Isobutyl vinyl ether

Endpoint summary

Description of key information

The oral LD50 in rats was >7700 mg/kg bw.
The dermal LD50 in rabbits was 15400 mg/kg bw.
In acute inhalation studies in rats the LC50 (4 h) was > 21000 mg/m³.  

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Restrictions: purity of test substance not reported; observation period only 7 days; no data about body weight.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(post exposure observation period 7 days)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: Gassner
Mean body weights: 199 g (males), 169 g (females)
no further details

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

aqueous carboxymethyl cellulose (CMC) emulsion, content of IBVE 30%.

Doses:

Dose levels: 6400, 8000, and 10000 µL/kg bw (i.e. 4920, 6150, 7690 mg/kg bw).

No. of animals per sex per dose:

5

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations: daily
- Weighing: initial weight
- Necropsy of survivors performed: yes

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7 700 mg/kg bw

Remarks on result:

other: (10 mL/kg bw); no mortality at this dose level

Mortality:

There was no mortality except 1/5 mid dose female that died within 48 h postdose.

Clinical signs:

other: Low dose animals: stagger within few minutes. Hunched posture, apathy, and dyspnoea within hours. Eyes reddish encrusted for several days. No findings on day 5 postdose and thereafter. Mid and high dose animals: abdominal position, apathy, dyspnoea. Hun

Gross pathology:

General congestion.

Other findings:

no data

Conclusions:

In an acute oral toxicity study in rats the LD50 was >10 mL/kg bw (corresponding to >7700 mg/kg bw) at a post exposure observation period of 7 days.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Mean body weights: 267 and 183 g for male and female rats, respectively
Age: 8 to 9 weeks at start of treatment
Rats received standard diets and water ad libitum
Room temperature was 20-24°C
Relative air humidity 30-70%.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: air

Details on inhalation exposure:

The animals were singly placed into compartments in an inhalation chamber (glass-steel, volume 200 l). Atmosphere was dynamically generated. Air passed an evaporator to which TS was pumped. Vapors were mixed with fresh air. Air was delivered to the inhalation chamber at a rate of 3000 l/h.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

(the concentration was measured using gas chromatography)

Duration of exposure:

4 h

Concentrations:

21.1 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Post exposure period was 14 days.
The animals were observed for clinical signs of toxicity on working days and daily for mortality for 14 days. Body weights were recorded on days 0, 7, and 14. At the end of the observation period the animals were sacrificed and necropsied.

Statistics:

Binominal test (Wittig 1974) was used.

Sex:

male/female

Dose descriptor:

LC0

Effect level:

21.1 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: clinical signs but no mortality, 14 d observation period

Mortality:

no mortality

Clinical signs:

other: During exposure: apathia, stagger, depressed breathing, reddened ears and extremities, unkempt fur. After exposure: unsteady gait. No symptoms were noted from the day following exposure.

Body weight:

Body weight development was comparable to historical controls but slightly delayed in females.

Gross pathology:

No effects detected at necropsy.

Other findings:

no

Conclusions:

In an acute inhalation study in rats no mortality was found after 4 h exposure to 21.1 mg/L and a post exposure period of 14 days (the recommended limit dose according to OECD TG403 is 5 mg/L); LC50 (4h) > 21 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Restriction: purity of test substance not stated; no data on clinical signs; no necropsy; only males.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

Male albino New Zealand rabbits weighing 2.5 to 3.5 kg were used.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Groups of 4 animals were used. Dosages up to 20 mL/kg bw were placed on the shaved rabbit skin under occlusive dressing. The animals were immobilized during the 24 hour contact period.

Duration of exposure:

24 h

Doses:

up to 20 mL/kg bw (corresponding to 15400 mg/kg bw)

No. of animals per sex per dose:

4

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no
- no data about clinical signs & body weight

Statistics:

LD50-values were estimated by the method of Thompson using the tables of Weil, based on mortalities noted during the 14-day observation period.

Sex:

male

Dose descriptor:

LD50

Effect level:

15 400 mg/kg bw

Remarks on result:

other: corresponding to 20 mL/kg bw

No further data available.

Conclusions:

In male New Zealand White rabbits the dermal LD50 was 20 mL/kg bw corresponding to 15400 mg/kg bw. The recommended limit dose according to OECD TG402 is 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

15 400 mg/kg bw

Additional information

Oral application

In an acute oral toxicity study in rats (BASF 1974; 5 male and 5 female rats gavaged with 6400, 8000, or 10000 µL/kg bw corresponding to 4920, 6150, 7690 mg/kg bw) no mortality was found, the LD50 was > 7700 mg/kg bw at a post exposure observation period of 7 days. Clinical signs were detected at >= 4920 mg/lg bw like staggered gait within few minutes and hunched posture, apathy, and dyspnoea within hours. Eyes reddish encrusted for several days. No findings were seen on day 5 postdose and thereafter at the low dose level and at mid and high dose level at day 7 postdose.

In a further study in male rats the LD50 was 13100 mg/kg bw (Smyth et al., 1962, limited documentation).

Inhalation

In an acute inhalation study in rats (BASF1988) no mortality was found after 4 h exposure to 21.1 mg/L and a post exposure period of 14 days (n=5 per sex; the recommended limit dose according to OECD TG403 is 5 mg/L); the LC50 (4h) is > 21 mg/L. During exposure apathia, stagger, depressed breathing, reddened ears and extremities, unkempt fur were recorded and after exposure an unsteady gait. No symptoms were noted from the day following exposure.

No mortality was seen in 6 males and 6 female rats after exposure to the saturated vapour (20°C) for 3 minutes but lethal effects in 2/3 males and 2/3 females at an exposure duration of 10 minutes (estimated concentration 480 mg/L; BASF 1974).

Dermal application

In a study with limited documentation (Smyth et al., 1962) it was reported that in male New Zealand White rabbits (n=4 per dose) the dermal LD50 was 20 mL/kg bw corresponding to 15400 mg/kg bw.

Justification for classification or non-classification

Classification for acute toxicity is not warranted according to the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.