Registration Dossier

Administrative data

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:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH:
Studies performed with various alkyl lactate, which can be considered as a valid analogues of C12-15 alkyl lactates.

2. SOURCE AND TARGET CHEMICAL(S):
ethyl lactate, n-butyl lactate, isobutyl lactate, and 2-ethylhexyl lactate

3. ANALOGUE APPROACH JUSTIFICATION
Effects observed were restricted to local effects in the respiratory tract, which comply with the potential for irritation of respiratory tract due to eventual exposure to the UVCB under registration.

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female

Administration / exposure

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
Doses / concentrationsopen allclose all
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

Results and discussion

Results of examinations

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.

Effect levels

open allclose all
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.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion