Registration Dossier

Administrative data

Description of key information

In the absence of data on acute toxicity on target substance Fatty acids, C14-22, C16-24-alkyl esters an analogue read-across approach was conducted on suitable source substances:

Oral (OECD 401), rat: LD50: > 20 mL/kg bw (corresponding to 17400 mg/kg bw based on a relative density of 0.87 g/cm³; limit test)

Inhalation (OECD 436), rat: LC50: > 5.7 mg/mL air

Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw

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:
13 Jan -2 Feb 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted Feb 1987
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Tuck & Sons Ltd, Battlesbridge, Essex, UK
- Weight at study initiation: 174 - 278 g (males and females)
- Fasting period before study: 16 - 20 h overnight
- Housing: 5 rats per cage in solid polypropylene cages, on softwood sawdust
- Diet: Rat Diet (Nottingham University, School of Agriculture, Nottingham, UK), ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw
Doses:
Range finding study: 10 and 20 mL/kg bw (corresponding to 8700 and 17400 mg/kg bw, respectively, based on a relative density of 0.87 g/cm³)
Main study: 20 mL/kg bw (corresponding to 17400 mg/kg bw based on a relative density of 0.87 g/cm³)
No. of animals per sex per dose:
Range finding study: 1
Main study: 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed to record mortality and clinical signs 1/2, 1 and 4 hour(s) after dosing and then once daily for fourteen days. The body weights of all animals were recorded on Day 0 and Day 14.
- Necropsy of survivors performed: yes
Preliminary study:
Based on the data of the dose range-finding study a dose level of 20 mL/kg bw was selected for the main test.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 mL/kg bw
Based on:
test mat.
Remarks on result:
other: corresponding to 17400 mg/kg bw based on a relative density of 0.87 g/cm³
Mortality:
No mortality occured during the observation period.
Clinical signs:
No overt signs of toxicity were observed up to the end of the observation period.
Body weight:
No effect on body weight was noted.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Conclusions:
In this acute oral toxicity study in rats a LD50 value of > 20 mL/kg bw (corresponding to 17400 mg/kg bw based on a relative density of 0.87 g/cm³) was found.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
27 May - 09 Jun 1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The analytical purity of the test substance was not specified; necropsy was not performed.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
necropsy not performed
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
yes
Remarks:
necropsy not performed
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 220.7 - 243.6 g (males) and 199.0 - 216.0 g (females)
- Fasting period before study: animals were fasted for 24 hours prior to dosing
- Housing: animals were housed 5 per cage in polycarbonate cages (450mm x 300mm x 200mm), which had a type E wire floor and contained absorbent material
- Diet: feed A04 (U.A.R., Epinay Sur Orge, France), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-75
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 27 May 1999 To: 9 Jun 1999
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for mortality and clinical signs immediately, 15 mins and 6 hours after administration, and daily thereafter (5 days per week); animals were weighed on Day 0, 7 and 14
- Necropsy of survivors performed: no
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality or clinical signs were observed at this dose level.
Mortality:
There was no mortality during the study period.
Clinical signs:
No clinical signs were observed during the 14-day study period.
Body weight:
No effect on body weight was noted.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
29 Aug - 21 Sep 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The analytical purity of the test substance was not reported.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted Feb 1987
Deviations:
yes
Remarks:
analytical purity of the test substance was not reported
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: OFA.Sprague-Dawley (IOPS Caw)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Iffa-Crédo, L'Arbresle, France
- Age at study initiation: 5 - 7 weeks
- Weight at study initiation: 145.0 g (mean, females) and 164.4 g (mean, males)
- Fasting period before study: 18 h
- Housing: animals were caged in groups of 5/sex in type FI polycarbonate cages (365 mm x 225 mm x 180 mm). Bedding was changed weekly.
- Diet: complete pelleted rat-mouse maintenance diet U.A.R. formule A.04 CR, U.A.R. (Epinay-S/Orge, France), ad libitum
- Water: softened and filtered drinking water, ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 35 mL/kg bw
Doses:
29.75 g/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations of mortality and signs of toxicity were made 15 minutes and 1, 2 and 4 hours after administration, and daily thereafter; animals were weighed on Day -1, Day 1 prior to dosing and on Day 8 and 15.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 29 750 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
No effect on body weight was noted.
Gross pathology:
No substance-related findings were noted during the necropsy and histopathological examination.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details). The selected study is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 Jun - 17 Jun 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Version / remarks:
adopted in 2009
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 9 weeks old
- Weight at study initiation: max. ± 20% of the sex mean
- Housing: Before exposure - Group housing of maximally 5 animals per sex per cage in labeled Makrolon cages (type IV; height 18cm.) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, UK). After exposure - Group housing as described above, maximally 3 animals per sex per cage.
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäteb GmbH, Soest, Germany), ad libitum except during exposure to the test substance.
- Water: tap-water, ad libitum except during exposure to the test substance.
- Acclimation period: 5 days before the start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: The design of the exposure chamber is based on the flow past nose-only inhalation chamber (Am.Ind.Hyg Assoc.J. 44(12): 923-928, 1983). The chamber consists of animal sections with eight animal ports each. Each animal port has its own atmosphere inlet and exhaust outlet.

- Method of holding animals in test chamber: Animals are placed in restraining tubes, which is then connected to the exposure chamber.

- Source and rate of air: The theoretical air flow was at least 1L/min.

- System of generating aerosols: An aerosol was generated by nebulization of the test substance by means of a nebulizer (type 950, Hospitak Inc., Lindenhurst, NY, USA). The primary aerosol was diluted with pressurized air before it entered the exposure chamber. The mean total airflow was 16 L/min. From the exposure chamber the test atmosphere was passed through a filter before it was released to the exhaust of the fume hood.

- Method of conditioning air: The direction of the flow of the test atmosphere guarantees a freshly generated atmosphere for each individual animal.

- Temperature, humidity, pressure in air chamber: The temperature of the atmosphere was between 20.0 and 20.7 °C and relative humidity was between 28 and 30%. These conditions were considered appropriate for the relatively short 4 hours exposure duration.


TEST ATMOSPHERE
- Brief description of analytical method used: Samples were drawn through a glass fiber filter (type APFC04700, Millipore, Billerica, MA, USA). The collected amount of test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter (type G 1.6, Actaris Meterfabriek B.V., Dordrecht, The Netherlands).
- Samples taken from breathing zone: yes


VEHICLE
- The test substance was used as delivered by the sponsor

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMAD was 2.5 µm (GSD 2.4) and 2.6 µm (GSD 2.3).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Target concentrations were based on the cut off concentration values specified in the UN and EC classification guidelines.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetrically
Duration of exposure:
4 h
Concentrations:
The mean actual concentration was 5.7 ± 0.4 mg/L. The nominal concentration was 15.4 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 37%. Data obtained from the opacity monitor showed that the aerosol was sufficiently stable.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: twice daily
Clinical signs: twice on the day of dosing (1 and 3 hours after exposure); daily thereafter until day 15
Body weight: recorded on day1 (pre-exposure), 2, 4, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
All animals were sacrificed at the end of the observation period by an intraperitoneal injection with Euthasol® (AST Farma BV, Oudewater, The Netherlands).
Statistics:
No statistical analysis was performed (the method used was not intended to calculate a LC50 value).
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.7 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No mortality occurred. Apart from hunched position observed in all rats on day 2 after exposure, no further signs of adverse toxicity were observed during the 14-day observation period.
Mortality:
No mortality occured during the 14-day observation period.
Clinical signs:
other: Hunched posture was shown by all animals on Day 2 after exposure. No clinical signs were noted during exposure.
Body weight:
Body weight gain in males and females were within the range expected for rats of this strain and age used in this type of study.

Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate, reliable (Klimisch score 1) and consistent study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details). The selected study is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 May - 2 Jun 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The test substance was applied with an occlusive dressing.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
the test substance was applied with an occlusive dressing
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
the test substance was applied with an occlusive dressing
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
the test substance was applied with an occlusive dressing
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No. 8147, November 2000; including the most recent partial revisions
Deviations:
yes
Remarks:
the test substance was applied with an occlusive dressing
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar Crl:WI (Han)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: 269-284 g (males), 181-194 g (females)
- Housing: animals were housed individually in labelled Makrolon cages (MIII type, height 18 cm) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd.), Surrey, UK). During the acclimation period the animals were housed in groups in Macrolon cages (MIV type).
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6-21.2
- Humidity (%): 39-62
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the back of the animals; approximately 25 cm² for males and 18 cm² for females
- % coverage: 10
- Type of wrap if used: the test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D) covered with aluminium foil and Coben elastic bandage, respectively. A piece of Micropore tape was used to fix the bandage in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was cleaned using tap water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes, the dose volume was calculated as dose level (g/kg) / density (g/mL)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: an untreated, adjacent skin area served as the control
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed twice daily for mortality; the body weight was recorded on Day 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes, on Day 15 the animals were subjected to necropsy and all gross macroscopical abnormalities were recorded
- Other examinations performed: clinical signs were observed at periodic intervals on the day of dosing (day 1) and once daily thereafter, until sacrifice. The time of onset, degree and duration were recorded and the symptoms graded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study period (see Table 1).
Clinical signs:
Piloerection was observed from 4 h - day 2 after dosing in 2/5 males (see Table 2). Chromodacryorrhoea (excessive secretion of a reddish-brown liquid from the eyes) (grade 1) was observed in 3/5 males 2-4 hours after dosing. No systemic clinical signs of toxicity were observed during the study period in females.
Body weight:
The body weight gains of males and females were within the normal ranges during the study period.
Gross pathology:
The necropsy and histopathological examination did not reveal substance-related findings.
Other findings:
- Other observations: On the treated skin area, erythema was observed for up to 4 days during Day 3-7 in 4/5 females. Scales or scabs (grade 1) were noted on the treated skin area in 5/5 females and 3/5 males for up to 9 days during Day 7-15 of the observation period.

Table 1: Mortality and clinical signs

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

2000

0/5/5

4 h – day 2 

Day 1-3

0

Females

2000

0/0/5

-

Day 1

0

LD50 > 2000 mg/kg bw

* first number = number of dead animals                                 

second number = number of animals with systemic clinical signs         

  third number = number of animals used                 Table 2: Clinical signs, systemic/local

Effect*

Max grade

Male No./duration (hours or day after dosing)

Female No./duration (hours or day after dosing)

 

 

1

2

3

4

5

6

7

8

9

10

Systemic

 

 

 

 

 

 

 

 

 

 

 

Piloerection

 1

4 h - 2 d

 

 

 

4 h - 2 d

 

 

 

 

 

Chromoda-cryorrhoea

 3

 

2 - 4 h

2 - 4 h

4 h

 

 

 

 

 

 

Local

 

 

 

 

 

 

 

 

 

 

 

Erythema, focal

 4

 

 

 

 

 

7 d

 

7 d

3 – 7 d

7 d

Scales

 3

 

 

8 – 10 d

7 – 15 d

 

7 – 8 d, 14 d

8 – 11 d

7 – 9 d

7 – 8 d

7 – 9 d

Scabs

 3

 

7 - 11 d

 

9 - 15 d

 

8 – 13 d

 

 

 

 

* all grade 1

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
12 - 26 Feb 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The test substance was applied with an occlusive dressing.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
occlusive dressing
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
occlusive dressing
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar Crl:(WI)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 292 ± 13 g (mean ± SD, males); 199 ± 9 (mean ± SD, females)
- Fasting period before study: no
- Housing: animls were individually housed in labelled polycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Helmond, the Netherlands)
- Diet: standard pelleted laboratory animal diet (Carfil Quality BVBA, Oud-Turnhout, Belgium), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12 Feb 1998 To: 26 Feb 1998
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the test substance was applied to an area of approximately 25 cm² for males and 18 cm² for females, using a gauze patch measuring 5x 5 cm and 3.5 x 5 cm, respectively
- % coverage: approximately 10% of total body surface
- Type of wrap if used: the gauze patch was fixed to aluminium foil and held in place with Coban elastic bandage (with drops of petrolatum). A piece of Micropore tape was used for additional fixation of the dressings in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed using a tissue moistened with tap water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw (10 mL/kg bw)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed twice daily for mortality; clinical signs were observed at periodic intervals during the dosing day and once daily for the rest of the study period; the body weight was measured on Day 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes, the animals were examined for macroscopic abnormalities
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study period (see Table 1).
Clinical signs:
Red staining of the neck fur (score 1 of 3) was observed in 1/5 females on Day 8-13. This is an effect that is frequently seen in rats under stressful conditions and is therefore not considered to be toxicologically relevant. No other clinical signs were noted in any animals during the study period.
Body weight:
The body weight gains were within the normal ranges in males and females during the whole study period.
Gross pathology:
The necropsy and histopathological examination did not revealed any substance-related findings.

Table 1: mortality and clinical signs

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

2000

0/0/5

- 

-

0

Females

2000

0/1/5

Day 8-13 

-

0

Overall LD50 > 2000 mg/kg bw

* first number = number of dead animals                                 

 second number = number of animals with systemic clinical signs         

 third number = number of animals used                               

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 1 - 2) and consistent studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details). The selected study is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Analogue justification

No data on the acute oral toxicity Fatty acids, C14-22, C16-24-alkyl esters (CAS 92797-30-3) are available. The assessment of acute toxicity was therefore based on studies conducted with source substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity

CAS 90990-29-7

The potential acute oral toxicity of Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7) was assessed in a study performed according to a protocol similar to OECD 401 (Key, 1982). 5 rats/sex were administered 20 mL/kg bw (corresponding 17400 mg/kg bw based on a relative density of 0.87 g/cm3) of the test substance by gavage. No mortality occurred. No clinical signs were observed during the 14-day observation period and no effect on body weight was noted. No unusual findings were reported during the macroscopic examination. Based on the results of the conducted study, the oral LD50 value is considered to be > 20 mL/kg bw (corresponding to 17400 mg/kg bw based on a relative density of 0.87 g/cm3).

CAS 72576-80-8

The potential acute oral toxicity of Hexadecanoic acid, -isooctadecyl ester (CAS 72575-80-8) was assessed in a study performed according to OECD 401 (Supporting, 1999). 5 rats/sex were administered 2000 mg/kg bw of the test substance by gavage. No mortality occurred. No clinical signs were observed during the 14-day observation period and the body weights were comparable between the control group and treatment group. A gross pathology examination was not performed. Based on the results of the conducted study, the oral LD50 is considered to be > 2000 mg/kg bw.

 

CAS 22766-83-2

In an acute oral toxicity study performed according to OECD guideline 401 and in compliance with GLP, 29.75 g 2-octyldodecyl myristate/kg bw was administered via gavage to 5 OFA.Sprague-Dawley (IOPS Caw) rats/sex (Supporting, 1989). No mortality occurred during the 14-day observation period. No clinical signs were observed in the animals during the study period. The increase in body weight was within the normal range reported for animals of this strain. Gross pathology did not reveal any substance-related findings in the treated animals. Therefore, the oral LD50 value for male and female rats is > 29.75 g/kg bw.

Acute inhalation toxicity

CAS 26399-02-0

An acute inhalation study was performed with 2-ethylhexyl oleate (CAS No. 26399-02-0) according to OECD guideline 436 as acute toxic class method in 3 male and 3 female Crl:WI(Han) rats (Key, 2010). The animals were exposed to an analytical concentration of 5.7 mg/L of the test substance for 4 hours nose only in an exposure chamber based on the flow past nose-only inhalation chamber. An aerosol was generated by nebulization of the test substance by means of a nebulizer. No mortalities were reported during the exposure or within the 14 days observation period. Hunched posture was shown by all animals on Day 2 after exposure. No clinical signs were noted during exposure. Additionally body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study. No abnormalities were found at macroscopic post-mortem examination of the animals. The inhalatory 4 hour LC50 value of 2-ethylhexyl oleate aerosol in Wistar rats was found to exceed 5.7 mg/L.

Acute dermal toxicity

CAS 93803-87-3

The potential acute dermal toxicity of 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) was assessed in a study (limit test) performed according to a protocol similar to OECD Guideline 402 (Key, 1998). 2000 mg/kg bw of the test substance was applied to the skin of 5 Wistar rats/sex/dose under an occlusive dressing for 24 hours. No mortality occurred. No toxicologically relevant clinical signs were noted during the 14-day observation period. The body weight increases were within the range expected for rats used in this type of study and no treatment-related findings were reported during the necropsy and histopathological examination. The LD50 is considered to be > 2000 mg/kg bw.

 

CAS 3687-46-5

An acute dermal toxicity study (limit test) was performed with decyl oleate (CAS 3687-46-5) according to OECD Guideline 402 (Supporting, 2010). 2000 mg/kg bw of the test substance was applied to the skin of 5 Wistar rats/sex/dose under an occlusive dressing for 24 hours. No mortality occurred. Piloerection and/or chromodacryorrhoea were noted in all males on Day 1 and/or 2. No clinical signs were noted in females. The body weight increases were within the range expected for rats used in this type of study and no treatment-related findings were reported during the necropsy and histopathological examination. Erythema was observed on the treated skin for up to 4 days during the first week in 3/5 females. Scales or scabs were noted on the treated skin area in 5/5 females and 3/5 males for up to 9 days during Day 7-15 of the observation period. The LD50 is considered to be > 2000 mg/kg bw.

 

Overall conclusion for acute toxicity

The reliable data available for the source substances indicate a very low level of acute toxicity via the oral route, as LD50 values were greater than the currently applied limit value of 2000 mg/kg bw. No mortality was observed in the acute inhalation study, leading to an LC50 of > 5.7 mg/L. The available acute dermal toxicity data for source substances consistently showed no mortality and no treatment-related effects. The overall LD50 dermal is therefore set at > 2000 mg/kg bw. Therefore, as the available data did not identify any hazard for acute toxicity, Fatty acids, C14-22, C16-24-alkyl esters (CAS 92797-30-3) is not expected to be hazardous following acute oral, inhalation or dermal exposure.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Fatty acids, C14-22, C16-24-alkyl esters (CAS 92797-30-3), data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the read-across approach, the available data of Fatty acids, C14-22, C16-24-alkyl esters (CAS 92797-30-3) on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.