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Toxicological information

Acute Toxicity: oral

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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  1  2  3  4  5  6  7  8 -14
    2000  Male  3  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  14
       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 4 10  11  12  13  14 
 1 - 0 Female  RrRdRl  RrRdRl CoRd RlPt CoRd RlPt  

 HPRd RdRl

DhWs

HPRd RIDh   HP 0   0
 1 - 1 Female  PrRdRl  RrRdRl  CoRdRlPt CoRdRlPt  HLARdRISe   H  0
 1 - 2 Female  PrRdRl  RrRdRl  CoRdRlPt CoRdRlPt  HLARdRI 

 H

  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 4 10  11  12  13  14 

2 - 0

Male

 PrRdRl  RrRdRl RrRdRl CoRd RlPt  

 HLPRd RIDh

 H H
 2 - 1 Male  HLARd RI  RrRdRl RrRdRl  CoRdRlPt  HPDhRdRI   H  H
 2 - 2 Male  HLASRdRI  PrSRdRI RrRdRl  CoRdRlPt  HPRdRI 

 HPEm

 HEm  H  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.