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Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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 conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
20 000 mg/kg bw
Quality of whole database:
High

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated 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.
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
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:
other: 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
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
2 000 mg/m³
Quality of whole database:
High; no mortality occurred at levels of > 2000 to > 5000 mg/m3.

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Sufficient data on materials and methods, but study probably not performed under GLP.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
not specified
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- The animals were caged in groups of 5 of the same gender in transparent polycarbonate cages (dimensions mm 425X266X180h).
- The housing room was mantained under the following conditions:
x Temperature: 20 ± 2 dC
x Humidity: 55% ± 15% R.H.: Air was changed at least 25 times per hour and maintained at a pressure higher than the outside atmosphere.
x Artificial lighting: 12 h/day.
x The cages and the housing room were cleaned and disinfected before the animals wereaccomodated, then cleaning and disinfection were performed periodically
- Source: "Nossan" - Correzzana MI - ITALY
- Weight at study initiation: 180-200 g
- Fasting period before study: not specified
- Housing: not specified
- Diet: Animals were fed with standard pellet complete diet supplied by the authorized breeder NOSSAN.
- Water: Filtered tap water from local network was supplied ad libitum.
- Quarantine/Acclimation period: Before being used in this study, the animals were kept in quarantine for one week. During this period they were observed daily. At the end of the quarantine week the animals were carefully examined in order to evaluate their suitability for the study.
- Animal selection: The animals used for this study were selected randomly from those suitable, available at that time.
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Approximately 24 hours before the test fur was removed by clipping and shaving a dorsal area about 25 cm2 wide.
- The sample was put on a patch (Hansamed strips) the dorsal area of animals. The patch was then covered by an impermeable and hypoallergenic plastic adhesive tape (Blenderm 3M).
- No control group was used.

REMOVAL OF TEST SUBSTANCE
The patch was removed 24 hours after application. The exceeding material was then washed away from skin using a pad soaked in distilled water.

Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
OBSERVATIONS
- General conditions of the animals were controlled daily for 14 days (5 days a week) .
- All data relative to the study, including observations and examination were recorded and signed daily.
- Mortality: Animals were observed in the morning of every working day.
- Clinical signs and behavior: Every clicnical symptom, including possible variations in somotomotor activity, was daily recorded in every single animal. Observations included: tegumentary apparatus, mucosae conditions, respiratory activity and sensorium conditions.
- Body weight: Animals were weighed before the experiment, after 7 days and then at the end of the study.
- Necropsy: At the end of the observation period rats were sacrificed and a necroptic survey was performed.
Statistics:
INTERPRETATION OF RESULTS
Results have been interpreted according to EEC Directives 93/21.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred during the study.
Clinical signs:
No clinical signs were observed during the experimental observation period.
Body weight:
The body weight gain was considered normal for the species and strain of rats used in this study.
Gross pathology:
At the ante-mortem and post-mortem examination in all animals no pathological symptoms were observed. No macroscopic abnormalities were seen at necropsy.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The results interpreted according to EEC Directives 93/21indicate that the test material, COSMACOL EL, can be considered NON TOXIC and NON
HARMFUL.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
High; dermal exposure to a combination of dodecyl and tridecyl lactates induced no mortality at levels of > 2000 mg/kg bw.

Additional information

Ceraphyl 41 containing C12-C15 lactates has an oral LD50 of 20,000 mg/kg and the inhalation LC50 of lactate esters is generally above 5000 mg/m3. Also dermal exposure to C12 -C13 alkyl lactates appears to be practically non-toxic.


Justification for selection of acute toxicity – oral endpoint
Key study performed with Ceraphyl 41.

Justification for selection of acute toxicity – inhalation endpoint
Key study referring to various tests with a range of alkyl lactates.

Justification for selection of acute toxicity – dermal endpoint
A combination of dodecyl and tridecyl lactates, linear and branched, proved to be non-toxic. Supporting test with other alkyl lactates confirm the lowacute dermal toxicity of the product for registration.

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.