Ethyl 2-naphthyl ether

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of target chemical Ethyl 2-naphthyl ether (CAS No. 93-18-5) was considered based on experimental study conducted on rats, the LD50 value was considered to be >2000 mg/kg bw in rats. Thus, comparing this value with the criteria of CLP regulation, Ethyl 2-naphthyl ether cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

According to column 2 of REACH Annex VIII, the acute toxicity inhalation study need not be conducted because exposure of humans via inhalation route is not likely taking into account the low vapour pressure of the substance Ethyl 2-naphthyl ether (CAS no: 93-18-5),which is reported as 0.5182 Pa (0.00389 mm Hg). Also considering the particle size distribution of the substance the majority of the particle size was determined to be in the range of 150-53 micron which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver.

Acute Dermal Toxicity:

Acute Dermal toxicity dose (LD50) for target chemical Ethyl 2-naphthyl ether (CAS no: 93-18-5) was considered based on different experimental studies conducted on rats and rabbits, the values were considered to be >2000 mg/kg bw in rats and >5000 mg/kg bw in rabbits. The study concluded that the LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, Ethyl 2-naphthyl ether cannot be classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study report.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

The purpose of this study was to assess the Toxicological profile of test item to a single administration via oral route to Sprague Dawley rats. This study was designed to determine the acute toxicity at fixed dose levels by oral route of the test item.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Test Item: Ethyl 2-naphthyl ether (CAS No. 93-18-5)
- Source of test material: Sustainability Support Services (Europe) AB, Sweden
- Batch No. of test material: MKBW6331V
- Manufacturing Date: October; 2016
- Expiration date of the lot/batch: September; 2020
- Purity test date: No data available
- Consistency: Solid, crystalline powder

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Test Item and prepared formulation(s) were stored at ambient temperature.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item was suspended in corn oil. The formulation was prepared fresh on the day of dosing.

OTHER SPECIFICS:
Safety Precautions: Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses).

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Female rats of the age of approximately 8 to 12 weeks old were used at the commencement of its dosing.
- Weight at study initiation: Body weight range was 197.5 to 210.4 grams.
Body weights at the start : Female Mean: 203.58 g (= 100 %); Minimum : 197.5 g (- 2.99 %); Maximum : 210.4 g (+ 3.35 %)
- Identification: Each female rat was individually identified by the picric acid marking.
- Fasting period before study: Approximately 16 hours or more.
- Housing: The rats were housed in polycarbonate cages.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 21.9 degree centigrade.
- Humidity (%): 56.3% to 59.8%
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES: 14-07-2017 to 02-08-2017

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 300 mg/kg, 300 mg/kg, 2000 mg/kg and 2000 mg/kg
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight.

Doses:

Dose Group I : 300 mg/kg
Dose Group I : 300 mg/kg
Dose Group II : 2000 mg/kg
Dose Group II : 2000 mg/kg

No. of animals per sex per dose:

Three females were used at each step.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical Observations and General Appearance: Animals were observed for clinical signs, mortality and morbidity, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at immediately (0 to 5 minutes), 5, 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time. The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.
Body weights: Individual animal body weights were recorded, before fasting, prior to administration of the test item (fasting body weights), weekly thereafter and at termination on day 14. Weight changes were calculated and recorded.
Gross Pathology: Necropsy was performed on all animals at the end of the study period on day 15. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique.
Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.

Statistics:

not specified

Preliminary study:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Group I Step I : Animals treated at the dose level of 300 mg/kg body weight: All animals survived through the study period of 14 days.
Group I Step II : Animals treated at the dose level of 300 mg/kg body weight: All animals survived through the study period of 14 days.
Group II Step I : Animals treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.
Group II Step II : Animals treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.

Clinical signs:

other: Group I Step I : Animals treated at the dose level of 300 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. Group I Step II : Animals treated at the dose level of 300 mg/kg body weight did not result in any s

Gross pathology:

Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.

Other findings:

not specified

Table No. I

Summary of Clinical Signs of Toxicity and Mortality

Test System : Sprague Dawley Rat

Sex : Female

Group I :   

Step No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days From - to	Mortality
I	300	No clinical signs observed	3	1,2,3	Day 0 - Day 14	0/3

 

Group I :

Step No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days From - to	Mortality
II	300	No clinical signs observed	3	4,5,6	Day 0 - Day 14	0/3

 

Group II :

Step No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days From - to	Mortality
I	2000	Polyurea	3	7,8,9	Day 2	0/3
		Diarrhoea	2	7,8	Day 2
		Ataxic gait	2	7,9	Day 2

 

Group II :

Step No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days From - to	Mortality
II	2000	Polyurea	3	10 11,12	Day 2 - Day 3 Day 1 - Day 3	0/3
		Diarrhoea	3	10,11,12	Day 2 - Day 3
		Ataxic gait	2	11,12	Day 2 - Day 3

 

 

Table No.II

Mean Body Weight and Percent Body Weight Gain (g)

Test System : Sprague Dawley Rat

Sex : Female

Group I :

Step No.	Dose (mg/kg body weight)		Before Fasting Body weight	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	300	Mean	202.27	215.57	6.58	229.50	6.47	13.47
		± SD	2.21	2.81	0.98	1.83	0.55	0.94

 

 

Group I :

Step No.	Dose (mg/kg body weight)		Before Fasting Body weight	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
II	300	Mean	204.17	217.07	6.31	230.67	6.27	12.98
		± SD	3.86	4.91	0.53	4.50	0.53	0.09

 

 

Group II :

Step No.	Dose (mg/kg body weight)		Before Fasting Body weight	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	2000	Mean	207.73	216.50	4.22	231.27	6.82	11.34
		± SD	3.55	3.34	0.36	2.71	0.40	0.64

 

 

Group II :

Step No.	Dose (mg/kg body weight)		Before Fasting Body weight	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
II	2000	Mean	200.17	208.03	3.93	221.47	6.46	10.66
		± SD	2.41	1.70	0.63	2.18	1.36	2.06

 

 

Table No.III

Summary of Gross Pathological Findings

Test System : Sprague Dawley Rat

Sex : Female

Group I :

Step No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	300	1 - 3	TS	No abnormality detected

 

Group I :

Step No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
II	300	4 - 6	TS	No abnormality detected

 

 Group II :

Step No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	2000	7 - 9	TS	No abnormality detected

 

 Group II :

Step No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
II	2000	10 - 12	TS	No abnormality detected

TS = Terminal Sacrifice

Interpretation of results:

other: Not classified

Conclusions:

Under the condition of the study, the acute oral LD50 value of Ethyl 2-naphthyl ether (CAS No. 93-18-5) was considered to be >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of Ethyl 2-naphthyl ether (CAS No. 93-18-5), when administered via oral route in Sprague Dawley rats falls into the “Category Not classified” criteria of CLP.

Executive summary:

The reported study was designed and conducted to determine the acute oral toxicity profile of Ethyl 2-naphthyl ether (CAS No. 93-18-5) in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in polyurea, diarrhoea and ataxic gait with onset on day 2 after the dosing and no mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg resulted in polyurea, diarrhoea and ataxic gait with onset from day 1 to day 2 after the dosing and no mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. Therefore, the acute oral LD50 value of Ethyl 2-naphthyl ether (CAS No. 93-18-5) was considered to be >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of Ethyl 2-naphthyl ether (CAS No. 93-18-5), when administered via oral route in Sprague Dawley rats falls into the “Category Not classified” criteria of CLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data is Klimisch 1 and from experimental study report.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Quality of whole database:

Waiver

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study report.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

This study was designed to determine the dermal LD50 of the test item (up to 2000 mg/kg) or to establish a non-lethal dose level of 2000 milligram of test item per kilogram of body weight.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Test Item: Ethyl 2-naphthyl ether (CAS No. 93-18-5)
- Source of test material: Sustainability Support Services (Europe) AB
- Batch No.of test material: MKBW6331V
- Manufacturing Date: October; 2016
- Expiration date of the lot/batch: September; 2020
- Purity test date: No data available
- Consistency: Solid, crystalline powder

RADIOLABELLING INFORMATION (Not applicable)
- Radiochemical purity: N/A
- Specific activity: N/A
- Locations of the label: N/A
- Expiration date of radiochemical substance: N/A

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient Temperature
- Stability under test conditions: No data available
- Solubility and stability of the test substance in the solvent/vehicle: No data available
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data available

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item was grounded to fine powder prior to application. The particulates were moistened
with distilled water before application.
- Preliminary purification step (if any):No data available
- Final dilution of a dissolved solid, stock liquid or gel: No data available
- Final preparation of a solid: No data available

FORM AS APPLIED IN THE TEST: Paste

OTHER SPECIFICS:
Safety Precautions : Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses).

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: No data available
- Age at study initiation: Young adult male and female rats aged between 8 – 12 weeks were used.
- Weight at study initiation: The weight range of approximately 222.8 to 255.5 grams at initiation of dosing.
Body weights at the start :
Male
Mean : 249.84 g (= 100 %)
Minimum : 244.7 g (- 2.06 %)
Maximum : 255.5 g (+ 2.27 %)
Total No. of animals : 5
Female
Mean : 226.06 g (= 100 %)
Minimum : 222.8 g (- 1.44 %)
Maximum : 230.6 g (+ 2.01 %)
Total No. of animals : 5
- Identification: Each rat was individually identified by the cage number.
- Fasting period before study: No data available
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 22.5 degree centigrade.
- Humidity (%): 53.2% to 58.8%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES: 20-07-2017 to 04-08-2017

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

(Distilled water)

Details on dermal exposure:

TEST SITE
- Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: Approximately 10% of the body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: Yes

Duration of exposure:

24 hours

Doses:

A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).

No. of animals per sex per dose:

10 (5/sex).

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical Observations and General Appearance: Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time. The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.
Evaluation of Dermal Reaction: Dermal reaction was observed daily for study period of 14 days.
Body weights: Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14.
Gross Pathology: Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).
Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.
Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.

Clinical signs:

other: Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result i

Gross pathology:

Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.

Other findings:

- Other observations: Evaluation of Dermal Reaction
Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.

Table No. I

Summary of Clinical Signs of Toxicity and Mortality

Test System : Sprague Dawley Rat

Sex : Male

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No clinical signs observed	5	1 - 5	Day 0 - Day 14	0/5

Sex : Female

Group  No.	Dose mg/kg	Observed Signs	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No clinical signs observed	5	6 - 10	Day 0 - Day 14	0/5

 

 

 Table No. II

Summary of Evaluation of Dermal Reaction

Test System : Sprague Dawley Rat

Sex : Male 

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No dermal reaction observed	5	1 - 5	Day 0 - Day 14	0/5

 

 

Sex : Female

Group  No.	Dose mg/kg	Dermal Reaction	Total Number of Animals	Animal Nos.	Period of signs in days  From - to	Mortality
I	2000	No dermal reaction observed	5	6 - 10	Day 0 - Day 14	0/5

 

 

Table No.III

Mean Body Weight and Percent Body Weight Gain (g)

Test System : Sprague Dawley Rat

Sex : Male

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	2000	Mean	249.84	271.82	8.77	295.12	8.57	18.10
		± SD	4.50	10.00	2.30	10.93	0.33	2.60

 

 Sex : Female

Group No.	Dose (mg/kg body weight)		Body weight Day 0	Body weight Day 7	% body weight gain day 0-7	Body weight Day 14	% body weight gain day 7- 14	% body weight gain day 0- 14
I	2000	Mean	226.06	239.92	6.11	251.88	4.98	11.40
		± SD	3.30	7.03	1.66	7.90	0.74	1.99

 

 

Table No.IV

Summary of Gross Pathological Findings

Test System : Sprague Dawley Rat

Sex : Male

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	2000	1 - 5	TS	No abnormality detected

 

Sex : Female

Group No.	Dose mg/kg	Animal Numbers	Animal Fate	Gross Pathological Findings
I	2000	6 - 10	TS	No abnormality detected

 TS = Terminal Sacrifice

Interpretation of results:

other: Not classified

Conclusions:

It was concluded that the acute dermal median lethal dose (LD50) of Ethyl 2-naphthyl ether (CAS No. 93-18-5), when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that Ethyl 2-naphthyl ether (CAS No. 93-18-5) does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

Executive summary:

The reported study was designed and conducted to determine the acute dermal toxicity profile of Ethyl 2-naphthyl ether (CAS No. 93-18-5) in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. It was concluded that the acute dermal median lethal dose (LD₅₀) of Ethyl 2-naphthyl ether (CAS No. 93-18-5), when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that Ethyl 2-naphthyl ether (CAS No. 93-18-5) does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data is Klimisch 1 and from experimental study report.

Additional information

Acute oral toxicity:

In different experimental studies, Ethyl 2-naphthyl ether (CAS No. 93-18-5) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for Ethyl 2-naphthyl ether. The studies are summarized as below –

The reported study was designed and conducted to determine the acute oral toxicity profile of Ethyl 2-naphthyl ether (CAS No. 93-18-5) in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in polyurea, diarrhoea and ataxic gait with onset on day 2 after the dosing and no mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg resulted in polyurea, diarrhoea and ataxic gait with onset from day 1 to day 2 after the dosing and no mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. The acute oral LD50 value of Ethyl 2-naphthyl ether (CAS No. 93-18-5) was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of Ethyl 2-naphthyl ether (CAS No. 93-18-5), when administered via oral route in Sprague Dawley rats falls into the “Category Not classified” criteria of CLP.

The above experimental study is supported with the study mentioned in peer-reviewed journals, handbooks, authoritative database and secondary sources, for the target chemical Ethyl 2-naphthyl ether (CAS no: 93-18-5). The acute oral toxicity study was conducted in male and female rats at the dose concentration range of 1940-5500 mg/kg bw. 50% mortality was observed at 3110 mg/kg bw. Therefore, LD50 value was considered to be 3110 mg/kg bw, with 95% confidence limits of 1940-5500 mg/kg bw, when male and female rats were treated with Ethyl 2-naphthyl ether (CAS no: 93-18-5) via oral route.

Both the above experimental studies are contradicted with the study mentioned in publication and secondary source, for the target chemical Ethyl 2-naphthyl ether (CAS no: 93-18-5). In an acute oral toxicity study, 6 male and female deer mice were treated orally used per geometrically spaced dosage level and observed for 3 days for mortality. Each mouse was offered 25 white wheat seeds treated with 2.0% (wt/wt) of the test chemical daily for 3 days. The statistical method used to estimate the acute oral LD50 is Thompson (1948) and Thompson and Weil. No mortality was observed in treated mice up to 1213 mg/kg bw. Therefore, LD50 was considered to be >1213 mg/kg bw, when deer mice were treated with Ethyl 2-naphthyl ether (CAS no: 93-18-5) orally by gavage.

From the above experimental studies, maximum number of studies concluded that the LD50 value is >2000 mg/kg bw, with detailed and reliable data. Also, the test animal “rats” are most preferred in animal toxicity studies. Thus, comparing this value with the criteria of CLP regulation, Ethyl 2-naphthyl ether (CAS no: 93-18-5) cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

According to column 2 of REACH Annex VIII, the acute toxicity inhalation study need not be conducted because exposure of humans via inhalation route is not likely taking into account the low vapour pressure of the substance Ethyl 2-naphthyl ether (CAS no: 93-18-5),which is reported as 0.5182 Pa (0.00389 mm Hg). Also considering the particle size distribution of the substance the majority of the particle size was determined to be in the range of 150-53 micron which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver.

Acute Dermal toxicity:

In different studies, Ethyl 2-naphthyl ether (CAS no: 93-18-5) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats and rabbits for Ethyl 2-naphthyl ether. The studies are summarized as below –

The reported study was designed and conducted to determine the acute dermal toxicity profile of Ethyl 2-naphthyl ether (CAS No. 93-18-5) in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. It was concluded that the acute dermal median lethal dose (LD50) of Ethyl 2-naphthyl ether (CAS No. 93-18-5), when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that Ethyl 2-naphthyl ether (CAS No. 93-18-5) does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

The above experimental study is supported with the study mentioned in publication and authoritative database, for the target chemical Ethyl 2-naphthyl ether (CAS no: 93-18-5) was conducted in rabbits at the dose concentration of 5000 mg/kg bw. No mortality was observed at 5000 mg/kg bw. Therefore, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with Ethyl 2-naphthyl ether (CAS no: 93-18-5) by dermal application.

Thus, based on the above experimental studies on Ethyl 2-naphthyl ether (CAS No. 93-18-5), it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Ethyl 2-naphthyl ether cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above experimental studies on Ethyl 2-naphthyl ether (CAS No. 93-18-5), it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral and acute dermal toxicity. Thus, comparing these values with the criteria of CLP regulation, Ethyl 2-naphthyl ether (CAS No. 93-18-5) cannot be classified for acute oral and acute dermal toxicity.For acute inhalation toxicity wavier were added so, not possible to classify.