Octadecene, reaction products with hexadecene, hydrogenated

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 July 2019 to 01 August 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

OECD Guidelines for the Testing of Chemicals (No.: 402, 09 October 2017)

Deviations:

yes

Remarks:

See "Any other information" for details

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

Commission Regulation (EC) No 440/2008, B.3 (L 142, 30 May 2008)
Note: This guideline has not yet been revised in line with the OECD 2017 version. The study does not fully comply with the older version of the guideline, but the study design is considered to be acceptable for all OECD countries.

Deviations:

yes

Remarks:

See "Any other information" for details

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

OPPTS 870.1200 (EPA 712-C-98-192, August 1998)
Note: The guideline has not yet been revised in line with the OECD 2017 version. The study does not fully comply with the older version of the guideline, but the study design is considered to be acceptable for all OECD countries.

Deviations:

yes

Remarks:

See "Any other information" for details

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Oligomerisation products of alpha-alkenes C16-18 (even numbered), hydrogenated, hydroisomerised

EC Number:

832-827-5

Cas Number:

2241366-04-9

Molecular formula:

Variable - UVCB

IUPAC Name:

Oligomerisation products of alpha-alkenes C16-18 (even numbered), hydrogenated, hydroisomerised

Test material form:

liquid

Details on test material:

Name: SynNova Base Oil
CAS number: 2241366-04-9
Batch/Lot number: TS20371/TS21270
Description: Liquid - water white colorless oil.
Purity: 100%
Expiry date: 25 February 2021/31 July 2021
Storage conditions: Controlled room temperature (15-25°C, ≤70% relative humidity)
Safety precautions: Routine safety precautions (gloves, goggles, face mask, lab coat) for unknown materials were applied to ensure personnel health and safety.

Specific details on test material used for the study:

No further details specified in the study report.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species and strain: Crl: WI Wistar rats
Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
Hygienic level at arrival: SPF
Hygienic level during the study: Standard housing conditions
Justification of strain: The Wistar rat is one of the standard rodent species used in acute toxicity studies.
Number of animals: 3 animals
Sex: Female, nulliparous and non-pregnant.
Age of animals at study start: 11 weeks old
Body weight range at dosing: Between 264 g and 288 g
Acclimation time: 28 or 30 days
Animal health: Only healthy animals were used for the study. The staff Veterinarian certified the health status.
Housing / Enrichment: Individual caging during the treatment, group caging after patch removal. Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities. Mini Fun Tunnel (produced by LBS (Serving Biotechnology) Ltd., United Kingdom) was also available for the animals during the study.
Cage type: Type II. polypropylene/polycarbonate
Bedding: SAFE 3/4-S Hygienic Animal Bedding (produced by J. Rettenmaier & Söhne GmbH+CO.KG, Germany) was available to animals during the study. The quality of the bedding was guaranteed by the supplier. Details of bedding quality are archived with the raw data.
Nesting: Nest building material Arbocel Crinklets natural (produced by J. Rettenmaier & Söhne GmbH+CO.KG, Germany) was available to animals during the study. The quality of the nest building material was guaranteed by the supplier. Details of nest building material quality are archived with the raw data.
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 20.2–26.0°C
Relative humidity: 32–74%
Ventilation: 15-20 air exchanges/hour
Temperature and relative humidity were recorded twice daily during the study.

Food and Water Supply: Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany (Batch number: 639 38520, expiry date: 30 April 2019) ad libitum, and tap water from the municipal supply, as for human consumption from a 500 mL bottle, ad libitum. The food is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study and the water was considered fit for human consumption.
The supplier provided an analytical certificate for the batch used.
Water quality control analysis is performed once every three months and microbiological assessment is performed monthly by Veszprém County Institute of State Public Health and Medical Officer Service.

Animal Identification: Animals were individually identified using numbers written on the tail with an indelible pen. The numbers were given on the basis of Citoxlab Hungary Ltd.'s Master File for each animal allocated to the treatment groups. The cages were identified by cards containing information about study code, sex, dose group, cage number and individual animal number.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The test item was administered as supplied (no formulation of the test item was done).
The back of each animal was shaved (approximately 10% area of the total body surface) approximately 24 hours prior to treatment. The test item was applied to the shaved skin as a single dose and remained in contact with the skin for the 24-hour exposure period. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.
At the end of the exposure period, the treated area of skin with the test item was washed with water at body temperature.

Duration of exposure:

24 hours

Doses:

A single dermal application at 2000 mg/kg bw

No. of animals per sex per dose:

Dose range finding test: 1 female
Min study: 2 females

Control animals:

not specified

Details on study design:

Mortality and Clinical Observations: Mortality/morbidity was checked twice daily during the 14-day observation period. Clinical observations were performed on the day of treatment at approximately 30 minutes, 1, 2 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Skin Irritation: Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.

Measurement of Body Weight: The body weights were recorded on Day 0 (before the test item administration) and on Days 7 and 14 (before necropsy).

Necropsy: Macroscopic examination was performed on all animals. All animals were anaesthetised with sodium pentobarbital and exsanguinated. Following confirmation of death, after examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.

Statistics:

Not specified

Results and discussion

Preliminary study:

Initially one animal was dosed at the selected limit dose (2000 mg/kg bw). As the animal survived, the second and third animal received the same dose.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item did not cause mortality at the dose level of 2000 mg/kg bw.

Clinical signs:

other: other: There were no adverse clinical signs noted in any animals during the 14-day observation period. No adverse local dermal signs (erythema/oedema) were noted in any animals during the 14-day observation period.

Gross pathology:

There was no evidence of any gross macroscopic changes at a dose level of 2000 mg/kg bw.

Any other information on results incl. tables

Clinical Observations and Local Dermal Signs

DOSE LEVEL: 2000 mg/kg bw, Treatment in Day 0                                                                                           SEX: FEMALE

Cage No.

Animal Number

Observations

Observation days

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

30’

1h

2h

5h

1

8388

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

18/18

2

8391

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

18/18

3

8392

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

18/18

 

Local Dermal Signs

DOSE LEVEL: 2000 mg/kg bw, Treatment in Day 0                                                                                           SEX: FEMALE

Cage No.	Animal Number	Observations	Observation days																		Frequency
			0				1	2	3	4	5	6	7	8	9	10	11	12	13	14
			30’	1h	2h	5h
1	8388	Erythema & Eschar-Draize	-	-	-	-	0	0	0	0	0	0	0	0	0	0	0	0	0	0	14/18
		Oedema-Draize	-	-	-	-	0	0	0	0	0	0	0	0	0	0	0	0	0	0	14/18
2	8391	Erythema & Eschar-Draize	-	-	-	-	0	0	0	0	0	0	0	0	0	0	0	0	0	0	14/18
		Oedema-Draize	-	-	-	-	0	0	0	0	0	0	0	0	0	0	0	0	0	0	14/18
3	8392	Erythema & Eschar-Draize	-	-	-	-	0	0	0	0	0	0	0	0	0	0	0	0	0	0	14/18
		Oedema-Draize	-	-	-	-	0	0	0	0	0	0	0	0	0	0	0	0	0	0	14/18

 

Remarks:         + = present                  - = absent

                       h = hour (s)                  ‘ = minute

                       Frequency of observations = number of occurrence of observation / total number of observations

                       Erythema severities: 0 = No erythema; 1 = very slight; 2 = Well-defined; 3 = Moderate to severe; 4 = Severe + slight eschar formation

                       Oedema severities: 0 = No oedema; 1 = Very slight; 2 = Slight; 3 = Moderate; 4 = Severe

 

Body Weight Data

DOSE LEVEL: 2000 mg/kg bw, Treatment on day 0                               SEX: FEMALE

Cage No.	Animal Number	Body weight (g)			Body Weight Gain (g)
		0	7	14	0-7	7-14	0-14
1	8388	288	294	313	6	19	25
2	8391	268	269	276	1	7	8
3	8392	264	266	267	2	1	3
Mean:		273.3	276.3	285.3	3.0	9.0	12.0
Standard deviation:		12.9	15.4	24.4	2.6	9.2	11.5

 

Macroscopic Findings

DOSE LEVEL: 2000 mg/kg bw, Treatment on Day 0                    SEX: FEMALE

Cage No.	Animal Number	Necropsy Date/ Necropsy Day	External Observations	Internal Observations	Organ/Tissue
1	8388	30 July 2019 Day 14	No external observations recorded	No internal observations recorded	Not applicable
2	8391	01 August 2019 Day 14	No external observations recorded	No internal observations recorded	Not applicable
3	8392	01 August 2019 Day 14	No external observations recorded	No internal observations recorded	Not applicable

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) of the test item SynNova Base Oil was found to be greater than 2000 mg/kg body weight in female Crl: WI rats.

According to the GHS criteria, SynNova Base Oil can be ranked as "Category 5 or Unclassified" for acute dermal exposure.

Executive summary:

An acute dermal toxicity study was performed with the test item SynNova Base Oil in female Crl: WI Wistar rats, in compliance with OECD Guideline No.: 402 (2017), Commission Regulation (EC) No 440/2008, B.3 and OPPTS 870.1200.

 

This study was being performed with vertebrate animals as no in vitro alternative is available. The Sponsor confirmed previously that the specific regulatory purpose of this study did not allow a waiving of this dermal acute study, taking account of the OECD guidance document 237.

 

A single animal at a dose level of 2000 mg/kg body weight (bw) was used in a range-finding phase, followed by two animals in the main phase to confirm the expected non-lethal dose level. The test item was applied as a single dermal 24-hour exposure followed by a 14-day observation period.

 

Clinical observations were performed on all animals at approximately 30 minutes, 1, 2, 5 hours after dosing and daily for 14 days thereafter. Body weight was measured on Day 0 (prior to dosing) and on Days 7 and 14 (before necropsy). Gross macroscopic examination was performed on all animals at necropsy at the end of the 2-week observation period (Day 14).

 

The results of the study were summarised as follows:

 

Mortality

Test item did not cause mortality at the dose level of 2000 mg/kg bw.

 

Clinical observations and local dermal signs

There were no adverse clinical signs noted in any animals during the 14-day observation period.

No adverse local dermal signs (erythema/oedema) were noted in any animals during the 14-day observation period.

 

Body weight and body weight gain

The body weights of the animals were within the range commonly recorded for this strain and age.

 

Necropsy

There was no evidence of any macroscopic changes at a dose level of 2000 mg/kg bw.

 

Conclusions

The acute dermal median lethal dose (LD50) of the test item SynNova Base Oil was found to be greater than 2000 mg/kg body weight in female Crl: WI rats.

According to the GHS criteria, SynNova Base Oil can be ranked as "Category 5 or Unclassified" for acute dermal exposure.