2-isobutyl-4-methyltetrahydro-2H-pyran-4-yl acetate

Endpoint summary

Description of key information

Oral:

The discriminating dose of the test substance in rat was ≥ 2000 mg/kg bw (BASF SE, 2017).

Dermal:

The discriminating dose of the test substance in rat was ≥ 2000 mg/kg bw (BASF SE, 2017).

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:

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch no.: ZH 291 A1 Fr.2-4
- Expiration date of the lot/batch: 2018-08

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young adults, ~10 weeks
- Weight at study initiation:
Group 1: 175.0 ±3.00 g
Group 2: 177.3 ±3.06 g
- Fasting period before study: Feed ~16 h before administration
- Housing: single housing in Makrolon cage, type III
- Diet: ad libitum, VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: ad libitum, tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): ~10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.08 mg/kgbw

CLASS METHOD:
- Rationale for the selection of the starting dose: request of the sponsor

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 female

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 (d7) and on the last day of observation (d14).
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

No clinical signs were observed.

Body weight:

All animals of group 1 showed a normal growth rate. In group 2, a decreased growth rate was observed in 2 out of 3 animals in the second week after administration. This effect was observed at times when the female rats have already reached slow growth age.

Gross pathology:

There were no macroscopic pathological findings in all animals sacrificed at the end of the observation period.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 1 study accoring to guideline and GLP

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: ZH 291 A1 Fr.2-4
- Expiration date of the lot/batch: 2018-08

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: ♂ ~ 8 weeks, ♀ ~ 12 weeks
- Weight at study initiation: ♂ 245.0 ± 2.55 g, ♀ 198.8 ± 7.85 g
- Housing: single housing in Makrolon cage, type III
- Diet: ad libitum, VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): ~ 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ~ 40 cm²
- % coverage: at least 10 %
- Type of wrap if used: 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: warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 2.08 mL/kg bw
- Concentration: 2000 mg/kg bw
- 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:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before application (day 0), weekly thereafter (d7) and on the last day of observation (d14).
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

No systemic or local clinical signs were observed.

Body weight:

The body weight of the animals increased within the normal range throughout the study period.

Gross pathology:

No macroscopical pathological abnormalities were observed.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 1 study accoring to guideline and GLP

Additional information

Oral:

In an acute oral toxicity study performed according to the Acute Toxic Class Method (OECD Guideline 423), 2000 mg/kg bw of the undiluted test substance pyranyl acetate pure were administered by gavage to two test groups of three fasted Wistar rats each (6 females). Clinical signs occurred within the first day after administration. The following test substance-related clinical observations were recorded:

• No mortality occurred
• Impaired general state in all animals
• Piloerection in all animals
• No macroscopic abnormalities
• Body weight increase within the normal range

 

The body weights of the animals of the first test group increased within the normal range throughout the study period. The mean body weights of the animals of the second administration group increased during the first observation week but did not adequately increase in two animals during the second week. This effect was observed at times when the female rats have already reached slow growth age. There were no macroscopic pathological findings at the end of the observation period.

 

The acute oral LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw.

 

Dermal:

In an acute dermal toxicity study (Limit Test) according to OECD Guideline 402, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of pyranyl acetate pure. The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days with the following results:

• No mortality occurred.
• No signs of systemic toxicity or local skin effects were observed 
• The 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 LD50, dermal, rat > 2000 mg/kg bw.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008.

Discriminating doses for acute oral (> 2000 mg/kg bw) and dermal (> 2000 mg/kg bw) toxicity were determined. As a result the substance is not considered to be classified for acute oral and dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the ninth time in Regulation (EC) No. 2016/1179.