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Description of key information

The test item cyclohexylvinylether was tested for acute oral toxicity in a GLP study according  to OECD 423 on oral gavage in rats. The LD50 was determined to be greater than 2000 mg/kg bw in female rats.
The test item cyclohexylvinylether was tested for acute dermal toxicity in a GLP and guideline study according to OECD guideline 402 on dermal administration in rats. The LD50 was determined to be greater than 2000 mg/kg bw in male and female rats.
The test item cyclohexylvinylether was tested for acute inhalation toxicity in a GLP study according to OECD 403 in rats. Under the conditions of this study the LC50 for male and female rats after vapor inhalation exposure of Cyclohexylvinylether was estimated to be > 22007 mg/m3(analytical concentration).

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
Study period:
2011-08-10 to 2012-02-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is regarded as reliable without restrictions because it was conducted in compliance with GLP regulation and guideline. The study is scientifically well described and complete in any parts.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted: 2001-12-17
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
adopted: 2008-05-30
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
adopted 2002-12
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF TG of 12 Nosan No. 8147
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Young adult animals (female animals approx. 10 weeks)
- Weight at study initiation: Animals of comparable weight (mean weight 171 g)
- Fasting period before study: 16 hours before administration
- Housing: Makrolon cage, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water (e.g. ad libitum): Tap water
- Acclimation period: Acclimatization period of at least 5 days before the beginning of the experimental phase


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 p.m. - 6.00 a.m. / 6.00 a.m. - 6.00 p.m.)
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Maximim dose volume applied: 2.30 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 femal rats per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation
- Necropsy of survivors performed: Necropsy with gross-pathology examination
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured.
Clinical signs:
Clinical signs in the first test group revealed impaired general state, dyspnoea and piloerection and were observed in all animals from hour 2, 3 or 4 until hour 5 after administration.
In the second administration group two animals showed impaired general state, dyspnoea and piloerection from hour 0 or 1 until study day 1. Non feces and exsiccosis in both animals and staggering in one animal were observed at study day 1. On study day 2 reduced feces was noted in one of these animals. In the third animal of this group dyspnoea and piloerection were observed from hour 1 until study day 3 after administration. Furthermore impaired general state was noted from hour 1 until hour 3 and at day 2 und 3, which increased temporarily to poor general state from hour 4 until study day 1.
This animal showed abdominal position from hour 4 until study day 1 and exsiccosis on study day 1 und 2.
Additionally non feces, atonia, lacrimation, pain and corneal reflex absent and narcotic like state were observed in this animal at study day 1 while reduced feces was observed on study day 2.
Body weight:
The mean body weight of the test groups increased throughout the study period within the normal range.
Gross pathology:
There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
One GLP and guideline study available and two supporting study not in compliance with GLP regulation.

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
Study period:
2011-08-02 to 2012-02-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
07 September 2009
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
Commission Regulation (EC) No 440/2008 of 30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst, NIEDERLANDE
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 10 weeks
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study:
- Housing: Single housing or up to 5 animals
- Diet : Kliba-Labordiät (Maus / Ratte Haltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland
- Water : Tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24°C
- Humidity (%): 30 – 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 60 (glass-steel construction, BASF SE)
- Exposure chamber volume: 90 L
- Method of holding animals in test chamber: Animals were restrained in glass tubes and their snouts projected into the inhalation system.
- Source and rate of air: Compressed air is produced by an oil-free compressor (HT 6, Josef Mehrer GmbH & Co KG, Germany). For this purpose, air is filtered by an inlet air strainer and introduced into the compressor. After passed through an second ultra filter (SMF 5/3, 108 mm, Donalson), the compressed air (15 bar) is stored in a storage of 1500 or 5000 L. The compressed air is conducted to the labs via pipes, where the pressure is reduced to 6 bar.
- Method of conditioning air: Central air conditioning system provides cold air of about 15°C. This cold air will pass through an activated charcoal filter, be adjusted to room temperature of 20 to 24°C and pass through a second particle filter (H13 (HEPA) Camfil Farr, Germany). The so generated conditioned air is used to generate inhalation atmospheres.
- System of generating vapour: The vapor was generated by supplying amounts of the test substance to the heated vaporizer by means of the pump. The vapors that developed were taken up by the supply air and passed into the exposure system after mixing with dilution air inside the mixing vessel.
- Method of particle size determination:
- Treatment of exhaust air: The exhaust air is filtered and conducted into the exhaust air of the building.
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: For the quantitative determination of the vapor concentration, a gas chromatographic method method was used.
- Samples taken from breathing zone: yes, immediately adjacent to the animals' noses at a separate spare port

CLASS METHOD
- Rationale for the selection of the starting concentration: The selection of the concentration for the test group was based on the limit test, OECD Guidelines, method 403; Commission Regulation (EC) No 440/2008 and Environmental Protection Agency (EPA) guidelines because from the available information concerning the test substance no pronounced inhalation toxicity was expected.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The nominal concentration was calculated from the amount of test substance dosed and the supply air flow.
Duration of exposure:
4 h
Concentrations:
22.007 mg/L (measured)
No. of animals per sex per dose:
Five male and five female rats were used for the test group.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights once during the acclimatization period, shortly before exposure (day 0) and at least on days 1, 3 and 7, and before the sacrifice of the animals at the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, organ weights, pathology
Statistics:
Binomial test
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 22.007 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No lethality occurred at the tested concentration of 22.007 mg/L during the study period of 14 days.
Clinical signs:
No abnormalities were detected in the animals during the post exposure observation period from study day 2 onwards.
Body weight:
The mean body weights of the animals decreased during the first post exposure observation day and increased from study day 3 onward.
Gross pathology:
No gross pathological abnormalities were detected during the necropsy in the animals at the termination of the study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
22 007 mg/m³
Quality of whole database:
One GLP and guideline study available and one supporting study not in compliance with GLP regulation.

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
Study period:
2011-08-24 to 2012-02-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Young adult animals (male animals approx. 8 weeks, female animals approx. 10 weeks)
- Weight at study initiation: males: mean 244.4 g; females: mean 205.4 g
- Fasting period before study: no
- Housing: Single housing in Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C
- Humidity: 30 – 70%
- Photoperiod: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

IN-LIFE DATES: From: 2011-08-31 To: 2011-09-14
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: about 40 cm²
- % coverage: at least 10% of the body surface
- Type of wrap if used: The test item was covered with an air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw
- Concentration: undiluted
- Constant volume or concentration used: 2.30 mL/kg bw


Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: daily; weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
Statistics:
NA
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Systemic effects: No systemic clinical signs were observed during clinical examination.
Local effects: No local effects were observed.
Body weight:
The mean body weight of the animals increased throughout the study period within the normal range.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Other findings:
None
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
GLP and guideline conform study.

Additional information

Acute oral toxicity:

In the key study, the test item cyclohexylvinylether was tested for acute oral toxicity in a GLP study according to OECD TG 423 acute toxic class method by oral gavage in rats. Two groups of three female animals were administered a dose of 2000 mg/kg bw. No mortality occurred in the observation period. Thus, the LD50 was determined to be greater than 2000 mg/kg bw in femal rats. (BASF, 2012).

In a second supporting study, the test item cyclohexylvinylether was tested for acute toxicity in a non-GLP study equivalent or similar to OECD 401 by oral gavage in rats. Five males and five female animals were administered doses of 6400 mg/kg bw, 3200 mg/kg bw, 1600 mg/kg bw and 200 mg/kg bw. In the highest dose, 9 of 10 animals died within a 7 days observation period. In the mid dose of 3200 mg/kg bw, 3 animals died within the 7 days observation period. In the 1600 mg/kg bw dose one animal died within the 7 days observation period, and no further animals died within 14 days observation. No animal died within the lowest dose group of 200 mg/kg bw in the 14 days observation period. The LD50 was determined to be 3100 mg/kg bw in male and female rats (BASF, 1964).

In a third experiment, the test item was administered orally by gavage to White Vienna rabbits at a dose of 2 mL/kg bw. The observation period was 7 days. Two of the three animals died within 24 hours after administration of the test item. The third animal was sacrified after the 7 day observation period. In the same study the test material Cyclohexylvinylether was administered orally by gavage at a dose of 1 mL/kg bw to 2 male and 2 female White Vienna rabbits. One animal died within 3 days after beginning of the study. The remaining three animals were sacrificed at termination of the study. All animals showed narcosis about 1 to two hours after administration of the test item. In the lowest dose group, animals showed also atony, apathy, latheral position and fluctuating movement. These symptoms ceased on the day after application. All surviving animals were sacrificed after the 7 days observation period and necropsied, as well as the animals who had died during the study. Necropsy showed lung edema, lung congestion, and increased thoracal fluids in the animals died during the study. In surviving animals, no pathological findings were seen. No estimation of an acute oral LD50 value was performed in this study (BASF, 1964).

 

Acute inhalation toxicity:

To determine the acute inhalation toxicity (single 4-hour exposure, head-nose only) of cyclohexylvinylether as a vapour, a study was performed in male and female Wistar rats according to OECD-Guideline method 403, as well as EC and EPA guidelines. A measured concentration of 22.007 mg/L was tested (analytical concentration, limit test). No mortality occurred at the tested concentration. Clinical signs of toxicity comprised depressed and labored respiration, intermittent respiration, unsteady gait, piloerection. These various findings were observed from hour 1 of exposure through to study day 1. No abnormalities were detected in the animals during the post exposure observation period from study day 2 onwards. The mean body weights of the animals decreased during the first post exposure observation day and increased from study day 3 onward. No gross pathological abnormalities were detected during the necropsy in the animals at the termination of the study. Under the conditions of this study the LC50 for male and female rats after vapor inhalation exposure of Cyclohexylvinylether was estimated to be > 22007 mg/m3(analytical concentration) (BASF, 2012).

In a supporting study, the test item cyclohexylvinylether was tested for acute inhalation toxicity in a non-GLP study equivalent or similar to OECD 403 in rats. In a first experiment, 6 male and 6 female rats were exposed for a period of 8 hours to an atmosphere saturated with the test item. The test item concentration was determined to 25.49 mg/L air. Test animals were observed for a seven day period. 5/12 animals died in the first experiment.

In a second experiment, 6 male and 6 female rats were exposed for a period of 3 hours to an atmosphere saturated with the item. The test item concentration was determined to be 37.55 mg/L air. Test animals were observed for a seven day period. 2/12 animals died in the second experiment. In a third experiment, 6 male and female rats were exposed for a period of 1 hour to an atmosphere saturated with the test item. The test item concentration was determined to be 36.1 mg/L air. Test animals were observed for a seven day period. No animals died in the third experiment. All animals were sacrified after the 7 days observation period. All dead and sacrified animals were necropsied. During the test period, in all test groups animals showed narcosis, gasping, nose and eye secretion. In the 8 h exposure group, the animals who died during the test period showed lung and liver congestion and defattening of the adrenal cortex. All surviving animals showed no clinical signs on necropsy. An inhalation LC50 could not be derived from this study. An inhalation LC0 was estimated to be 36100 mg/m³ air for 1 h exposure duration (BASF, 1964).

 

Acute dermal toxicity:

In the key acute dermal toxicity GLP and OECD guideline 402 study (Limit Test) , young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of undiluted Cyclohexylvinylether to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi- occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. The following test item-related effects were recorded during the course of the study: No mortality occurred. No signs of systemic toxicity or skin effects were observed. The mean body weight of the animals increased within the normal range throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg bw in rats (Bioassay, 2012).

 

Acute toxicity: Other routes

In a further non-standard, non-GLP supporting study, Cyclohexylvinylether was tested for acute toxicity in mice. The test item was administered intraperitoneal as an aqueous emulsion to 5 male and 5 female Hannover mice in test concentrations of 1600, 200, 160 125, 100 and 50 mg/kg bw. The observation period was 14 days. The mortality rates were 10/10, 7/10, 8/10, 7/10 1/10 and 2/10. At the end of the observation period, all surviving animals were sacrificed and necropsied as well as all animals died during the study. 5 animals showed minor adhesions in the abdominal cavity. No further pathological signs could be detected. The LD50 on intraperitoneal administration was determined to be approximately 0.11 mL/kg bw, corresponding to a LD50 of approximately 98 mg/kg bw, assuming a density of 0.89 g/mL of the test item (BASF, 1964).


Justification for selection of acute toxicity – oral endpoint
GLP and guideline conform study.

Justification for selection of acute toxicity – inhalation endpoint
GLP and guideline conform study of current date.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

The test item Cyclohexylvinylether was tested for acute toxicity by oral, dermal and inhalation exposure. The oral acute LD50 was determined to be >2000 mg/kg bw. The inhalation LC50 was found to be 36100 mg/m³ air. The acute dermal LD50 was determined to be greater than 2000 mg/kg bw. No classification and labelling for acute oral, dermal, and inhalation toxicity is necessary according to Directive 67/548/EEC (DSD) or Regulation (EC) No 1272/2008 (CLP, GHS) criteria.