2-(ethoxymethyl)oxolane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The work described was performed in compliance with UK GLP standards (Schedule 1, Good Laboratory Practice Regulations 1997 (SI 1997/654)). These Regulations are in accordance with GLP standards published as OECD Principles on Good Laboratory Practice (revised 1997, ENV/MC/CHEM(98)17); and are in accordance with, and implement, the requirements of Directives 87/18/EEC and 88/320/EEC.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report Date:

1999

Materials and methods

Test guideline

Qualifier:

according to

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. certificate)

Test type:

acute toxic class method

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

Description, Identification and storage conditions

-Sponser's Identification: Ethyl Tetrahydrofurfuryl Ether
-Date Recieved: 18 November 1998

Data relating to the identity, purity and stability of the test material are responsibilty of the Sponsor.
-Description: Colourless Liquid
-Storage Conditions: Room Temperature in the dark under nitrogen

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Doses:

Using all available information, 2000 mg/kg bodyweight was selected as the starting dose.

A group of three fasted females was treated with the starting dose of 2000 mg/kg. This was followed by a group of three fasted males at the same
dose level.

No. of animals per sex per dose:

3 females per starting dose of 2000 mg/kg
3 males per starting dose of 2000 mg/kg

Details on study design:

The information available suggested a starting dose of 2000 mg/kg.
All animals were dosed once only by gavage, using a metal cannula attached to a graduate syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each sex to confirm the survival of the previously dosed animals.

Animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

Individual bodyweights were recorded prior to dosing and seven and fourteen days aftyer treatment.

At the end of the observtion period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths

Clinical signs:

Common signs of systemic toxicity noted in males and females were prostration, loss of righting reflex, decreased respiratory rate, laboured respiration, coma, prosis and hunched posture. Dehydration and pilo-erection were also commonly noted in males with lethargy and ataxia also commonly noted in females. Incidents of increased salivation and emaciation were noted in males and incidents of dehydration and pilo-erection in females. Isolated incidents of lethargy were noted in males and isolated incidents of splayed gait and red/brown staining around eyes noted in females.

Females recovered three or four days after dosing and males recovered six days after dosing.

Body weight:

All animals showed expected gains in bodyweight over the study period.

Other findings:

Necropsy: No abnormalties were noted at necrospy.

Any other information on results incl. tables

MORTALITY DATA

Dose Level mg/kg	Sex	Number of Animals Treated	Deaths During Day of Dosing (Hour)				Deaths During Period After Dosing (Days)								Deaths
			1/2	1	2	4	1	2	3	4	5	6	7	8 -14
2000	Male	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3
	Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3

INDIVIDUAL BODYWEIGHTS AND WEEKLY BODYWEIGHT CHANGES: FEMALE

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	1 - 0 Female	223	281	297	58	16
	1 - 1 Female	243	250	263	7	13
	1 - 2 Female	238	271	282	33	11

INDIVIDUAL BODYWEIGHTS AND WEEKLY BODYWEIGHT CHANGES: MALE

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	2 - 0 Male	216	254	323	38	69
	2 - 1 Male	219	271	342	52	71
	2 - 2 Male	232	233	309	1	76

INDIVIDUAL CLINICAL OBSERVATIONS: FEMALE

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
2000		1/2	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
	1 - 0 Female	RrRdRl	RrRdRl	CoRd RlPt	CoRd RlPt	HPRd RdRl DhWs	HPRd RIDh	HP	0	0	0	0	0	0	0	0	0	0	0
	1 - 1 Female	PrRdRl	RrRdRl	CoRdRlPt	CoRdRlPt	HLARdRISe	H	0	0	0	0	0	0	0	0	0	0	0	0
	1 - 2 Female	PrRdRl	RrRdRl	CoRdRlPt	CoRdRlPt	HLARdRI	H	0	0	0	0	0	0	0	0	0	0	0	0

INDIVIDUAL CLINICAL OBSERVATIONS: MALE

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
2000		1/2	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
	2 - 0 Male	PrRdRl	RrRdRl	RrRdRl	CoRd RlPt	HLPRd RIDh	H	H	H	H	0	0	0	0	0	0	0	0	0
	2 - 1 Male	HLARd RI	RrRdRl	RrRdRl	CoRdRlPt	HPDhRdRI	H	H	H	H	0	0	0	0	0	0	0	0	0
	2 - 2 Male	HLASRdRI	PrSRdRI	RrRdRl	CoRdRlPt	HPRdRI	HPEm	HEm	H	H	0	0	0	0	0	0	0	0	0

INDIVIDUAL NECROPSY FINDINGS: FEMALE

Dose Level mg/kg	Animal Number and Sex	Macroscopic Observations
	1 - 0 Female	No abnormalities detected
	1 - 1 Female	No abnormalities detected
	1 - 2 Female	No abnormalities detected

INDIVIDUAL NECROPSY FINDINGS: MALE

Dose Level mg/kg	Animal Number and Sex	Macroscopic Observations
	2 - 0 Female	No abnormalities detected
	2 - 1 Female	No abnormalities detected
	2 - 2 Female	No abnormalities detected

A= Ataxia

Co = Coma

Dh = Dehydration

Em = Emaciation

H = Hunched Posture

L = Lethargy

P = Pilo-erection

Pr = Prostration

Pt = Ptosis

Rd = Decreased respiratory rate

Rl = Laboured respiration

Rr = Loss of righting reflex

Ws = splayed gait

Se = red/brown staining around eyes

S= increased salivation

O = no signs of systemic toxicity

Applicant's summary and conclusion

Conclusions:

The acute oral LD50 of the test material, ETHYL TETRAHYDROFURFURYL, in the SPrague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg.

No mortalities were noted at 2000 mg/kg bodyweight.