1,4-Dioxaspiro[4.5]decane, 8-[4-(4-methylphenyl)-3-cyclohexen-1-yl]-

Endpoint summary

Description of key information

Based on the results of an acute oral toxicity study according to OECD guideline 423, the LD50 value of the test item is higher than 2000 mg/kg bw after single oral administration in rats. It is concluded that the test material has no acute toxic potential up to the limit dose of 2000 mg/kg bw (reference 7.2.1-1). Mortality after dermal exposure to the test item is not expected as the key acute oral toxicity study showed no effects up to the limit dose of 2000 mg/kg bw and physicochemical properties of the test substance suggest a very low dermal absorption. A study for acute inhalation toxicity does not need to be conducted because exposure of humans via inhalation is unlikely. For this reason, further acute inhalation and dermal toxicity studies will be waived (reference 7.2.2-1 and 7.2.3-1).

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:

April 22, 2003 - July 23, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Official Journal of the European communities No. L 248, September 30, 1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

HsdCpb:WU

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 6 to 11 weeks
- Weight at study initiation: 165 – 185 g
- Fasting period before study: 17 hours before until up to 4 hours after treatment
- Housing: Separately in type III Makrolon cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 49 – 68%
- Photoperiod (hrs dark / hrs light): 12 hour light - 12 hour dark regime
IN-LIFE DATES: From day 1 to day 15

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

Methocel® K4M Premium solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 g/L
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: well tolerated and established standard vehicle

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 (m) / 3 (f)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Daily
- Frequency of weighing: day 1, 2, 4, 6, 8, 11, 13 and 15
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, gross pathology

Statistics:

Standard statistical methods have been applied for data processing.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

All rats survived the observation period.

Clinical signs:

No signs of intoxication occurred after treatment.

Body weight:

Body weight development of the treated rats was normal.

Gross pathology:

At necropsy, no organ alterations were seen.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the result of this study, it is concluded that the test material has no acute toxic potential up to the limit dose of 2000 mg/kg bw. Therefore, the LD50 value is higher than 2000 mg/kg bw after single oral administration in rats.

Executive summary:

The test material was tested for acute toxicity in rats after single oral administration of 2000 mg/kg body weight according to OECD test guideline 423 and under GLP conditions. Directly before administration, the test material was prepared with aqueous Methocel K4M Premium solution as a vehicle. No signs of intoxication occurred after treatment. Body weight development of the treated rats was normal. All the rats survived the observation period. At necropsy, no organ alterations were seen. Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 423.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

According to (EC) No 1907/2006, Annex VIII, 8.5, column 2, at least one other route for substances other than gases shall be tested for acute toxicity in addition to the oral route. As the oral and dermal route have already been addressed, there is no need for further acute inhalation toxicity testing. Furthermore, due to the very low vapour pressure (1.1e-8 hPa) of the substance, exposure of humans via inhalation of vapours is unlikely. Although the test material is composed of relatively small particle sizes, the planned use of the substance at industrial sites is strictrly controlled and prevents exposure of humans to test material dusts.

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Justification for type of information:

The test item is not harmful after single acute oral administration and no clinical signs were observed in the skin irritation test. The test item is structural highly similar to the LC class compounds shown in this report. There exist no additional structural elements of concern. Therefore, it is justified to use the information provided in this report for filling the endpoint of acute dermal toxicity.

This attached report compiles information on LC class compounds that have been tested for acute dermal toxicity. In these assays no effects have been observed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

other: read across information

Remarks on result:

other: see attached justification for details.

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

The test material was tested for acute toxicity in rats after single oral administration of 2000 mg/kg body weight according to OECD test guideline 423 and under GLP conditions. Directly before administration, the test material was prepared with aqueous Methocel K4M Premium solution as a vehicle. No signs of intoxication occurred after treatment. Body weight development of the treated rats was normal. All the rats survived the observation period. At necropsy, no organ alterations were seen. Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

 

Acute dermal toxicity

The evaluation on the necessity of an acute test via the dermal route was done in accordance with Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance, Version 6.0, July 2017, p 374f. A DermWin calculation shows a dermally absorbed dose of 7.7*10^-5 to 5.3*10^-6 mg/cm2/event. Based on the very low dermally absorbed rate and the absence of systemic effects after acute oral administration, a study on acute dermal toxicity is not required. Furthermore, on 15 July 2014, the Competent Authorities for REACH and CLP (Caracal) have agreed that substances that are not toxic in acute oral tests don’t need to be tested for acute dermal toxicity. Caracal agreed on proposals to amend REACH Annex VIII (point 8.5.3) so that substances that have not shown oral acute toxicity up to a limit dose of 2000mg/kg body weight not require dermal data. The test material does not provide evidence for acute oral toxicity. The LD50 exceeds 2000 mg/kg bw. Additionally, the test item is structural highly similar to the LC class compounds shown which are not acute toxic after dermal administration. The test item contains no additional structural elements that would indicate toxicological concerns. Based on the available information, the test item is not considered to be acute toxic after dermal and no further testing for dermal toxicity is justified.

 

Acute inhalation toxicity

According to (EC) No 1907/2006, Annex VIII, 8.5, column 2, at least one other route for substances other than gases shall be tested for acute toxicity in addition to the oral route. As the oral and dermal route have already been addressed, there is no need for further acute inhalation toxicity testing. Furtheromore, due to the very low vapour pressure (1.1e-8 hPa) of the substance, exposure of humans via inhalation of vapours is unlikely. Although the test material is composed of relatively small particle sizes, the planned use of the substance at industrial sites is strictrly controlled and prevents exposure of humans to test material dusts.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

 

The available test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Thus, the test item does not require classification for acute toxicity according to Regulation (EC) No 1272/2008, as amended for fifteenth time in Regulation (EU) No 2020/217.