Registration Dossier

No acute oral, dermal, or inhalation toxicity data is available for the registered substance. However, key oral toxicity and supporting dermal and inhalation toxicity data is available from structurally related substances, C18-C50 branched, cyclic and linear hydrocarbons – Distillates (CAS# 848301-69-9) and C8-C26 branched and linear hydrocarbons – Distillates (CAS# 848301-67-7) and is presented below.

1) Acute oral toxicity: The acute oral median lethal dose (LD₅₀) of C18-C50 branched, cyclic and linear hydrocarbons – Distillates (CAS# 848301-69-9) in the female Sprague-Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight.

2) Acute inhalation and dermal toxicity: Based on lack of skin irritation and systemic effects in a read across skin irritation study, the registered substance is not considered to be acutely harmful in contact with skin. Moreover, the substance is unlikely to form aerosols or particles of inhalable size. Therefore it is considered justifiable not to conduct these studies.

Supporting data on a related substance C8-C26 branched and linear hydrocarbons – Distillates (CAS# 848301-67-7) indicate the low dermal and inhalation toxicity:

a) Acute inhalation toxicity study (Shell, 2013a), conducted according to OECD 436 and GLP, reported an acute inhalation median lethal concentration (4 hr LC₅₀) of Distillates (Fischer-Tropsch), C8-26-branched and linear, in the RccHanTM: WIST strain rat >5 mg/L.

b) Acute dermal toxicity study (Shell, 2015a), conducted according to OECD 402 (Acute Dermal Toxicity) and GLP, reported an LD₅₀ in male and female rats >2000 mg/Kg bw.

The above data is used for read across to Alkanes, C16 -47, branched and linear.

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Preliminary study:

There was no death and no signs of systemic toxicity at 5000 mg/kg.
In the absence of toxicity at 5000 mg/kg, an additional group of 4 animals was treated at a dose level of 5000 mg/kg.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight.

Executive summary:

Introduction.

The study was performed to assess the acute oral toxicity of the test material 'Distillates (Fischer-Tropsch), heavy C18-50 - branched, cyclic and linear' in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following:

• OECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method" (adopted 17 December 2001)

• Method B1 bis Acute Toxicity (Oral) of Commission Directive 2004/73/EC Method.

Method.

Following a preliminary test in which there was no death at a dose level of 5000 mg/kg, an additional four fasted female animals were given a single oral dose of undiluted test material at a dose level of 5000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality.

There were no deaths.

Clinical Observations.

There were no signs of systemic toxicity.

Bodyweight.

All animals showed expected gains in bodyweight.

Necropsy.

No abnormalities were noted at necropsy.

Conclusion.

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The study is GLP compliant and has Klimisch score 1.

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

supporting study

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Duration of exposure:

h

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 - 5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

1 male (Day 2) and 3 females (Day 1) animals were found dead post-exposure
1 male (Day 2) and 1 female (Day 1) animal were found dead post-exposure

Clinical signs:

other: Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection and wet fur. There were occasional instances of tip-toe gait, isolated occurrences of labored respiration and ataxia were also noted. Survivi

Body weight:

Group 1 – All surviving animals exhibited body weight losses on Day 1 post-exposure. None of the female animals survived past Day 1 post-exposure, however, reasonable body weight development was noted in both of the surviving male animals during the remainder of the recovery period.

Group 2 – All animals exhibited body weight losses on Day 1 post-exposure. Reasonable body weight development was noted in all surviving male animals during the remainder of the recovery period. In contrast, two surviving female animals exhibited a slight body weight loss or showed no body weight gain from Days 1 to 3 post-exposure. Reasonable body weight gains were noted in these two animals during the remainder of the recovery period.

Gross pathology:

Pale patches on the lungs were noted in one of two surviving animals from Group 1 at necropsy. Dark patches on the lungs or pale lungs were noted in all four surviving animals from Group 2 at necropsy.

Abnormally dark lungs were detected in the animals that died during the course of the study at necropsy.

From consideration of results of Histopathological examinations of tissues retained from a study conducted on a similar test item (Harlan Study Number: 41300142) the deaths noted during this study may be attributable to hydrocarbon aspiration induced inflammation (i.e. a chemical pneumonitis).

Other findings:

Not Applicable

Exposure Chamber Atmosphere Concentrations – Dose Group 1

Duration of Exposure (minutes)	Net Weight of Sample (mg)	Volume of Air Sampled (L)	Chamber Flow Rate (L/min)	Atmosphere Concentration (mg/L)
5	10.16	2	60	5.08
15	10.51	2	60	5.26
30	10.15	2	60	5.08
45	10.03	2	60	5.02
60	10.22	2	60	5.11
75	10.14	2	60	5.07
90	10.11	2	60	5.06
105	10.05	2	60	5.03
120	10.18	2	60	5.09
135	9.94	2	60	4.97
150	10.38	2	60	5.19
165	10.41	2	60	5.21
180	10.00	2	60	5.00
195	10.17	2	60	5.09
210	10.12	2	60	5.06
225	10.24	2	60	5.12
238	10.14	2	60	5.07

Exposure Chamber Atmosphere Concentrations – Dose Group 2

Duration of Exposure (minutes)	Net Weight of Sample (mg)	Volume of Air Sampled (L)	Chamber Flow Rate (L/min)	Atmosphere Concentration (mg/L)
5	4.85	4	60	1.21
15	4.87	4	60	1.22
30	4.21	4	60	1.05
45	4.08	4	60	1.02
60	4.01	4	60	1.00
75	4.13	4	60	1.03
90	4.03	4	60	1.01
105	4.08	4	60	1.02
120	4.04	4	60	1.01
135	4.03	4	60	1.01
150	4.17	4	60	1.04
165	4.09	4	60	1.02
180	4.15	4	60	1.04
195	4.11	4	60	1.03
210	4.15	4	60	1.04
225	4.10	4	60	1.03
238	4.29	4	60	1.07

Particle Size Distribution – Dose Group 1

Cascade Impactor Data

Impactor Stage Number	Cut Point (µm)	Amount Collected (mg) per Sample Number			Mean Amount Collected (mg)
Impactor Stage Number	Cut Point (µm)	1	2	3	Mean Amount Collected (mg)
3	8.9	0.12	0.14	0.06	0.11
4	6.2	0.17	0.11	0.09	0.12
5	3.6	0.48	0.36	0.27	0.37
6	1.6	1.09	0.71	0.66	0.82
7	0.93	0.15	0.13	0.11	0.13
8	0.37	0.57	0.38	0.40	0.45
Back-up Filter	<0.37	0.16	0.05	0.14	0.12
Total Mean Amount of Test Item Collected					2.12

Calculation

Cut Point (µm)	Log₁₀ Cut Point	Mean Cumulative Amount Less Than Cut Point
Cut Point (µm)	Log₁₀ Cut Point	(mg)	(%)	Probit
8.9	0.949	2.01	94.8	6.63
6.2	0.792	1.89	89.2	6.24
3.6	0.556	1.52	71.7	5.57
1.6	0.204	0.70	33.0	4.56
0.93	-0.032	0.57	26.9	4.38
0.37	-0.432	0.12	5.66	3.42

Results

Mean Mass Median Aerodynamic Diameter (MMAD) =1.92µm

Geometric Standard Deviation (GSD) =2.69

Predicted amount less than 4 µm =77.3%

Particle Size Distribution – Dose Group 2

Cascade Impactor Data

Impactor Stage Number	Cut Point (µm)	Amount Collected (mg) per Sample Number			Mean Amount Collected (mg)
Impactor Stage Number	Cut Point (µm)	1	2	3	Mean Amount Collected (mg)
3	8.9	0.00	0.00	0.02	0.01
4	6.2	0.00	0.02	0.02	0.01
5	3.6	0.05	0.09	0.11	0.08
6	1.6	0.26	0.59	0.58	0.48
7	0.93	0.00	0.09	0.00	0.03
8	0.37	0.11	0.28	0.26	0.22
Back-up Filter	<0.37	0.00	0.04	0.03	0.02
Total Mean Amount of Test Item Collected					0.85

Calculation

Cut Point (µm)	Log₁₀ Cut Point	Mean Cumulative Amount Less Than Cut Point
Cut Point (µm)	Log₁₀ Cut Point	(mg)	(%)	Probit
8.9	0.949	0.84	98.8	7.27
6.2	0.792	0.83	97.6	6.99
3.6	0.556	0.75	88.2	6.19
1.6	0.204	0.27	31.8	4.53
0.93	-0.032	0.24	28.2	4.42
0.37	-0.432	0.02	2.35	3.01

Results

Mean Mass Median Aerodynamic Diameter (MMAD) = 1.64 µm

Geometric Standard Deviation (GSD) = 2.05

Predicted amount less than 4 µm = 89.4 %

KEY TO CLINICAL OBSERVATIONS

A	=	ataxia
H	=	hunched posture
P	=	pilo-erection
Ri	=	increased respiratory rate
Rl	=	labored respiration
Wf	=	wet fur
Wt	=	tip-toe gait
0	=	no abnormalities detected
X	=	animal dead

Individual Clinical Observations (Day of Exposure) – Dose Group 1

Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	Hours During Exposure			On Removal From Chamber	One Hour Post-Exposure
Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	1	2	3	On Removal From Chamber	One Hour Post-Exposure
5.09	1 Male	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri Wt	H P Ri Wt
	2 Male	Wf	Wf Ri	Wf Ri	Wf H P Ri	H P Ri
	3 Male	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri
	4 Female	Wf	Wf Ri	Wf Ri	Wf H P Ri Wt	Wf H P Ri Wt
	5 Female	Wf	Wf Ri	Wf Ri	Wf H P Ri Wt	Wf H P Ri Wt
	6 Female	Wf	Wf Ri	Wf Ri	Wf H P Ri	H P Ri

Individual Clinical Observations (Recovery Period) – Dose Group 1

Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	Days Post Exposure
Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	1	2	3	4	5	6	7	8 - 14
5.09	1 Male	H P Ri	X
	2 Male	H P Ri	H P Ri	H Ri	H Ri	H Ri	Ri	Ri	0
	3 Male	H P Ri	H P Ri	H Ri	H Ri	Ri	Ri	Ri	0
	4 Female	X
	5 Female	X
	6 Female	H P Ri Rl A X_{later in the day}

Individual Clinical Observations (Day of Exposure) – Dose Group 2

Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	Hours During Exposure			On Removal From Chamber	One Hour Post-Exposure
Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	1	2	3	On Removal From Chamber	One Hour Post-Exposure
1.05	7 Male	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri
	8 Male	Wf	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri
	9 Male	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri
	10 Female	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri
	11 Female	Wf	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri
	12 Female	Wf Ri	Wf Ri	Wf Ri	Wf H P Ri	Wf H P Ri

Individual Clinical Observations (Recovery Period) – Dose Group 2

Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	Days Post Exposure
Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	1	2	3	4	5	6	7
1.05	7 Male	H P Ri	H P Ri	P Ri	P Ri	Ri	Ri	0
	8 Male	H P Ri	X
	9 Male	H P Ri	H P Ri	P Ri	P Ri	Ri	Ri	0
	10 Female	H P Ri	H P Ri	H P Ri	H P Ri	Ri	Ri	Ri
	11 Female	H P Ri	H P Ri	H P Ri Rl	H P Ri	Ri	Ri	Ri
	12 Female	H P Ri A X_{Later in the day}

(Continued) Individual Clinical Observations (Recovery Period) – Dose Group 2

Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	Days Post Exposure
Mean Achieved Atmosphere Concentration (mg/L)	Animal Number and Sex	8	9	10	11	12	13	14
1.05	7 Male	0	0	0	0	0	0	0
	8 Male
	9 Male	0	0	0	0	0	0	0
	10 Female	Ri	Ri	Ri	Ri	Ri	0	0
	11 Female	Ri	Ri	Ri	Ri	Ri	0	0
	12 Female

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Criteria used for interpretation of results: other: Globally Harmonized Classification System

Conclusions:

Four out of six animals died at a mean achieved atmosphere concentration of 5.09 mg/L, whereas, two deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 1.05 mg/L. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of GTL Base oil 3, in the RccHanTM : WIST strain rat, was in the range >1 mg/L to 5 mg/L (Globally Harmonized Classification System – Category 4).

Executive summary:

Introduction

A study was performed to assess the acute inhalation toxicity of the test item. The method used was compatible with that described in the OECD Guidelines for Testing of Chemicals (2009) No. 436 “Acute Inhalation Toxicity – Acute Toxic Class Method”.

Methods.......

Two groups of six RccHan™ : WIST strain rats (three males and three females) were exposed to an aerosol atmosphere. The animals were exposed for four hours using a nose only exposure system, followed by a fourteen day observation period.

Results……..

The mean achieved atmosphere concentration was as follows:

Group Number	Atmosphere Concentration
Group Number	Mean Achieved (mg/L)	Standard Deviation	Nominal (mg/L)
1	5.09	0.07	12.7
2	1.05	0.06	2.14

The characteristics of the achieved atmosphere were as follows:

Group Number

Mean Achieved Atmosphere Concentration (mg/L)

Mean Mass Median Aerodynamic Diameter (µm)

Inhalable Fraction

(% <4 µm)

Geometric Standard Deviation

1

5.09

1.92

77.3

2.69

2

1.05

1.64

89.4

2.05

The mortality data were summarized as follows:

Group Number	Mean Achieved Atmosphere Concentration (mg/L)	Deaths
Group Number	Mean Achieved Atmosphere Concentration (mg/L)	Male	Female	Total
1	5.09	1/3	3/3	4/6
2	1.05	1/3	1/3	2/6

Clinical Observations

Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection and wet fur. There were occasional instances of tip-toe gait, isolated occurrences of labored respiration and ataxia were also noted. Surviving Group 1 animals recovered to appear normal on Day 8 post-exposure. Surviving Group 2 animals recovered to appear normal from Days 7 to 13 post-exposure.

Body Weight

Group 1 – All surviving animals exhibited body weight losses on Day 1 post-exposure. None of the female animals survived past Day 1 post-exposure, however, reasonable body weight development was noted in both of the surviving male animals during the remainder of the recovery period.

Group 2 – All animals exhibited body weight losses on Day 1 post-exposure. Reasonable body weight development was noted in all surviving male animals during the remainder of the recovery period. In contrast, two surviving female animals exhibited a slight body weight loss or showed no body weight gain from Days 1 to 3 post-exposure. Reasonable body weight gains were noted in these two animals during the remainder of the recovery period.

Necropsy

Pale patches on the lungs were noted in one of two surviving animals from Group 1 at necropsy. Dark patches on the lungs or pale lungs were noted in all four surviving animals from Group 2 at necropsy.

Abnormally dark lungs were detected in the animals that died during the course of the study at necropsy.

From consideration of results of Histopathological examinations of tissues retained from a study conducted on a similar test item (Harlan Study Number: 41300142) the deaths noted during this study may be attributable to hydrocarbon aspiration induced inflammation (i.e. a chemical pneumonitis).

Conclusion

Four out of six animals died at a mean achieved atmosphere concentration of 5.09 mg/L, whereas, two deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 1.05 mg/L. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC₅₀) ofGTL Base oil3, in the RccHan^TM: WIST strain rat, was in the range >1 mg/L to 5 mg/L (Globally Harmonized Classification System – Category 4).

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

Quality of whole database:

The available studies are GLP compliant and have Klimisch score 2.

Reference

Endpoint:: acute toxicity: dermal
Type of information:: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:: supporting study
Justification for type of information:: A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:: read-across source
: Key result
Sex:: male/female
Dose descriptor:: LD50
Effect level:: > 2 000 mg/kg bw
Based on:: test mat.
Mortality:: There were no deaths.
Clinical signs:: other: There were no signs of systemic toxicity.
Gross pathology:: No abnormalities were noted at necropsy.
Other findings:: Very slight erythema and crust formation and/or small superficial scattered scabs were noted at the test sites of four females. There were no signs of dermal irritation noted at the test sites of the remaining animals.
Interpretation of results:: other: Not classified
Remarks:: Criteria used for interpretation of results: EU
Conclusions:: An LD50 value of >2000 mg/kg bw is reported in a reliable study conducted according to an OECD test guideline and in compliance with GLP.
Executive summary:: The acute dermal toxicity study is a reliable test performed with Distillates (Fischer-Tropsch), C8-26 – branched and linear, in accordance with OECD 402 and in compliance with GLP. 2000 mg/kg bw of test substance was applied to five male and five female Wistar rats for a twenty-four hour exposure period under semiocclusive conditions. The animals were observed for deaths or overt signs of toxicity, and the test sites were observed for primary irritation for fourteen days before sacrifice and necroscopy. No deaths occurred and no signs of overt toxicity were observed. There were no abnormalities noted at necroscopy. Very slight erythema and crust formation and/or small superficial scattered scabs were noted at the test sites of four females. There were no signs of dermal irritation noted at the test sites of the remaining animals.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available study is GLP compliant and have Klimisch score 2.

No acute oral, dermal, or inhalation toxicity data is available for the registered substance. However, key oral toxicity and supporting dermal and inhalation toxicity data is available from structurally related substances, C18-C50 branched, cyclic and linear hydrocarbons – Distillates (CAS# 848301-69-9) and C8-C26 branched and linear hydrocarbons – Distillates (CAS# 848301-67-7) and is presented below.

Acute oral toxicity:

The study was performed to assess the acute oral toxicity of C18-C50 branched, cyclic and linear hydrocarbons – Distillates (CAS# 848301-69-9) in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of OECD Guideline No 420 "Acute Oral Toxicity - Fixed Dose Method" and Method B1 bis Acute Toxicity (Oral) of Commission Directive 2004/73/EC. A dose level of 5000 mg/kg bodyweight resulted in no deaths, no signs of systemic toxicity, expected gains in bodyweight and no abnormalities at necropsy, in a total of 5 animals. The acute oral median lethal dose (LD₅₀) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight.

Acute inhalation and dermal toxicity:

No studies conducted on the registered substance. However, based on lack of skin irritation and systemic effects in a skin irritation study the substance is not considered to acute harmful in contact with skin. The substance is unlikely to form aerosols or particles of inhalable size and therefore it is considered justifiable not to conduct inhalation study.

Moreover, supporting data on a related substance (with range C8 -26) indicate the low toxicity of the test substance:

- Acute inhalation toxicity study (Shell, 2013a), conducted according to OECD 436 and GLP, reported an acute inhalation median lethal concentration (4 hr LC₅₀) of Distillates (Fischer-Tropsch), C8-26-branched and linear, in the RccHanTM: WIST strain rat >5 mg/L.

- Acute dermal toxicity study (Shell, 2015a), conducted according to OECD 402 (Acute Dermal Toxicity) and GLP, reported an LD₅₀ in male and female rats >2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
No study available for substance defined in Section 1. For the endpoint conclusion a study of a related substance C18-C50 branched, cyclic and linear hydrocarbons – Distillates (CAS# 848301-69-9) was selected.

Justification for selection of acute toxicity – inhalation endpoint
No study available for substance defined in section 1. For the endpoint conclusion a study of a related substance with a limited range (C8-C26) was selected.

Justification for selection of acute toxicity – dermal endpoint
No study available for substance defined in section 1. For the endpoint conclusion a study of a related substance with a limited range (C8-C26) was selected.

On the basis of the available read across oral, inhalation and dermal data, the registered substance does not require classification for lethal effects following a single exposure according to Regulation 1272/2008/EC.