosing (day 0), on day l, or on day 10. Body weight gains were observed for 3 surviving males, and a small weight loss was observed for the fourth surviving male. Body weight losses were observed for all other animals that were found dead. Lethargy and salivation were observed for all animals, and crusty muzzle was observed for 9 animals on the day of dosing and as late as day 9 for one female. Other abnormal clinical signs observed for some animals on the day of dosing and as late as day 2 included ataxia, prostration, irregular breathing, noisy breathing, squinting, lacrimation, crusty eyes, crusty nose, and body cool to touch» Other abnormal clinical signs observed prior to death of one female on day 10 included yellow/brown stained fur in the perianal region, abdomen swollen, no stools, and few stools. No other abnormal clinical signs were observed during the study. Necropsy of the 6 found dead animals revealed black discolorations of the glandular stomach, and dark contents in the stomachs of 4 of these animals. Grey-green discoloration of the lung and grey-black discoloration of the trachea were also observed during necropsy of one female found dead on day 0, and liver to stomach adhesions and severe dilation of the stomach (with food material) were also observed during necropsy of the female found dead on day 10. Necropsy of 2 surviving males revealed: a depression on one kidney and red discolorations on the lung of one animal; and dilation of the stomach, mucosal sloughing of the stomach, a yellow-white discoloration on the liver, and liver to stomach adhesions for one animal. No other abnormalities were observed during necropsy of all animals after death or after sacrifice on day 14. Based on the results and in accordance with EPA OPP-81-1 guideline, the LD50 values of the test article were determined to be higher to 5000 mg/kg bw for males and lower to 5000 mg/kg bw for females.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 543 mg/kg bw

Quality of whole database:

Guideline study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987-04-11 to 1987-12-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of the test material: SY-83
- Batch/Lot No.: AP6853
- Purity: 80-85%
- Storage conditions: room temperature

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Fischer 344 rats were obtained from Charles River Breeding Laboratories, Raleigh, North Carolina. Upon arrival, animals were quarantined for approximately 21days. Stringent disease control procedures were followed during quarantine to assure the use of healthy animals. Rats were observed for signs of illness. The animals were judged to be healthy prior to utilization in this study and were 9-10 weeks old at initiation of exposure.
Animals were housed in an AAAIAC-accredited facility with a controlled environment. The temperature range was 71 ± 5 °F, while the humidity range was 50 ± 22% with a brief excursion down to 18% during one day. The light cycle was maintained on a 12 hour light/dark cycle. Rats were individually housed in polycarbonate cages with filter tops and automatic watering devices. Corn-cob bedding was used, and animals had free access to certified laboratory rodent chow which had been analyzed for environmental contaminants. Water and food were provided ad libitum, except during exposure.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

Atmosphere Generation:
A collision nebulizer (BGI Industries) was used to generate the aerosol. Compressed air was attached to the generator and the output from the aerosol was directed into a 4 litter dilution jar. Room air was allowed to dilute the aerosol before it was drawn into the exposure module under vacuum. A continuous, dynamic exposure to aerosolized test material was achieved with the nose-only exposure units. The air flow in the exposure module was adjusted to approximately 5 L/min using a calibrated rotameter and was periodically monitored during exposure. The exposure module consisted of a 360 ml cylindrical chamber mounted horizontally with an inlet, outlet and sampling port. Sampling of the test atmosphere was done from a sampling port situated on the side of the exposure module. Samples from the exposure module were taken for gravimetric and particle size determinations. Determinations of oxygen content could not be performed due to a malfunction of the oxygen sensor.
Conditions for animal exposures:
Rats were held in cylindrical tubes which aligned the heads of the animals with the conical shaped openings on the exposure chamber. The nose of each animal protruded into the chamber for nose-only inhalation. The animals were held in place by a soft sponge which served as a plunger in the cylinder and prevented the animal from turning or backing out. Five rats were restrained on each side of the exposure module (males on one side, females on the other) as diagrammed in Figure l of Appendix B. All rats of each concentration level were exposed at the same time.
Determination of aerosol concentration and particle size distribution:
Gravimetric determinations were made by pre-weighing a 24 mm diameter Whatman glass-fiber filter (GF/A), placing the filter in a filter holder, and connecting the filter to the sampling port of the exposure module. Air samples were drawn through the filter using a vacuum supply regulated by a flow meter. Flow rates were set 0.5 L/min and a sampling time of 4-8 min was used. The concentration of aerosol present in the chamber was calculated by the difference in weight of the filter divided by the volume of air sampled. Seven separate determinations were made, and a time-weighted average was calculated for the total aerosol concentration.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric, using a filter interception

Duration of exposure:

4 h

Concentrations:

7.94 mg/L

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

Five male and five female rats were exposed to a nominal concentration of 7.94 mg/L of aerosolized test material for 4 hours. Analysis of at least three filter samples was performed to determine the purity of test material in the exposure module. The exposure atmosphere was also sampled to determine particle size distribution. A sham control group of 5 male and 5 female rats was used and was exposed to air alone for 4 hours. Animals were weighed prior to treatment and at weekly intervals thereafter. The animals were observed for mortality and pharmacotoxicity signs during exposure, at l and 3 hours following exposure and once daily thereafter for 14 days. Survival was recorded for each group. Complete necropsies were performed on all animals on day 15 of the study. At necropsy, all organs showing gross lesions, if any, were fixed in 10% buffered formalin. Histopathology was not performed.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 7.94 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

1 female died.

Clinical signs:

other: Please refer to box "Any other information on results incl. tables".

Body weight:

At the beginning of the study, mean body weicihts for individual groups were within 20% of the overall mean for each sex. All groups of male rats gained weight within the first week after exposure in comparison to pre-exposure weights (3% for sham-exposed, 2< for L(+)-lactic acid,respectively). Female rats in the sham group gained weight during the first week after exposure (less than 1%). Female rats in the treated group lost weight during the first week after exposure (7%). After 14 days, all surviving animals had gained weight in comparison to pre-exposure weights (14% for males, 7% for females). No significant differences were observed in body weight between treated and control groups.

Gross pathology:

All surviving animals were necropsied at the termination of the study. The animal that died during the study was necropsied immediately. No gross lesions were observed at necropsy.

Clinical signs:

Rapid breathing and eye tearing were observed during exposure. At one and three hours after exposure, all animals (including the sham controls) had a hunched posture, ruffled and ungroomed fur, brown stained fur and red-stained fur surrounding the eyes (tearing). By 24 hours, female treated rats had ruffled and stained coats. All other animals appeared normal at 24 hours and for the remainder of the 14 day observation period. Several treated female rats continued to have ruffled fur up to 4 days after exposure.

Mass Median Diameter:

The Mass Median Diameters ranged from 2.03 to 2.14 microns and averaged 2.09.

Interpretation of results:

other: CLP criteria not met

Conclusions:

Based on these results, the LC50 of L(+)-lactic acid is greater than 7.94 mg/L.

Executive summary:

In an acute inhalation toxicity study according to OECD 403, groups of young adult F344 rats (5/sex/dose) were exposed by inhalation route to L(+)-lactic acid in a concentration of approximately 7.94 mg/L for 4 hours.

Rapid breathing and eye tearing were observed during exposure. At one and three hours after exposure, all animnals (including the sham controls) had a hunched posture, ruffled and ungroomed fur, brown stained fur and red-stained fur surrounding the eyes (tearing). After 24 hours, female treated rats had ruffled and stained coats. All other animals appeared normal at 24 hours and for the remainder of the 14 day observation period. Several treated female rats continued to have ruffled fur up to 4 days after exposure. One female rat from the treated group died on day 9. All other animals survived until the end of the study. At gross pathology no adverse lesions were observed.

Based on these results, the LC50 of L(+)-lactic acid is greater than 7.94 mg/L.

This acute inhalation study is classified as acceptable. It does satisfy the guideline requirement for an acute inhaltion study (OECD TG 403) in rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

> 7.94 mg/L air

Physical form:

inhalation: aerosol

Quality of whole database:

Guideline study

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

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

Specific details on test material used for the study:

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

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.

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.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Guideline study

Additional information

Suitable data is available for the target substance L(+)-lactic acid to assess the acute toxicity via the standard routes of administration (oral, inhalation, dermal).

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 occurred after dosing mainly on day 0 or in the morning of day 1 in a dose-dependent manner. At the highest dose, no animal survived. The LD50 was determined to be 3543 mg/kg bw for females and 4936 mg/kg bw for males.

In an acute inhalation toxicity study conducted according to OECD 403, groups of young adult F344 rats (5/sex/dose) were exposed by inhalation to L(+)-lactic acid at a concentration of approximately 7.94 mg/L for 4 hours. One female rat from the treated group died on day 9. All other animals survived until the end of the study. Based on these results, the inhalation LC50 of (L(+)-lactic acid is greater than 7.94 mg/L.

In an acute dermal toxicity study according to EPA OPP 81-2, young adult New Zealand White rabbits (5/sex) were dermally exposed to L(+)-lactic acid for 24 hours via 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 oedema were observed at the test sites of all animals after removal on day 1. The dermal LD50 is > 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available data, the target substance L(+)- lactic acid does not warrant classification for acute toxicity in accordance with CLP Regulation 1272/2008. LD50 and LC50 values for the oral, dermal and inhalation route are above the limit values of the relevant OECD guidelines.