2-(3,3-dimethylcyclohex-1-enyl)-2,5,5-trimethyl-1,3-dioxane

Endpoint summary

Description of key information

Oral LD50 > 2000 mg/kg bw (OECD 423, K, Rel.1)

Dermal LD50 > 2000 mg/kg bw (OECD 402, K, Rel.1)

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:

From 22 July to 6 August, 2015.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 423 with minor deviation: a relative humidity higher than 70% was registered only in one day. This deviation does not affect the quality of the study.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 December 2001.

Deviations:

yes

Remarks:

a relative humidity higher than 70% was registered only in one day. The maximum value measured was 71%. This deviation do not affect the quality of the study and are not considered to be relevant.

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

a relative humidity higher than 70% was registered only in one day. The maximum value measured was 71%. This deviation do not affect the quality of the study and are not considered to be relevant.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2013-06-3&4 / Signed on 2013-09-13

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle, France)
- Age at study initiation: 8 weeks
- Weight at study initiation: 174 - 204 g
- Housing: housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff (A04, SAFE), ad libitum but food was removed at D-1 and then redistributed 4 hours after the test item administration.
- Water: tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70%
- Air changes: at least ten changes per hour.
- Photoperiod: 12 h light/12 h darkness.

IN-LIFE DATES: From 22 July to 06 August 2015.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.11 mL/kg bw

ADMINISTRATION OF TEST ITEM:
Animals received an effective dose of 2000 mg/kg bw of the test item, administered by force-feeding under a volume of 2.11 mL/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min, 1, 3 and 4 hours after test item administration and thereafter once daily for 14 days. Animals were weighed pretest (Day 0) and on Day 2, 7 and 14.
- Necropsy of survivors performed: Yes; Animals were killed on Day 14 and subjected to macroscopic examination.

Statistics:

None

Preliminary study:

Not applicable

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occurred during the study.

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical signs related to the administration of the test item were observed during the study.

Gross pathology:

The macroscopic axamination of the animals at the end of the study did not reveal treatment related changes.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the oral LD50 for test substance is higher than 2000 mg/kg bw and the LD50 cut-off may be considered to be higher than 5000 mg/kg bw in female rats. Therefore, the substance is not classified according to the annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, 6 female Sprague Dawley rats were given a single oral (gavage) dose of test item at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

No mortality occurred during the study. No clinical signs related to the administration of the test item were observed during the study. The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals. The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

 

Under the test conditions, the oral LD50 for test substance is higher than 2000 mg/kg bw and the LD50 cut-off may be considered to be higher than 5000 mg/kg bw in female rats. Therefore, the substance is not classified according to the annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP compliant and of high quality.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

Between 22 July and 05 August, 2015.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 402 with minor deviation: a relative humidity higher than 70% was registered. The maximum value measured was 71%. This deviation is considered as without impact on the conclusion of the study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987.

Deviations:

yes

Remarks:

A relative humidity higher than 70% was registered. The maximum value measured was 71%. This deviation is considered as without impact on the conclusion of the study.

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

A relative humidity higher than 70% was registered. The maximum value measured was 71%. This deviation is considered as without impact on the conclusion of the study.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2013-06-3&4 / Signed on 2013-09-13.

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:

TEST ANIMALS
- Source: Elevage JANVIER (539040 Le Genest St Isle-France)
- Age at study initiation: 7 weeks (males) and 8 weeks (females)
- Weight at study initiation: 231 - 255 g (males) and 206 - 219 g (females).
- Housing: Animals were housed individually during the 24 h exposure period and in groups of five by sex for the remainder of the study in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff (SAFE - A04), ad libitum
- Water: tap-water (from public distribution), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: at least 10 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: from 22 July to 05 August, 2015.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back and flank area
- % coverage: approximately 10% of the total body surface area.
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none reported.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw administered under a volume of 2.11 mL/kg bw, during 24 hours.
- Constant volume or concentration used: Yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality or clinical signs of toxicity at 1, 3 and 5 h after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the Draize scale.
- Necropsy of survivors performed: Yes; at the end of the study animals were anaesthetised with sodium pentobarbitol and administration continued to fatal levels. After, they subjected to gross necropsy.

Statistics:

None

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed.

Mortality:

No mortality was observed.

Clinical signs:

other: - No signs of systemic toxicity were noted during the observation period. - Dermal reactions: slight erythema was noted on the treated area in females of treated group, 48 h post dose. The skin recovered a normal aspect on day 5.

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal treatment- related changes.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the dermal LD50 Combined for test substance is higher than 2000 mg/kg bw in rats. Therefore, the substance is not classified according to the annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute dermal toxicity study (limit test) performed according to OECD Guideline No. 402 and in compliance with GLP, a group of Sprague Dawley rats (5/sex) was given a single dermal application of the test material to intact skin of the back and flank area at a dose level of 2000 mg/kg bw. Test sites were covered with a semi-occlusive dressing for 24 h. Animals were observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. Skin irritation was assessed and scored according to the Draize scale at 24 h after removal of the dressings and then daily for 14 days. 

No mortality or systemic toxicity was observed. Slight erythema was noted on the treated area in females of treated group, 48 h post dose. The skin recovered a normal aspect on day 5. All animals showed gains in body weight over the observation period. No abnormalities were noted at necropsy.

 

Dermal LD50 Combined > 2000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS. 

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP compliant and of high quality.

Additional information

Acute toxicity: oral

A key study was identified (Phycher, 2015, rel.1). In this acute oral toxic class method study performed according to the OECD guideline No. 423 and in compliance with GLP, six female Sprague Dawley rats received a single oral (gavage) dose of the test substance at a dose level of 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

No mortality occurred during the study. No clinical signs related to the administration of the test item were observed during the study.The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals. The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

 

Oral LD50 > 2000 mg/kg bw

Acute toxicity: dermal

A key study was identified (Phycher, 2015, rel.1). In this acute dermal toxicity study (limit test) performed according to OECD Guideline No. 402 and in compliance with GLP, a group of SD rats (5/sex) was given a single dermal application of the undiluted test material to intact skin of the back and flank area at a dose level of 2000 mg/kg bw. Test sites were covered with a semi-occlusive dressing for 24 h. Animals were observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. Skin irritation was assessed and scored according to the Draize scale at 24 h after removal of the dressings and then daily for 14 days. 

No mortality or systemic toxicity was observed. Slight erythema was noted on the treated area in females of treated group, 48 h post dose. The skin recovered a normal aspect on day 5. All animals showed gains in body weight over the observation period. No abnormalities were noted at necropsy.

Dermal LD50 Combined > 2000 mg/kg bw

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 (CLP).

 

Self classification:

Acute toxicity (Oral):

Based on the available information, the substance is:

- not classified according to the CLP as the oral LD50 is higher than 2000 mg/kg bw

- not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

 

Acute toxicity (Dermal):

Based on the available information, the substance is:

- not classified according to the CLP as the dermal LD50 is higher than 2000 mg/kg bw

- not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

 

Acute toxicity (Inhalation):

No information was available. Not required for substances at the REACH Annex VII tonnage level.

 

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to CLP and to the GHS are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and the GHS are not met since narcotic effects were not observed in the acute oral toxicity study.

 

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the CLP and to the GHS are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw ≥ C > 1000 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute dermal toxicity study.

 

Specific target organ toxicity: single exposure (Inhalation):

No information was available. Not required for substances at the REACH Annex VII tonnage level.

 

Aspiration hazard:

The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.