Tetradecyl lactate

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Original tests performed according to an international guideline under GLP.

Justification for type of information:

Data originate from testing with shorter chain alkyl lactates.See section 13 for justification of read across.

Qualifier:

according to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Details on inhalation exposure:

Ethyl, n-butyl, and isobutyl-L-lactates were vapor studies, whereas 2-ethylhexyl-L-lactate was evaluated in an aerosol study and in a supplemental study comparing vapor and aerosol exposure.

Duration of treatment / exposure:

6 h

Frequency of treatment:

5 days a week

Remarks:

Doses / Concentrations:
ethyl-L-lactate: 0, 150, 600, or 2500 mg/m3 and 0, 25, 75, or 200 mg/m3
Basis:
nominal conc.

Remarks:

Doses / Concentrations:
isobutyl-L-lactate: 0, 100, 200, 400, or 800 mg/m3
Basis:
nominal conc.

Remarks:

Doses / Concentrations:
n- butyl- L-lactate: 0, 75, 200, or 600 mg/m3
Basis:
nominal conc.

Remarks:

Doses / Concentrations:
2-ethylhexyl-L-lactate: 0, 75, 200, 600, or 1800 mg/m3
Basis:
nominal conc.

No. of animals per sex per dose:

ethyl, isobutyl, and the primary 2-ethylhexyl studies: 5 males and 5 females;
n-butyl and the supplemental 2-ethylhexyl study: 6 males

Clinical signs:

not specified

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not specified

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Main histopathological changes were observed in the nasal cavity (epithelial degeneration, hyperplasia, metaplasia, and inflammatory changes) larynx and trachea (slight epithelial hyperplasia and squamous metaplasia), and lungs (septal fibrosis).

Details on results:

2-Ethylhexyl-L-lactate appeared to be the most reactive in causing irritation of the nasal airways. In general, the local toxicity NOECs of alkyl lactate are lower than the systemic NOECs. This is probably mainly related to the activity of free lactic acid generated by enzymatic hydrolysis of the alkyl lactates.

Dose descriptor:

NOAEC

Effect level:

200 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

ethyl, n-butyl, and isobutyl lactates

Sex:

male/female

Basis for effect level:

other: Local effects: hyperplasia of the nasal respiratory epithelium, including hyperplasia of goblet cells.

Key result

Dose descriptor:

NOAEC

Effect level:

600 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

butyl- L-lactate

Sex:

male

Basis for effect level:

other: Systemic toxicity

Key result

Dose descriptor:

NOAEC

Effect level:

200 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

butyl- L-lactate

Sex:

male

Basis for effect level:

other: Local effects

Dose descriptor:

NOAEC

Effect level:

800 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

isobutyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Systemic toxicity

Dose descriptor:

NOAEC

Effect level:

200 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

isobutyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Local effects

Dose descriptor:

NOAEC

Effect level:

600 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

2-ethylhexyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Systemic toxicity

Dose descriptor:

NOAEC

Based on:

test mat.

Remarks:

2-ethylhexyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Local effects (nasal epithelium)

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Dose descriptor:

LOAEC

Effect level:

75 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

2-ethylhexyl-L-lactate (aerosol or vapor)

Sex:

male/female

Basis for effect level:

other: Local effects: slight focal hyperplasia of the nasal respiratory epithelium, including hyperplasia of goblet cells.

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

600 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

Based on tests with shorter chain alkyl lactates.

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Original tests performed according to an international guideline under GLP.

Justification for type of information:

Data originate from testing with shorter chain alkyl lactates.See section 13 for justification of read across.

Qualifier:

according to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Details on inhalation exposure:

Ethyl, n-butyl, and isobutyl-L-lactates were vapor studies, whereas 2-ethylhexyl-L-lactate was evaluated in an aerosol study and in a supplemental study comparing vapor and aerosol exposure.

Duration of treatment / exposure:

6 h

Frequency of treatment:

5 days a week

Remarks:

Doses / Concentrations:
ethyl-L-lactate: 0, 150, 600, or 2500 mg/m3 and 0, 25, 75, or 200 mg/m3
Basis:
nominal conc.

Remarks:

Doses / Concentrations:
isobutyl-L-lactate: 0, 100, 200, 400, or 800 mg/m3
Basis:
nominal conc.

Remarks:

Doses / Concentrations:
n- butyl- L-lactate: 0, 75, 200, or 600 mg/m3
Basis:
nominal conc.

Remarks:

Doses / Concentrations:
2-ethylhexyl-L-lactate: 0, 75, 200, 600, or 1800 mg/m3
Basis:
nominal conc.

No. of animals per sex per dose:

ethyl, isobutyl, and the primary 2-ethylhexyl studies: 5 males and 5 females;
n-butyl and the supplemental 2-ethylhexyl study: 6 males

Clinical signs:

not specified

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not specified

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Main histopathological changes were observed in the nasal cavity (epithelial degeneration, hyperplasia, metaplasia, and inflammatory changes) larynx and trachea (slight epithelial hyperplasia and squamous metaplasia), and lungs (septal fibrosis).

Details on results:

2-Ethylhexyl-L-lactate appeared to be the most reactive in causing irritation of the nasal airways. In general, the local toxicity NOECs of alkyl lactate are lower than the systemic NOECs. This is probably mainly related to the activity of free lactic acid generated by enzymatic hydrolysis of the alkyl lactates.

Dose descriptor:

NOAEC

Effect level:

200 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

ethyl, n-butyl, and isobutyl lactates

Sex:

male/female

Basis for effect level:

other: Local effects: hyperplasia of the nasal respiratory epithelium, including hyperplasia of goblet cells.

Key result

Dose descriptor:

NOAEC

Effect level:

600 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

butyl- L-lactate

Sex:

male

Basis for effect level:

other: Systemic toxicity

Key result

Dose descriptor:

NOAEC

Effect level:

200 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

butyl- L-lactate

Sex:

male

Basis for effect level:

other: Local effects

Dose descriptor:

NOAEC

Effect level:

800 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

isobutyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Systemic toxicity

Dose descriptor:

NOAEC

Effect level:

200 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

isobutyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Local effects

Dose descriptor:

NOAEC

Effect level:

600 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

2-ethylhexyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Systemic toxicity

Dose descriptor:

NOAEC

Based on:

test mat.

Remarks:

2-ethylhexyl-L-lactate

Sex:

male/female

Basis for effect level:

other: Local effects (nasal epithelium)

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Dose descriptor:

LOAEC

Effect level:

75 mg/m³ air (nominal)

Based on:

test mat.

Remarks:

2-ethylhexyl-L-lactate (aerosol or vapor)

Sex:

male/female

Basis for effect level:

other: Local effects: slight focal hyperplasia of the nasal respiratory epithelium, including hyperplasia of goblet cells.

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

200 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

Based on tests with shorter chain alkyl lactates.

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Referenced study in summarizing report with limited details on test conditions.

Justification for type of information:

HYPOTHESIS FOR THE ANALOGUE APPROACH:
The experiment was performed with hexadecyl lactate.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Thirty day skin irritation test.

GLP compliance:

not specified

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Body weights: 2.0 to 3.0 kg

Type of coverage:

not specified

Vehicle:

other: mineral oil

Duration of treatment / exposure:

For 30 days, the solution was applied each morning to the back of each animal, after which the animals were restrained in stocks for four hours.

Dose / conc.:

500 mg/kg bw/day

Remarks:

Doses / Concentrations:
5 ml of a 25% solution corresponds with approx. 1250 mg. Considering an average body weight of 2.5 kg this corresponds with an estimated dose of 500 mg/kg bw.

No. of animals per sex per dose:

3

Observations and examinations performed and frequency:

Blood counts were made at the beginning of the experiment, at the end of the second week, when the last application was made, and one week after the last application.
Sections of skin were removed from test application sites and fixed in formalin for histological examination.
Body weights and weight gain were recorded weekly.

Clinical signs:

no effects observed

Dermal irritation:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Haematological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Details on results:

Weight gains and blood counts were normal throughout the test period. No irritation as evidenced by erythema and edema was found following any of the applications. Scarified areas showed normal healing, and histological examination of the skin showed a normal picture. It was concluded that no irritation occurred upon daily application of a 25% solution of Cetyl Lactate for 30 days.

Key result

Dose descriptor:

NOEL

Effect level:

>= 500 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: Dermal irritation, clinical signs, body weights, haematology and histopathology.

Critical effects observed:

not specified

Conclusions:

No irritation occurred upon daily application of a 25% solution of Cetyl Lactate for 30 days.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Low (not assignable).

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Referenced study in summarizing report with limited details on test conditions.

Justification for type of information:

HYPOTHESIS FOR THE ANALOGUE APPROACH:
The experiment was performed with hexadecyl lactate.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Thirty day skin irritation test.

GLP compliance:

not specified

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Body weights: 2.0 to 3.0 kg

Type of coverage:

not specified

Vehicle:

other: mineral oil

Duration of treatment / exposure:

For 30 days, the solution was applied each morning to the back of each animal, after which the animals were restrained in stocks for four hours.

Dose / conc.:

500 mg/kg bw/day

Remarks:

Doses / Concentrations:
5 ml of a 25% solution corresponds with approx. 1250 mg. Considering an average body weight of 2.5 kg this corresponds with an estimated dose of 500 mg/kg bw.

No. of animals per sex per dose:

3

Observations and examinations performed and frequency:

Blood counts were made at the beginning of the experiment, at the end of the second week, when the last application was made, and one week after the last application.
Sections of skin were removed from test application sites and fixed in formalin for histological examination.
Body weights and weight gain were recorded weekly.

Clinical signs:

no effects observed

Dermal irritation:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Haematological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Details on results:

Weight gains and blood counts were normal throughout the test period. No irritation as evidenced by erythema and edema was found following any of the applications. Scarified areas showed normal healing, and histological examination of the skin showed a normal picture. It was concluded that no irritation occurred upon daily application of a 25% solution of Cetyl Lactate for 30 days.

Key result

Dose descriptor:

NOEL

Effect level:

>= 500 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: Dermal irritation, clinical signs, body weights, haematology and histopathology.

Critical effects observed:

not specified

Conclusions:

No irritation occurred upon daily application of a 25% solution of Cetyl Lactate for 30 days.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

subacute

Species:

rat

Quality of whole database:

Low (not assignable).

Justification for classification or non-classification

The effect concentration for an analogue of alkyl lactates ( 2-ethylhexyl-L-lactate) was above the classification limt of 0.2 mg/L (> 200 mg/m³) for inhalatory exposure of aerosol or mist. Local effects of repeated inhalatory exposure to a concentration of 200 mg/m³ of butyl lactate included slight focal hyperplasia of the nasal respiratory epithelium, including hyperplasia of goblet cells. Due to the longer carbon chain, the predicted NOAEC for tetradecyl lactate would be significantly higher. In case of dermal exposure, the effect concentration for an analogue of alkyl lactates (Cetyl lactate) was above the classification limt of 200 mg/kg bw/d (> 500 mg/kg bw/d).