Sodium lactate

Endpoint summary

Description of key information

By way of read-across from lactic acid (constituting the toxicologically relevant moiety) and sodium chloride, Sodium 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

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

supporting 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:

3 750 mg/kg bw

Based on:

test mat.

Convulsions, diarrhea, muscular rigidity and prostration preceded death which was caused by respiratory failure with acute encephalopathy. Major pathologic findings were vascular congestion, particularly in meninges and brain, dehydration, and lysis of columnar epitheli of the gastro-intestinal tract. Survivors suffered a brief anorexia, polyuria, fever and acidosis.

Interpretation of results:

other: CLP criteria not met

Conclusions:

The LD50 for Sodium chloride in rats was found to be 3750 ± 430 mg/kg bw.

Executive summary:

In an acute oral toxicity study, 169 albino Wistar rats (male/female) were exposed once by oral gavage to doses of 0 (controls), 800, 3000, 3200, 3500, 3800, 4000, 5000, 10000 and 16000 mg/kg bw. Animals were observed for 15 days. The rats were observed for toxic signs and mortalities during the acute phase. Food consumption, water intake, bodyweight, urine volume and pH, glucose, protein, and colonic temperature were determined on survivors during the first three days of the test. Fatalities, and survivors after 15 days, were autopsied and examined for gross and microscopic pathologic changes. Based on the results, the LD50 for Sodium chloride in rats was found to be 3750 +/- 430 mg/kg bw (re-calculated to 7190 mg/kg bw Sodium (S)-lactate).

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.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

supporting 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

Preliminary study:

not applicable

Sex:

male

Dose descriptor:

LD50

Effect level:

3 550 mg/kg bw

Based on:

test mat.

95% CL:

>= 3 040 - <= 4 140

Mortality:

2150 mg/kg bw - 0/5
3160 mg/kg bw - 1/5
4640 mg/kg bw - 5/5
6810 mg/kg bw - 5/5

Clinical signs:

other: Hypoactivity, muscular weakness, sedation and ruffled fur

Gross pathology:

No significant findings noted in those animals sacrified at termination and inflammation of gastrointestinal tract was noted in those decedents during the course of the study.

Other findings:

not specified in the report

Interpretation of results:

other: CLP criteria not met

Conclusions:

The acute oral LD50 of Sodium chloride (administered as 25% water solution) was 3550 mg/kg bw to male rats.

Executive summary:

In this study, the acute oral toxicity of Sodium chloride was evaluated in male Wistar rats (5/dose group) at doses of 2150, 3160, 4640 and 6810 mg/kg bw administered as a 25% water solution. 100% mortality was observed at the 4640 and 6810 mg/kg bw dose groups. The LD50 was 3550 mg/kg with fiducial limits of 3040 - 4140 mg/kg bw.

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.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

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 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 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 conducted 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 bw 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.

Lactic acid does not need to be classified in accordance with CLP Regulation 1272/2008.

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:

adverse effect observed

Dose descriptor:

LD50

Value:

3 543 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

other:

Reference 2

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 details and 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:

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.

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

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

> 7 940 mg/m³ air

Physical form:

inhalation: aerosol

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

supporting 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

Preliminary study:

not applicable

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed

Clinical signs:

other: no signs of toxicity observed

Gross pathology:

no significant findings were noted at necropsy

Other findings:

Slight erythema was observed

Interpretation of results:

other: CLP criteria not met

Conclusions:

Based on the results it can be stated, that Sodium chloride is not dermally toxic and the LD50 is greater than 10000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study, New Zealand White rabbits were dermally exposed to Sodium chloride at a dose of 10000 mg/kg bw.

All animals survived and no adverse effects were observed following treatment. Based on the results the dermal LD50 is > 10000 mg/kg bw.

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.

Reference 2

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 details and 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:

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.

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Additional information

No studies are available for the assessment of the acute oral, inhalation and dermal toxicity for the target substance Sodium lactate. Therefore, data available from the suitable read-across substances lactic acid and sodium chloride were used 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 LC50 of L(+)-lactic acid is greater than 7.94 mg/L.

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 via 10% of the body surface area at a dose of 2000 mg/kg bw. Animals were then 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.

Supporting evidence that the target substance reveals no acute toxic properties were derived from available data with Sodium chloride. In acute oral and acute dermal toxicity studies, the derived LD50 values were clearly > 2000 mg/kg bw.

Based on the available data from the source substances L(+)-lactic acid and sodium chloride and as in all studies the LD50 or LC50 values for the oral, dermal or inhalation route are above the limit values of the relevant OECD guideline and of the CLP Regulation 1272/2008, no classification for acute toxicity is warranted for the target substance Sodium lactate. For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Justification for classification or non-classification

Based on the available data, Sodium 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 1272/2008.