Potassium (S)-lactate

Endpoint summary

Description of key information

By way of read-across from lactic acid, constituting the toxicologically relevant moiety, potassium-S-lactate is evaluated to be acutely non-toxic via any of the standard routes of administration (oral, inhalation, dermal).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Sex:

female

Dose descriptor:

LD50

Effect level:

3 543 mg/kg bw

Based on:

test mat.

95% CL:

9.7

Remarks on result:

other: %

Sex:

male

Dose descriptor:

LD50

Effect level:

4 936 mg/kg bw

Based on:

test mat.

95% CL:

10.8

Remarks on result:

other: %

Mortality:

All main study mortalties and range-finding mortalities occurred 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. Range-finding animals dosed at 1000, 1585, 2512, and 3981 mg/kg 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 3162 mg/kg. 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, 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) 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:

GHS criteria not met

Conclusions:

The oral LD50 value in rats after treatment with 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 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.

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.

Lactic acid does not need to be classified according to GHS criteria.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Guideline study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 7.94 mg/L air

Exp. duration:

4 h

Mortality:

1One female died.

Clinical signs:

other: Animals were observed during exposure for signs of toxicity. Rapid breathing and eye tearing was observed in the treated group, while in the sham control group, respiration was calm and steady during exposure. One and three hours after exposure, the treat

Body weight:

Individual body weights for animals on test are given in Tables 4 and 5. At the beginning of the study, mean body weights 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 SY-83, 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.

Interpretation of results:

GHS criteria not met

Conclusions:

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

According to GHS criteria lactic acid is considered to be non acute toxic by inhalation route.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Guideline study

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

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.

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.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Guideline study

Additional information

No data on acute toxicity of potassium-S-lactate itself are available. Thus, available data from lactic acid were used to assess in a read-across approach the specific toxicity of potassium-S-lactate.

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 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.

Supporting information on the acute oral toxicity of the target substance was derived from an acute oral toxicity study in female rats exposed to potassium chloride. In study the LD50 was determined to be 3020 mg/kg bw (re-calculated to 5194 mg/kg bw Potassium-S-lactate).

In an acute inhalation toxicity study according to OECD 403, groups of young adult F344 rats (5/sex/dose) were exposed by inhalation to 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 lactic acid is greater than 7.94 mg/L.

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 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, potassium-S-lactate does not warrant classification for acute toxicity. LD₅₀ and LC₅₀ values for the oral, dermal and inhalation route are above the limit values of the relevant OECD guidelines and of the CLP Regulation.