Hydrocarbons, C18-C24, iso-alkanes <2% aromatics

Toxicity to birds

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to birds: dietary toxicity test

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Experimental Starting Date: February 01, 2011 Experimental Completion Date: March 05, 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions. Read-across is considered to be reliability 2.

Qualifier:

according to guideline

Guideline:

OECD Guideline 205 (Avian Dietary Toxicity Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

This study was performed in compliance with the Swiss Ordinance relating to Good Laboratory Practice, adopted May 18th, 2005 [SR 813.112.1].

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

no

Details on preparation and analysis of diet:

Test Item Preparation
Diets containing the required amount of the test item were prepared by uniformly mixing in a Hobart mixer an appropriate amount of the test item with the basal diet for young birds. The test item was added to the diet under continuous stirring and diet portions were further mixed for at least three minutes after the test item had been added.

For the pre-test, 1 kg diet portions were prepared with a target test item concentrations of 200 mg/kg diet, 1000 mg/kg diet and 5000 mg/kg diet.

For the limit test, a 3 kg portion was prepared with a target test item concentration of 5000 mg/kg diet. An amount of 16.5 g test item (including an appropriate excess) was mixed to 3 kg diet.

Analysis of Test Item in the Diet
Concentration of Test Item in the Diet

Representative samples of approx. 50 g were taken at discharge from the Hobart mixer.

Homogeneity and Stability of Test Item in the Diet

Representative samples (approx. 50 g) were taken at discharge from the Hobart mixer as follows:

- one random sample from the top of the discharge
- duplicate random sample from the approximate centre of the discharge
- one random sample from the bottom of the discharge

One sample from each level of the discharge was retained for analysis to determine the homogeneous distribution of the test item the diet. The remaining sample from the middle of the discharge was stored at ambient temperature under animal room conditions for 6 days. This sample was additionally analyzed. A control diet sample was taken and analyzed as well.

All samples were stored at -20 °C until analyses.

Duplicate subsamples (2 g) were analyzed in accordance with the analytical procedure (see attached Appendix E). The analyses were performed in the Analytical Laboratories of Harlan Laboratories Ltd.

Test organisms (species):

other: Japanese quails (Coturnix coturnix japonica)

Details on test organisms:

Test System
Species: Japanese quails (Coturnix coturnix japonica)

Rationale: Recognised by international guidelines as the recommended test system.

Number of Animals per Group: 5 (range finding test) or 10 birds (limit test). No attempt was made to determine the sex of the birds because of their size and age.

Age: 17 days old at the beginning of the exposure period, and all birds of the same age (± 1 day).

Average Body Weights at the Start of the Exposure: 84.2-93.0 g

Identification: Due to rapid growth of the animals, it was not possible to number the animals with leg bands. Therefore, for determination of body weights and at sacrifice, animals were randomly numbered within each group.

Randomisation: Randomly selected at time of delivery

Acclimatisation: 6 days under laboratory conditions after arrival and health examination. The acclimatization period is appropriate when considering that according to the guideline 10 to 17 day-old birds have to be used for the test. Only animals without any visible signs of illness were used in the study.

Limit test:

yes

Total exposure duration (if not single dose):

5 d

Post exposure observation period:

3 observation days where the animals obtained basal diet.

No. of animals per sex per dose and/or stage:

The test item was administered to one group of 10 Japanese quails by dietary ingestion. No attempt was made to determine the sex of the birds because of their size and age.

Control animals:

yes, plain diet

Nominal and measured doses / concentrations:

The limit test was performed with a nominal concentration of 5000 mg/kg diet. Additionally, two control groups received diet without test item.

Details on test conditions:

Conditions: Continuously monitored environment with a temperature of about 30-38 °C (<14 days old) or 25-30 °C (>14 days old), a relative humidity between 50-70 %, 14 hours fluorescent light (approx. 1000 Lux)/10 hours dark, music during the light period. The temperature was maintained with red light lamps installed above the pens. Pen temperatures were measured in representative positions.

Accommodation: In groups of five or ten in cages with a grid floor. The floor space was about 700 cm²/ bird and the cage height at least 40 cm. By using cardboard boxes, structure was added to the cages (e.g. hiding place, elevated platform, dust bathing area with sawdust bedding).

Water: Community tap water from Füllinsdorf/Switzerland, ad libitum. Results of the bacteriological, chemical and contaminant analyses are given in the attached Appendix F.

Diet: Pelleted bird diet (Beweka Kraftfutterwerk GmbH, 74076 Heilbronn/Germany) ad libitum. The information concerning the basal composition of the diet as provided by the manufacturer is also presented in the attached Appendix G.

Allocation
Pre-test (range finding):
 
Group:                             Number of Animals / Group   Animal Number (Group Housing):
1          5000 mg/kg diet           5                                              1 – 5
2          1000 mg/kg diet           5                                             6 – 10
3          200 mg/kg diet 5                                             11 – 15
 
Limit test:
Group                          Number of Animals / Group           Animal Number (Group Housing)
1          Control             10                                            1 – 10
2          Control             10                                            11 – 20
3          5000 mg/kg diet  10                                            21 - 30

Pre-test

A pre-test with 5 birds each at nominal 5000, 1000 and 200 mg/kg diet was performed. No mortalities occurred at all concentration during a 5 days observation period. Therefore, a limit test was performed.

Limit Test

The animals received the test item by dietary ingestion for a period of five days, followed by three days on basal diet. Diets containing the test item or control diets were available ad libitum.
The limit test was performed with a nominal concentration of 5000 mg/kg diet. Additionally, two control groups received diet without test item.

Method: Orally, by feed admix. The control animals received the same diet but without test item.

Rationale: Dietary administration was selected as a possible route of bird exposure in the field.

Test item Concentration
in the Diet: Group 1: 0 mg/kg
Group 2: 0 mg/kg
Group 3: 5000 mg/kg

Details on examinations and observations:

Observations
Mortality/ Viablity: 1-2 times daily

Clinical signs: Two times during test day 1 and once daily thereafter

Body Weight: On day 1 (pre-dose), end of day 5 and end of day 8

Food Consumption: Measured for the exposure period and the 3-day postexposure period


Pathology
Necropsies of the test group and the control groups were performed by experienced personnel.

All animals surviving to the end of the observation period were sacrificed by intraperitoneal injection of Esconarkon AD US.VET (Streuli Pharma AG, 8730 Uznach/Switzerland) at a dose of at least 1.0 mL/kg body weight (equivalent to at least 300 mg sodium pentobarbitone/kg body weight) followed by exsanguination. The animals were examined macroscopically and all abnormalities were recorded.

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

> 5 000 mg/kg diet

Conc. / dose based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: No test item related mortalities and no symptoms were observed within the observation period. At necropsy, no macroscopic findings were observed for the treated animals

Duration (if not single dose):

5 d

Dose descriptor:

NOEC

Effect level:

>= 5 000 mg/kg diet

Conc. / dose based on:

test mat.

Basis for effect:

other:

Remarks on result:

other: No test item related mortalities and no symptoms were observed within the observation period. At necropsy, no macroscopic findings were observed for the treated animals.

Mortality and sub-lethal effects:

1.1 Mortality
Results of the limit test are presented in Appendix A.

Pre-Test
In the pre-test, the test item was administered to 5 Japanese quails each at dose levels of 200, 1000 and 5000 mg/kg diet. No mortality and no symptoms were observed during a
5-day observation period in all of the dose groups. Therefore, a limit test was performed with a concentration level of 5000 mg/kg diet.

Limit-Test
In the limit test at a concentration level of 5000 mg/kg diet, no mortality of the treated birds was observed within the observation period of 8 days. Therefore, the LC50 level for the test item was > 5000 mg/kg diet.

Three of the 20 control animal died. However, taking into account the 20 control animals of a second study (Harlan Laboratories Study D19794) and 17 reserve animals, in total, only 3 of 57 non-treated animals died during the test period. This is confirmation that the maintenance of the birds was appropriate.


Clinical Signs
Results are presented in the attached Appendix A.

No symptoms were observed at a concentration level of 5000 mg/kg diet. Therefore, the NOEC (no observed effect concentration) was > 5000 mg/kg diet.


Macroscopic Findings
For the Limit test, all animals of groups 1-3 were necropsied at the end of the observation period. The results are presented in the attached Appendix B.
No findings were observed in all the animals necropsied at the end of the study. In one of the control animals that died during the test, inflammatory foci were seen on the outside of the heart. One animal had coagulated blood in the abdominal cavity, probably resulting form the i.p. injection of Esconarkon.


Body Weight
Tabulated body weights are presented in the attached Appendix C.

Average body weights before the start of the treatment ranged from 84.2 to 93.0 g for groups 1 to 3. The body weight of the treated animals was on average 124.6 ± 10.2 g on day 5 and 144.3 ± 11.6 on day 8. These weights were similar to the weights of control groups 1 and 2.


Food Consumption and Test Item Intake
Results are presented in the attached Appendix D.

Individual food consumption

The Individual Food Consumption (IFC) during observation days 0-5 (average values, per animal per day) in group 3 (20.2 g food/animal/day) was similar to the IFC of groups 1 and 2 (17.9-20.3 g) Also after termination of the treatment, the IFC for group 3 (21.1 g) was similar to the control groups (21.0-22.5 g).

Relative food consumption

The Relative Food Consumption (RFC) during observation days 0-5 was 176.1 g (average values, per kg body weight per day) of group 3 (234.1g/kg body weight/day) was similar to the RFC of control group 2 (231.0 g). RFC of group 1 (188.8 g was slightly lower when compared to groups 2 and 3. After termination of the treatment, the relative food consumption of all three groups was similar (169.5-177.4 g).

In conclusion, there was no difference in individual food consumption and relative food consumption between the treated group and the control groups.

Test item intake

The test item intake (TII) was calculated based on the food consumption and the nominal test item concentration in the diet:

Group 3: 1170.6 mg test item per kg body weight per day

The LC50 based on test item intake was therefore > 1170.6 mg per kg body weight per day.

Analysis of Test Item in the Diet

Results are presented in the attached Appendix E.

 

The mean concentration of the substance in the diet samples was 106.9% (see “Results” of the analytical report) of the nominal concentration.

 

Maximal deviation of the homogeneity samples was 8.8% of the mean concentration. Therefore, the test item was found to be homogeneously distributed in the diet. Furthermore, the test item was found to be sufficiently stable in the diet during storage at room temperature for 6 days (average 88.6%).

Schedule

Limit test:

 

Groups	Hatch	Arrival of animals	Start of the limit test	End of the limit test
1-3	28-JAN-2011	08-FEB-2011	14-FEB-2011	22-FEB-2011

Validity criteria fulfilled:

yes

Conclusions:

The median lethal concentration (LC50) for the dietary oral toxicity of the test item in young Japanese quails was determined as > 5000 mg test item/kg diet.

No test item related mortalities and no symptoms were observed within the observation period. At necropsy, no macroscopic findings were observed for the treated animals. Therefore, the NOEC (no observed effect concentration) was determined as > 5000 mg/kg diet.

Body weights were similar for treated group and the control groups. Food consumption was also similar for the treated group and the control groups.

The LC50 based on test item intake was > 1170.6 mg per kg body weight per day.

Executive summary:

In a dose range finding pre-test, the test item 'Distillates (Fischer-Tropsch), heavy, C18-50 - branched, cyclic and linear' was administered to 5 Japanese quails each at dietary dose levels of 200, 1000 and 5000 mg/kg diet. All quails survived an observation period of 5 days and no symptoms were observed.

 

Based on the pre-test, a limit test was performed. The test item was administered to one group of 10 Japanese quails by dietary ingestion at a nominal dose level of 5000 mg test item/kg diet for 5 treatment days followed by 3 observation days where the animals obtained basal diet.

 

No mortality was observed in the main study at a dose level of 5000 mg/kg diet, therefore, the LC50 of 'Distillates (Fischer-Tropsch), heavy, C18-50 - branched, cyclic and linear' was determined as > 5000 mg/kg diet.

 

No symptoms and no macroscopic findings were observed in the treated animals. Therefore, the NOEC (no observed effect concentration) was determined as >5000 mg/kg diet.

Body weights and food consumption were similar for treated group and the control groups.

 

The mean test item intake over the treatment period of five days was as follows: 

Group	Dietary test item concentration (mg/kg)	IFC g food per animal per day	RFC g per kg body weight per day	TII mg test item per kg body weight per day
1	0	17.9	188.8
2	0	20.3	231.0
3	5000	20.0	234.1	1170.6

IFC:    Individual Food Consumption

RFC:   Relative Food Consumption

TII:      Test Item Intake

 

CONCLUSION

The median lethal concentration (LC50) for the dietary oral toxicity of the test item in young Japanese quails was determined as > 5000 mg test item/kg diet.  

No test item related mortalities and no symptoms were observed within the observation period. At necropsy, no macroscopic findings were observed for the treated animals. Therefore, the NOEC (no observed effect concentration) was determined as >5000 mg/kg diet.

Body weights were similar for treated group and the control groups. Food consumption was also similar for the treated group and the control groups.

The LC50 based on test item intake was >1170.6 mg per kg body weight per day.

Reference 2

Endpoint:

short-term toxicity to birds: dietary toxicity test

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental Starting Date: February 01, 2011 Experimental Completion Date: March 04, 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 205 (Avian Dietary Toxicity Test)

Deviations:

no

Guideline:

EPA OPPTS 850.2200 (Avian Dietary Toxicity Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Dose method:

feed

Analytical monitoring:

yes

Vehicle:

no

Details on preparation and analysis of diet:

Test Item Preparation
Diets containing the required amount of the test item were prepared by uniformly mixing in a Hobart mixer an appropriate amount of the test item with the basal diet for young birds. The test item was added to the diet under continuous stirring and diet portions were further mixed for at least three minutes after the test item had been added.
For the pre-test, 1 kg diet portions were prepared with a target test item concentrations of 200 mg/kg diet, 1000 mg/kg diet and 5000 mg/kg diet.
For the limit test, a 3 kg portion was prepared with a target test item concentration of 5000 mg/kg diet. An amount of 16.5 g test item (including an appropriate excess) was mixed to 3 kg diet.

Analysis of Test Item in the Diet
Concentration of Test Item in the Diet
Representative samples of approx. 50 g were taken at discharge from the Hobart mixer.

Homogeneity and Stability of Test Item in the Diet
Representative samples (approx. 50 g) were taken at discharge from the Hobart mixer as follows:
- one random sample from the top of the discharge
- duplicate random sample from the approximate centre of the discharge
- one random sample from the bottom of the discharge
One sample from each level of the discharge was retained for analysis to determine the homogeneous distribution of the test item the diet. The remaining sample from the middle of the discharge was stored at ambient temperature under animal room conditions for 6 days. This sample was additionally analyzed. A control diet sample was taken and analyzed as well.
All samples were stored at -20 °C until analyses.
Duplicate subsamples (5 g) were analyzed in accordance with the analytical procedure (see attached Appendix E). The analyses were performed in the Analytical Laboratories of Harlan Laboratories Ltd.

Test organisms (species):

Coturnix coturnix japonica

Details on test organisms:

Test System
Species: Japanese quails (Coturnix coturnix japonica)

Rationale: Recognised by international guidelines as the recommended test system.

Source: Accredited animal supplier for full details see full study report


Age: 17 days old at the beginning of the exposure period, and all birds of the same age (± 1 day).
Average Body Weights at the Start of the Exposure: 79.3-88.0 g

Identification: Due to rapid growth of the animals, it was not possible to number the animals with leg bands. Therefore, for determination of body weights and at sacrifice, animals were randomly numbered within each group.

Randomisation: Randomly selected at time of delivery

Acclimatisation: 6 days under laboratory conditions after arrival and health examination. The acclimatization period is appropriate when considering that according to the guideline 10 to 17 day-old birds have to be used for the test. Only animals without any visible signs of illness were used in the study.

Limit test:

yes

Total exposure duration (if not single dose):

5 d

Post exposure observation period:

3 observation days where the animals obtained basal diet.

No. of animals per sex per dose and/or stage:

Number of Animals per Group: 5 (range finding test) or 10 birds (limit test). No attempt was made to determine the sex of the birds because of their size and age.

Control animals:

yes, concurrent no treatment

Nominal and measured doses / concentrations:

A pre-test with 5 birds each at nominal 5000, 1000 and 200 mg/kg diet was performed.

The limit test was performed with a nominal concentration of 5000 mg/kg diet.

Two control groups received diet without test item.

Details on test conditions:

Husbandry
Conditions: Continuously monitored environment with a temperature of about 30-38 °C (<14 days old) or 25-30 °C (>14 days old), a relative humidity between 50-70 %, 14 hours fluorescent light (approx. 1000 Lux)/10 hours dark, music during the light period. The temperature was maintained with red light lamps installed above the pens. Pen temperatures were measured in representative positions.
Accommodation: In groups of five or ten in cages with a grid floor. The floor space was about 700 cm²/ bird and the cage height at least 40 cm. By using cardboard boxes, structure was added to the cages (e.g. hiding place, elevated platform, dust bathing area with sawdust bedding).
Water: Community tap water from Füllinsdorf/Switzerland, ad libitum. Results of the bacteriological, chemical and contaminant analyses are given in the attached Appendix F.
Diet: Pelleted bird diet ad libitum. The information concerning the basal composition of the diet as provided by the manufacturer is also presented in the attached Appendix G.
Pre-test
A pre-test with 5 birds each at nominal 5000, 1000 and 200 mg/kg diet was performed. No mortalities occurred at all concentration during a 5 days observation period. Therefore, a limit test was performed.

Details on examinations and observations:

Treatment

Limit Test
The animals received the test item by dietary ingestion for a period of five days, followed by three days on basal diet. Diets containing the test item or control diets were available ad libitum.
The limit test was performed with a nominal concentration of 5000 mg/kg diet. Additionally, two control groups received diet without test item.
Method: Orally, by feed admix. The control animals received the same diet but without test item.
Rationale: Dietary administration was selected as a possible route of bird exposure in the field.
Test item Concentration
in the Diet: Group 1: 0 mg/kg
Group 2: 0 mg/kg
Group 3: 5000 mg/kg

Observations
Mortality/ Viablity: 1-2 times daily
Clinical signs: Two times during test day 1 and once daily thereafter
Body Weight: On day 1 (pre-dose), end of day 5 and end of day 8
Food Consumption: Measured for the exposure period and the 3-day postexposure period
Pathology
Necropsies of the test group and the control groups were performed by experienced personnel.

All animals surviving to the end of the observation period were sacrificed by intraperitoneal injection of Esconarkon AD US.VET (Streuli Pharma AG, 8730 Uznach/Switzerland) at a dose of at least 1.0 mL/kg body weight (equivalent to at least 300 mg sodium pentobarbitone/kg body weight) followed by exsanguination. The animals were examined macroscopically and all abnormalities were recorded.
Calculation of Food Consumption

Individual Food Consumption:
The individual food consumption expresses the average food consumed per day over the food consumption interval.

IFC = C / AD

IFC = Individual food consumption (in g of food per animal per day).
C = Measured food consumption over the consumption interval (in g of food).
AD = Animal days: Total of consumption days for the animals per group during the consumption interval.
Relative Food Consumption:
The relative food consumption (RFC) was calculated according to the following formula:

RFC = daily food consumption (IFC) / BW

Unit : gram food per kg body weight per day.
BW : Body weight

Test Item Intake (Nominal Value):
The test item intake (TII) was calculated for each group using the following formula:

TII = C x ND / AD x BW
C = Measured food consumption per group over the consumption interval (in g food).
ND = Nominal dose (mg test item/g food).
AD = Total of consumption days over all animals of one group during the consumption interval.
BW = Average body weight per group measured at the beginning of the consumption interval (in kg).

Data Analysis
The Dunnett-test (many to one t-test) based on a pooled variance estimate was applied for the comparison of body weights of the treated group and the control groups. No significant differences were found.

Details on reproductive parameters:

Not applicable

Reference substance (positive control):

no

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

> 5 000 mg/kg diet

Conc. / dose based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: No mortality was observed in the main study at a dose level of 5000 mg/kg diet, therefore, the LC50 of the test substance was determined as > 5000 mg/kg diet.

Duration (if not single dose):

5 d

Dose descriptor:

NOEC

Effect level:

>= 5 000 mg/kg diet

Conc. / dose based on:

test mat.

Basis for effect:

other: No symptoms and no macroscopic findings were observed in the treated animals. Therefore, the NOEC (no observed effect concentration) was determined as > 5000 mg/kg diet.

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

> 1 163.9 mg/kg bw

Conc. / dose based on:

test mat.

Basis for effect:

other: Body weights were similar for control and treated groups. Food consumption was also similar for the treated group and the control groups. The LC50 based on test item intake was > 1163.9 mg per kg body weight per day.

Mortality and sub-lethal effects:

Mortality
Results of the limit test are presented in the attached Appendix A.
Pre-Test
In the pre-test, the test item was administered to 5 Japanese quails each at dose levels of 200, 1000 and 5000 mg/kg diet. No mortality and no symptoms were observed during a 5-day observation period in all of the dose groups. Therefore, a limit test was performed with a concentration level of 5000 mg/kg diet.

Limit-Test
In the limit test at a concentration level of 5000 mg/kg diet, no mortality of the treated birds was observed within the observation period of 8 days. Therefore, the LC50 level for the test item was > 5000 mg/kg diet.
In the control groups, there were also no mortalities observed.

Clinical Signs
Results are presented in the attached Appendix A.
No symptoms were observed at a concentration level of 5000 mg/kg diet. Therefore, the NOEC (no observed effect concentration) was > 5000 mg/kg diet.

Macroscopic Findings
For the Limit test, all animals of groups 1-3 were necropsied at the end of the observation period. The results are presented in the attachedAppendix B.
No findings were observed in all the animals necropsied.


Body Weight
Tabulated body weights are presented in the attached Appendix C.
Average body weights before the start of the treatment ranged from 79.3 to 88.0 g for groups 1 to 3. The body weight of the treated animals was 130.0 ± 9.7 g on day 5 and was similar to the average body weight of groups 1 and 2 (127.4 g and 116.0 g, respectively). Also, no difference was found at the end of the study. Average body weights at day 8 ranged from 138.4 to 152.9 g for groups 1 to 3.

Food Consumption and Test Item Intake
Results are presented in the attached Appendix D.
Individual food consumption
The Individual Food Consumption (IFC) during observation days 0-5 (average values, per animal per day) in group 3 (20.5 g food/animal/day) was similar to the IFC of groups 1 and 2 (18.9-20.4 g) Also after termination of the treatment, the IFC for group 3 (21.8 g) was similar to the control groups (20.7-22.4 g).

Relative food consumption
The Relative Food Consumption (RFC) during observation days 0-5 (average values, per kg body weight per day) in group 3 (232.8 g food/kg/day) was similar to the RFC of groups 1 and 2 (232.1- 238.6 g). After termination of the treatment, the relative food consumption of all groups was similar (167.9-178.2 g).
In conclusion, there was no difference in individual food consumption and relative food consumption between the treated group and the control groups.

Test item intake
The test item intake (TII) was calculated based on the food consumption and the nominal test item concentration in the diet:
Group 3: 1163.9 mg test item per kg body weight per day
The LC50 based on test item intake was therefore > 1163.9 mg per kg body weight per day.

Effects on reproduction:

Not applicable

Results with reference substance (positive control):

Not applicable

Further details on results:

Analysis of Test Item in the Diet
Results are presented in the attached Appendix E.
The mean concentration of the test substance in the diet samples was 115.9% (see “Results” of the analytical report) of the nominal concentration.
Maximal deviation of the homogeneity samples was 3.0% of the mean concentration. Therefore, the test item was found to be homogeneously distributed in the diet. Furthermore, the test item was found to be sufficiently stable in the diet during storage at room temperature for 6 days (average 110.9%).

Validity criteria fulfilled:

yes

Conclusions:

The median lethal concentration (LC50) for the dietary oral toxicity of the test item in young Japanese quails was determined as > 5000 mg test item/kg diet.
No test item related mortalities and no symptoms were observed within the observation period. At necropsy, no macroscopic findings were observed for the treated animals. Therefore, the NOEC (no observed effect concentration) was determined as ≥ 5000 mg/kg diet.
Body weights were similar for control and treated groups. Food consumption was also similar for the treated group and the control groups.
The LC50 based on test item intake was > 1163.9 mg per kg body weight per day.

Executive summary:

In a dose range finding pre-test, the test item was administered to 5 Japanese quails each at dietary dose levels of 200, 1000 and 5000 mg/kg diet. All quails survived an observation period of 5 days and no symptoms were observed.

Based on the pre-test, a limit test was performed. The test item was administered to one group of 10 Japanese quails by dietary ingestion at a nominal dose level of 5000 mg test item/kg diet for 5 treatment days followed by 3 observation days where the animals obtained basal diet.

No mortality was observed in the main study at a dose level of 5000 mg/kg diet, therefore, the LC50 of the test substance was determined as > 5000 mg/kg diet.

No symptoms and no macroscopic findings were observed in the treated animals. Therefore, the NOEC (no observed effect concentration) was determined as > 5000 mg/kg diet.

Body weights were similar for control and treated groups. There was no difference in individual food consumption and relative food consumption between the treated group and the control groups.

The mean test item intake over the treatment period of five days was as follows:Group	Dietary test item concentration (mg/kg)	IFC g food per animal per day	RFC g per kg body weight per day	TII mg test item per kg body weight per day
1	0	20.4	232.1	---
2	0	18.9	238.6	---
3	5000	20.5	232.8	1163.9

IFC: Individual Food Consumption

RFC: Relative Food Consumption

TII: Test Item Intake

The LC50 based on test item intake was > 1163.9 mg test item/kg body weight/d

Reference 3

Endpoint:

short-term toxicity to birds: dietary toxicity test

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

1. Hypothesis for the analogue approach:
The hypothesis for the analogue approach is that the test substance GTL Base Oil Distillates (C18-C50 branched, cyclic and linear hydrocarbons – Distillates / 848301-69-9 / 482-220-0) is produced in the same Fischer-Tropsch process as GTL Gasoil which is the starting material from which the registration substance is produced by fractional distillation. The source substances contain constituents of the target substance, Hydrocarbons, C18-C24, iso-alkanes <2% aromatics, although it covers a wider carbon number distribution. The substances therefore have qualitatively similar properties (RAAF Scenario 2 applies). See Endpoint Summary (CSR Section 7.3 for additional information).
2. Source and target chemical(s)
The source substance GTL Base Oil Distillates (Distillates (Fischer-Tropsch), heavy, C18-50 - branched, cyclic and linear) is composed of linear, branched and cyclic hydrocarbons of chain length C18-C50.
The source substance GTL Gasoil (C8-C26) (C8-C26 branched and linear hydrocarbons – Distillates) is the substance from which the registration substance is produced. GTL Gasoil is composed of linear, branched and cyclic hydrocarbons of chain length C8-C26.
The target substance, Hydrocarbons, C18-C24, iso-alkanes <2% aromatics, is composed of linear, branched and cyclic hydrocarbons of chain length C18-24.
3. Analogue approach justification
The constituents of the source and target substances are all hydrocarbons. Identical constituents have identical toxicity profiles. There is no evidence of toxicity in the studies on the source substances.

Reason / purpose for cross-reference:

read-across source

Remarks:

supporting study

Reason / purpose for cross-reference:

read-across source

Remarks:

supporting study

Duration (if not single dose):

5 d

Dose descriptor:

LC50

Effect level:

> 5 000 mg/kg diet

Duration (if not single dose):

5 d

Dose descriptor:

NOEC

Effect level:

>= 5 000 mg/kg diet

Description of key information

(5-d) LC50 >5000 mg/kg diet 
(5-d NOEC ≥5000 mg/kg diet

Key value for chemical safety assessment

Short-term EC50 or LC50 for birds:

5 000 mg/kg food

Additional information

Acute avian toxicity studies have been conducted with GTL Gasoil and GTL Base Oil Distillates (Burri, 2011a and 2011b). The tests were conducted in accordance with OECD 205 and GLP.

The acute oral LC₅₀ of GTL Gasoil and GTL Base Oil Distillates in Japanese quail was determined to be >5000 mg/kg diet. The NOEC was determined to be ≥5000 mg/kg diet. The LC₅₀ based on GTL Gasoil intake was >1163.9 mg/kg body weight/day, and for GTL Base Oil Distillates >1170 mg/kg body weight/day.

These data are used as read-across data to Hydrocarbons, C18-C24, isoalkanes, <2% aromatics.