Dilactide

Endpoint summary

Description of key information

There are no studies available for the assessment of the oral, inhalation and dermal acute toxicity for the target substance dilactide. Therefore, data available from the suitable read-across substance L(+)-lactic acid, D-lactide and L-lactide was used to assess the acute toxicity via the standard routes of administration (oral, inhalation, dermal).

A sample of D-lactide (purity >99.5%) was examined for acute oral toxicity in an experiment conducted according to OECD guideline 423 with female rats. A dose level of 2000 mg/kg bw was examined. No mortality or distinct clinical signs were observed after treatment of 6 females with 2000 mg/kg bw.
In an acute dermal toxicity study, a group of young adult Wistar rats (5 males and 5 females) were dermally exposed to D-lactide (purity 99%) in polyethylene glycol 400 for 24 hours to approximately 10% of body surface area at 2000 mg/kg bw. Animals were observed for 14 days. No mortality occurred. There were no treatment related clinical signs, necropsy findings or changes in body weight. In addition, L-lactide was examined in an acute oral toxicity test and in an acute dermal toxicity study. In both GLP guideline studies no effects were observed after treatment with 2000 mg/kg bw . D- and L-lactide are suitable read across partners as Dilactide is a mixture of D- and L-lactide isomers.
L(+)-lactic acid is used additionally as a read-across partner for dilactide in an acute inhalation toxicity study (OECD TG 403) in rats, in which a LC50 of > 7.94 mg/L was determined.

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:

weight of evidence

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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: None

Body weight:

other body weight observations

Remarks:

No adverse effects on body weight

Gross pathology:

Examination at autopsy of the males and females did not reveal treatment-related gross alterations.

Interpretation of results:

other: CLP criteria not met

Conclusions:

Since no mortality occurred during the 14-day observation period, the LD50 of L-lactide exceeds 2000 mg/kg bw in both male and female rats. Therefore, L-lactide is considered not harmful after oral ingestion.

Executive summary:

In an acute oral toxicity study conducted according to OECD guideline 423, a group of male and female Wistar outbred rats; Crl:(WI) WU BRA (n = 3/sex) were given a single oral dose of L-lactide (purity > 99.5%) at a dose level of 2000 mg/kg body weight.

No mortality or distinct clinical signs were observed after treatment. Macroscopic examination of the animals at the end of the observation period did not reveal any treatment-related gross changes. Since no mortality occurred during the 14-day observation period, the acute oral LD50 of L-lactide is considered to exceed 2000 mg/kg body weight, in both male and female rats. L-lactide is considered to be not harmful after oral ingestion.

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.

Reference 2

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 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

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture was noted for all animals on day 1. In addition, lethargy and piloerection were noted among the majority of animals on day 1.

Body weight:

other body weight observations

Remarks:

No adverse effects observed

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

N.A.

Interpretation of results:

other: CLP criteria not met

Conclusions:

Since no mortality occurred during the 14-day observation period, the LD50 of D-lactide exceeds 2000 mg/kg bw in female rats. Therefore, D-lactide is considered as not harmful upon ingestion.

Executive summary:

In an acute oral toxicity study conducted according to OECD guideline 423, group of male and female Wistar rats (n= 3/sex) were given a single oral dose of D-lactide (purity >99%) at a dose level of 2000 mg/kg body weight.

No mortality or distinct clinical signs, except hunched posture, piloerection and lethargy on day 1, were observed after treatment of 6 females with the 2000 mg/kg bw dose level. Macroscopic examination of the animals at the end of the observation period did not reveal any treatment-related gross changes. Since no mortality occurred during the 14-day observation period, the oral LD50 of D-lactide is considered to exceed 2000 mg/kg bw in female rats. D-lactide is considered as not harmful upon ingestion.

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

Quality of whole database:

Guideline studies

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 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

Duration of exposure:

h

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:

> 7.94 mg/L air

Physical form:

inhalation: aerosol

Quality of whole database:

Guideline study

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

weight of evidence

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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred

Clinical signs:

other: Chromodacryorrhoea (snout) was noted for one male on Day 1. No further clinical signs were observed

Body weight:

other body weight observations

Remarks:

No adverse effects observed

Gross pathology:

Reddish discolouration of the uterine adipose tissue in the abdominal cavity was observed for one female.

Interpretation of results:

other: CLP criteria not met

Conclusions:

The dermal LD50 value of L-lactide in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study conducted according to OECD guideline 402, a group of young adult Wistar rats (5 males and 5 females) was dermally exposed to L-lactide (purity 99%) in polyethylene glycol 400 for 24 hours to approximately 10% of body surface area at 2000 mg/kg bw. Animals were observed for 14 days. No mortality occurred. There were no treatment related clinical signs, necropsy findings or changes in body weight. The dermal LD50 value of L-lactide in Wistar rats was established to exceed 2000 mg/kg body weight.

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

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

weight of evidence

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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Chromodacryorrhoea (left eye) was noted for one male on day 2. One male showed scabs on day 6 and scales on day 7 in the treated skin area.

Body weight:

other body weight observations

Remarks:

No adverse effects were observed

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

other: CLP criteria not met

Conclusions:

The dermal LD50 value of D-lactide in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study conducted according to OECD guideline 402, a group of young adult Wistar rats (5 males and 5 females) was dermally exposed to D-lactide (purity 99%) in polyethylene glycol 400 for 24 hours to approximately 10% of body surface area at 2000 mg/kg bw. Animals were observed for 14 days. No mortality occurred. There were no treatment related necropsy findings or changes in body weight. Clinical signs as e.g. chromodacryorrhoea (left eye) was noted in one male on day 2 and one male shoed scabs on day 6 and scales on day 7 in treated skin area.

The dermal LD50 value of D-lactide in Wistar rats was established to exceed 2000 mg/kg body weight.

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

Quality of whole database:

Guideline studies

Additional information

There are no studies available for the assessment of the oral, inhalation and dermal acute toxicity for the target substance dilactide. Therefore, data available from the suitable read-across substance L(+)-lactic acid, D-lactide and L-lactide was used to assess the acute toxicity via the standard routes of administration (oral, inhalation, dermal).

After oral application of rats on the one hand with L-lactide and on the other hand with D-lactidein studies conducted in accordance with OECD 423 an acute oral LD50 of L-lactide and D-lactide of > 2000 mg/kg bw was determined. After dermal application in studies conducted in accordance to OECD guideline 402, the LD50 of L-lactide and D-lactide was determined with > 2000 mg/kg bw. L- and D-lactide are suitable read across partners as dilactide is a mixture of D- and L-lactide isomers.

L(+)-lactic acid is an acceptable read-across partner as lactide is rapidly converted by hydrolysis into lactic acid under aqueous conditions. In an acute inhalation toxicity study in rats with lactic acid conducted in accordance with OECD guideline 403 a LC50 of > 7.94 mg/L air was determined.

Justification for classification or non-classification

Based on the available data, the target substance dilactide does not warrant classification for acute toxicity in accordance with CLP Regulation 1272/2008.