Registration Dossier

Administrative data

Description of key information

Justification for selection of acute toxicity

– oral endpoint:
Key studies performed with products containing C12 -C16 (even) lactates and C12 -C15 lactates.

Ceraphyl®31 containing C12 -C16 (even) lactates and Ceraphyl®41 containing C12 -C15 lactates all have an oral LD50 of 20,000 mg/kg

- inhalation endpoint:

The inhalation LC50 of lactate esters is generally above 5000 mg/m3.

– dermal endpoint:
Testing with analogue alkyl lactates confirm the low acute dermal toxicity of the product for registration.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is non-GLP, but well described except for ommissions in experimental conditions like temperature and humidity.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Twenty-five young adult rats were distributed into five dosage groups and exposed to various dosages of test material administered by intragastric intubation.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Type: young adult albino rats
Housing: in mesh bottom cages and fasted 24 h prior to dosing
TEST ANIMALS
- Source: Wistar
- Age at study initiation: young adult
- Weight at study initiation: 20 - 300 g
- Fasting period before study: 24 h
- Housing: mesh bottom cages
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No further details.
Doses:
2.5, 5.0, 10, 20, 40 ml/kg bw.
No. of animals per sex per dose:
Males: 3
Females: 2
Control animals:
no
Details on study design:
The rats received food and water ad libitum after dosage and were observed daily for 14 days following administration.
Statistics:
The LD50 was calculated according to the method of Miller and Tainter (Proc. Soc. Biol. Med. 57, 261, 1944)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
21 mL/kg bw
Based on:
test mat.
Remarks on result:
other: Standard deviation: 9.2 mL/kg bw
Mortality:
Dosage Animals Number of deaths daily day 14
mL/kg dosed 1 2 3 4 5 6 7 8 9 10 11 12 13 14 % Mortality
2.5 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
5.0 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
10.0 5 0 0 0 1 0 0 0 0 0 0 0 0 0 0 20
20.0 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
40.0 5 0 0 0 1 0 1 1 0 1 0 0 0 0 0 80

Clinical signs:
No details.
Body weight:
Rats were weighing between 200-300 grams, no effects recorded on body weights.
Gross pathology:
No details.
Other findings:
No details.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of Ceraphyl 41 for rats is more than 10 times higher than the maximum limit for classification of 2000 mg/kg bw .
Executive summary:

The acute oral LD50 of CERAPHYL® 41 was 21 ml/kg bodyweight in rats. Twenty five Wistar albino rats (3 male, 2 female/group) were dosed orally with CERAPHYL® 41 at 2.5, 5, 10, 20 and 40 ml/kg bodyweight. Animals were observed daily for mortality for 14 days. Four animals in the 40 ml/kg group died. One animal in the 10 ml/kg group died.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1964
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is non-GLP, but well described except for ommissions in experimental conditions like temperature and humidity.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Thirty young adult rats were distributed into three dosage groups of each ten rats and exposed to various dosages of test material administered by intragastric intubation.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Holtzman
Sex:
female
Details on test animals and environmental conditions:
Type: young adult albino rats
Housing: in mesh bottom cages and fasted 24 h prior to dosing
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
yelow liquid
Details on oral exposure:
No further details.
Doses:
5, 10, 20 ml/kg bw.
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
The rats received food and water ad libitum after dosage and were observed daily for 7 days following administration.
Statistics:
The LD50 was calculated according to the method of Miller and Tainter (Proc. Soc. Biol. Med. 57, 261, 1944)
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 20 mL/kg bw
Based on:
test mat.
Mortality:
Dosage Animals Number of deaths daily day 14
mL/kg dosed 1 2 3 4 5 6 7 8 9 10 11 12 13 14 % Mortality
2.5 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
5.0 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
10.0 5 0 0 0 1 0 0 0 0 0 0 0 0 0 0 20
20.0 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
40.0 5 0 0 0 1 0 1 1 0 1 0 0 0 0 0 80

Clinical signs:
No details.
Body weight:
Rats were weighing between 200-300 grams, no effects recorded on body weights.
Gross pathology:
No details.
Other findings:
No details.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of Ceraphyl 31 for rats is more than 10 times higher than the maximum limit for classification of 2000 mg/kg bw .
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
20 000 mg/kg bw
Quality of whole database:
High

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute 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:
Information based on safety assessment of lactate esters.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
The temperature of the experimental animal room should have been 22°C ± 3° and the relative humidity 30-70 %.
Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
air
Duration of exposure:
4 h
Concentrations:
The target concentration was 5000 mg/m3 or the highest vapor concentration obtained using a compressed air nebulizer.
No. of animals per sex per dose:
5
Control animals:
not specified
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 000 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality.
Clinical signs:
During exposure decrease in breathing rates; wet head, nares and fur; piloerection; lachrymation; hunched appearance.
Postexposure: Wet fur, sniffing, and slow movement; incidentallly apnea .
Body weight:
no effects reported.
Gross pathology:
Gross necropsy revealed pale lungs in incidental cases, and rusty brown lungs in two females exposed to benzyl lactate.

Acute Inhalation Toxicity ofLactate Esters in Rats:

Lactate

4 -h LC50 (mg/m3)

Observations

Methyl

>5030

 During exposure decrease in breathing rates and wet nares; Wet fur postexposure; Gross necropsy revealed 7 of 10 with grayish lungs; two lungs had irregular surfaces

Ethyl

>5400

 During exposure decrease in breathing rates; piloerection; wet nares; lachrymation; Gross necropsy revealed pale lungs with spots

Butyl

 >5140

 During exposure decrease in breathing rates and wet head and fur; No gross necropsy changes;

Isobutyl

>6160

 During exposure decrease in breathing rates; piloerection; hunched appearance; Postexposure: Apnea; No gross necropsy changes

Isoamyl

>4310

 During exposure decrease in breathing rates and wet head and fur; Wet fur, sniffing, and slow movement postexposure; Gross necropsy revealed 1 of 10 with pale lungs

Benzyl

>2420

 During exposure increase in breathing rates, irregular breathing patterns and wet nares and fur; Gross necropsy revealed rusty brown lungs in two females

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No mortality was noted in the acute inhalation toxicity tests for the lactate esters at levels of > 2000 to > 5000 mg/m3. Clinical signs indicating acute irritant response are most likely due to the acute toxicity of the acid produced by rapid hydrolysis to lactic acid and the alcohol.
Endpoint conclusion
Dose descriptor:
discriminating conc.
5 000 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
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:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
tests with n-propyl lactate
Deviations:
no
GLP compliance:
yes
Remarks:
tests with n-propyl lactate
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Duration of exposure:
Not specified
Doses:
ethyl lactate and n-butyl lactate: 5000 mg/kg
propyl-L-lactate: 2000 mg/kg
No. of animals per sex per dose:
Not specified.
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks:
ethyl lactate
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks:
n-butyl lactate
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks:
propyl-L-lactate
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
5 000 mg/kg bw
Quality of whole database:
Review article.

Additional information

Justification for classification or non-classification

The data are conclusive but not sufficient for classification. This is because the acute toxicity estimates (ATEs) exceed the upper limits for classification.